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Sample records for cholinergic enhancement reduces

  1. Cholinergic enhancement reduces orientation-specific surround suppression but not visual crowding.

    PubMed

    Kosovicheva, Anna A; Sheremata, Summer L; Rokem, Ariel; Landau, Ayelet N; Silver, Michael A

    2012-01-01

    Acetylcholine (ACh) reduces the spatial spread of excitatory fMRI responses in early visual cortex and receptive field size of V1 neurons. We investigated the perceptual consequences of these physiological effects of ACh with surround suppression and crowding, two phenomena that involve spatial interactions between visual field locations. Surround suppression refers to the reduction in perceived stimulus contrast by a high-contrast surround stimulus. For grating stimuli, surround suppression is selective for the relative orientations of the center and surround, suggesting that it results from inhibitory interactions in early visual cortex. Crowding refers to impaired identification of a peripheral stimulus in the presence of flankers and is thought to result from excessive integration of visual features. We increased synaptic ACh levels by administering the cholinesterase inhibitor donepezil to healthy human subjects in a placebo-controlled, double-blind design. In Experiment 1, we measured surround suppression of a central grating using a contrast discrimination task with three conditions: (1) surround grating with the same orientation as the center (parallel), (2) surround orthogonal to the center, or (3) no surround. Contrast discrimination thresholds were higher in the parallel than in the orthogonal condition, demonstrating orientation-specific surround suppression (OSSS). Cholinergic enhancement decreased thresholds only in the parallel condition, thereby reducing OSSS. In Experiment 2, subjects performed a crowding task in which they reported the identity of a peripheral letter flanked by letters on either side. We measured the critical spacing between the targets and flanking letters that allowed reliable identification. Cholinergic enhancement with donepezil had no effect on critical spacing. Our findings suggest that ACh reduces spatial interactions in tasks involving segmentation of visual field locations but that these effects may be limited to early

  2. NO-flurbiprofen reduces amyloid β, is neuroprotective in cell culture, and enhances cognition in response to cholinergic blockade

    PubMed Central

    Abdul-Hay, Samer O.; Luo, Jia; Ashghodom, Rezene T.; Thatcher, Gregory R.J.

    2009-01-01

    The nonsteroidal anti-inflamatory drug (NSAID) flurbiprofen is a selective amyloid lowering agent (SALA) which has been studied clinically in Alzheimer’s disease. HCT-1026 is an ester prodrug of flurbiprofen incorporating a nitrate carrier moiety that in vivo provides NO bioactivity and an improved safety profile. In vitro, HCT-1026 retained the COX inhibitory and NSAID activity of flurbiprofen, but at concentrations at which levels of Aβ1–42 were lowered by flurbiprofen, Aβ1–42 levels were elevated 200% by HCT-1026. Conversely, at lower concentrations, HCT-1026 behaved as a SALA with greater potency than flurbiprofen. The difference in concentration responses between flurbiprofen and HCT-1026 in vitro suggests different cellular targets; and in no case did a combination of nitrate drug with flurbiprofen provide similar actions. In vivo, HCT-1026 was observed to reverse cognitive deficits induced by scopolamine in two behavioral assays; activity that was also shown by a classical nitrate drug, but not by flurbiprofen. The ability to restore aversive memory and spatial working and reference memory after cholinergic blockade has been demonstrated by other agents that stimulate NO/cGMP signaling. These observations add positively to the preclinical profile of HCT-1026 and NO chimeras in Alzheimer’s disease. PMID:19702655

  3. NO-flurbiprofen reduces amyloid-beta, is neuroprotective in cell culture, and enhances cognition in response to cholinergic blockade.

    PubMed

    Abdul-Hay, Samer O; Luo, Jia; Ashghodom, Rezene T; Thatcher, Gregory R J

    2009-11-01

    The non-steroidal anti-inflammatory drug flurbiprofen is a selective amyloid lowering agent which has been studied clinically in Alzheimer's disease. HCT-1026 is an ester prodrug of flurbiprofen incorporating a nitrate carrier moiety that in vivo provides NO bioactivity and an improved safety profile. In vitro, HCT-1026 retained the cyclooxygenase inhibitory and non-steroidal anti-inflammatory drug activity of flurbiprofen, but at concentrations at which levels of amyloid-beta 1-42 amino acid were lowered by flurbiprofen, amyloid-beta 1-42 amino acid levels were elevated 200% by HCT-1026. Conversely, at lower concentrations, HCT-1026 behaved as a selective amyloid lowering agent with greater potency than flurbiprofen. The difference in concentration-responses between flurbiprofen and HCT-1026 in vitro suggests different cellular targets; and in no case did a combination of nitrate drug with flurbiprofen provide similar actions. In vivo, HCT-1026 was observed to reverse cognitive deficits induced by scopolamine in two behavioral assays; activity that was also shown by a classical nitrate drug, but not by flurbiprofen. The ability to restore aversive memory and spatial working and reference memory after cholinergic blockade has been demonstrated by other agents that stimulate NO/cGMP signaling. These observations add positively to the preclinical profile of HCT-1026 and NO chimeras in Alzheimer's disease.

  4. Acupuncture reduces memory impairment and oxidative stress and enhances cholinergic function in an animal model of alcoholism.

    PubMed

    Phunchago, Nattaporn; Wattanathorn, Jintanaporn; Chaisiwamongkol, Kowit; Muchimapura, Supaporn; Thukham-Mee, Wipawee

    2015-02-01

    Currently, the therapeutic strategy against memory deficit induced by alcoholism is not satisfactory and is expensive. Therefore, an effective, low-cost strategy is required. On the basis of the memory-enhancing effect of stimulation of the HT7 acupoint, we aimed to determine whether acupuncture at the HT7 acupoint can reduce alcoholism-induced memory impairment. The possible underlying mechanism was also explored. Alcoholism was induced in male Wistar rats weighing 180-220 g. The alcoholic rats received either acupuncture at HT7 or sham acupuncture for 1 minute bilaterally once daily for 14 days. Their spatial memory was assessed after 1 day, 7 days, and 14 days of treatment. At the end of the study, the malondialdehyde level and the activities of catalase, superoxide dismutase, glutathione peroxidase, and acetylcholinesterase enzymes in the hippocampus were determined using colorimetric assays. The results showed that acupuncture at HT7 significantly decreased the acetylcholinesterase activity and the malondialdehyde level, but increased the activities of catalase, superoxide dismutase, and glutathione peroxidase in the hippocampus. These results suggest that acupuncture at HT7 can effectively reduce the alcoholism-induced memory deficit. However, further studies concerning the detailed relationships between the location of the HT7 acupoint and the changes in the observed parameters are required.

  5. Suppression of glucocorticoid secretion enhances cholinergic transmission in rat hippocampus.

    PubMed

    Mizoguchi, Kazushige; Shoji, Hirotaka; Ikeda, Ryuji; Tanaka, Yayoi; Maruyama, Wakako; Tabira, Takeshi

    2008-08-15

    We previously demonstrated that suppression of glucocorticoid secretion by adrenalectomy (ADX) impaired prefrontal cortex-sensitive working memory, but not reference memory. Since the cholinergic system in the hippocampus is also involved in these memories, we examined the effects of glucocorticoid suppression on cholinergic transmission in the rat hippocampus. A microdialysis study revealed that ADX did not affect the basal acetylcholine release, but enhanced the KCl-evoked response. This enhanced response was reversed by the corticosterone replacement treatment. The extracellular choline concentrations increased under both basal and KCl-stimulated conditions in the ADX rats, and these increases were also reversed by the corticosterone replacement. These results indicate that suppression of glucocorticoid secretion enhances cholinergic transmission in the hippocampus in response to stimuli. It is possible that this enhanced cholinergic transmission may not contribute to the ADX-induced working memory impairment, but it may be involved in maintenance of reference memory.

  6. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

    PubMed Central

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee

    2016-01-01

    Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. Materials and Methods We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. Results During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Conclusion Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism. PMID:26632397

  7. Extracts and constituents of Leontopodium alpinum enhance cholinergic transmission: Brain ACh increasing and memory improving properties

    PubMed Central

    Hornick, Ariane; Schwaiger, Stefan; Rollinger, Judith M.; Vo, Nguyen Phung; Prast, Helmut; Stuppner, Hermann

    2012-01-01

    Leontopodium alpinum (‘Edelweiss’) was phytochemically investigated for constituents that might enhance cholinergic neurotransmission. The potency to increase synaptic availability of acetylcholine (ACh) in rat brain served as key property for the bioguided isolation of cholinergically active compounds using different chromatographic techniques. The dichlormethane (DCM) extract of the root, fractions and isolated constituents were injected i.c.v. and the effect on brain ACh was detected via the push–pull technique. The DCM extract enhanced extracellular ACh concentration in rat brain and inhibited acetylcholinesterase (AChE) in vitro. The extracellular level of brain ACh was significantly increased by the isolated sesquiterpenes, isocomene and 14-acetoxyisocomene, while silphiperfolene acetate and silphinene caused a small increasing tendency. Only silphiperfolene acetate showed in vitro AChE inhibitory activity, thus suggesting the other sesquiterpenes to stimulate cholinergic transmission by an alternative mechanism of action. Isocomene was further investigated with behavioural tasks in mice. It restored object recognition in scopolamine-impaired mice and showed nootropic effects in the T-maze alternation task in normal and scopolamine-treated mice. Additionally, this sesquiterpene reduced locomotor activity of untreated mice in the open field task, while the activity induced by scopolamine was abolished. The enhancement of synaptic availability of ACh, the promotion of alternation, and the amelioration of scopolamine-induced deficit are in accordance with a substance that amplifies cholinergic transmission. Whether the mechanism of action is inhibition of AChE or another pro-cholinergic property remains to be elucidated. Taken together, isocomene and related constituents of L. alpinum deserve further interest as potential antidementia agents in brain diseases associated with cholinergic deficits. PMID:18541221

  8. Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure.

    PubMed

    Lara, Aline; Damasceno, Denis D; Pires, Rita; Gros, Robert; Gomes, Enéas R; Gavioli, Mariana; Lima, Ricardo F; Guimarães, Diogo; Lima, Patricia; Bueno, Carlos Roberto; Vasconcelos, Anilton; Roman-Campos, Danilo; Menezes, Cristiane A S; Sirvente, Raquel A; Salemi, Vera M; Mady, Charles; Caron, Marc G; Ferreira, Anderson J; Brum, Patricia C; Resende, Rodrigo R; Cruz, Jader S; Gomez, Marcus Vinicius; Prado, Vania F; de Almeida, Alvair P; Prado, Marco A M; Guatimosim, Silvia

    2010-04-01

    Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction.

  9. The benefits of cholinergic enhancement during perceptual learning are long-lasting.

    PubMed

    Rokem, Ariel; Silver, Michael A

    2013-01-01

    The neurotransmitter acetylcholine (ACh) regulates many aspects of cognition, including attention and memory. Previous research in animal models has shown that plasticity in sensory systems often depends on the behavioral relevance of a stimulus and/or task. However, experimentally increasing ACh release in the cortex can result in experience-dependent plasticity, even in the absence of behavioral relevance. In humans, the pharmacological enhancement of ACh transmission by administration of the cholinesterase inhibitor donepezil during performance of a perceptual task increases the magnitude of perceptual learning (PL) and its specificity to physical parameters of the stimuli used for training. Behavioral effects of PL have previously been shown to persist for many months. In the present study, we tested whether enhancement of PL by donepezil is also long-lasting. Healthy human subjects were trained on a motion direction discrimination task during cholinergic enhancement, and follow-up testing was performed 5-15 months after the end of training and without additional drug administration. Increases in performance associated with training under donepezil were evident in follow-up retesting, indicating that cholinergic enhancement has beneficial long-term effects on PL. These findings suggest that cholinergic enhancement of training procedures used to treat clinical disorders should improve long-term outcomes of these procedures.

  10. Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning.

    PubMed

    Brown, Matthew T C; Tan, Kelly R; O'Connor, Eoin C; Nikonenko, Irina; Muller, Dominique; Lüscher, Christian

    2012-12-20

    The ventral tegmental area (VTA) and nucleus accumbens (NAc) are essential for learning about environmental stimuli associated with motivationally relevant outcomes. The task of signalling such events, both rewarding and aversive, from the VTA to the NAc has largely been ascribed to dopamine neurons. The VTA also contains GABA (γ-aminobutyric acid)-releasing neurons, which provide local inhibition and also project to the NAc. However, the cellular targets and functional importance of this long-range inhibitory projection have not been ascertained. Here we show that GABA-releasing neurons of the VTA that project to the NAc (VTA GABA projection neurons) inhibit accumbal cholinergic interneurons (CINs) to enhance stimulus-outcome learning. Combining optogenetics with structural imaging and electrophysiology, we found that VTA GABA projection neurons selectively target NAc CINs, forming multiple symmetrical synaptic contacts that generated inhibitory postsynaptic currents. This is remarkable considering that CINs represent a very small population of all accumbal neurons, and provide the primary source of cholinergic tone in the NAc. Brief activation of this projection was sufficient to halt the spontaneous activity of NAc CINs, resembling the pause recorded in animals learning stimulus-outcome associations. Indeed, we found that forcing CINs to pause in behaving mice enhanced discrimination of a motivationally important stimulus that had been associated with an aversive outcome. Our results demonstrate that VTA GABA projection neurons, through their selective targeting of accumbal CINs, provide a novel route through which the VTA communicates saliency to the NAc. VTA GABA projection neurons thus emerge as orchestrators of dopaminergic and cholinergic modulation in the NAc.

  11. Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain.

    PubMed Central

    Pedersen, W A; Kloczewiak, M A; Blusztajn, J K

    1996-01-01

    The characteristic features of a brain with Alzheimer disease (AD) include the presence of neuritic plaques composed of amyloid beta-protein (Abeta) and reductions in the levels of cholinergic markers. Neurotoxic responses to Abeta have been reported in vivo and in vitro, suggesting that the cholinergic deficit in AD brain may be secondary to the degeneration of cholinergic neurons caused by Abeta. However, it remains to be determined if Abeta contributes to the cholinergic deficit in AD brain by nontoxic effects. We examined the effects of synthetic Abeta peptides on the cholinergic properties of a mouse cell line, SN56, derived from basal forebrain cholinergic neurons. Abeta 1-42 and Abeta 1-28 reduced the acetylcholine (AcCho) content of the cells in a concentration-dependent fashion, whereas Abeta 1-16 was inactive. Maximal reductions of 43% and 33% were observed after a 48-h treatment with 100 nM of Abeta 1-42 and 50 pM of Abeta 1-28, respectively. Neither Abeta 1-28 nor Abeta 1-42 at a concentration of 100 nM and a treatment period of 2 weeks was toxic to the cells. Treatment of the cells with Abeta 25-28 (48 h; 100 nM) significantly decreased AcCho levels, suggesting that the sequence GSNK (aa 25-28) is responsible for the AcCho-reducing effect of Abeta. The reductions in AcCho levels caused by Abeta 1-42 and Abeta 1-28 were accompanied by proportional decreases in choline acetyltransferase activity. In contrast, acetylcholinesterase activity was unaltered, indicating that Abeta specifically reduces the synthesis of AcCho in SN56 cells. The reductions in AcCho content caused by Abeta 1-42 could be prevented by a cotreatment with all-trans-retinoic acid (10 nM), a compound previously shown to increase choline acetyltransferase mRNA expression in SN56 cells. These results demonstrate a nontoxic, suppressive effect of Abeta on AcCho synthesis, an action that may contribute to the cholinergic deficit in AD brain. Images Fig. 3 Fig. 4 PMID:8755604

  12. Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward

    PubMed Central

    Stouffer, Melissa A.; Woods, Catherine A.; Patel, Jyoti C.; Lee, Christian R.; Witkovsky, Paul; Bao, Li; Machold, Robert P.; Jones, Kymry T.; de Vaca, Soledad Cabeza; Reith, Maarten E. A.; Carr, Kenneth D.; Rice, Margaret E.

    2015-01-01

    Insulin activates insulin receptors (InsRs) in the hypothalamus to signal satiety after a meal. However, the rising incidence of obesity, which results in chronically elevated insulin levels, implies that insulin may also act in brain centres that regulate motivation and reward. We report here that insulin can amplify action potential-dependent dopamine (DA) release in the nucleus accumbens (NAc) and caudate–putamen through an indirect mechanism that involves striatal cholinergic interneurons that express InsRs. Furthermore, two different chronic diet manipulations in rats, food restriction (FR) and an obesogenic (OB) diet, oppositely alter the sensitivity of striatal DA release to insulin, with enhanced responsiveness in FR, but loss of responsiveness in OB. Behavioural studies show that intact insulin levels in the NAc shell are necessary for acquisition of preference for the flavour of a paired glucose solution. Together, these data imply that striatal insulin signalling enhances DA release to influence food choices. PMID:26503322

  13. Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward.

    PubMed

    Stouffer, Melissa A; Woods, Catherine A; Patel, Jyoti C; Lee, Christian R; Witkovsky, Paul; Bao, Li; Machold, Robert P; Jones, Kymry T; de Vaca, Soledad Cabeza; Reith, Maarten E A; Carr, Kenneth D; Rice, Margaret E

    2015-01-01

    Insulin activates insulin receptors (InsRs) in the hypothalamus to signal satiety after a meal. However, the rising incidence of obesity, which results in chronically elevated insulin levels, implies that insulin may also act in brain centres that regulate motivation and reward. We report here that insulin can amplify action potential-dependent dopamine (DA) release in the nucleus accumbens (NAc) and caudate-putamen through an indirect mechanism that involves striatal cholinergic interneurons that express InsRs. Furthermore, two different chronic diet manipulations in rats, food restriction (FR) and an obesogenic (OB) diet, oppositely alter the sensitivity of striatal DA release to insulin, with enhanced responsiveness in FR, but loss of responsiveness in OB. Behavioural studies show that intact insulin levels in the NAc shell are necessary for acquisition of preference for the flavour of a paired glucose solution. Together, these data imply that striatal insulin signalling enhances DA release to influence food choices. PMID:26503322

  14. Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward.

    PubMed

    Stouffer, Melissa A; Woods, Catherine A; Patel, Jyoti C; Lee, Christian R; Witkovsky, Paul; Bao, Li; Machold, Robert P; Jones, Kymry T; de Vaca, Soledad Cabeza; Reith, Maarten E A; Carr, Kenneth D; Rice, Margaret E

    2015-10-27

    Insulin activates insulin receptors (InsRs) in the hypothalamus to signal satiety after a meal. However, the rising incidence of obesity, which results in chronically elevated insulin levels, implies that insulin may also act in brain centres that regulate motivation and reward. We report here that insulin can amplify action potential-dependent dopamine (DA) release in the nucleus accumbens (NAc) and caudate-putamen through an indirect mechanism that involves striatal cholinergic interneurons that express InsRs. Furthermore, two different chronic diet manipulations in rats, food restriction (FR) and an obesogenic (OB) diet, oppositely alter the sensitivity of striatal DA release to insulin, with enhanced responsiveness in FR, but loss of responsiveness in OB. Behavioural studies show that intact insulin levels in the NAc shell are necessary for acquisition of preference for the flavour of a paired glucose solution. Together, these data imply that striatal insulin signalling enhances DA release to influence food choices.

  15. Pairing Cholinergic Enhancement with Perceptual Training Promotes Recovery of Age-Related Changes in Rat Primary Auditory Cortex

    PubMed Central

    Voss, Patrice; Thomas, Maryse; Chou, You Chien; Cisneros-Franco, José Miguel; Ouellet, Lydia; de Villers-Sidani, Etienne

    2016-01-01

    We used the rat primary auditory cortex (A1) as a model to probe the effects of cholinergic enhancement on perceptual learning and auditory processing mechanisms in both young and old animals. Rats learned to perform a two-tone frequency discrimination task over the course of two weeks, combined with either the administration of a cholinesterase inhibitor or saline. We found that while both age groups learned the task more quickly through cholinergic enhancement, the young did so by improving target detection, whereas the old did so by inhibiting erroneous responses to nontarget stimuli. We also found that cholinergic enhancement led to marked functional and structural changes within A1 in both young and old rats. Importantly, we found that several functional changes observed in the old rats, particularly those relating to the processing and inhibition of nontargets, produced cortical processing features that resembled those of young untrained rats more so than those of older adult rats. Overall, these findings demonstrate that combining auditory training with neuromodulation of the cholinergic system can restore many of the auditory cortical functional deficits observed as a result of normal aging and add to the growing body of evidence demonstrating that many age-related perceptual and neuroplastic changes are reversible. PMID:27057359

  16. Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation

    PubMed Central

    Kang, Jun-Il; Huppé-Gourgues, Frédéric; Vaucher, Elvire

    2015-01-01

    Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1) induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR), M1 and M2 muscarinic (mAChR) or GABAergic A (GABAAR) receptors was performed during the training session and visual evoked potentials (VEPs) were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABAAR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD), suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by nAChRs, M2 m

  17. Cholinergic Stimulation Enhances Bayesian Belief Updating in the Deployment of Spatial Attention

    PubMed Central

    Bauer, Markus; Mathys, Christoph; Adams, Rick A.; Dolan, Raymond J.; Stephan, Klaas E.; Friston, Karl J.

    2014-01-01

    The exact mechanisms whereby the cholinergic neurotransmitter system contributes to attentional processing remain poorly understood. Here, we applied computational modeling to psychophysical data (obtained from a spatial attention task) under a psychopharmacological challenge with the cholinesterase inhibitor galantamine (Reminyl). This allowed us to characterize the cholinergic modulation of selective attention formally, in terms of hierarchical Bayesian inference. In a placebo-controlled, within-subject, crossover design, 16 healthy human subjects performed a modified version of Posner's location-cueing task in which the proportion of validly and invalidly cued targets (percentage of cue validity, % CV) changed over time. Saccadic response speeds were used to estimate the parameters of a hierarchical Bayesian model to test whether cholinergic stimulation affected the trial-wise updating of probabilistic beliefs that underlie the allocation of attention or whether galantamine changed the mapping from those beliefs to subsequent eye movements. Behaviorally, galantamine led to a greater influence of probabilistic context (% CV) on response speed than placebo. Crucially, computational modeling suggested this effect was due to an increase in the rate of belief updating about cue validity (as opposed to the increased sensitivity of behavioral responses to those beliefs). We discuss these findings with respect to cholinergic effects on hierarchical cortical processing and in relation to the encoding of expected uncertainty or precision. PMID:25411501

  18. Cholinergic stimulation enhances Bayesian belief updating in the deployment of spatial attention.

    PubMed

    Vossel, Simone; Bauer, Markus; Mathys, Christoph; Adams, Rick A; Dolan, Raymond J; Stephan, Klaas E; Friston, Karl J

    2014-11-19

    The exact mechanisms whereby the cholinergic neurotransmitter system contributes to attentional processing remain poorly understood. Here, we applied computational modeling to psychophysical data (obtained from a spatial attention task) under a psychopharmacological challenge with the cholinesterase inhibitor galantamine (Reminyl). This allowed us to characterize the cholinergic modulation of selective attention formally, in terms of hierarchical Bayesian inference. In a placebo-controlled, within-subject, crossover design, 16 healthy human subjects performed a modified version of Posner's location-cueing task in which the proportion of validly and invalidly cued targets (percentage of cue validity, % CV) changed over time. Saccadic response speeds were used to estimate the parameters of a hierarchical Bayesian model to test whether cholinergic stimulation affected the trial-wise updating of probabilistic beliefs that underlie the allocation of attention or whether galantamine changed the mapping from those beliefs to subsequent eye movements. Behaviorally, galantamine led to a greater influence of probabilistic context (% CV) on response speed than placebo. Crucially, computational modeling suggested this effect was due to an increase in the rate of belief updating about cue validity (as opposed to the increased sensitivity of behavioral responses to those beliefs). We discuss these findings with respect to cholinergic effects on hierarchical cortical processing and in relation to the encoding of expected uncertainty or precision. PMID:25411501

  19. Sustained subcutaneous infusion of nicotine enhances cholinergic vasodilation in the cerebral cortex induced by stimulation of the nucleus basalis of Meynert in rats.

    PubMed

    Uchida, Sae; Hotta, Harumi; Misawa, Hidemi; Kawashima, Koichiro

    2011-03-11

    The present study examined the effects of sustained nicotine exposure on the cholinergic vasodilative system originating in the nucleus basalis of Meynert (NBM) and projecting to the cerebral cortex in rats. Rats received sustained subcutaneous nicotine (100μg/kg/h) for 14 days. Under urethane anesthesia, the vasodilation response and acetylcholine release in the parietal cortex induced by electrical stimulation of the NBM (10-200μA) were measured. The basal level of acetylcholine release was significantly higher in nicotine-treated rats than in saline-treated control rats. In the control rats, both the acetylcholine release and blood flow were increased by NBM stimulation in a stimulus intensity-dependent manner, and a threshold of 50μA. In nicotine-treated rats, the threshold intensity of NBM stimulation producing increases in acetylcholine release and blood flow was reduced to 20μA. The stimulus intensity-dependent acetylcholine release and vasodilation by NBM stimulation were significantly larger in nicotine-treated rats than in control rats. We conclude that sustained subcutaneous infusion of nicotine enhances cholinergic vasodilative system in the cerebral cortex originating in the NBM.

  20. Cortical cholinergic signaling controls the detection of cues

    PubMed Central

    Gritton, Howard J.; Howe, William M.; Mallory, Caitlin S.; Hetrick, Vaughn L.; Berke, Joshua D.; Sarter, Martin

    2016-01-01

    The cortical cholinergic input system has been described as a neuromodulator system that influences broadly defined behavioral and brain states. The discovery of phasic, trial-based increases in extracellular choline (transients), resulting from the hydrolysis of newly released acetylcholine (ACh), in the cortex of animals reporting the presence of cues suggests that ACh may have a more specialized role in cognitive processes. Here we expressed channelrhodopsin or halorhodopsin in basal forebrain cholinergic neurons of mice with optic fibers directed into this region and prefrontal cortex. Cholinergic transients, evoked in accordance with photostimulation parameters determined in vivo, were generated in mice performing a task necessitating the reporting of cue and noncue events. Generating cholinergic transients in conjunction with cues enhanced cue detection rates. Moreover, generating transients in noncued trials, where cholinergic transients normally are not observed, increased the number of invalid claims for cues. Enhancing hits and generating false alarms both scaled with stimulation intensity. Suppression of endogenous cholinergic activity during cued trials reduced hit rates. Cholinergic transients may be essential for synchronizing cortical neuronal output driven by salient cues and executing cue-guided responses. PMID:26787867

  1. The effect of enhancing cholinergic neurotransmission by nicotine on EEG indices of inhibition in the human brain.

    PubMed

    Logemann, H N A; Böcker, K B E; Deschamps, P K H; Kemner, C; Kenemans, J L

    2014-07-01

    The role of the cholinergic system in inhibition remains to be elucidated. Nicotine is a potent tool to augment this system, but most studies investigated its effects solely on behavior. Reference to brain activity is important to specifically identify inhibition-related mechanisms. In the current study the objective was to elucidate the role of the cholinergic system in inhibition. 16 healthy non-smokers performed in a stop task while EEG was recorded. A pre- versus post-treatment, within subjects, placebo controlled, single-blind design was used. It was hypothesized that nicotine would decrease stop-signal reaction time (SSRT) and increase the amplitude of inhibition-related event related potentials, the stop N2 and stop P3. Behavioral measures show nicotine shortened SSRT, but only when pretreatment values were not taken into account. On EEG measures, an enhanced stop P3 under nicotine was found, but only in a subsample sensitive to nicotine based on diastolic blood pressure. The results are indicative of enhanced inhibitory activity possibly reflecting enhanced activation in the superior frontal gyrus.

  2. The effect of enhancing cholinergic neurotransmission by nicotine on EEG indices of inhibition in the human brain.

    PubMed

    Logemann, H N A; Böcker, K B E; Deschamps, P K H; Kemner, C; Kenemans, J L

    2014-07-01

    The role of the cholinergic system in inhibition remains to be elucidated. Nicotine is a potent tool to augment this system, but most studies investigated its effects solely on behavior. Reference to brain activity is important to specifically identify inhibition-related mechanisms. In the current study the objective was to elucidate the role of the cholinergic system in inhibition. 16 healthy non-smokers performed in a stop task while EEG was recorded. A pre- versus post-treatment, within subjects, placebo controlled, single-blind design was used. It was hypothesized that nicotine would decrease stop-signal reaction time (SSRT) and increase the amplitude of inhibition-related event related potentials, the stop N2 and stop P3. Behavioral measures show nicotine shortened SSRT, but only when pretreatment values were not taken into account. On EEG measures, an enhanced stop P3 under nicotine was found, but only in a subsample sensitive to nicotine based on diastolic blood pressure. The results are indicative of enhanced inhibitory activity possibly reflecting enhanced activation in the superior frontal gyrus. PMID:24690513

  3. Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

    PubMed

    Lujan, Heidi L; DiCarlo, Stephen E

    2013-05-01

    Chronic diseases are the leading cause of death in the world and chronic inflammation is a key contributor to many chronic diseases. Accordingly, interventions that reduce inflammation may be effective in treating multiple adverse chronic conditions. In this context, physical activity is documented to reduce systemic low-grade inflammation and is acknowledged as an anti-inflammatory intervention. Furthermore, physically active individuals are at a lower risk of developing chronic diseases. However the mechanisms mediating this anti-inflammatory phenotype and range of health benefits are unknown. We hypothesize that the "cholinergic anti-inflammatory pathway" (CAP) mediates the anti-inflammatory phenotype and range of health benefits associated with physical activity. The CAP is an endogenous, physiological mechanism by which acetylcholine from the vagus nerve, interacts with the innate immune system to modulate and restrain the inflammatory cascade. Importantly, higher levels of physical activity are associated with enhanced parasympathetic (vagal) tone and lower levels of C-reactive protein, a marker of low-grade inflammation. Accordingly, physical activity, by enhancing parasympathetic tone and activating the CAP, may be a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

  4. Increases in cholinergic neurotransmission measured by using choline-sensitive microelectrodes: enhanced detection by hydrolysis of acetylcholine on recording sites?

    PubMed Central

    Giuliano, Chiara; Parikh, Vinay; Ward, Josh.R.; Chiamulera, Christian; Sarter, Martin

    2008-01-01

    Previous experiments demonstrated that second-based transient increases in choline concentrations measured by electrodes coated with choline oxidase (ChOx) and the amperometric detection of hydrogen peroxide validly indicate the depolarization-dependent release of acetylcholine (ACh) and its hydrolysis by endogenous acetylcholinesterase (AChE). Therefore, choline-sensitive microelectrodes have become valuable tools in neuropharmacological and behavioral research. The present experiments were designed to test the possibility that co-immobilization of ChOx plus AChE on recording sites increases the level of detection for evoked ACh release in the brain. If newly released ACh is not completely hydrolyzed by endogenous AChE and capable of reaching the extracellular space, currents recorded via sites equipped with both enzymes should be greater when compared with sites coated with ChOx only. Pairs of Platinum-recordings sites were coated either with AChE plus ChOx or ChOx alone. Potassium or nicotine-evoked currents were recorded throughout the entire dorsal-ventral extent of the medial prefrontal cortex (mPFC). The amplitudes of evoked cholinergic signals did not differ significantly between AChE+ChOx and ChOx-only coated recording sites. Additional experiments controlling for several potential confounds suggested that, in vivo, ACh levels ≥150 fmol were detected by recordings sites featuring dual enzyme coating. Collectively, these results indicate that co-coating of microelectrodes with AChE does not enhance the detection of cholinergic activity in the cortex compared with measurements via recording sites coated only with ChOx. PMID:18346819

  5. Developmental exposure to cuprizone reduces intermediate-stage progenitor cells and cholinergic signals in the hippocampal neurogenesis in rat offspring.

    PubMed

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2015-05-01

    The exposure to cuprizone (CPZ) leads to demyelination in the central nervous system in rodents. To examine the developmental effects of CPZ exposure on hippocampal neurogenesis, pregnant rats were treated with 0, 0.1 or 0.4% CPZ in the diet from gestational day 6 to day 21 after delivery. On postnatal day 21, male offspring had a decreased density of new glue2(+) oligodendrocyte progenitor cells in the dentate hilus and in the area of the cerebellar medulla in the presence of 0.4% CPZ. With regard to neurogenesis-related parameters, offspring had decreased T box brain 2(+) progenitor cells and increased apoptotic cells, as detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, which was accompanied by the up-regulation of Casp12 and Bcl2l11 in the subgranular zone, and increased reelin(+) interneurons in the dentate hilus. In addition, the density of phosphorylated TrkB(+) interneurons decreased in the dentate hilus, which was accompanied by transcript down-regulation of Bdnf and Chrna7 in the dentate gyrus. Moreover, granule cells expressing gene products of immediate-early genes, i.e., Arc and Fos, decreased. These results suggest that maternal exposure to 0.4% CPZ decreases proliferative type-2 progenitor cells via endoplasmic reticulum stress-mediated apoptosis and inhibition of cholinergic signals to intermediate-stage progenitor cells following reduced oligodendrocyte production and suppression of the brain-derived neurotrophic factor signaling cascade. Increases in reelin-expressing interneurons may compensate for impaired granule cell migration and/or correct positioning due to decreased immediate-early gene-mediated neuronal plasticity. However, all observed fluctuations disappeared at the adult stage, suggesting that CPZ-induced developmental neurotoxicity was reversible.

  6. The chemokine interleukin-8 acutely reduces Ca(2+) currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs.

    PubMed

    Puma, C; Danik, M; Quirion, R; Ramon, F; Williams, S

    2001-09-01

    The chemokine IL-8 is known to be synthesized by glial cells in the brain. It has traditionally been shown to have an important role in neuroinflammation but recent evidence indicates that it may also be involved in rapid signaling in neurons. We investigated how IL-8 participates in rapid neuronal signaling by using a combination of whole-cell recording and single-cell RT-PCR on dissociated rat septal neurons. We show that IL-8 can acutely reduce Ca(2+) currents in septal neurons, an effect that was concentration-dependent, involved the closure of L- and N-type Ca(2+) channels, and the activation of G(ialpha1) and/or G(ialpha2) subtype(s) of G-proteins. Analysis of the mRNAs from the recorded neurons revealed that the latter were all cholinergic in nature. Moreover, we found that all cholinergic neurons that responded to IL-8, expressed mRNAs for either one or both IL-8 receptors CXCR1 and CXCR2. This is the first report of a chemokine that modulates ion channels in neurons via G-proteins, and the first demonstration that mRNAs for CXCR1 are expressed in the brain. Our results suggest that IL-8 release by glial cells in vivo may activate CXCR1 and CXCR2 receptors on cholinergic septal neurons and acutely modulate their excitability by closing calcium channels. PMID:11553670

  7. Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood–Brain Barrier Permeability following Experimental Traumatic Brain Injury

    PubMed Central

    Zhao, Jing; Kobori, Nobuhide; Redell, John B.; Hylin, Michael J.; Hood, Kimberly N.; Moore, Anthony N.

    2016-01-01

    Traumatic brain injury (TBI) is a major human health concern that has the greatest impact on young men and women. The breakdown of the blood–brain barrier (BBB) is an important pathological consequence of TBI that initiates secondary processes, including infiltration of inflammatory cells, which can exacerbate brain inflammation and contribute to poor outcome. While the role of inflammation within the injured brain has been examined in some detail, the contribution of peripheral/systemic inflammation to TBI pathophysiology is largely unknown. Recent studies have implicated vagus nerve regulation of splenic cholinergic nicotinic acetylcholine receptor α7 (nAChRa7) signaling in the regulation of systemic inflammation. However, it is not known whether this mechanism plays a role in TBI-triggered inflammation and BBB breakdown. Following TBI, we observed that plasma TNF-α and IL-1β levels, as well as BBB permeability, were significantly increased in nAChRa7 null mice (Chrna7−/−) relative to wild-type mice. The administration of exogenous IL-1β and TNF-α to brain-injured animals worsened Evans Blue dye extravasation, suggesting that systemic inflammation contributes to TBI-triggered BBB permeability. Systemic administration of the nAChRa7 agonist PNU-282987 or the positive allosteric modulator PNU-120596 significantly attenuated TBI-triggered BBB compromise. Supporting a role for splenic nAChRa7 receptors, we demonstrate that splenic injection of the nicotinic receptor blocker α-bungarotoxin increased BBB permeability in brain-injured rats, while PNU-282987 injection decreased such permeability. These effects were not seen when α-bungarotoxin or PNU-282987 were administered to splenectomized, brain-injured rats. Together, these findings support the short-term use of nAChRa7-activating agents as a strategy to reduce TBI-triggered BBB permeability. SIGNIFICANCE STATEMENT Breakdown of the blood–brain barrier (BBB) in response to traumatic brain injury (TBI

  8. Electroacupuncture-Induced Cholinergic Nerve Activation Enhances the Hypoglycemic Effect of Exogenous Insulin in a Rat Model of Streptozotocin-Induced Diabetes

    PubMed Central

    Lee, Yu-Chen; Li, Te-Mao; Tzeng, Chung-Yuh; Cheng, Yu-Wen; Chen, Ying-I; Ho, Wai-Jane; Lin, Jaung Geng; Chang, Shih-Liang

    2011-01-01

    The aim of this study is to explore the mechanisms by which electroacupuncture (EA) enhances the hypoglycemic effect of exogenous insulin in a streptozotocin- (STZ-) diabetic rats. Animals in the EA group were anesthetized and subjected to the insulin challenge test (ICT) and EA for 60 minutes. In the control group, rats were subjected to the same treatment with the exception of EA stimulation. Blood samples were drawn to measure changes in plasma glucose, free fatty acids (FFA), and insulin levels. Western blot was used to assay proteins involved in insulin signaling. Furthermore, atropine, hemicholinium-3 (HC-3), and Eserine were used to explore the relationship between EA and cholinergic nerve activation during ICT. EA augmented the blood glucose-lowering effects of EA by activating the cholinergic nerves in STZ rats that had been exposed to exogenous insulin. This phenomenon may be related to enhancement of insulin signaling rather than to changes in FFA concentration. PMID:21754922

  9. Electroacupuncture-induced cholinergic nerve activation enhances the hypoglycemic effect of exogenous insulin in a rat model of streptozotocin-induced diabetes.

    PubMed

    Lee, Yu-Chen; Li, Te-Mao; Tzeng, Chung-Yuh; Cheng, Yu-Wen; Chen, Ying-I; Ho, Wai-Jane; Lin, Jaung Geng; Chang, Shih-Liang

    2011-01-01

    The aim of this study is to explore the mechanisms by which electroacupuncture (EA) enhances the hypoglycemic effect of exogenous insulin in a streptozotocin- (STZ-) diabetic rats. Animals in the EA group were anesthetized and subjected to the insulin challenge test (ICT) and EA for 60 minutes. In the control group, rats were subjected to the same treatment with the exception of EA stimulation. Blood samples were drawn to measure changes in plasma glucose, free fatty acids (FFA), and insulin levels. Western blot was used to assay proteins involved in insulin signaling. Furthermore, atropine, hemicholinium-3 (HC-3), and Eserine were used to explore the relationship between EA and cholinergic nerve activation during ICT. EA augmented the blood glucose-lowering effects of EA by activating the cholinergic nerves in STZ rats that had been exposed to exogenous insulin. This phenomenon may be related to enhancement of insulin signaling rather than to changes in FFA concentration. PMID:21754922

  10. Natural compounds endowed with cholinergic or anticholinergic activity. Enhancement of acetylcholine release by a quaternary derivative of L-hyoscyamine.

    PubMed

    Souccar, Caden; Salamanca, Ana Lucia V; Tanae, Mirtes M; Lima-Landman, Maria Teresa R; Lapa, Antonio José

    2010-01-01

    New compounds that target nicotinic receptors (nAChRs) have been sought to correct disorders affecting cholinergic transmission in central and peripheral synapses. A quaternary derivate of l-hyoscyamine, phenthonium (Phen), was shown by our group to enhance the spontaneous acetylcholine (ACh) release without altering the nerve-induced transmitter release at the neuromuscular junction. The effect was unrelated to membrane depolarization, and was not induced by an increase of calcium influx into the nerve terminal. Phen also presented a competitive antimuscarinic activity and blocked noncompetitively the neuromuscular transmission. In this work we re-examined the mechanisms underlying the facilitatory actions of Phen on [(3)H]-ACh release in isolated ganglia of the guinea pig ileal myenteric plexus. Exposure of the preparations to Phen (10-50 microM) increased the release of [(3)H]-ACh by 81 to 68% over the basal. The effect was not affected by the ganglionic nAChR antagonist hexamethonium (1 nM) at a concentration that inhibited the increase of [(3)H]-ACh release induced by the nicotinic agonist dimethylphenylpiperazinium (DMPP, 30 microM). Association of Phen (10 microM) with DMPP potentiated the facilitatory effect of Phen. [(3)H]-ACh release was not altered by the muscarinic antagonists atropine (1 nM) or pirenzepine (1 microM). However, both antagonists inhibited the release of [(3)H]-ACh induced by either the muscarinic M1 agonist McN-343 (10 microM) or Phen (20 microM). The facilitatory effect of Phen was not altered by CdCl(2) (50 mM), but it was potentiated in the presence of tetraethylammonium (40 mM). The results indicate that the facilitatory action of Phen appears to be mediated by an increase of the inwardly rectifying potassium channels conductance probably related to the compound antimuscarinic activity.

  11. Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon.

    PubMed

    Suply, Etienne; de Vries, Philine; Soret, Rodolphe; Cossais, François; Neunlist, Michel

    2012-06-15

    Postnatal changes in the enteric nervous system (ENS) are involved in the establishment of colonic motility. In adult rats, butyrate induced neuroplastic changes in the ENS, leading to enhanced colonic motility. Whether butyrate can induce similar changes during the postnatal period remains unknown. Enemas (Na-butyrate) were performed daily in rat pups between postnatal day (PND) 7 and PND 17. Effects of butyrate were evaluated on morphological and histological parameters in the distal colon at PND 21. The neurochemical phenotype of colonic submucosal and myenteric neurons was analyzed using antibodies against Hu, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS). Colonic motility and neuromuscular transmission was assessed in vivo and ex vivo. Butyrate (2.5 mM) enemas had no impact on pup growth and histological parameters compared with control. Butyrate did not modify the number of Hu-immunoreactive (IR) neurons per ganglia. A significant increase in the proportion (per Hu-IR neurons) of nNOS-IR myenteric and submucosal neurons and ChAT-IR myenteric neurons was observed in the distal colon after butyrate enemas compared with control. In addition, butyrate induced a significant increase in both nitrergic and cholinergic components of the neuromuscular transmission compared with control. Finally, butyrate increased distal colonic transit time compared with control. We concluded that butyrate enemas induced neuroplastic changes in myenteric and submucosal neurons, leading to changes in gastrointestinal functions. Our results support exploration of butyrate as potential therapy for motility disorders in preterm infants with delayed maturation of the ENS.

  12. Enhanced alcohol-seeking behavior by nicotine in the posterior ventral tegmental area of female alcohol-preferring (P) rats: modulation by serotonin-3 and nicotinic cholinergic receptors

    PubMed Central

    Deehan, Gerald A.; Toalston, Jamie E.; Bell, Richard L.; McBride, William J.; Rodd, Zachary A.

    2015-01-01

    Rationale Alcohol and nicotine co-use can reciprocally promote self-administration and drug-craving/drug-seeking behaviors. To date, the neurocircuitry in which nicotine influences ethanol (EtOH) seeking has not been elucidated. Clinical and preclinical research has suggested that the activation of the mesolimbic dopamine system is involved in the promotion of drug seeking. Alcohol, nicotine, and serotonin-3 (5-HT3) receptors interact within the posterior ventral tegmental area (pVTA) to regulate drug reward. Recently, our laboratory has reported that systemic administration of nicotine can promote context-induced EtOH seeking. Objectives The goals of the current study were to (1) determine if microinjections of pharmacologically relevant levels of nicotine into the pVTA would enhance EtOH seeking, (2) determine if coadministration of nicotinic cholinergic receptor antagonist (nACh) or 5-HT3 receptor antagonists would block the ability of nicotine microinjected into the pVTA to promote EtOH seeking, and (3) determine if 5-HT3 receptors in the pVTA can modulate EtOH seeking. Results Nicotine (100 and 200 µM) microinjected into the pVTA enhanced EtOH seeking. Coinfusion with 200 µM mecamylamine (nACh antagonist) or 100 and 200 µM zacopride (5-HT3 receptor antagonist) blocked the observed nicotine enhancement of EtOH seeking. The data also indicated that microinjection of 1 µM CPBG (5-HT3 receptor agonist) promotes context-induced EtOH seeking; conversely microinjection of 100 and 200 µM zacopride alone reduced context-induced EtOH seeking. Conclusions Overall, the results show that nicotine-enhanced EtOH-seeking behavior is modulated by 5-HT3 and nACh receptors within the pVTA and that the 5-HT3 receptor system within pVTA may be a potential pharmacological target to inhibit EtOH-seeking behaviors. PMID:24599396

  13. Modes and Models of Forebrain Cholinergic Neuromodulation of Cognition

    PubMed Central

    Hasselmo, Michael E; Sarter, Martin

    2011-01-01

    As indicated by the profound cognitive impairments caused by cholinergic receptor antagonists, cholinergic neurotransmission has a vital role in cognitive function, specifically attention and memory encoding. Abnormally regulated cholinergic neurotransmission has been hypothesized to contribute to the cognitive symptoms of neuropsychiatric disorders. Loss of cholinergic neurons enhances the severity of the symptoms of dementia. Cholinergic receptor agonists and acetylcholinesterase inhibitors have been investigated for the treatment of cognitive dysfunction. Evidence from experiments using new techniques for measuring rapid changes in cholinergic neurotransmission provides a novel perspective on the cholinergic regulation of cognitive processes. This evidence indicates that changes in cholinergic modulation on a timescale of seconds is triggered by sensory input cues and serves to facilitate cue detection and attentional performance. Furthermore, the evidence indicates cholinergic induction of evoked intrinsic, persistent spiking mechanisms for active maintenance of sensory input, and planned responses. Models have been developed to describe the neuronal mechanisms underlying the transient modulation of cortical target circuits by cholinergic activity. These models postulate specific locations and roles of nicotinic and muscarinic acetylcholine receptors and that cholinergic neurotransmission is controlled in part by (cortical) target circuits. The available evidence and these models point to new principles governing the development of the next generation of cholinergic treatments for cognitive disorders. PMID:20668433

  14. The anterior cingulate cortex may enhance inhibition of lateral prefrontal cortex via m2 cholinergic receptors at dual synaptic sites.

    PubMed

    Medalla, Maria; Barbas, Helen

    2012-10-31

    The anterior cingulate cortex (ACC) and dorsolateral prefrontal cortices (DLPFC) share robust excitatory connections. However, during rapid eye movement (REM) sleep, when cortical activity is dominated by acetylcholine, the ACC is activated but DLPFC is suppressed. Using pathway tracing and electron microscopy in nonhuman primates (Macaca mulatta), we tested the hypothesis that the opposite states may reflect specific modulation by acetylcholine through strategic synaptic localization of muscarinic m2 receptors, which inhibit neurotransmitter release presynaptically, but are thought to be excitatory postsynaptically. In the ACC pathway to DLPFC (area 32 to area 9), m2 receptors predominated in ACC axon terminals and in more than half of the targeted dendrites of presumed inhibitory neurons, suggesting inhibitory cholinergic influence. In contrast, in a pathway linking the DLPFC area 46 to DLPFC area 9, postsynaptic m2 receptors predominated in targeted spines of presumed excitatory neurons, consistent with their mutual activation in working memory. These novel findings suggest that presynaptic and postsynaptic specificity of m2 cholinergic receptors may help explain the differential engagement of ACC and DLPFC areas in REM sleep for memory consolidation and synergism in awake states for cognitive control.

  15. Small Molecule p75NTR Ligands Reduce Pathological Phosphorylation and Misfolding of Tau, Inflammatory Changes, Cholinergic Degeneration, and Cognitive Deficits in AβPPL/S Transgenic Mice

    PubMed Central

    Nguyen, Thuy-Vi V.; Shen, Lin; Griend, Lilith Vander; Quach, Lisa N.; Belichenko, Nadia P.; Saw, Nay; Yang, Tao; Shamloo, Mehrdad; Wyss-Coray, Tony; Massa, Stephen M.; Longo, Frank M.

    2014-01-01

    The p75 neurotrophin receptor (p75NTR ) is involved in degenerative mechanisms related to Alzheimer’s disease (AD). In addition, p75NTR levels are increased in AD and the receptor is expressed by neurons that are particularly vulnerable in the disease. Therefore, modulating p75NTR function may be a significant disease-modifying treatment approach. Prior studies indicated that the non-peptide, small molecule p75NTR ligands LM11A-31, and chemically unrelated LM11A-24, could block amyloid-β-induced deleterious signaling and neurodegeneration in vitro, and LM11A-31 was found to mitigate neuritic degeneration and behavioral deficits in a mouse model of AD. In this study, we determined whether these in vivo findings represent class effects of p75NTR ligands by examining LM11A-24 effects. In addition, the range of compound effects was further examined by evaluating tau pathology and neuroinflammation. Following oral administration, both ligands reached brain concentrations known to provide neuroprotection in vitro. Compound induction of p75NTR cleavage provided evidence for CNS target engagement. LM11A-31 and LM11A-24 reduced excessive phosphorylation of tau, and LM11A-31 also inhibited its aberrant folding. Both ligands decreased activation of microglia, while LM11A-31 attenuated reactive astrocytes. Along with decreased inflammatory responses, both ligands reduced cholinergic neurite degeneration. In addition to the amelioration of neuropathology in AD model mice, LM11A-31, but not LM11A-24, prevented impairments in water maze performance, while both ligands prevented deficits in fear conditioning. These findings support a role for p75NTR ligands in preventing fundamental tau-related pathologic mechanisms in AD, and further validate the development of these small molecules as a new class of therapeutic compounds. PMID:24898660

  16. Reducing or enhancing chaos using periodic orbits.

    PubMed

    Bachelard, R; Chandre, C; Leoncini, X

    2006-06-01

    A method to reduce or enhance chaos in Hamiltonian flows with two degrees of freedom is discussed. This method is based on finding a suitable perturbation of the system such that the stability of a set of periodic orbits changes (local bifurcations). Depending on the values of the residues, reflecting their linear stability properties, a set of invariant tori is destroyed or created in the neighborhood of the chosen periodic orbits. An application on a paradigmatic system, a forced pendulum, illustrates the method.

  17. Effect of Cholinergic Signaling on Neuronal Cell Bioenergetics

    PubMed Central

    Lu, Jianghua; Lezi, E; Roy, Nairita; Hutfles, Lewis; Selfridge, Eva; Funk, Eric; Burns, Jeffrey M.; Swerdlow, Russell H.

    2012-01-01

    Alzheimer's disease (AD) patients have reduced brain acetylcholine and reversing this deficit yields clinical benefits. In this study we explored how increased cholinergic tone impacts cell bioenergetics, which are also perturbed in AD. We treated SHSY5Y neuroblastoma cells with carbachol, a cholinergic agonist, and tested for bioenergetic flux and bioenergetic infrastructure changes. Carbachol rapidly increased both oxidative phosphorylation and glycolysis fluxes. ATP levels rose slightly, as did cell energy demand, and AMPK phosphorylation occurred. At least some of these effects depended on muscarinic receptor activation, ER calcium release, and ER calcium re-uptake. Our data show that increasing cholinergic signaling enhances cell bioenergetics, and reveal mechanisms that mediate this effect. Phenomena we observed could potentially explain why cholinesterase inhibitor therapy increases AD brain glucose utilization and N-acetyl aspartate levels. The question of whether cholinesterase inhibitors have a disease modifying effect in AD has long been debated; our data suggest a theoretical mechanism through which such an effect could potentially arise. PMID:23099815

  18. Cholinergic Activity as a New Target in Diseases of the Heart

    PubMed Central

    Roy, Ashbeel; Guatimosim, Silvia; Prado, Vania F; Gros, Robert; Prado, Marco A M

    2014-01-01

    The autonomic nervous system is an important modulator of cardiac signaling in both health and disease. In fact, the significance of altered parasympathetic tone in cardiac disease has recently come to the forefront. Both neuronal and nonneuronal cholinergic signaling likely play a physiological role, since modulating acetylcholine (ACh) signaling from neurons or cardiomyocytes appears to have significant consequences in both health and disease. Notably, many of these effects are solely due to changes in cholinergic signaling, without altered sympathetic drive, which is known to have significant adverse effects in disease states. As such, it is likely that enhanced ACh-mediated signaling not only has direct positive effects on cardiomyocytes, but it also offsets the negative effects of hyperadrenergic tone. In this review, we discuss recent studies that implicate ACh as a major regulator of cardiac remodeling and provide support for the notion that enhancing cholinergic signaling in human patients with cardiac disease can reduce morbidity and mortality. These recent results support the idea of developing large clinical trials of strategies to increase cholinergic tone, either by stimulating the vagus or by increased availability of Ach, in heart failure. PMID:25222914

  19. Enhanced GABAergic Inputs Contribute to Functional Alterations of Cholinergic Interneurons in the R6/2 Mouse Model of Huntington’s Disease1,2,3

    PubMed Central

    Holley, Sandra M.; Joshi, Prasad R.; Parievsky, Anna; Galvan, Laurie; Chen, Jane Y.; Fisher, Yvette E.; Huynh, My N.; Cepeda, Carlos

    2015-01-01

    Abstract In Huntington’s disease (HD), a hereditary neurodegenerative disorder, striatal medium-sized spiny neurons undergo degenerative changes. In contrast, large cholinergic interneurons (LCIs) are relatively spared. However, their ability to release acetylcholine (ACh) is impaired. The present experiments examined morphological and electrophysiological properties of LCIs in the R6/2 mouse model of HD. R6/2 mice show a severe, rapidly progressing phenotype. Immunocytochemical analysis of choline acetyltransferase-positive striatal neurons showed that, although the total number of cells was not changed, somatic areas were significantly smaller in symptomatic R6/2 mice compared to wild-type (WT) littermates, For electrophysiology, brain slices were obtained from presymptomatic (3-4 weeks) and symptomatic (>8 weeks) R6/2 mice and their WT littermates. Striatal LCIs were identified by somatic size and spontaneous action potential firing in the cell-attached mode. Passive and active membrane properties of LCIs were similar in presymptomatic R6/2 and WT mice. In contrast, LCIs from symptomatic R6/2 animals displayed smaller membrane capacitance and higher input resistance, consistent with reduced somatic size. In addition, more LCIs from symptomatic mice displayed irregular firing patterns and bursts of action potentials. They also displayed a higher frequency of spontaneous GABAergic IPSCs and larger amplitude of electrically evoked IPSCs. Selective optogenetic stimulation of somatostatin- but not parvalbumin-containing interneurons also evoked larger amplitude IPSCs in LCIs from R6/2 mice. In contrast, glutamatergic spontaneous or evoked postsynaptic currents were not affected. Morphological and electrophysiological alterations, in conjunction with the presence of mutant huntingtin in LCIs, could explain impaired ACh release in HD mouse models. PMID:26203463

  20. Potential animal model of multiple chemical sensitivity with cholinergic supersensitivity.

    PubMed

    Overstreet, D H; Miller, C S; Janowsky, D S; Russell, R W

    1996-07-17

    Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemicals, commonly organophosphate pesticides (OPs), become overly sensitive to a wide variety of chemically-unrelated compounds, which can include ethanol, caffeine and other psychotropic drugs. The Flinders Sensitive Line (FSL) rats were selectively bred to be more sensitive to the OP diisopropylfluorophosphate (DFP) compared to their control counterparts, the Flinders Resistant Line (FRL) rats. The present paper will summarize evidence which indicates that the FSL rats exhibit certain similarities to individuals with MCS. In addition to their greater sensitivity to DFP, the FSL rats are more sensitive to nicotine and the muscarinic agonists arecoline and oxotremorine, suggesting that the number of cholinergic receptors may be increased, a conclusion now supported by biochemical evidence. The FSL rats have also been found to exhibit enhanced responses to a variety of other drugs, including the serotonin agonists m-chlorophenylpiperazine and 8-OH-DPAT, the dopamine antagonist raclopride, the benzodiazepine diazepam, and ethanol. MCS patients report enhanced responses to many of these drugs, indicating some parallels between FSL rats and MCS patients. The FSL rats also exhibit reduced activity and appetite and increased REM sleep relative to their FRL controls. Because these behavioral features and the enhanced cholinergic responses are also observed in human depressives, the FSL rats have been proposed as a genetic animal model of depression. It has also been reported that MCS patients have a greater incidence of depression, both before and after onset of their chemical sensitivities, so cholinergic supersensitivity may be a state predisposing individuals to depressive disorders and/or MCS. Further exploration of the commonalities and differences between MCS patients, human depressives, and FSL rats will help to elucidate the

  1. Cholinergic dysfunction in Parkinson's disease.

    PubMed

    Müller, Martijn L T M; Bohnen, Nicolaas I

    2013-09-01

    There is increasing interest in the clinical effects of cholinergic basal forebrain and tegmental pedunculopontine complex (PPN) projection degeneration in Parkinson's disease (PD). Recent evidence supports an expanded role beyond cognitive impairment, including effects on olfaction, mood, REM sleep behavior disorder, and motor functions. Cholinergic denervation is variable in PD without dementia and may contribute to clinical symptom heterogeneity. Early in vivo imaging evidence that impaired cholinergic integrity of the PPN associates with frequent falling in PD is now confirmed by human post-mortem evidence. Brainstem cholinergic lesioning studies in primates confirm the role of the PPN in mobility impairment. Degeneration of basal forebrain cholinergic projections correlates with decreased walking speed. Cumulatively, these findings provide evidence for a new paradigm to explain dopamine-resistant features of mobility impairments in PD. Recognition of the increased clinical role of cholinergic system degeneration may motivate new research to expand indications for cholinergic therapy in PD. PMID:23943367

  2. Nematode cholinergic pharmacology

    SciTech Connect

    Segerberg, M.A.

    1989-01-01

    Nematode acetylcholine (ACh) receptors were characterized using both biochemical and electrophysiological techniques, including: (1) receptor binding studies in crude homogenates of the free-living nematode Caenorhabditis elegans and the parasitic nematode Ascaris lumbricoides with the high-affinity probe ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) which binds to muscarinic receptors in many vertebrate and invertebrate tissues (2) measurement of depolarization and contraction induced by a variety of cholinergic agents, including N-methylscopolamine (NMS), in an innervated dorsal muscle strip preparation of Ascaris; (3) examination of the antagonistic actions of d-tubocurarine (dTC) and NMS at dorsal neuromuscular junction; (4) measurement of input resistance changes in Ascaris commissural motorneurons induced by ACh, dTC, NMS, pilocarpine and other cholinergic drugs.

  3. Cholinergic synaptic circuitry in the macaque prefrontal cortex.

    PubMed

    Mrzljak, L; Pappy, M; Leranth, C; Goldman-Rakic, P S

    1995-07-10

    Surprisingly little is known about the synaptic architecture of the cholinergic innervation in the primate cerebral cortex in spite of its acknowledged relevance to cognitive processing and Alzheimer's disease. To address this knowledge gap, we examined serially sectioned cholinergic axons in supra- and infragranular layers of the macaque prefrontal cortex by using an antibody against the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). The tissue bound antibody was visualized with both immunoperoxidase and silver-enhanced diaminobenzidine sulfide (SEDS) techniques. Both methods revealed that cholinergic axons make synapses in all cortical layers and that these synapses are exclusively symmetric. Cholinergic axons formed synapses primarily on dendritic shafts (70.5%), dendritic spines (25%), and, to a lesser extent, cell bodies (4.5%). Both pyramidal neurons and cells exhibiting the morphological features of GABAergic cells were targets of the cholinergic innervation. Some spiny dendritic shafts received multiple, closely spaced synapses, suggesting that a subset of pyramidal neurons may be subject to a particularly strong cholinergic influence. Analysis of synaptic incidence of cholinergic profiles in the supragranular layers of the prefrontal cortex by the SEDS technique revealed that definitive synaptic junctions were formed by 44% of the cholinergic boutons. An unexpected finding was that cholinergic boutons were frequently apposed to spines and small dendrites without making any visible synaptic specializations. These same spines and dendrites often received asymmetric synapses, presumably of thalamocortical or corticocortical origin. Present ultrastructural findings suggest that acetylcholine may have a dual modulatory effect in the neocortex: one through classical synaptic junctions on dendritic shafts and spines, and the other through nonsynaptic appositions in close vicinity to asymmetric synapses. Further physiological studies are

  4. Enhancement of the post-training cholinergic tone antagonizes the impairment of retention induced by a nitric oxide synthase inhibitor in mice.

    PubMed

    Kopf, S R; Baratti, C M

    1996-05-01

    The present experiments examined the role of the central cholinergic system in the memory impairment induced by post-training administration of a nitric oxide synthase (NOS) inhibitor in mice. Male Swiss mice received a one-trial inhibitory avoidance training (0.8 mA, 50 Hz, 1-s footshock) followed immediately by an ip injection of the NOS inhibitor L-NG-nitroarginine methyl ester (L-NAME; 100 mg/kg). Retention (cut-off time, 300 s) was tested 48 h after training. The administration of L-NAME results in memory impairment for the inhibitory avoidance task. The effects of L-NAME (100 mg/kg, ip) on retention were reversed in a dose-related manner by the centrally acting anticholinesterase physostigmine (35, 70, or 150 microg/kg, sc) administered 30 min after the NOS inhibitor. Further, L-NAME (100 mg/kg, ip)-induced memory impairment was completely antagonized by the centrally acting muscarinic cholinergic agonist oxotremorine (OTM; 25, 50, or 100 microg/kg, sc) when given 30 min after L-NAME. The peripherally acting anticholinesterase neostigmine (150 microg/kg, sc) did not modify the memory-impairing effects of L-NAME. These findings suggest that the memory impairment following post-training administration of a NOS inhibitor is mediated, at least in part, by a reduction of the activity of central muscarinic cholinergic mechanisms and are consistent with our previous view that nitric oxide may be involved in post-training neural processes underlying the storage of newly acquired information. PMID:8616584

  5. Enhancement of the post-training cholinergic tone antagonizes the impairment of retention induced by a nitric oxide synthase inhibitor in mice.

    PubMed

    Kopf, S R; Baratti, C M

    1996-05-01

    The present experiments examined the role of the central cholinergic system in the memory impairment induced by post-training administration of a nitric oxide synthase (NOS) inhibitor in mice. Male Swiss mice received a one-trial inhibitory avoidance training (0.8 mA, 50 Hz, 1-s footshock) followed immediately by an ip injection of the NOS inhibitor L-NG-nitroarginine methyl ester (L-NAME; 100 mg/kg). Retention (cut-off time, 300 s) was tested 48 h after training. The administration of L-NAME results in memory impairment for the inhibitory avoidance task. The effects of L-NAME (100 mg/kg, ip) on retention were reversed in a dose-related manner by the centrally acting anticholinesterase physostigmine (35, 70, or 150 microg/kg, sc) administered 30 min after the NOS inhibitor. Further, L-NAME (100 mg/kg, ip)-induced memory impairment was completely antagonized by the centrally acting muscarinic cholinergic agonist oxotremorine (OTM; 25, 50, or 100 microg/kg, sc) when given 30 min after L-NAME. The peripherally acting anticholinesterase neostigmine (150 microg/kg, sc) did not modify the memory-impairing effects of L-NAME. These findings suggest that the memory impairment following post-training administration of a NOS inhibitor is mediated, at least in part, by a reduction of the activity of central muscarinic cholinergic mechanisms and are consistent with our previous view that nitric oxide may be involved in post-training neural processes underlying the storage of newly acquired information.

  6. Methods Reduce Cost, Enhance Quality of Nanotubes

    NASA Technical Reports Server (NTRS)

    2009-01-01

    For all the challenges posed by the microgravity conditions of space, weight is actually one of the more significant problems NASA faces in the development of the next generation of U.S. space vehicles. For the Agency s Constellation Program, engineers at NASA centers are designing and testing new vessels as safe, practical, and cost-effective means of space travel following the eventual retirement of the space shuttle. Program components like the Orion Crew Exploration Vehicle, intended to carry astronauts to the International Space Station and the Moon, must be designed to specific weight requirements to manage fuel consumption and match launch rocket capabilities; Orion s gross liftoff weight target is about 63,789 pounds. Future space vehicles will require even greater attention to lightweight construction to help conserve fuel for long-range missions to Mars and beyond. In order to reduce spacecraft weight without sacrificing structural integrity, NASA is pursuing the development of materials that promise to revolutionize not only spacecraft construction, but also a host of potential applications on Earth. Single-walled carbon nanotubes are one material of particular interest. These tubular, single-layer carbon molecules - 100,000 of them braided together would be no thicker than a human hair - display a range of remarkable characteristics. Possessing greater tensile strength than steel at a fraction of the weight, the nanotubes are efficient heat conductors with metallic or semiconductor electrical properties depending on their diameter and chirality (the pattern of each nanotube s hexagonal lattice structure). All of these properties make the nanotubes an appealing material for spacecraft construction, with the potential for nanotube composites to reduce spacecraft weight by 50 percent or more. The nanotubes may also feature in a number of other space exploration applications, including life support, energy storage, and sensor technologies. NASA s various

  7. Decreased subcortical cholinergic arousal in focal seizures

    PubMed Central

    Motelow, Joshua E.; Li, Wei; Zhan, Qiong; Mishra, Asht M.; Sachdev, Robert N. S.; Liu, Geoffrey; Gummadavelli, Abhijeet; Zayyad, Zaina; Lee, Hyun Seung; Chu, Victoria; Andrews, John P.; Englot, Dario J.; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Blumenfeld, Hal

    2015-01-01

    SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures. PMID:25654258

  8. Striatal cholinergic interneurons Drive GABA release from dopamine terminals.

    PubMed

    Nelson, Alexandra B; Hammack, Nora; Yang, Cindy F; Shah, Nirao M; Seal, Rebecca P; Kreitzer, Anatol C

    2014-04-01

    Striatal cholinergic interneurons are implicated in motor control, associative plasticity, and reward-dependent learning. Synchronous activation of cholinergic interneurons triggers large inhibitory synaptic currents in dorsal striatal projection neurons, providing one potential substrate for control of striatal output, but the mechanism for these GABAergic currents is not fully understood. Using optogenetics and whole-cell recordings in brain slices, we find that a large component of these inhibitory responses derive from action-potential-independent disynaptic neurotransmission mediated by nicotinic receptors. Cholinergically driven IPSCs were not affected by ablation of striatal fast-spiking interneurons but were greatly reduced after acute treatment with vesicular monoamine transport inhibitors or selective destruction of dopamine terminals with 6-hydroxydopamine, indicating that GABA release originated from dopamine terminals. These results delineate a mechanism in which striatal cholinergic interneurons can co-opt dopamine terminals to drive GABA release and rapidly inhibit striatal output neurons.

  9. Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits

    PubMed Central

    Dautan, Daniel; Souza, Albert S.; Huerta-Ocampo, Icnelia; Valencia, Miguel; Assous, Maxime; Witten, Ilana B.; Deisseroth, Karl; Tepper, James M.; Bolam, J. Paul; Gerdjikov, Todor V.; Mena-Segovia, Juan

    2016-01-01

    Dopamine neurons in the ventral tegmental area (VTA) receive cholinergic innervation from brainstem structures associated with either movement or reward. While cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. Here we used optogenetic methods combined with in vivo juxtacellular recording/labeling to dissect the influence of brainstem cholinergic innervation of distinct neuronal subpopulations in the VTA. We found that LDT cholinergic axons selectively enhance the bursting activity of mesolimbic dopamine neurons that are excited by aversive stimulation. In contrast, PPN cholinergic axons activate and change the discharge properties of VTA neurons that are integrated in distinct functional circuits and are inhibited by aversive stimulation. While both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of cholinergic transmission operate in the VTA and segregate neurons involved in different reward circuits. PMID:7666171

  10. Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits.

    PubMed

    Dautan, Daniel; Souza, Albert S; Huerta-Ocampo, Icnelia; Valencia, Miguel; Assous, Maxime; Witten, Ilana B; Deisseroth, Karl; Tepper, James M; Bolam, J Paul; Gerdjikov, Todor V; Mena-Segovia, Juan

    2016-08-01

    Dopamine neurons in the ventral tegmental area (VTA) receive cholinergic innervation from brainstem structures that are associated with either movement or reward. Whereas cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. We used optogenetics and in vivo juxtacellular recording and labeling to examine the influence of brainstem cholinergic innervation of distinct neuronal subpopulations in the VTA. We found that LDT cholinergic axons selectively enhanced the bursting activity of mesolimbic dopamine neurons that were excited by aversive stimulation. In contrast, PPN cholinergic axons activated and changed the discharge properties of VTA neurons that were integrated in distinct functional circuits and were inhibited by aversive stimulation. Although both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of cholinergic transmission operate in the VTA and segregate the neurons involved in different reward circuits.

  11. The nicotinic cholinergic system function in the human brain.

    PubMed

    Nees, Frauke

    2015-09-01

    Research on the nicotinic cholinergic system function in the brain was previously mainly derived from animal studies, yet, research in humans is growing. Up to date, findings allow significant advances on the understanding of nicotinic cholinergic effects on human cognition, emotion and behavior using a range of functional brain imaging approaches such as pharmacological functional magnetic resonance imaging or positron emission tomography. Studies provided insights across various mechanistic psychological domains using different tasks as well as at rest in both healthy individuals and patient populations, with so far partly mixed results reporting both enhancements and decrements of neural activity related to the nicotinic cholinergic system. Moreover, studies on the relation between brain structure and the nicotinic cholinergic system add important information in this context. The present review summarizes the current status of human brain imaging studies and presents the findings within a theoretical and clinical perspective as they may be useful not only for an advancement of the understanding of basic nicotinic cholinergic-related mechanisms, but also for the development and integration of psychological and pharmacological treatment approaches. Patterns of functional neuroanatomy and neural circuitry across various cognitive and emotional domains may be used as neuropsychological markers of mental disorders such as addiction, Alzheimer's disease, Parkinson disease or schizophrenia, where nicotinic cholinergic system changes are characteristic. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'.

  12. Cholinergic Plasticity of Oscillating Neuronal Assemblies in Mouse Hippocampal Slices

    PubMed Central

    Zylla, Maura M.; Zhang, Xiaomin; Reichinnek, Susanne; Draguhn, Andreas; Both, Martin

    2013-01-01

    The mammalian hippocampus expresses several types of network oscillations which entrain neurons into transiently stable assemblies. These groups of co-active neurons are believed to support the formation, consolidation and recall of context-dependent memories. Formation of new assemblies occurs during theta- and gamma-oscillations under conditions of high cholinergic activity. Memory consolidation is linked to sharp wave-ripple oscillations (SPW-R) during decreased cholinergic tone. We hypothesized that increased cholinergic tone supports plastic changes of assemblies while low cholinergic tone favors their stability. Coherent spatiotemporal network patterns were measured during SPW-R activity in mouse hippocampal slices. We compared neuronal activity within the oscillating assemblies before and after a transient phase of carbachol-induced gamma oscillations. Single units maintained their coupling to SPW-R throughout the experiment and could be re-identified after the transient phase of gamma oscillations. However, the frequency of SPW-R-related unit firing was enhanced after muscarinic stimulation. At the network level, these changes resulted in altered patterns of extracellularly recorded SPW-R waveforms. In contrast, recording of ongoing SPW-R activity without intermittent cholinergic stimulation revealed remarkably stable repetitive activation of assemblies. These results show that activation of cholinergic receptors induces plasticity at the level of oscillating hippocampal assemblies, in line with the different role of gamma- and SPW-R network activity for memory formation and –consolidation, respectively. PMID:24260462

  13. Monitoring cholinergic activity during attentional performance in mice heterozygous for the choline transporter: a model of cholinergic capacity limits.

    PubMed

    Paolone, Giovanna; Mallory, Caitlin S; Koshy Cherian, Ajeesh; Miller, Thomas R; Blakely, Randy D; Sarter, Martin

    2013-12-01

    Reductions in the capacity of the human choline transporter (SLC5A7, CHT) have been hypothesized to diminish cortical cholinergic neurotransmission, leading to risk for cognitive and mood disorders. To determine the acetylcholine (ACh) release capacity of cortical cholinergic projections in a mouse model of cholinergic hypofunction, the CHT+/- mouse, we assessed extracellular ACh levels while mice performed an operant sustained attention task (SAT). We found that whereas SAT-performance-associated increases in extracellular ACh levels of CHT+/- mice were significantly attenuated relative to wildtype littermates, performance on the SAT was normal. Tetrodotoxin-induced blockade of neuronal excitability reduced both dialysate ACh levels and SAT performance similarly in both genotypes. Likewise, lesions of cholinergic neurons abolished SAT performance in both genotypes. However, cholinergic activation remained more vulnerable to the reverse-dialyzed muscarinic antagonist atropine in CHT+/- mice. Additionally, CHT+/- mice displayed greater SAT-disrupting effects of reverse dialysis of the nAChR antagonist mecamylamine. Receptor binding assays revealed a higher density of α4β2* nAChRs in the cortex of CHT+/- mice compared to controls. These findings reveal compensatory mechanisms that, in the context of moderate cognitive challenges, can overcome the performance deficits expected from the significantly reduced ACh capacity of CHT+/- cholinergic terminals. Further analyses of molecular and functional compensations in the CHT+/- model may provide insights into both risk and resiliency factors involved in cognitive and mood disorders.

  14. Monitoring cholinergic activity during attentional performance in mice heterozygous for the choline transporter: a model of cholinergic capacity limits

    PubMed Central

    Cherian, Ajeesh Koshy; Miller, Thomas R.; Blakely, Randy D.; Sarter, Martin

    2013-01-01

    Reductions in the capacity of the human choline transporter (SLC5A7, CHT) have been hypothesized to diminish cortical cholinergic neurotransmission, leading to risk for cognitive and mood disorders. To determine the acetylcholine (ACh) release capacity of cortical cholinergic projections in a mouse model of cholinergic hypofunction, the CHT+/− mouse, we assessed extracellular ACh levels while mice performed an operant sustained attention task (SAT). We found that whereas SAT-performance-associated increases in extracellular ACh levels of CHT+/− mice were significantly attenuated relative to wildtype littermates, performance on the SAT was normal. Tetrodotoxin-induced blockade of neuronal excitability reduced both dialysate ACh levels and SAT performance similarly in both genotypes. Likewise, lesions of cholinergic neurons abolished SAT performance in both genotypes. However, cholinergic activation remained more vulnerable to the reverse-dialyzed muscarinic antagonist atropine in CHT+/− mice. Additionally, CHT+/− mice displayed greater SAT-disrupting effects of reverse dialysis of the nAChR antagonist mecamylamine. Receptor binding assays revealed a higher density of α4β2* nAChRs in the cortex of CHT+/− mice compared to controls. These findings reveal compensatory mechanisms that, in the context of moderate cognitive challenges, can overcome the performance deficits expected from the significantly reduced ACh capacity of CHT+/− cholinergic terminals. Further analyses of molecular and functional compensations in the CHT +/− model may provide insights into both risk and resiliency factors involved in cognitive and mood disorders. PMID:23958450

  15. Boosting visual cortex function and plasticity with acetylcholine to enhance visual perception

    PubMed Central

    Kang, Jun Il; Huppé-Gourgues, Frédéric; Vaucher, Elvire

    2014-01-01

    The cholinergic system is a potent neuromodulatory system that plays critical roles in cortical plasticity, attention and learning. In this review, we propose that the cellular effects of acetylcholine (ACh) in the primary visual cortex during the processing of visual inputs might induce perceptual learning; i.e., long-term changes in visual perception. Specifically, the pairing of cholinergic activation with visual stimulation increases the signal-to-noise ratio, cue detection ability and long-term facilitation in the primary visual cortex. This cholinergic enhancement would increase the strength of thalamocortical afferents to facilitate the treatment of a novel stimulus while decreasing the cortico-cortical signaling to reduce recurrent or top-down modulation. This balance would be mediated by different cholinergic receptor subtypes that are located on both glutamatergic and GABAergic neurons of the different cortical layers. The mechanisms of cholinergic enhancement are closely linked to attentional processes, long-term potentiation (LTP) and modulation of the excitatory/inhibitory balance. Recently, it was found that boosting the cholinergic system during visual training robustly enhances sensory perception in a long-term manner. Our hypothesis is that repetitive pairing of cholinergic and sensory stimulation over a long period of time induces long-term changes in the processing of trained stimuli that might improve perceptual ability. Various non-invasive approaches to the activation of the cholinergic neurons have strong potential to improve visual perception. PMID:25278848

  16. Cholinergic Signaling through Synaptic SK Channels: It’s a Protein Kinase but Which One?

    PubMed Central

    Maylie, James; Adelman, John P.

    2016-01-01

    Cholinergic signaling modulates synaptic responses and influences cognition. In this issue of Neuron, two groups (Buchanan et al. and Giessel and Sabatini) present evidence that cholinergic signaling enhances postsynaptic responses in CA1 neurons by decreasing synaptic SK channel activity. However, they come to different conclusions about the protein kinases involved in this process. PMID:21144995

  17. Cholinergic modulation of appetite-related synapses in mouse lateral hypothalamic slice.

    PubMed

    Jo, Young-Hwan; Wiedl, Denise; Role, Lorna W

    2005-11-30

    Nicotine administration reduces appetite and alters feeding patterns; a major deterrent to smoking cessation is hyperphagia and resultant weight gain. We demonstrate here that lateral hypothalamic (LH) circuits involving melanin-concentrating hormone (MCH) neurons are subject to cholinergic modulation that may be related to the effects of nicotine on appetite control. Cholinergic input to the perifornical LH area of the mouse is confirmed by examination of immunostaining for vesicular acetylcholine (ACh) transporter (VAT) in conjunction with antibodies to MCH and the vesicular GABA transporter (vGABAT). vAChT-positive neurons border the LH, and VAT-positive projections are detected throughout the perifornical area. MCH-positive dendrites appear studded with vGABAT-positive contacts, consistent with recordings of GABAergic inputs to LH/MCH neurons identified by their location, morphology, electrophysiological profile, and MCH expression. Activation of presynaptic nicotinic ACh receptors (nAChRs) enhances GABAergic transmission. GABAergic transmission is potentiated by (1) direct nicotine application, (2) increasing local ACh concentration, and (3) stimulation of cholinergic projections. Based on pharmacological studies and comparisons of wild-type versus alpha7 nAChR subunit mutant mice, we propose that alpha7*-nAChRs are required for the modulation of GABAergic inputs in LH. Prenatal exposure to nicotine elicits a persistent elevation of GABAergic transmission in the LH of postnatal pups. Furthermore, GABAergic inputs to LH of prenatal nicotine-exposed pups are insensitive to subsequent nicotine challenge. Our studies support the hypothesis that nicotine administration or elevated cholinergic tone enhance inhibition of perifonical LH/MCH neurons via activation of presynaptic alpha7*-nAChRs. PMID:16319313

  18. Cholinergic mechanisms in spinal locomotion—potential target for rehabilitation approaches

    PubMed Central

    Jordan, Larry M.; McVagh, J. R.; Noga, B. R.; Cabaj, A. M.; Majczyński, H.; Sławińska, Urszula; Provencher, J.; Leblond, H.; Rossignol, Serge

    2014-01-01

    Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our

  19. [Cholinergic system of the heart].

    PubMed

    Kučera, Matej; Hrabovská, Anna

    2015-12-01

    The cholinergic system of the heart can be either of neuronal or non-neuronal origin. The neuronal cholinergic system in the heart is represented by preganglionic parasympathetic pathways, intracardiac parasympathetic ganglia and postganglionic parasympathetic neurons projecting to the atria, SA node and AV node. The non-neuronal cholinergic system consists of cardiomyocytes that have complete equipment for synthesis and secretion of acetylcholine. Current knowledge suggests that the non-neuronal cholinergic system in the heart affects the regulation of the heart during sympathetic activation. The non-neuronal cholinergic system of the heart plays also a role in the energy metabolism of cardimyocites. Acetylcholine of both neuronal and non-neuronal origin acts in the heart through muscarinic and nicotinic receptors. The effect of acetylcholine in the heart is terminated by cholinesterases acetylcholinesterase and butyrylcholinesterase. Recently, papers suggest that the increased cholinergic tone in the heart by cholinesterase inhibitors has a positive effect on some cardiovascular disorders such as heart failure. For this reason, the cholinesterase inhibitors might be used in the treatment of certain cardiovascular disorders in the future.

  20. Pain sensitivity following loss of cholinergic basal forebrain (CBF) neurons in the rat.

    PubMed

    Vierck, C J; Yezierski, R P; Wiley, R G

    2016-04-01

    Flexion/withdrawal reflexes are attenuated by spinal, intracerebroventricular (ICV) and systemic delivery of cholinergic agonists. In contrast, some affective reactions to pain are suppressed by systemic cholinergic antagonism. Attention to aversive stimulation can be impaired, as is classical conditioning of fear and anxiety to aversive stimuli and psychological activation of stress reactions that exacerbate pain. Thus, in contrast to the suppressive effects of cholinergic agonism on reflexes, pain sensitivity and affective reactions to pain could be attenuated by reduced cerebral cholinergic activation. This possibility was evaluated in the present study, using an operant test of escape from nociceptive thermal stimulation (10 °C and 44.5 °C) before and after destruction of basal forebrain cholinergic neurons. ICV injection of 192 IgG-saporin produced widespread loss of basal forebrain cholinergic innervation of the cerebral cortex and hippocampus. Post-injection, escape from thermal stimulation was decreased with no indication of recovery for upto 19 weeks. Also, the normal hyperalgesic effect of sound stress was absent after ICV 192-sap. Effects of cerebral cholinergic denervation or stress on nociceptive licking and guarding reflexes were not consistent with the effects on operant escape, highlighting the importance of evaluating pain sensitivity of laboratory animals with an operant behavioral test. These results reveal that basal forebrain cholinergic transmission participates in the cerebral processing of pain, which may be relevant to the pain sensitivity of patients with Alzheimer's disease who have prominent degeneration of basal forebrain cholinergic neurons. PMID:26812034

  1. Cholinergic Neurons in the Basal Forebrain Promote Wakefulness by Actions on Neighboring Non-Cholinergic Neurons: An Opto-Dialysis Study

    PubMed Central

    Zant, Janneke C.; Kim, Tae; Prokai, Laszlo; Szarka, Szabolcs; McNally, James; McKenna, James T.; Shukla, Charu; Yang, Chun; Kalinchuk, Anna V.; McCarley, Robert W.; Brown, Ritchie E.

    2016-01-01

    Understanding the control of sleep–wake states by the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical arousal and sleep–wake control. Thus, nonspecific stimulation or inhibition studies do not reveal the roles of these different neuronal types. Recent studies using optogenetics have shown that “selective” stimulation of BF cholinergic neurons increases transitions between NREM sleep and wakefulness, implicating cholinergic projections to cortex in wake promotion. However, the interpretation of these optogenetic experiments is complicated by interactions that may occur within the BF. For instance, a recent in vitro study from our group found that cholinergic neurons strongly excite neighboring GABAergic neurons, including the subset of cortically projecting neurons, which contain the calcium-binding protein, parvalbumin (PV) (Yang et al., 2014). Thus, the wake-promoting effect of “selective” optogenetic stimulation of BF cholinergic neurons could be mediated by local excitation of GABA/PV or other non-cholinergic BF neurons. In this study, using a newly designed opto-dialysis probe to couple selective optical stimulation with simultaneous in vivo microdialysis, we demonstrated that optical stimulation of cholinergic neurons locally increased acetylcholine levels and increased wakefulness in mice. Surprisingly, the enhanced wakefulness caused by cholinergic stimulation was abolished by simultaneous reverse microdialysis of cholinergic receptor antagonists into BF. Thus, our data suggest that the wake-promoting effect of cholinergic stimulation requires local release of acetylcholine in the basal forebrain and activation of cortically projecting, non-cholinergic neurons, including the GABAergic/PV neurons. SIGNIFICANCE STATEMENT Optogenetics is a revolutionary tool to assess the roles of

  2. Sexually dimorphic effects of hippocampal cholinergic deafferentation in rats.

    PubMed

    Jonasson, Zachariah; Cahill, Jonathan F X; Tobey, Rachel E; Baxter, Mark G

    2004-12-01

    To determine whether the basal forebrain-hippocampal cholinergic system supports sexually dimorphic functionality, male and female Long-Evans rats were given either selective medial septum/vertical limb of the diagonal band (MS/VDB) cholinergic lesions using the neurotoxin 192 IgG-saporin or a control surgery and then postoperatively tested in a set of standard spatial learning tasks in the Morris water maze. Lesions were highly specific and effective as confirmed by both choline acetyltransferase/parvalbumin immunostaining and acetylcholinesterase histochemistry. Female controls performed worse than male controls in place learning and MS/VDB lesions failed to impair spatial learning in male rats, both consistent with previous findings. In female rats, MS/VDB cholinergic lesions facilitated spatial reference learning. A subsequent test of learning strategy in the water maze revealed a female bias for a response, relative to a spatial, strategy; MS/VDB cholinergic lesions enhanced the use of a spatial strategy in both sexes, but only significantly so in males. Together, these results indicate a sexually dimorphic function associated with MS/VDB-hippocampal cholinergic inputs. In female rats, these neurons appear to support sex-specific spatial learning processes.

  3. Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees

    PubMed Central

    Palmer, Mary J.; Moffat, Christopher; Saranzewa, Nastja; Harvey, Jenni; Wright, Geraldine A.; Connolly, Christopher N.

    2013-01-01

    Pesticides that target cholinergic neurotransmission are highly effective, but their use has been implicated in insect pollinator population decline. Honeybees are exposed to two widely used classes of cholinergic pesticide: neonicotinoids (nicotinic receptor agonists) and organophosphate miticides (acetylcholinesterase inhibitors). Although sublethal levels of neonicotinoids are known to disrupt honeybee learning and behaviour, the neurophysiological basis of these effects has not been shown. Here, using recordings from mushroom body Kenyon cells in acutely isolated honeybee brain, we show that the neonicotinoids imidacloprid and clothianidin, and the organophosphate miticide coumaphos oxon, cause a depolarization-block of neuronal firing and inhibit nicotinic responses. These effects are observed at concentrations that are encountered by foraging honeybees and within the hive, and are additive with combined application. Our findings demonstrate a neuronal mechanism that may account for the cognitive impairments caused by neonicotinoids, and predict that exposure to multiple pesticides that target cholinergic signalling will cause enhanced toxicity to pollinators. PMID:23535655

  4. Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees.

    PubMed

    Palmer, Mary J; Moffat, Christopher; Saranzewa, Nastja; Harvey, Jenni; Wright, Geraldine A; Connolly, Christopher N

    2013-01-01

    Pesticides that target cholinergic neurotransmission are highly effective, but their use has been implicated in insect pollinator population decline. Honeybees are exposed to two widely used classes of cholinergic pesticide: neonicotinoids (nicotinic receptor agonists) and organophosphate miticides (acetylcholinesterase inhibitors). Although sublethal levels of neonicotinoids are known to disrupt honeybee learning and behaviour, the neurophysiological basis of these effects has not been shown. Here, using recordings from mushroom body Kenyon cells in acutely isolated honeybee brain, we show that the neonicotinoids imidacloprid and clothianidin, and the organophosphate miticide coumaphos oxon, cause a depolarization-block of neuronal firing and inhibit nicotinic responses. These effects are observed at concentrations that are encountered by foraging honeybees and within the hive, and are additive with combined application. Our findings demonstrate a neuronal mechanism that may account for the cognitive impairments caused by neonicotinoids, and predict that exposure to multiple pesticides that target cholinergic signalling will cause enhanced toxicity to pollinators.

  5. Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase calpha expression.

    PubMed

    Ferreira, Fabiano; Filiputti, Eliane; Arantes, Vanessa C; Stoppiglia, Luis F; Araújo, Eliana P; Delghingaro-Augusto, Viviane; Latorraca, Márcia Q; Toyama, Marcos H; Boschero, Antonio C; Carneiro, Everardo M

    2003-03-01

    Undernutrition has been shown to affect the autonomic nervous system, leading to permanent alterations in insulin secretion. To understand these interactions better, we investigated the effects of carbamylcholine (CCh) and phorbol 12-myristate 13-acetate (PMA) on insulin secretion in pancreatic islets from rats fed a normal (17%; NP) or low (6%; LP) protein diet for 8 wk. Isolated islets were incubated for 1 h in Krebs-bicarbonate solution containing 8.3 mmol glucose/L, with or without PMA (400 nmol/L) and CCh. Increasing concentrations of CCh (0.1-1000 micro mol/L) dose dependently increased insulin secretion by islets from both groups of rats. However, insulin secretion by islets from rats fed the NP diet was significantly higher than that of rats fed the LP diet, and the dose-response curve to CCh was shifted to the right in islets from rats fed LP with a 50% effective concentration (EC(50)) of 2.15 +/- 0.7 and 4.64 +/- 0.1 micro mol CCh/L in islets of rats fed NP and LP diets, respectively (P < 0.05). PMA-induced insulin secretion was higher in islets of rats fed NP compared with those fed LP. Western blotting revealed that the protein kinase (PK)Calpha and phospholipase (PL)Cbeta(1) contents of islets of rats fed LP were 30% lower than those of islets of rats fed NP (P < 0.05). In addition, PKCalpha mRNA expression was reduced by 50% in islets from rats fed LP. In conclusion, a reduced expression of PKCalpha and PLCbeta(1) may be involved in the decreased insulin secretion by islets from LP rats after stimulation with CCh and PMA. PMID:12612139

  6. Cholinergic Blockade Reduces Theta-Gamma Phase Amplitude Coupling and Speed Modulation of Theta Frequency Consistent with Behavioral Effects on Encoding

    PubMed Central

    Gillet, Shea N.; Climer, Jason R.; Hasselmo, Michael E.

    2013-01-01

    Large-scale neural activation dynamics in the hippocampal-entorhinal circuit local field potential, observable as theta and gamma rhythms and coupling between these rhythms, is predictive of encoding success. Behavioral studies show that systemic administration of muscarinic acetylcholine receptor antagonists selectively impairs encoding, suggesting that they may also disrupt the coupling between the theta and gamma bands. Here, we tested the hypothesis that muscarinic antagonists selectively disrupt coupling between theta and gamma. Specifically, we characterized the effects of systemically administered scopolamine on movement-induced theta and gamma rhythms recorded in the superficial layers of the medial entorhinal cortex (MEC) of freely moving rats. We report the novel result that gamma power at the peak of theta was most reduced following muscarinic blockade, significantly shifting the phase of maximal gamma power to occur at later phases of theta. We also characterize the existence of multiple distinct gamma bands in the superficial layers of the MEC. Further, we observed that theta frequency was significantly less modulated by movement speed following muscarinic blockade. Finally, the slope relating speed to theta frequency, a correlate of familiarity with a testing enclosure, increased significantly less between the preinjection and recovery trials when scopolamine was administered during the intervening injection session than when saline was administered, suggesting that scopolamine reduced encoding of the testing enclosure. These data are consistent with computational models suggesting that encoding and retrieval occur during the peak and trough of theta, respectively, and support the theory that acetylcholine regulates the balance between encoding versus retrieval. PMID:24336727

  7. Cholinergic Targets in Lung Cancer.

    PubMed

    Spindel, Eliot R

    2016-01-01

    Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review. PMID:26818857

  8. Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons

    PubMed Central

    Hawryluk, J. M.; Ferrari, L. L.; Keating, S. A.

    2012-01-01

    Adenosine has been proposed as an endogenous homeostatic sleep factor that accumulates during waking and inhibits wake-active neurons to promote sleep. It has been specifically hypothesized that adenosine decreases wakefulness and promotes sleep recovery by directly inhibiting wake-active neurons of the basal forebrain (BF), particularly BF cholinergic neurons. We previously showed that adenosine directly inhibits BF cholinergic neurons. Here, we investigated 1) how adenosine modulates glutamatergic input to BF cholinergic neurons and 2) how adenosine uptake and adenosine metabolism are involved in regulating extracellular levels of adenosine. Our experiments were conducted using whole cell patch-clamp recordings in mouse brain slices. We found that in BF cholinergic neurons, adenosine reduced the amplitude of AMPA-mediated evoked glutamatergic excitatory postsynaptic currents (EPSCs) and decreased the frequency of spontaneous and miniature EPSCs through presynaptic A1 receptors. Thus we have demonstrated that in addition to directly inhibiting BF cholinergic neurons, adenosine depresses excitatory inputs to these neurons. It is therefore possible that both direct and indirect inhibition may synergistically contribute to the sleep-promoting effects of adenosine in the BF. We also found that blocking the influx of adenosine through the equilibrative nucleoside transporters or inhibiting adenosine kinase and adenosine deaminase increased endogenous adenosine inhibitory tone, suggesting a possible mechanism through which adenosine extracellular levels in the basal forebrain are regulated. PMID:22357797

  9. Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction

    PubMed Central

    Gavioli, Mariana; Lara, Aline; Almeida, Pedro W. M.; Lima, Augusto Martins; Damasceno, Denis D.; Rocha-Resende, Cibele; Ladeira, Marina; Resende, Rodrigo R.; Martinelli, Patricia M.; Melo, Marcos Barrouin; Brum, Patricia C.; Fontes, Marco Antonio Peliky; Souza Santos, Robson A.; Prado, Marco A. M.; Guatimosim, Silvia

    2014-01-01

    Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the α2A/α2C-adrenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease. PMID:24992197

  10. Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids.

    PubMed

    Fernández-Fernández, Laura; Esteban, Gerard; Giralt, Mercedes; Valente, Tony; Bolea, Irene; Solé, Montse; Sun, Ping; Benítez, Susana; Morelló, José Ramón; Reguant, Jordi; Ramírez, Bartolomé; Hidalgo, Juan; Unzeta, Mercedes

    2015-04-01

    The possible modulatory effect of the functional LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids, on the catecholaminergic and cholinergic neurotransmission, affecting cognition decline during aging has been studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or control diets. The enzymes involved in catecholaminergic and cholinergic metabolism were determined by both immunohistological and western blot analyses. Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis. Theobromine, present in cocoa, the main LMN diet component, was analysed in parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both cholinergic and catecholaminergic transmissions was observed on 20 day fed mice. Similar effect was observed with theobromine, besides its antioxidant capacity inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and theobromine on the levels of acetylcholine-related enzymes, dopamine and specially noradrenalin confirms the beneficial role of this diet on the "cognitive reserve" and hence a possible reducing effect on cognitive decline underlying aging and Alzheimer's disease. PMID:25756794

  11. Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity

    PubMed Central

    Su, Yuan; Zhu, Liping; Yu, Xiangyuan; Cai, Lei; Lu, Yankai; Zhang, Jiwei; Li, Tongfei; Li, Jiansha; Xia, Jingyan; Xu, Feng; Hu, Qinghua

    2016-01-01

    Increased cholinergic activity has been highlighted in the pathogenesis of airway hyperresponsiveness, and alternations of mitochondrial structure and function appear to be involved in many lung diseases including airway hyperresponsiveness. It is crucial to clarify the cause-effect association between mitochondrial dysfunction and cholinergic hyperactivity in the pathogenesis of airway hyperresponsiveness. Male SD rats and cultured airway epithelial cells were exposed to cigarette smoke plus lipopolysaccharide administration; mitochondria isolated from airway epithelium were delivered into epithelial cells in vitro and in vivo. Both the cigarette smoke plus lipopolysaccharide-induced cholinergic hyperactivity in vitro and the airway hyperresponsiveness to acetylcholine in vivo were reversed by the transplantation of exogenous mitochondria. The rescue effects of exogenous mitochondria were imitated by the elimination of excessive reactive oxygen species or blockage of muscarinic M3 receptor, but inhibited by M receptor enhancer. Mitochondrial transplantation effectively attenuates cigarette smoke plus lipopolysaccharide-stimulated airway hyperresponsiveness through the inhibition of ROS-enhanced epithelial cholinergic hyperactivity. PMID:27279915

  12. Riboflavin enhanced fluorescence of highly reduced graphene oxide

    NASA Astrophysics Data System (ADS)

    Iliut, Maria; Gabudean, Ana-Maria; Leordean, Cosmin; Simon, Timea; Teodorescu, Cristian-Mihail; Astilean, Simion

    2013-10-01

    The improvement of graphene derivates' fluorescence properties is a challenging topic and very few ways were reported up to now. In this Letter we propose an easy method to enhance the fluorescence of highly reduced graphene oxide (rGO) through non-covalent binding to a molecular fluorophore, namely the riboflavin (Rb). While the fluorescence of Rb is quenched, the Rb - decorated rGO exhibits strong blue fluorescence and significantly increased fluorescence lifetime, as compared to its pristine form. The data reported here represent a promising start towards tailoring the optical properties of rGOs, having utmost importance in optical applications.

  13. Cholinergic modulation of event-related oscillations (ERO).

    PubMed

    Sanchez-Alavez, Manuel; Robledo, Patricia; Wills, Derek N; Havstad, James; Ehlers, Cindy L

    2014-04-22

    The cholinergic system in the brain modulates patterns of activity involved in general arousal, attention processing, memory and consciousness. In the present study we determined the effects of selective cholinergic lesions of the medial septum area (MS) or nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs). A time-frequency based representation was used to determine ERO energy, phase synchronization across trials, recorded within a structure (phase lock index, PLI), and phase synchronization across trials, recorded between brain structures (phase difference lock index, PDLI), in the frontal cortex (Fctx), dorsal hippocampus (DHPC) and central amygdala (Amyg). Lesions in MS produced: (1) decreases in ERO energy in delta, theta, alpha, beta and gamma frequencies in Amyg, (2) reductions in gamma ERO energy and PLI in Fctx, (3) decreases in PDLI between the Fctx-Amyg in the theta, alpha, beta and gamma frequencies, and (4) decreases in PDLI between the DHPC-Amyg and Fctx-DHPC in the theta frequency bands. Lesions in NBM resulted in: (1) increased ERO energy in delta and theta frequency bands in Fctx, (2) reduced gamma ERO energy in Fctx and Amyg, (3) reductions in PLI in the theta, beta and gamma frequency ranges in Fctx, (4) reductions in gamma PLI in DHPC and (5) reduced beta PLI in Amyg. These studies suggest that the MS cholinergic system can alter phase synchronization between brain areas whereas the NBM cholinergic system modifies phase synchronization/phase resetting within a brain area. PMID:24594019

  14. Cholinergic modulation of event-related oscillations (ERO)

    PubMed Central

    Sanchez-Alavez, Manuel; Robledo, Patricia; Wills, Derek N.; Havstad, James; Ehlers, Cindy L.

    2014-01-01

    The cholinergic system in the brain modulates patterns of activity involved in general arousal, attention processing, memory and consciousness. In the present study we determined the effects of selective cholinergic lesions of the medial septum area (MS) or nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs). A time–frequency based representation was used to determine ERO energy, phase synchronization across trials, recorded within a structure (phase lock index, PLI), and phase synchronization across trials, recorded between brain structures (phase difference lock index, PDLI), in the frontal cortex (Fctx), dorsal hippocampus (DHPC) and central amygdala (Amyg). Lesions in MS produced: (1) decreases in ERO energy in delta, theta, alpha, beta and gamma frequencies in Amyg, (2) reductions in gamma ERO energy and PLI in Fctx, (3) decreases in PDLI between the Fctx–Amyg in the theta, alpha, beta and gamma frequencies, and (4) decreases in PDLI between the DHPC–Amyg and Fctx–DHPC in the theta frequency bands. Lesions in NBM resulted in: (1) increased ERO energy in delta and theta frequency bands in Fctx, (2) reduced gamma ERO energy in Fctx and Amyg, (3) reductions in PLI in the theta, beta and gamma frequency ranges in Fctx, (4) reductions in gamma PLI in DHPC and (5) reduced beta PLI in Amyg. These studies suggest that the MS cholinergic system can alter phase synchronization between brain areas whereas the NBM cholinergic system modifies phase synchronization/phase resetting within a brain area. PMID:24594019

  15. Enhanced Osteogenesis by Reduced Graphene Oxide/Hydroxyapatite Nanocomposites

    PubMed Central

    Lee, Jong Ho; Shin, Yong Cheol; Lee, Sang-Min; Jin, Oh Seong; Kang, Seok Hee; Hong, Suck Won; Jeong, Chang-Mo; Huh, Jung Bo; Han, Dong-Wook

    2015-01-01

    Recently, graphene-based nanomaterials, in the form of two dimensional substrates or three dimensional foams, have attracted considerable attention as bioactive scaffolds to promote the differentiation of various stem cells towards specific lineages. On the other hand, the potential advantages of using graphene-based hybrid composites directly as factors inducing cellular differentiation as well as tissue regeneration are unclear. This study examined whether nanocomposites of reduced graphene oxide (rGO) and hydroxyapatite (HAp) (rGO/HAp NCs) could enhance the osteogenesis of MC3T3-E1 preosteoblasts and promote new bone formation. When combined with HAp, rGO synergistically promoted the spontaneous osteodifferentiation of MC3T3-E1 cells without hindering their proliferation. This enhanced osteogenesis was corroborated from determination of alkaline phosphatase activity as early stage markers of osteodifferentiation and mineralization of calcium and phosphate as late stage markers. Immunoblot analysis showed that rGO/HAp NCs increase the expression levels of osteopontin and osteocalcin significantly. Furthermore, rGO/HAp grafts were found to significantly enhance new bone formation in full-thickness calvarial defects without inflammatory responses. These results suggest that rGO/HAp NCs can be exploited to craft a range of strategies for the development of novel dental and orthopedic bone grafts to accelerate bone regeneration because these graphene-based composite materials have potentials to stimulate osteogenesis. PMID:26685901

  16. Cholinergic modulation of hippocampal network function

    PubMed Central

    Teles-Grilo Ruivo, Leonor M.; Mellor, Jack R.

    2013-01-01

    Cholinergic septohippocampal projections from the medial septal area to the hippocampus are proposed to have important roles in cognition by modulating properties of the hippocampal network. However, the precise spatial and temporal profile of acetylcholine release in the hippocampus remains unclear making it difficult to define specific roles for cholinergic transmission in hippocampal dependent behaviors. This is partly due to a lack of tools enabling specific intervention in, and recording of, cholinergic transmission. Here, we review the organization of septohippocampal cholinergic projections and hippocampal acetylcholine receptors as well as the role of cholinergic transmission in modulating cellular excitability, synaptic plasticity, and rhythmic network oscillations. We point to a number of open questions that remain unanswered and discuss the potential for recently developed techniques to provide a radical reappraisal of the function of cholinergic inputs to the hippocampus. PMID:23908628

  17. New Etiology of Cholinergic Urticaria.

    PubMed

    Tokura, Yoshiki

    2016-01-01

    Cholinergic urticaria (CholU) is characterized by pinpoint-sized, highly pruritic wheals occurring upon sweating. Both direct and indirect theories in the interaction of acetylcholine (ACh) with mast cells have been put forward in the sweating-associated histamine release from mast cells. In the mechanism of indirect involvement of ACh, patients are hypersensitive to sweat antigen(s) and develop wheals in response to sweat substances leaking from the syringeal ducts to the dermis, possibly by obstruction of the ducts. Some patients with CholU exhibit a positive reaction to intradermal injection of their own diluted sweat, representing 'sweat allergy (hypersensitivity)'. Regarding the direct interaction theory between ACh and mast cells, we found that CholU with anhidrosis and hypohidrosis lacks cholinergic receptor M3 (CHRM3) expression in eccrine sweat gland epithelial cells. The expression of CHRM3 is completely absent in the anhidrotic areas and lowly expressed in the hypohidrotic areas. In the hypohidrotic area, where CholU occurs, it is hypothesized that ACh released from nerves cannot be completely trapped by cholinergic receptors of eccrine glands and overflows to the adjacent mast cells, leading to wheals. PMID:27584968

  18. Memory-Relevant Mushroom Body Output Synapses Are Cholinergic.

    PubMed

    Barnstedt, Oliver; Owald, David; Felsenberg, Johannes; Brain, Ruth; Moszynski, John-Paul; Talbot, Clifford B; Perrat, Paola N; Waddell, Scott

    2016-03-16

    Memories are stored in the fan-out fan-in neural architectures of the mammalian cerebellum and hippocampus and the insect mushroom bodies. However, whereas key plasticity occurs at glutamatergic synapses in mammals, the neurochemistry of the memory-storing mushroom body Kenyon cell output synapses is unknown. Here we demonstrate a role for acetylcholine (ACh) in Drosophila. Kenyon cells express the ACh-processing proteins ChAT and VAChT, and reducing their expression impairs learned olfactory-driven behavior. Local ACh application, or direct Kenyon cell activation, evokes activity in mushroom body output neurons (MBONs). MBON activation depends on VAChT expression in Kenyon cells and is blocked by ACh receptor antagonism. Furthermore, reducing nicotinic ACh receptor subunit expression in MBONs compromises odor-evoked activation and redirects odor-driven behavior. Lastly, peptidergic corelease enhances ACh-evoked responses in MBONs, suggesting an interaction between the fast- and slow-acting transmitters. Therefore, olfactory memories in Drosophila are likely stored as plasticity of cholinergic synapses. PMID:26948892

  19. Memory-Relevant Mushroom Body Output Synapses Are Cholinergic

    PubMed Central

    Barnstedt, Oliver; Owald, David; Felsenberg, Johannes; Brain, Ruth; Moszynski, John-Paul; Talbot, Clifford B.; Perrat, Paola N.; Waddell, Scott

    2016-01-01

    Summary Memories are stored in the fan-out fan-in neural architectures of the mammalian cerebellum and hippocampus and the insect mushroom bodies. However, whereas key plasticity occurs at glutamatergic synapses in mammals, the neurochemistry of the memory-storing mushroom body Kenyon cell output synapses is unknown. Here we demonstrate a role for acetylcholine (ACh) in Drosophila. Kenyon cells express the ACh-processing proteins ChAT and VAChT, and reducing their expression impairs learned olfactory-driven behavior. Local ACh application, or direct Kenyon cell activation, evokes activity in mushroom body output neurons (MBONs). MBON activation depends on VAChT expression in Kenyon cells and is blocked by ACh receptor antagonism. Furthermore, reducing nicotinic ACh receptor subunit expression in MBONs compromises odor-evoked activation and redirects odor-driven behavior. Lastly, peptidergic corelease enhances ACh-evoked responses in MBONs, suggesting an interaction between the fast- and slow-acting transmitters. Therefore, olfactory memories in Drosophila are likely stored as plasticity of cholinergic synapses. PMID:26948892

  20. Memory-Relevant Mushroom Body Output Synapses Are Cholinergic.

    PubMed

    Barnstedt, Oliver; Owald, David; Felsenberg, Johannes; Brain, Ruth; Moszynski, John-Paul; Talbot, Clifford B; Perrat, Paola N; Waddell, Scott

    2016-03-16

    Memories are stored in the fan-out fan-in neural architectures of the mammalian cerebellum and hippocampus and the insect mushroom bodies. However, whereas key plasticity occurs at glutamatergic synapses in mammals, the neurochemistry of the memory-storing mushroom body Kenyon cell output synapses is unknown. Here we demonstrate a role for acetylcholine (ACh) in Drosophila. Kenyon cells express the ACh-processing proteins ChAT and VAChT, and reducing their expression impairs learned olfactory-driven behavior. Local ACh application, or direct Kenyon cell activation, evokes activity in mushroom body output neurons (MBONs). MBON activation depends on VAChT expression in Kenyon cells and is blocked by ACh receptor antagonism. Furthermore, reducing nicotinic ACh receptor subunit expression in MBONs compromises odor-evoked activation and redirects odor-driven behavior. Lastly, peptidergic corelease enhances ACh-evoked responses in MBONs, suggesting an interaction between the fast- and slow-acting transmitters. Therefore, olfactory memories in Drosophila are likely stored as plasticity of cholinergic synapses.

  1. Cholinergic gating of hippocampal auditory evoked potentials in freely moving rats.

    PubMed

    Klinkenberg, Inge; Sambeth, Anke; Blokland, Arjan

    2013-08-01

    As perturbations in auditory filtering appear to be a candidate trait marker of schizophrenia, there has been considerable interest in the development of translational rat models to elucidate the underlying neural and neurochemical mechanisms involved in sensory gating. This is the first study to investigate the effects of the non-selective muscarinic antagonist scopolamine, the muscarinic M1 antagonist biperiden and the cholinesterase inhibitor donepezil (also in combination with scopolamine and biperiden) on auditory evoked potentials (AEPs) and sensory gating. In the saline condition, only the N50 peak displayed sensory gating. Scopolamine and biperiden both disrupted sensory gating by increasing N50 amplitude for the S2 click. Donepezil was able to fully reverse the effects of biperiden on N50 sensory gating, but had residual effects when combined with scopolamine; i.e., it enhanced sensory gating by increasing N50 amplitude of the S1 stimulus. Donepezil by itself improved sensory gating by enhancing N50 amplitude of S1, and reducing N50 amplitude of the S2 click. In conclusion, due to its relatively more selective effects biperiden is to be preferred over scopolamine as a means for pharmacologically inducing cholinergic impairments in auditory processing in healthy rats. Changes in auditory processing and sensory gating induced by cholinergic drugs may serve as a translational model for aging instead of schizophrenia.

  2. Presynaptic Excitation via GABAB Receptors in Habenula Cholinergic Neurons Regulates Fear Memory Expression.

    PubMed

    Zhang, Juen; Tan, Lubin; Ren, Yuqi; Liang, Jingwen; Lin, Rui; Feng, Qiru; Zhou, Jingfeng; Hu, Fei; Ren, Jing; Wei, Chao; Yu, Tao; Zhuang, Yinghua; Bettler, Bernhard; Wang, Fengchao; Luo, Minmin

    2016-07-28

    Fear behaviors are regulated by adaptive mechanisms that dampen their expression in the absence of danger. By studying circuits and the molecular mechanisms underlying this adaptive response, we show that cholinergic neurons of the medial habenula reduce fear memory expression through GABAB presynaptic excitation. Ablating these neurons or inactivating their GABAB receptors impairs fear extinction in mice, whereas activating the neurons or their axonal GABAB receptors reduces conditioned fear. Although considered exclusively inhibitory, here, GABAB mediates excitation by amplifying presynaptic Ca(2+) entry through Cav2.3 channels and potentiating co-release of glutamate, acetylcholine, and neurokinin B to excite interpeduncular neurons. Activating the receptors for these neurotransmitters or enhancing neurotransmission with a phosphodiesterase inhibitor reduces fear responses of both wild-type and GABAB mutant mice. We identify the role of an extra-amygdalar circuit and presynaptic GABAB receptors in fear control, suggesting that boosting neurotransmission in this pathway might ameliorate some fear disorders. PMID:27426949

  3. Cholinergic behaviors, emotions, and the "self".

    PubMed

    Karczmar, Alexander G

    2014-07-01

    Macromolecular cholinergic pathways are involved in the regulation of addiction, emotions, and motivations, as described at this ISCM. Indeed, in view of the omnipresence in the brain of cholinergic pathways and of their connections with other transmitters' sites and pathways, their involvement in all known human and animal behaviors could be expected and numerous current reports describe such cholinergic correlates. This minireview describes the current status and the future of the cholinergic impact on behavior and emotions, and particularly on one important human phenomenon, the "self" or the "I" (it is only speculative to impute the self to animals).

  4. Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts.

    PubMed

    Downs, Anthony M; Jalloh, Hawa B; Prater, Kayla J; Fregoso, Santiago P; Bond, Cherie E; Hampton, Thomas G; Hoover, Donald B

    2016-05-01

    The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development.

  5. Frequency encoding of cholinergic- and purinergic-mediated signaling to mouse urinary bladder smooth muscle: modulation by BK channels.

    PubMed

    Werner, Matthias E; Knorn, Anna-Maria; Meredith, Andrea L; Aldrich, Richard W; Nelson, Mark T

    2007-01-01

    In the urinary bladder, contractions of the detrusor muscle and urine voiding are induced by the neurotransmitters ACh and ATP, released from parasympathetic nerves. Activation of K(+) channels, in particular the large-conductance Ca(2+)-activated K(+) (BK) channels, opposes increases in excitability and contractility of urinary bladder smooth muscle (UBSM). We have shown that deleting the gene mSlo1 in mice (Slo(-/-)), encoding the BK channel, leads to enhanced nerve-mediated and neurotransmitter-dependent contractility of UBSM (38). Here, we examine the location of the BK channel in urinary bladder strips from mouse. Immunohistochemical analysis revealed that the channel is expressed in UBSM but not in nerves that innervate the smooth muscle. The relationship between electrical field stimulation and force generation of the cholinergic and purinergic pathways was examined by applying blockers of the respective receptors in UBSM strips from wild-type and from Slo(-/-) (knockout) mice. In wild-type strips, the stimulation frequency required to obtain a half-maximal force was significantly lower for the purinergic (7.2 +/- 0.3 Hz) than the cholinergic pathway (19.1 +/- 1.5 Hz), whereas the maximum force was similar. Blocking BK channels with iberiotoxin or ablation of the Slo gene increased cholinergic- and purinergic-mediated force at low frequencies, i.e., significantly decreased the frequency for a half-maximal force. Our results indicate that the BK channel has a very significant role in reducing both cholinergic- and purinergic-induced contractility and suggest that alterations in BK channel expression or function could contribute to pathologies such as overactive detrusor.

  6. Porous reduced graphene oxide membrane with enhanced gauge factor

    NASA Astrophysics Data System (ADS)

    Li, Jen-Chieh; Weng, Cheng-Hsi; Tsai, Fu-Cheng; Shih, Wen-Pin; Chang, Pei-Zen

    2016-01-01

    This paper shows that a porous structure for a reduced graphene oxide (rGO) membrane effectively enhances its gauge factor. A porous graphene-based membrane was synthesized in a liquid phase by combining a GO sheet with copper hydroxide nanostrands (CHNs). A chemical reduction treatment using L-ascorbic acid was utilized to simultaneously improve the conductivity of GO and remove the CHNs from each GO sheet. The intrinsic gauge factors of the porous rGO membrane with varying applied tensile strains were obtained and found to increase monotonically with the increased porosity of the rGO membrane. For a membrane porosity of 15.78%, the maximum gauge factor is 46.1 under an applied strain of less than 1%. The main mechanism behind the enhanced gauge factor is attributed to the structure of the porous rGO membrane. The relationships between the initial electrical resistance, tunneling distance, and gauge factor of the rGO membrane were found by adjusting the membrane porosity and the results completely confirmed the physical phenomena.

  7. Cholinergic inhibition of adrenergic neurosecretion in the rabbit iris-ciliary body

    SciTech Connect

    Jumblatt, J.E.; North, G.T.

    1988-04-01

    The prejunctional effects of cholinergic agents on release of norepinephrine from sympathetic nerve endings were investigated in the isolated, superfused rabbit iris-ciliary body. Stimulation-evoked release of /sup 3/H-norepinephrine was inhibited by the cholinergic agonists methacholine, oxotremorine, muscarine, carbamylcholine and acetylcholine (plus eserine), but was unmodified by pilocarpine or nicotine. Agonist-induced inhibition was antagonized selectively by atropine, indicating a muscarinic response. Atropine alone markedly enhanced norepinephrine release, revealing considerable tonic activation of prejunctional cholinergic receptors in this system. Prejunctional inhibition by carbamylcholine was found to completely override the facilitative action of forskolin or 8-bromo-cyclic AMP on neurotransmitter release. Cholinergic and alpha 2-adrenergic effects on neurosecretion were non-additive, suggesting that the underlying receptors coexist at neurotransmitter release sites.

  8. Opposing regulation of dopaminergic activity and exploratory motor behavior by forebrain and brainstem cholinergic circuits.

    PubMed

    Patel, Jyoti C; Rossignol, Elsa; Rice, Margaret E; Machold, Robert P

    2012-01-01

    Dopamine transmission is critical for exploratory motor behaviour. A key regulator is acetylcholine; forebrain acetylcholine regulates striatal dopamine release, whereas brainstem cholinergic inputs regulate the transition of dopamine neurons from tonic to burst firing modes. How these sources of cholinergic activity combine to control dopamine efflux and exploratory motor behaviour is unclear. Here we show that mice lacking total forebrain acetylcholine exhibit enhanced frequency-dependent striatal dopamine release and are hyperactive in a novel environment, whereas mice lacking rostral brainstem acetylcholine are hypoactive. Exploratory motor behaviour is normalized by the removal of both cholinergic sources. Involvement of dopamine in the exploratory motor phenotypes observed in these mutants is indicated by their altered sensitivity to the dopamine D2 receptor antagonist raclopride. These results support a model in which forebrain and brainstem cholinergic systems act in tandem to regulate striatal dopamine signalling for proper control of motor activity.

  9. Cholinergic nicotinic receptors in the vestibular epithelia.

    PubMed

    Thornhill, R A

    1991-10-01

    Receptor binding studies specific for nicotinic cholinergic receptors have been carried out on isolated vestibular epithelia of the frogs Rana catesbiana and Rana temporaria. Evidence is presented for the presence of nicotinic-like cholinergic receptors specifically associated with the sensory areas. PMID:1797345

  10. Cellular and molecular basis of cholinergic function

    SciTech Connect

    Dowdall, M.J.; Hawthorne, J.N.

    1987-01-01

    This book contains 105 selections. Some of the titles are: Functional correlates of brain nicotine receptors; Muscarinic receptor subclasses; Cholinergic innervation and levels of nerve growth factor and its mRNA in the central nervous system; Developmentally regulated neurontrophic activities of Torpedo electric organ tissue; and Association of a regulatory peptide with cholinergic neurons.

  11. Reducing and filtering point clouds with enhanced vector quantization.

    PubMed

    Ferrari, Stefano; Ferrigno, Giancarlo; Piuri, Vincenzo; Borghese, N Alberto

    2007-01-01

    Modern scanners are able to deliver huge quantities of three-dimensional (3-D) data points sampled on an object's surface, in a short time. These data have to be filtered and their cardinality reduced to come up with a mesh manageable at interactive rates. We introduce here a novel procedure to accomplish these two tasks, which is based on an optimized version of soft vector quantization (VQ). The resulting technique has been termed enhanced vector quantization (EVQ) since it introduces several improvements with respect to the classical soft VQ approaches. These are based on computationally expensive iterative optimization; local computation is introduced here, by means of an adequate partitioning of the data space called hyperbox (HB), to reduce the computational time so as to be linear in the number of data points N, saving more than 80% of time in real applications. Moreover, the algorithm can be fully parallelized, thus leading to an implementation that is sublinear in N. The voxel side and the other parameters are automatically determined from data distribution on the basis of the Zador's criterion. This makes the algorithm completely automatic. Because the only parameter to be specified is the compression rate, the procedure is suitable even for nontrained users. Results obtained in reconstructing faces of both humans and puppets as well as artifacts from point clouds publicly available on the web are reported and discussed, in comparison with other methods available in the literature. EVQ has been conceived as a general procedure, suited for VQ applications with large data sets whose data space has relatively low dimensionality.

  12. Cholinergic Crisis after Rodenticide Poisoning

    PubMed Central

    Waseem, Muhammad; Perry, Christopher; Bomann, Scott; Pai, Meena; Gernsheimer, Joel

    2010-01-01

    Rodenticides have historically been common agents in attempted suicides. As most rodenticides in the United States (U.S.) are superwarfarins, these ingestions are generally managed conservatively with close monitoring for coagulopathy, and if necessary, correction of any resulting coagulopathy. However, alternate forms of rodenticides are imported illegally into the U.S. and may be ingested either accidentally or in suicide attempts. We present an unusual case of poisoning by the illegally imported rodenticide, “Tres Pasitos.” The main ingredient of this rat poison is aldicarb, a potent carbamate pesticide that causes fulminant cholinergic crisis. This case is relevant and timely because carbamates and organophosphates are still used as insecticides and emergency physicians (EP) working in rural areas may have to evaluate and manage patients with these poisonings. As international travel and immigration have increased, so has the possibility of encountering patients who have ingested toxic substances from other countries. In addition, there has been increased concern about the possibility of acts of terrorism using chemical substances that cause cholinergic toxidromes.1,2 EPs must be able to recognize and manage these poisonings. This report describes the mechanism of action, clinical manifestations, laboratory evaluation and management of this type of poisoning. The pertinent medical literature on poisoning with aldicarb and similar substances is reviewed. PMID:21293782

  13. Assessment of Cholinergic Properties of Ashwagandha Leaf-Extract in the Amnesic Mouse Brain

    PubMed Central

    Gautam, Akash; Wadhwa, Renu; Thakur, Mahendra K.

    2016-01-01

    Background In our earlier study, we have shown the memory enhancing and scopolamine-induced amnesia recovery properties of Ashwagandha leaf extract using behavioral paradigm and expression analysis of synaptic plasticity genes. Purpose However, the exact mechanism through which Ashwagandha demonstrates these effects is still unknown. Methods In the present study, we hypothesized that the alcoholic extract of Ashwagandha leaves (i-Extract) possesses cholinergic properties, which in turn inhibit the anti-cholinergic nature of scopolamine. Therefore, the potential of i-Extract to recover from the scopolamine-induced cholinergic deficits was assessed by measuring acetylcholine (neurotransmitter) and Arc (synaptic activity-related gene) expression level in the mouse brain. Results The enzymatic activity of acetyl cholinesterase and choline acetyltransferase was assessed through colorimetric assays, and expression level of Arc protein was examined by Western blotting. Furthermore, mRNA level of these genes was examined by semi-quantitative reverse-transcriptase PCR. We observed that the treatment of i-Extract in scopolamine-induced amnesic mouse attenuates scopolamine-induced detrimental alterations in the cholinergic system. Conclusion Thus, our study provided biochemical and molecular evidence of cholinergic properties of Ashwagandha leaf extract during brain disorders associated with cholinergic dysfunction. PMID:27647956

  14. Assessment of Cholinergic Properties of Ashwagandha Leaf-Extract in the Amnesic Mouse Brain

    PubMed Central

    Gautam, Akash; Wadhwa, Renu; Thakur, Mahendra K.

    2016-01-01

    Background In our earlier study, we have shown the memory enhancing and scopolamine-induced amnesia recovery properties of Ashwagandha leaf extract using behavioral paradigm and expression analysis of synaptic plasticity genes. Purpose However, the exact mechanism through which Ashwagandha demonstrates these effects is still unknown. Methods In the present study, we hypothesized that the alcoholic extract of Ashwagandha leaves (i-Extract) possesses cholinergic properties, which in turn inhibit the anti-cholinergic nature of scopolamine. Therefore, the potential of i-Extract to recover from the scopolamine-induced cholinergic deficits was assessed by measuring acetylcholine (neurotransmitter) and Arc (synaptic activity-related gene) expression level in the mouse brain. Results The enzymatic activity of acetyl cholinesterase and choline acetyltransferase was assessed through colorimetric assays, and expression level of Arc protein was examined by Western blotting. Furthermore, mRNA level of these genes was examined by semi-quantitative reverse-transcriptase PCR. We observed that the treatment of i-Extract in scopolamine-induced amnesic mouse attenuates scopolamine-induced detrimental alterations in the cholinergic system. Conclusion Thus, our study provided biochemical and molecular evidence of cholinergic properties of Ashwagandha leaf extract during brain disorders associated with cholinergic dysfunction.

  15. The Cholinergic System and Parkinson Disease

    PubMed Central

    Bohnen, Nicolaas I.; Albin, Roger L.

    2010-01-01

    Although Parkinson disease (PD) is viewed traditionally as a motor syndrome secondary to nigrostriatal dopaminergic denervation, recent studies emphasize non-motor features. Non-motor comorbidities, such as cognitive impairment, are likely the result of an intricate interplay of multi-system degenerations and neurotransmitter deficiencies extending beyond the loss of dopaminergic nigral neurons. The pathological hallmark of parkinsonian dementia is the presence of extra-nigral Lewy bodies that can be accompanied by other pathologies, such as senile plaques. Lewy first identified the eponymous Lewy body in neurons of the nucleus basalis of Meynert (nbM), the source of cholinergic innervation of the cerebral cortex. Although cholinergic denervation is recognized as a pathological hallmark of Alzheimer disease (AD), in vivo neuroimaging studies reveal loss of cerebral cholinergic markers in parkinsonian dementia similar to or more severe than in prototypical AD. Imaging studies agree with post-mortem evidence suggesting that basal forebrain cholinergic system degeneration appears early in PD and worsens coincident with the appearance of dementia. Early cholinergic denervation in PD without dementia appears to be heterogeneous and may make specific contributions to the PD clinical phenotype. Apart from well-known cognitive and behavioral deficits, central, in particular limbic, cholinergic denervation may be associated with progressive deficits of odor identification in PD. Recent evidence indicates also that subcortical cholinergic denervation, probably due to degeneration of brainstem pedunculopontine nucleus neurons, may relate to the presence of dopamine non-responsive gait and balance impairments, including falls, in PD. PMID:20060022

  16. Using Bibliotherapy to Enhance Probation and Reduce Recidivism

    ERIC Educational Resources Information Center

    Schutt, Russell K.; Deng, Xiaogang; Stoehr, Taylor

    2013-01-01

    Prior research indicates that probation programs that include efforts to change cognitive orientations and social patterns can enhance their effectiveness. This article reports an evaluation of an enhanced probation program, Changing Lives Through Literature, which uses a form of bibliotherapy to increase its rehabilitative effect. Controlling for…

  17. The Cholinergic Signaling Responsible for the Expression of a Memory-Related Protein in Primary Rat Cortical Neurons.

    PubMed

    Chen, Tsan-Ju; Chen, Shun-Sheng; Wang, Dean-Chuan; Hung, Hui-Shan

    2016-11-01

    Cholinergic dysfunction in the brain is closely related to cognitive impairment including memory loss. In addition to the degeneration of basal forebrain cholinergic neurons, deficits in the cholinergic receptor signaling may also play an important role. In the present study, to examine the cholinergic signaling pathways responsible for the induction of a memory-related postsynaptic protein, a cholinergic agonist carbachol was used to induce the expression of activity-regulated cytoskeleton associated protein (Arc) in primary rat cortical neurons. After pretreating neurons with various antagonists or inhibitors, the levels of carbachol-induced Arc protein expression were detected by Western blot analysis. The results show that carbachol induces Arc protein expression mainly through activating M1 acetylcholine receptors and the downstream phospholipase C pathway, which may lead to the activation of the MAPK/ERK signaling pathway. Importantly, carbachol-mediated M2 receptor activation exerts negative effects on Arc protein expression and thus counteracts the enhanced effects of M1 activation. Furthermore, it is suggested for the first time that M1-mediated enhancement of N-methyl-D-aspartate receptor (NMDAR) responses, leading to Ca(2+) entry through NMDARs, contributes to carbachol-induced Arc protein expression. These findings reveal a more complete cholinergic signaling that is responsible for carbachol-induced Arc protein expression, and thus provide more information for developing treatments that can modulate cholinergic signaling and consequently alleviate cognitive impairment. J. Cell. Physiol. 231: 2428-2438, 2016. © 2016 Wiley Periodicals, Inc. PMID:26895748

  18. Sex differences in brain cholinergic activity in MSG-obese rats submitted to exercise.

    PubMed

    Sagae, Sara Cristina; Grassiolli, Sabrina; Raineki, Charlis; Balbo, Sandra Lucinei; Marques da Silva, Ana Carla

    2011-11-01

    Obesity is an epidemic disease most commonly caused by a combination of increased energy intake and lack of physical activity. The cholinergic system has been shown to be involved in the regulation of food intake and energy expenditure. Moreover, physical exercise promotes a reduction of fat pads and body mass by increasing energy expenditure, but also influences the cholinergic system. The aim of this study is to evaluate the interaction between physical exercise (swimming) and central cholinergic activity in rats treated with monosodium glutamate (MSG, a model for obesity) during infancy. Our results show that MSG treatment is able to induce obesity in male and female rats. Specifically, MSG-treated rats presented a reduced body mass and nasoanal length, and increased perigonadal and retroperitoneal fat pads in relation to the body mass. Physical exercise was able to reduce body mass in both male and female rats, but did not change the fat pads in MSG-treated rats. Increased food intake was only seen in MSG-treated females submitted to exercise. Cholinergic activity was increased in the cortex of MSG-treated females and physical exercise was able to reduce this activity. Thalamic cholinergic activity was higher in sedentary MSG-treated females and exercised MSG-treated males. Hypothalamic cholinergic activity was higher in male and female MSG-treated rats, and was not reduced by exercise in the 2 sexes. Taken together, these results show that MSG treatment and physical exercise have different effects in the cholinergic activity of males and females. PMID:22039988

  19. Cholinergic mediation of small intestinal transit in the rat

    SciTech Connect

    Nemeth, P.R.; Ems, B.L.; Pepple, S.C

    1986-03-05

    It has been reported that small intestinal transit (SIT) in the rat is not cholinergically mediated. The geometric mean of a marker may be a more powerful method for SIT studies. Therefore, it was their goal to evaluate the effect of muscarinic blockade in normal and prostaglandin E/sub 2/ (PGE/sub 2/)-enhanced SIT using this method. Male, food-fasted rats (190 to 240 g) were first dosed subcutaneously with atropine. 30 min after the atropine the rats received an oral dose of PGE/sub 2/ at 5.0 mg/kg. 5 min after PGE/sub 2/, a /sup 51/Cr-labeled marker was dosed intraduodenally, and a 25 min transit period followed. The results are: (1) 5.0 mg/kg of PGE/sub 2/ significantly stimulates the geometric mean of the marker in agreement with previous findings and (2) atropine is inhibitory at doses as low as 0.20 mg/kg for basal SIT and 0.10 mg/kg for PGE/sub 2/-stimulated SIT. This indicates (1) the rat has cholinergically mediated SIT, and (2) cholinergic activation may be important for PGE/sub 2/ effects on SIT in the rat.

  20. Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice: possible involvement of glutamatergic and cholinergic systems.

    PubMed

    Le, Xoan Thi; Pham, Hang Thi Nguyet; Do, Phuong Thi; Fujiwara, Hironori; Tanaka, Ken; Li, Feng; Van Nguyen, Tai; Nguyen, Khoi Minh; Matsumoto, Kinzo

    2013-10-01

    This study investigated the effects of alcoholic extract of Bacopa monnieri (L.) Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its action. OBX mice were treated daily with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week before and continuously 3 days after OBX. Cognitive performance of the animals was analyzed by the novel object recognition test, modified Y maze test, and fear conditioning test. Brain tissues of OBX animals were used for neurochemical and immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial working memory, and long-term fair memory. BM administration ameliorated these memory disturbances. The effect of BM on short-term memory deficits was abolished by a muscarinic receptor antagonist, scopolamine. OBX downregulated phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of N-methyl-D-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein (CREB), and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX also reduced choline acetyltransferase in the hippocampus and cholinergic neurons in the medial septum, and enlarged the size of lateral ventricle. BM administration reversed these OBX-induced neurochemical and histological alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB phosphorylation. Moreover, BM treatment inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BM treatment ameliorates OBX-induced cognition dysfunction via a mechanism involving enhancement of synaptic plasticity-related signaling and BDNF transcription and protection of cholinergic systems from OBX-induced neuronal damage.

  1. Inhibition of airway surface fluid absorption by cholinergic stimulation

    PubMed Central

    Joo, Nam Soo; Krouse, Mauri E.; Choi, Jae Young; Cho, Hyung-Ju; Wine, Jeffrey J.

    2016-01-01

    In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20–70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways. PMID:26846701

  2. Dysfunctional penile cholinergic nerves in diabetic impotent men

    SciTech Connect

    Blanco, R.; Saenz de Tejada, I.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A. )

    1990-08-01

    Impotence in the diabetic man may be secondary to a neuropathic condition of the autonomic penile nerves. The relationship between autonomic neuropathy and impotence in diabetes was studied in human corporeal tissue obtained during implantation of a penile prosthesis in 19 impotent diabetic and 15 nondiabetic patients. The functional status of penile cholinergic nerves was assessed by determining their ability to accumulate tritiated choline (34), and synthesize (34) and release (19) tritiated-acetylcholine after incubation of corporeal tissue with tritiated-choline (34). Tritiated-choline accumulation, and tritiated-acetylcholine synthesis and release were significantly reduced in the corporeal tissue from diabetic patients compared to that from nondiabetic patients (p less than 0.05). The impairment in acetylcholine synthesis worsened with the duration of diabetes (p less than 0.025). No differences in the parameters measured were found between insulin-dependent (11) and noninsulin-dependent (8) diabetic patients. The ability of the cholinergic nerves to synthesize acetylcholine could not be predicted clinically with sensory vibration perception threshold testing. It is concluded that there is a functional penile neuropathic condition of the cholinergic nerves in the corpus cavernosum of diabetic impotent patients that may be responsible for the erectile dysfunction.

  3. A cholinergic hypothesis of the unconscious in affective disorders

    PubMed Central

    Vakalopoulos, Costa

    2013-01-01

    The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioral repertoires at the core of affective disorders and ADHD. Behavioral adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o) and its modulation of M1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signaling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial, recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behavior and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone. PMID:24319409

  4. Cholinergic connectivity: it's implications for psychiatric disorders

    PubMed Central

    Scarr, Elizabeth; Gibbons, Andrew S.; Neo, Jaclyn; Udawela, Madhara; Dean, Brian

    2013-01-01

    Acetylcholine has been implicated in both the pathophysiology and treatment of a number of psychiatric disorders, with most of the data related to its role and therapeutic potential focusing on schizophrenia. However, there is little thought given to the consequences of the documented changes in the cholinergic system and how they may affect the functioning of the brain. This review looks at the cholinergic system and its interactions with the intrinsic neurotransmitters glutamate and gamma-amino butyric acid as well as those with the projection neurotransmitters most implicated in the pathophysiologies of psychiatric disorders; dopamine and serotonin. In addition, with the recent focus on the role of factors normally associated with inflammation in the pathophysiologies of psychiatric disorders, links between the cholinergic system and these factors will also be examined. These interfaces are put into context, primarily for schizophrenia, by looking at the changes in each of these systems in the disorder and exploring, theoretically, whether the changes are interconnected with those seen in the cholinergic system. Thus, this review will provide a comprehensive overview of the connectivity between the cholinergic system and some of the major areas of research into the pathophysiologies of psychiatric disorders, resulting in a critical appraisal of the potential outcomes of a dysregulated central cholinergic system. PMID:23653591

  5. Central cholinergic neurons are rapidly recruited by reinforcement feedback

    PubMed Central

    Hangya, Balázs; Ranade, Sachin P.; Lorenc, Maja; Kepecs, Adam

    2015-01-01

    Summary Basal forebrain cholinergic neurons constitute a major neuromodulatory system implicated in normal cognition and neurodegenerative dementias. Cholinergic projections densely innervate neocortex, releasing acetylcholine to regulate arousal, attention and learning. However, their precise behavioral function is poorly understood because identified cholinergic neurons have never been recorded during behavior. To determine which aspects of cognition their activity might support we recorded cholinergic neurons using optogenetic identification in mice performing an auditory detection task requiring sustained attention. We found that a non-cholinergic basal forebrain population — but not cholinergic neurons — were correlated with trial-to-trial measures of attention. Surprisingly, cholinergic neurons responded to reward and punishment with unusual speed and precision (18±3ms). Cholinergic responses were scaled by the unexpectedness of reinforcement and were highly similar across neurons and two nuclei innervating distinct cortical areas. These results reveal that the cholinergic system broadcasts a rapid and precisely timed reinforcement signal supporting fast cortical activation and plasticity. PMID:26317475

  6. TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine

    PubMed Central

    Vu, Michael T.; Du, Guizhi; Bayliss, Douglas A.

    2015-01-01

    . Basal forebrain cholinergic neurons are important modulators of cortical arousal and γ activity, and in this study we investigated the mechanism by which these neurons are activated by the wake-active neurotransmitter histamine. We found that histamine inhibited a class of K+ leak channels called TASK channels and that deletion of TASK channels selectively on cholinergic neurons modulated baseline EEG activity as well as histamine-induced changes in γ activity. By identifying a discrete brain circuit where TASK channels can influence γ activity, these results represent new knowledge that enhances our understanding of how subcortical arousal systems may contribute to the generation of attentive states. PMID:26446210

  7. Glucose enhances indolic glucosinolate biosynthesis without reducing primary sulfur assimilation

    PubMed Central

    Miao, Huiying; Cai, Congxi; Wei, Jia; Huang, Jirong; Chang, Jiaqi; Qian, Hongmei; Zhang, Xin; Zhao, Yanting; Sun, Bo; Wang, Bingliang; Wang, Qiaomei

    2016-01-01

    The effect of glucose as a signaling molecule on induction of aliphatic glucosinolate biosynthesis was reported in our former study. Here, we further investigated the regulatory mechanism of indolic glucosinolate biosynthesis by glucose in Arabidopsis. Glucose exerted a positive influence on indolic glucosinolate biosynthesis, which was demonstrated by induced accumulation of indolic glucosinolates and enhanced expression of related genes upon glucose treatment. Genetic analysis revealed that MYB34 and MYB51 were crucial in maintaining the basal indolic glucosinolate accumulation, with MYB34 being pivotal in response to glucose signaling. The increased accumulation of indolic glucosinolates and mRNA levels of MYB34, MYB51, and MYB122 caused by glucose were inhibited in the gin2-1 mutant, suggesting an important role of HXK1 in glucose-mediated induction of indolic glucosinolate biosynthesis. In contrast to what was known on the function of ABI5 in glucose-mediated aliphatic glucosinolate biosynthesis, ABI5 was not required for glucose-induced indolic glucosinolate accumulation. In addition, our results also indicated that glucose-induced glucosinolate accumulation was due to enhanced sulfur assimilation instead of directed sulfur partitioning into glucosinolate biosynthesis. Thus, our data provide new insights into molecular mechanisms underlying glucose-regulated glucosinolate biosynthesis. PMID:27549907

  8. Glucose enhances indolic glucosinolate biosynthesis without reducing primary sulfur assimilation.

    PubMed

    Miao, Huiying; Cai, Congxi; Wei, Jia; Huang, Jirong; Chang, Jiaqi; Qian, Hongmei; Zhang, Xin; Zhao, Yanting; Sun, Bo; Wang, Bingliang; Wang, Qiaomei

    2016-01-01

    The effect of glucose as a signaling molecule on induction of aliphatic glucosinolate biosynthesis was reported in our former study. Here, we further investigated the regulatory mechanism of indolic glucosinolate biosynthesis by glucose in Arabidopsis. Glucose exerted a positive influence on indolic glucosinolate biosynthesis, which was demonstrated by induced accumulation of indolic glucosinolates and enhanced expression of related genes upon glucose treatment. Genetic analysis revealed that MYB34 and MYB51 were crucial in maintaining the basal indolic glucosinolate accumulation, with MYB34 being pivotal in response to glucose signaling. The increased accumulation of indolic glucosinolates and mRNA levels of MYB34, MYB51, and MYB122 caused by glucose were inhibited in the gin2-1 mutant, suggesting an important role of HXK1 in glucose-mediated induction of indolic glucosinolate biosynthesis. In contrast to what was known on the function of ABI5 in glucose-mediated aliphatic glucosinolate biosynthesis, ABI5 was not required for glucose-induced indolic glucosinolate accumulation. In addition, our results also indicated that glucose-induced glucosinolate accumulation was due to enhanced sulfur assimilation instead of directed sulfur partitioning into glucosinolate biosynthesis. Thus, our data provide new insights into molecular mechanisms underlying glucose-regulated glucosinolate biosynthesis. PMID:27549907

  9. BMP9 Protects Septal Neurons from Axotomy-Evoked Loss of Cholinergic Phenotype

    PubMed Central

    Lopez-Coviella, Ignacio; Mellott, Tiffany J.; Schnitzler, Aletta C.; Blusztajn, Jan K.

    2011-01-01

    Background Cholinergic projection from the septum to the hippocampus is crucial for normal cognitive function and degeneration of cells and nerve fibers within the septohippocampal pathway contributes to the pathophysiology of Alzheimer's disease. Bone morphogenetic protein (BMP) 9 is a cholinergic differentiating factor during development both in vivo and in vitro. Methodology/Principal Findings To determine whether BMP9 could protect the adult cholinergic septohippocampal pathway from axotomy-evoked loss of the cholinergic phenotype, we performed unilateral fimbria-fornix transection in mice and treated them with a continuous intracerebroventricular infusion of BMP9 for six days. The number of choline acetyltransferase (CHAT)-positive cells was reduced by 50% in the medial septal nucleus ipsilateral to the lesion as compared to the intact, contralateral side, and BMP9 infusion prevented this loss in a dose-dependent manner. Moreover, BMP9 prevented most of the decline of hippocampal acetylcholine levels ipsilateral to the lesion, and markedly increased CHAT, choline transporter CHT, NGF receptors p75 (NGFR-p75) and TrkA (NTRK1), and NGF protein content in both the lesioned and unlesioned hippocampi. In addition, BMP9 infusion reduced bilaterally hippocampal levels of basic FGF (FGF2) protein. Conclusions/Significance These data indicate that BMP9 administration can prevent lesion-evoked impairment of the cholinergic septohippocampal neurons in adult mice and, by inducing NGF, establishes a trophic environment for these cells. PMID:21695154

  10. Genetically determined cholinergic deficiency in the forebrain of C57BL/6 mice.

    PubMed

    Bentivoglio, A R; Altavista, M C; Granata, R; Albanese, A

    1994-02-21

    This study demonstrates that a deficiency of forebrain cholinergic neurons occurs in C57BL/6 (C57) mice, a strain characterized by poor learning capabilities. The brains of 21-day-old and 18-week-old C57 and DBA/2 (DBA) mice were studied by means of acetylcholinesterase (AChE) histochemistry and of choline acetyltransferase (ChAT) immunocytochemistry. Computer-assisted image analysis was performed on sections through the medial septum, the diagonal band of Broca, the basal nucleus of Meynert and the neostriatum. As compared to the DBA strain, C57 mice had a reduced number of forebrain cholinergic neurons. This feature was present at the age of 21 days and persisted to 18 weeks. Between-strain variations in the density of neurons were more obvious in ChAT-stained material than in AChE-stained sections. These data show that C57 mice can be regarded as a genetic mutant, whose phenotype is characterized by a reduced number of forebrain cholinergic neurons and by cognitive abnormalities. C57 mice represent a valuable model for studying the influence of genetic factors on central nervous system cholinergic mechanisms and the effects of genetically determined cholinergic deficiency on behavior and learning.

  11. Enhancing imagined contact to reduce prejudice against people with schizophrenia

    PubMed Central

    West, Keon; Holmes, Emily; Hewstone, Miles

    2015-01-01

    Four studies investigated the effect of imagining intergroup contact on prejudice against people with schizophrenia. Experiments 1 and 2 demonstrated that a neutral imagined contact task can have negative effects, compared to a control condition, even when paired with incidental positive information (Experiment 2). Experiments 3 and 4 demonstrated, however, that an integrated positive imagined contact scenario does result in less intergroup anxiety and more positive attitudes, even toward this challenging group. Analyses of participants’ descriptions of the imagined interactions in and across the first three studies confirm that positive and high quality imagined contact is important for reducing prejudice, but failing to ensure that imagined contact is positive may have deleterious consequences. We emphasize the importance of investigating the quality of the imagined contact experience, and discuss the implications for using imagined contact as a prejudice-reducing intervention. PMID:26435686

  12. Cholinergic modulation of large-conductance calcium-activated potassium channels regulates synaptic strength and spine calcium in cartwheel cells of the dorsal cochlear nucleus.

    PubMed

    He, Shan; Wang, Ya-Xian; Petralia, Ronald S; Brenowitz, Stephan D

    2014-04-01

    Acetylcholine is a neuromodulatory transmitter that controls synaptic plasticity and sensory processing in many brain regions. The dorsal cochlear nucleus (DCN) is an auditory brainstem nucleus that integrates auditory signals from the cochlea with multisensory inputs from several brainstem nuclei and receives prominent cholinergic projections. In the auditory periphery, cholinergic modulation serves a neuroprotective function, reducing cochlear output under high sound levels. However, the role of cholinergic signaling in the DCN is less understood. Here we examine postsynaptic mechanisms of cholinergic modulation at glutamatergic synapses formed by parallel fiber axons onto cartwheel cells (CWCs) in the apical DCN circuit from mouse brainstem slice using calcium (Ca) imaging combined with two-photon laser glutamate uncaging onto CWC spines. Activation of muscarinic acetylcholine receptors (mAChRs) significantly increased the amplitude of both uncaging-evoked EPSPs (uEPSPs) and spine Ca transients. Our results demonstrate that mAChRs in CWC spines act by suppressing large-conductance calcium-activated potassium (BK) channels, and this effect is mediated through the cAMP/protein kinase A signaling pathway. Blocking BK channels relieves voltage-dependent magnesium block of NMDA receptors, thereby enhancing uEPSPs and spine Ca transients. Finally, we demonstrate that mAChR activation inhibits L-type Ca channels and thus may contribute to the suppression of BK channels by mAChRs. In summary, we demonstrate a novel role for BK channels in regulating glutamatergic transmission and show that this mechanism is under modulatory control of mAChRs.

  13. Cholinergic Modulation of Large-Conductance Calcium-Activated Potassium Channels Regulates Synaptic Strength and Spine Calcium in Cartwheel Cells of the Dorsal Cochlear Nucleus

    PubMed Central

    He, Shan; Wang, Ya-Xian; Petralia, Ronald S.

    2014-01-01

    Acetylcholine is a neuromodulatory transmitter that controls synaptic plasticity and sensory processing in many brain regions. The dorsal cochlear nucleus (DCN) is an auditory brainstem nucleus that integrates auditory signals from the cochlea with multisensory inputs from several brainstem nuclei and receives prominent cholinergic projections. In the auditory periphery, cholinergic modulation serves a neuroprotective function, reducing cochlear output under high sound levels. However, the role of cholinergic signaling in the DCN is less understood. Here we examine postsynaptic mechanisms of cholinergic modulation at glutamatergic synapses formed by parallel fiber axons onto cartwheel cells (CWCs) in the apical DCN circuit from mouse brainstem slice using calcium (Ca) imaging combined with two-photon laser glutamate uncaging onto CWC spines. Activation of muscarinic acetylcholine receptors (mAChRs) significantly increased the amplitude of both uncaging-evoked EPSPs (uEPSPs) and spine Ca transients. Our results demonstrate that mAChRs in CWC spines act by suppressing large-conductance calcium-activated potassium (BK) channels, and this effect is mediated through the cAMP/protein kinase A signaling pathway. Blocking BK channels relieves voltage-dependent magnesium block of NMDA receptors, thereby enhancing uEPSPs and spine Ca transients. Finally, we demonstrate that mAChR activation inhibits L-type Ca channels and thus may contribute to the suppression of BK channels by mAChRs. In summary, we demonstrate a novel role for BK channels in regulating glutamatergic transmission and show that this mechanism is under modulatory control of mAChRs. PMID:24719104

  14. How Distinctive Processing Enhances Hits and Reduces False Alarms

    PubMed Central

    Hunt, R. Reed; Smith, Rebekah E.

    2015-01-01

    Distinctive processing is a concept designed to account for precision in memory, both correct responses and avoidance of errors. The principal question addressed in two experiments is how distinctive processing of studied material reduces false alarms to familiar distractors. Jacoby (Jacoby, Kelley, & McElree, 1999) has used the metaphors early selection and late correction to describe two different types of control processes. Early selection refers to limitations on access whereas late correction describes controlled monitoring of accessed information. The two types of processes are not mutually exclusive, and previous research has provided evidence for the operation of both. The data reported here extend previous work to a criterial recollection paradigm and to a recognition memory test. The results of both experiments show that variables that reduce false memory for highly familiar distracters continue to exert their effect under conditions of minimal post-access monitoring. Level of monitoring was reduced in the first experiment through test instructions and in the second experiment through speeded test responding. The results were consistent with the conclusion that both early selection and late correction operate to control accuracy in memory. PMID:26034343

  15. Enhancing Tomo-PIV reconstruction quality by reducing ghost particles

    NASA Astrophysics Data System (ADS)

    de Silva, C. M.; Baidya, R.; Marusic, I.

    2013-02-01

    A technique to enhance the reconstruction quality and consequently the accuracy of the velocity vector field obtained in Tomo-PIV experiments is presented here. The methodology involves detecting and eliminating spurious outliers in the reconstructed intensity field (ghost particles). A simulacrum matching-based reconstruction enhancement (SMRE) technique is proposed, which utilizes the characteristic shape and size of actual particles to remove ghost particles in the reconstructed intensity field. An assessment of SMRE is performed by a quantitative comparison of Tomo-PIV simulation results and DNS data, together with a comparison to Tomo-PIV experimental data measured in a turbulent channel flow at a matched Reynolds number (Reτ = 937) to the DNS study. For the simulation data, a comparative study is performed on the reconstruction quality based on an ideal reconstruction determined from known particle positions. The results suggest that a significant improvement in the reconstruction quality and flow statistics is achievable at typical seeding densities used in Tomo-PIV experiments. This improvement is further amplified at higher seeding densities, enabling the use of up to twice the typical seeding densities currently used in Tomo-PIV experiments. A reduction of spurious vectors present in the velocity field is also observed based on a median outlier detection criterion. The application of SMRE to Tomo-PIV experimental data shows an improvement in flow statistics, comparable to the improvement seen in simulations. Finally, due to the non-iterative nature of SMRE, the increase in processing time is marginal since only a single pass of the reconstruction algorithm is required.

  16. Hormonal and cholinergic influences on pancreatic lysosomal and digestive enzymes in rats.

    PubMed

    Evander, A; Ihse, I; Lundquist, I

    1983-01-01

    Hormonal and cholinergic influences on lysosomal and digestive enzyme activities in pancreatic tissue were studied in normal adult rats. Hormonal stimulation by the cholecystokinin analogue, caerulein, induced a marked enhancement of the activities of cathepsin D and N-acetyl-beta-D-glucosaminidase in pancreatic tissue, whereas the activities of amylase and lipase tended to decrease. Acid phosphatase activity was not affected. Further, caerulein was found to induce a significant increase of cathepsin D output in bile-pancreatic juice. This output largely parallelled that of amylase. Cholinergic stimulation by the muscarinic agonist carbachol, at a dose level giving the same output of amylase as caerulein, did not affect pancreatic activities of cathepsin D and N-acetyl-beta-D-glucosaminidase. Further, cholinergic stimulation induced an increase of amylase activity and a slight decrease of acid phosphatase activity in pancreatic tissue. Lipase activity was not affected. No apparent effect on cathepsin D output in bile-pancreatic juice was encountered after cholinergic stimulation. The activities of neither the digestive nor the lysosomal enzymes were influenced by the administration of secretin. The results suggest a possible lysosomal involvement in caerulein-induced secretion and/or inactivation of pancreatic digestive enzymes, whereas cholinergic stimulation seems to act through different mechanisms.

  17. Endogenous cholinergic input to the pontine REM sleep generator is not required for REM sleep to occur.

    PubMed

    Grace, Kevin P; Vanstone, Lindsay E; Horner, Richard L

    2014-10-22

    Initial theories of rapid eye movement (REM) sleep generation posited that induction of the state required activation of the pontine subceruleus (SubC) by cholinergic inputs. Although the capacity of cholinergic neurotransmission to contribute to REM sleep generation has been established, the role of cholinergic inputs in the generation of REM sleep is ultimately undetermined as the critical test of this hypothesis (local blockade of SubC acetylcholine receptors) has not been rigorously performed. We used bilateral microdialysis in freely behaving rats (n = 32), instrumented for electroencephalographic and electromyographic recording, to locally manipulate neurotransmission in the SubC with select drugs. As predicted, combined microperfusion of D-AP5 (glutamate receptor antagonist) and muscimol (GABAA receptor agonist) in the SubC virtually eliminated REM sleep. However, REM sleep was not reduced by scopolamine microperfusion in this same region, at a concentration capable of blocking the effects of cholinergic receptor stimulation. This result suggests that transmission of REM sleep drive to the SubC is acetylcholine-independent. Although SubC cholinergic inputs are not majorly involved in REM sleep generation, they may perform a minor function in the reinforcement of transitions into REM sleep, as evidenced by increases in non-REM-to-REM sleep transition duration and failure rate during cholinergic receptor blockade. Cholinergic receptor antagonism also attenuated the normal increase in hippocampal θ oscillations that characterize REM sleep. Using computational modeling, we show that our in vivo results are consistent with a mutually excitatory interaction between the SubC and cholinergic neurons where, importantly, cholinergic neuron activation is gated by SubC activity.

  18. Adult mouse basal forebrain harbors two distinct cholinergic populations defined by their electrophysiology

    PubMed Central

    Unal, Cagri T.; Golowasch, Jorge P.; Zaborszky, Laszlo

    2012-01-01

    We performed whole-cell recordings from basal forebrain (BF) cholinergic neurons in transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the choline acetyltransferase promoter. BF cholinergic neurons can be differentiated into two electrophysiologically identifiable subtypes: early and late firing neurons. Early firing neurons (∼70%) are more excitable, show prominent spike frequency adaptation and are more susceptible to depolarization blockade, a phenomenon characterized by complete silencing of the neuron following initial action potentials. Late firing neurons (∼30%), albeit being less excitable, could maintain a tonic discharge at low frequencies. In voltage clamp analysis, we have shown that early firing neurons have a higher density of low voltage activated (LVA) calcium currents. These two cholinergic cell populations might be involved in distinct functions: the early firing group being more suitable for phasic changes in cortical acetylcholine release associated with attention while the late firing neurons could support general arousal by maintaining tonic acetylcholine levels. PMID:22586380

  19. Modulation of inflammatory pathways by the immune cholinergic system.

    PubMed

    Nizri, Eran; Brenner, Talma

    2013-07-01

    Research done in the past years pointed to a novel function of cholinergic transmission. It has been shown that cholinergic transmission can modulate various aspects of the immune function, whether innate or adaptive. Cholinergic transmission affects immune cell proliferation, cytokine production, T helper differentiation and antigen presentation. Theses effects are mediated by cholinergic muscarinic and nicotinic receptors and other cholinergic components present in immune cells, such as acetylcholinesterase (AChE) and cholineacetyltransferase. The α7 nicotinic acetylcholine receptor was designated anti-inflammatory activity and has shown promise in pre-clinical models of inflammatory disorders. We herein describe the various components of the immune cholinergic system, and specifically the immune suppressive effects of α7 activation. This activation can be accomplished either by direct stimulation or indirectly, by inhibition of AChE. Thus, the presence of the immune cholinergic system can pave the way for novel immunomodulatory agents, or to the broadening of use of known cholinergic agents.

  20. Botrytis infection warnings in strawberry: reduced enhanced chemical control.

    PubMed

    Van Laer, S; Hauke, K; Meesters, P; Creemers, P

    2005-01-01

    The fungal pathogen Botrytis cinerea is the causal agent of grey mould, the most important fungal fruit rot disease in strawberry in Europe. Currently disease control for grey mould is based on preventive spraying every five to seven days during flowering and harvest. Replacing preventive spraying with applications based on infection warnings can optimize performance and reduce the amount of sprays needed. Success of this approach will depend on the accuracy of the model used to predict disease outbreak. For this reason three infection models (BOTEM, BoWaS, DSS-Italy) were evaluated during the growth seasons of 2003 and 2004. The experiments included June bearing, retarded June bearing and ever bearing strawberries. In all experiments the use of infection models leaded to a reduced number of fungicide applications. However the efficacy of the different models towards the control of B. cinerea also decreased compared to the efficacy obtained with a standard 7 day schedule. Best results were obtained with BOTEM, developed by HRI (Horticultural Research International, East-Malling, UK): 17-60% reduction in fungicide use and an efficacy between 66-93 depending on the growth season, culture practice and the fungicides used. Compared with routine preventive spraying, the Botrytis fruit rot percentage is slightly higher. A higher efficacy with Botrytis infection warnings can only be obtained if infection warnings change from curative to preventive. A retroactive evaluation of a preventive warning system was included. Making use of the 48h weather forecasts supplied by the Royal Meteorological Institute of Belgium (KMI) based on ALADIN for the region of Haspengouw, it was possible to replace 30 up to 100% of the curative application by preventive spraying depending on the experiment and the threshold set for the preventive model.

  1. Features of cholinergic cardia regulation under conditions of hypokinesia

    NASA Technical Reports Server (NTRS)

    Markova, Y. A.; Bondarenko, Y. I.; Bolyarskaya, V. A.; Fayfura, V. V.; Rosolovskiy, A. P.; Babinskaya, L. N.

    1980-01-01

    The features of cholinergic processes in the heart on the 4th, 8th, 16th and 30th days of hypokinesia were studied in experiments on 382 albino rats. It was shown that hypokinesia is attended by increased acetylcholine content in the atria, reduced choline acetyltransferase activity in the atria and ventricles and by increased activity of acetylcholinesterase in the ventricles and of pseudocholinesterase in both parts of the heart. The sensitivity of the heart to exogenic acetylcholine and to stimulation of the vagus nerve increases.

  2. Cholinergic regulation of the vasopressin neuroendocrine system

    SciTech Connect

    Michels, K.M.

    1987-01-01

    To clarify the physical and functional relationship between the cholinergic system, and the neurodocrine cells of the supraoptic nucleus, a combination of experiments on receptor binding, localization and function were carried out. The putative nicotinic receptor probe (/sup 125/I)alpha bungarotoxin ((/sup 125/I)alpha BTX) bound with high affinity and specificity to the vasopressin and oxytocin magnocellular neurons of the supraoptic nucleus, nucleus circularis, and paraventricular nucleus. Binding of (/sup 125/I)alpha BTX within the neural lobe was very low. In contrast, the muscarinic cholinergic receptor probe (/sup 3/H)quinuclidinylbenzilate ((/sup 3/H)QNB) did not bind to magnocellular vasopressin and oxytocin cell groups. The median eminence, which contains the neurosecretory axons, and the neural lobe of the pituitary contain low levels of (/sup 3/H)QNB binding. The physiological significance of these cholinergic receptors in regulation of vasopressin release was tested using an in vitro preparation of the supraoptic - neural lobe system.

  3. Memantine acts as a cholinergic stimulant in the mouse hippocampus.

    PubMed

    Drever, Benjamin D; Anderson, William G L; Johnson, Helena; O'Callaghan, Matthew; Seo, Sangwon; Choi, Deog-Young; Riedel, Gernot; Platt, Bettina

    2007-12-01

    The non-competitive NMDA receptor antagonist memantine, currently prescribed for the treatment of Alzheimer's disease, is assumed to prevent the excitotoxicity implicated in neurodegenerative processes. Here, we investigated the actions of memantine on hippocampal function and signalling. In behavioural experiments using the water maze, we observed that memantine (at 2 mg/kg) reversed scopolamine-induced learning deficits in mice. When acutely applied to mouse hippocampal slices, memantine caused a significant upward shift in the population spike input-output relationship at 10 and 100 microM, and a corresponding downward shift in latency, indicative of overall enhanced synaptic transmission. This action was blocked by the muscarinic antagonist scopolamine (10 microM) but not by the NMDA antagonist MK-801 (10 microM) or the GABA antagonist bicuculline (20 microM). Further, memantine occluded potentiation induced by 50 nM carbachol (CCh), while enhancing inhibitory actions of CCh at 1 microM, suggesting additive actions. As anticipated for an NMDA antagonist, 100 microM (but not 10 microM) memantine also inhibited tetanus-induced long-term potentiation (LTP), and NMDA-induced Ca;{2+} signals were blocked in cultured hippocampal neurones at 10 microM (by 88%). Overall, our data suggest actions of memantine beyond NMDA receptor antagonism, including stimulating effects on cholinergic signalling via muscarinic receptors. These interactions with the cholinergic system are likely to contribute to memantine's therapeutic potential.

  4. Cholinergic neuromodulation by prostaglandin D2 in canine airway smooth muscle.

    PubMed

    Tamaoki, J; Sekizawa, K; Graf, P D; Nadel, J A

    1987-10-01

    To determine whether prostaglandin D2 (PGD2) modulates cholinergic neurotransmission in airway smooth muscle and, if so, what the mechanism of action is, we studied bronchial segments from dogs under isometric conditions in vitro. PGD2 (10(-8)-10(-5) M) elicited dose-dependent muscle contraction, which was reduced after blockade of muscarinic receptors, so that 50% effective dose (ED50) increased from 1.3 +/- 0.3 X 10(-6) to 3.9 +/- 1.0 X 10(-6) M by atropine (10(-6) M) (mean +/- SE, P less than 0.05). Physostigmine, at a concentration insufficient to alter base-line tension (10(-8) M), enhanced the PGD2-induced contraction and decreased ED50 to 6.4 +/- 0.5 X 10(-7) M (P less than 0.05). When added at the highest doses that did not cause spontaneous contraction (1.9 +/- 0.5 X 10(-7) M), PGD2 increased the contractile response to electrical field stimulation (1-50 Hz) by 21.9 +/- 6.6% (P less than 0.001). In contrast to this effect, the response to administered acetylcholine was not affected by PGD2. On the other hand, PGD2-induced augmentation of the response to electrical field stimulation (5 Hz) was further increased from 23.6 +/- 3.0 to 70.4 +/- 8.8% in the presence of physostigmine (10(-8) M) and was abolished by atropine but not affected by the alpha-adrenergic antagonist phentolamine or the histamine H1-blocker pyrilamine. These results suggest that the contraction of airway smooth muscle induced by PGD2 is in in part mediated by a cholinergic action and that PGD2 prejunctionally augments the parasympathetic contractile response, likely involving the accelerated release of acetylcholine at the neuromuscular junction.

  5. Sexually dimorphic effects of the Lhx7 null mutation on forebrain cholinergic function.

    PubMed

    Fragkouli, A; Stamatakis, A; Zographos, E; Pachnis, V; Stylianopoulou, F

    2006-01-01

    It has been reported recently that mice lacking both alleles of the LIM-homeobox gene Lhx7, display dramatically reduced number of forebrain cholinergic neurons. In the present study, we investigated whether the Lhx7 mutation affects male and female mice differently, given the fact that gender differences are consistently observed in forebrain cholinergic function. Our results show that in adult male as well as female Lhx7 homozygous mutants there is a dramatic loss of choline acetyltransferase immunoreactive forebrain neurons, both projection and interneurons. The reduction of forebrain choline acetyltransferase immunoreactive neurons in Lhx7 homozygous mutants is accompanied by a decrease of acetylcholinesterase histochemical staining in all forebrain cholinergic neuron target areas of both male and female homozygous mutants. Furthermore, there was an increase of M1-, but not M2-, muscarinic acetylcholine receptor binding site density in the somatosensory cortex and basal ganglia of only the female homozygous mutant mice. Such an increase can be regarded as a mechanism acting to compensate for the dramatically reduced cholinergic input, raising the possibility that the forebrain cholinergic system in female mice may be more plastic and responsive to situations of limited neurotransmitter availability. Finally, our study provides additional data for the sexual dimorphism of the forebrain cholinergic system, as female mice appear to have a lower density of M1-muscarinic acetylcholine receptors in the striatal areas of the basal ganglia and a higher density of M2-muscarinic acetylcholine receptors, in a number of cortical areas, as well as the striatal areas of the basal ganglia.

  6. Alterations in Cholinergic Pathways and Therapeutic Strategies Targeting Cholinergic System after Traumatic Brain Injury

    PubMed Central

    Shin, Samuel S.

    2015-01-01

    Abstract Traumatic brain injury (TBI) results in varying degrees of disability in a significant number of persons annually. The mechanisms of cognitive dysfunction after TBI have been explored in both animal models and human clinical studies for decades. Dopaminergic, serotonergic, and noradrenergic dysfunction has been described in many previous reports. In addition, cholinergic dysfunction has also been a familiar topic among TBI researchers for many years. Although pharmacological agents that modulate cholinergic neurotransmission have been used with varying degrees of success in previous studies, improving their function and maximizing cognitive recovery is an ongoing process. In this article, we review the previous findings on the biological mechanism of cholinergic dysfunction after TBI. In addition, we describe studies that use both older agents and newly developed agents as candidates for targeting cholinergic neurotransmission in future studies. PMID:25646580

  7. Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test.

    PubMed

    Addy, N A; Nunes, E J; Wickham, R J

    2015-07-15

    Recent studies revealed a causal link between ventral tegmental area (VTA) phasic dopamine (DA) activity and pro-depressive and antidepressant-like behavioral responses in rodent models of depression. Cholinergic activity in the VTA has been demonstrated to regulate phasic DA activity, but the role of VTA cholinergic mechanisms in depression-related behavior is unclear. The goal of this study was to determine whether pharmacological manipulation of VTA cholinergic activity altered behavioral responding in the forced swim test (FST) in rats. Here, male Sprague-Dawley rats received systemic or VTA-specific administration of the acetylcholinesterase inhibitor, physostigmine (systemic; 0.06 or 0.125mg/kg, intra-cranial; 1 or 2μg/side), the muscarinic acetylcholine receptor (AChR) antagonist scopolamine (2.4 or 24μg/side), or the nicotinic AChR antagonist mecamylamine (3 or 30μg/side), prior to the FST test session. In control experiments, locomotor activity was also examined following systemic and intra-cranial administration of cholinergic drugs. Physostigmine administration, either systemically or directly into the VTA, significantly increased immobility time in FST, whereas physostigmine infusion into a dorsal control site did not alter immobility time. In contrast, VTA infusion of either scopolamine or mecamylamine decreased immobility time, consistent with an antidepressant-like effect. Finally, the VTA physostigmine-induced increase in immobility was blocked by co-administration with scopolamine, but unaltered by co-administration with mecamylamine. These data show that enhancing VTA cholinergic tone and blocking VTA AChRs has opposing effects in FST. Together, the findings provide evidence for a role of VTA cholinergic mechanisms in behavioral responses in FST.

  8. Cholinergic transmission underlies modulation of frustration by open field exposure.

    PubMed

    Psyrdellis, Mariana; Pautassi, Ricardo Marcos; Mustaca, Alba; Justel, Nadia

    2016-01-01

    Frustration can be defined as an emotional state generated by the omission or devaluation in the quantity or quality of an expected appetitive reward. Thus, reactivity to a reward is affected by prior experience with the different reinforcer values of that reward. This phenomenon is known as incentive relativity, and can be studied by different paradigms. Although methodologically simple, the exploration of a novel open field (OF) is a complex situation that involves several behavioral processes, including stress induction and novelty detection. OF exposure can enhance or block the acquisition of associative and non-associative memories. These experiments evaluated the effect of OF exploration on frustration and the role played by the cholinergic system in this phenomenon. OF exploration before first or second trial of incentive downshift modulated the expression of frustration. This effect of OF was blocked by the administration of scopolamine either before or after OF exploration. These results indicate that the cholinergic system is involved in the acquisition and consolidation of OF information. PMID:26546747

  9. Mutual Control of Cholinergic and Low-Threshold Spike Interneurons in the Striatum

    PubMed Central

    Elghaba, Rasha; Vautrelle, Nicolas; Bracci, Enrico

    2016-01-01

    The striatum is the largest nucleus of the basal ganglia and is crucially involved in action selection and reward processing. Cortical and thalamic inputs to the striatum are processed by local networks in which several classes of interneurons play an important, but still poorly understood role. Here we investigated the interactions between cholinergic and low-threshold spike (LTS) interneurons. LTS interneurons were hyperpolarized by co-application of muscarinic and nicotinic receptor antagonists (atropine and mecamylamine, respectively). Mecamylamine alone also caused hyperpolarizations, while atropine alone caused depolarizations and increased firing. LTS interneurons were also under control of tonic GABA, as application of the GABAA receptor antagonist picrotoxin caused depolarizations and increased firing. Frequency of spontaneous GABAergic events in LTS interneurons was increased by co-application of atropine and mecamylamine or by atropine alone, but reduced by mecamylamine alone. In the presence of picrotoxin and tetrodotoxin (TTX), atropine and mecamylamine depolarized the LTS interneurons. We concluded that part of the excitatory effects of tonic acetylcholine (ACh) on LTS interneurons were due to cholinergic modulation of tonic GABA. We then studied the influence of LTS interneurons on cholinergic interneurons. Application of antagonists of somatostatin or neuropeptide Y (NPY) receptors or of an inhibitor of nitric oxide synthase (L-NAME) did not cause detectable effects in cholinergic interneurons. However, prolonged synchronized depolarizations of LTS interneurons (elicited with optogenetics tools) caused slow-onset depolarizations in cholinergic interneurons, which were often accompanied by strong action potential firing and were fully abolished by L-NAME. Thus, a mutual excitatory influence exists between LTS and cholinergic interneurons in the striatum, providing an opportunity for sustained activation of the two cell types. This activation may

  10. Adenosine Inhibits the Excitatory Synaptic Inputs to Basal Forebrain Cholinergic, GABAergic, and Parvalbumin Neurons in Mice

    PubMed Central

    Yang, Chun; Franciosi, Serena; Brown, Ritchie E.

    2013-01-01

    Coffee and tea contain the stimulants caffeine and theophylline. These compounds act as antagonists of adenosine receptors. Adenosine promotes sleep and its extracellular concentration rises in association with prolonged wakefulness, particularly in the basal forebrain (BF) region involved in activating the cerebral cortex. However, the effect of adenosine on identified BF neurons, especially non-cholinergic neurons, is incompletely understood. Here we used whole-cell patch-clamp recordings in mouse brain slices prepared from two validated transgenic mouse lines with fluorescent proteins expressed in GABAergic or parvalbumin (PV) neurons to determine the effect of adenosine. Whole-cell recordings were made from BF cholinergic neurons and from BF GABAergic and PV neurons with the size (>20 μm) and intrinsic membrane properties (prominent H-currents) corresponding to cortically projecting neurons. A brief (2 min) bath application of adenosine (100 μM) decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in all groups of BF cholinergic, GABAergic, and PV neurons we recorded. In addition, adenosine decreased the frequency of miniature EPSCs in BF cholinergic neurons. Adenosine had no effect on the frequency of spontaneous inhibitory postsynaptic currents in cholinergic neurons or GABAergic neurons with large H-currents but reduced them in a group of GABAergic neurons with smaller H-currents. All effects of adenosine were blocked by a selective, adenosine A1 receptor antagonist, cyclopentyltheophylline (CPT, 1 μM). Adenosine had no postsynaptic effects. Taken together, our work suggests that adenosine promotes sleep by an A1 receptor-mediated inhibition of glutamatergic inputs to cortically projecting cholinergic and GABA/PV neurons. Conversely, caffeine and theophylline promote attentive wakefulness by inhibiting these A1 receptors in BF thereby promoting the high-frequency oscillations in the cortex required

  11. Morphine attenuates cholinergic nerve activity in human isolated colonic muscle.

    PubMed Central

    Burleigh, D. E.; Trout, S. J.

    1986-01-01

    The action of morphine on cholinergic nerves in human sigmoid taenia coli muscle strips (taenia) was investigated using a radiolabelling technique. Basal release of tritiated material from taenia was increased by electrical field stimulation (EFS). This increase was tetrodotoxin (3.14 microM)-sensitive and calcium-dependent. Analysis of basal and stimulated release of tritiated material indicated that evoked release (i.e. stimulated minus basal) is almost entirely due to an increase in [3H]-acetylcholine ([3H]-ACh) output. Evoked release of [3H]-ACh was dependent on the current strength and could be greatly reduced by exposing taenia to hemicholinium (34.8, 87.0 microM) before and during incubation with [3H]-choline (4 microCi ml-1, 15 Ci mmol-1). Spontaneous activity, muscle tone and the motor response of taenia to EFS were unaffected by morphine. Evoked, but not basal, release of tritiated material was inhibited by morphine (1.32-13.20 microM) in a concentration-dependent manner. The inhibition of release was frequency-dependent and naloxone (0.28 microM)-sensitive. The possible relationship between the effects of morphine on cholinergic nerves in taenia muscle and its actions in vivo are discussed. PMID:2873856

  12. Cholinergic medial septum neurons do not degenerate in aged 129/Sv control or p75(NGFR)-/-mice.

    PubMed

    Ward, N L; Stanford, L E; Brown, R E; Hagg, T

    2000-01-01

    Cholinergic medial septum neurons express TrkA and p75 nerve growth factor receptor (p75(NGFR)) and interactions between TrkA and p75(NGFR) are necessary for high-affinity binding and signaling of nerve growth factor (NGF) through TrkA. In adult p75(NGFR)-deficient (-/-) mice, retrograde transport of NGF and other neurotrophins by these neurons is greatly reduced, however, these neurons maintain their cholinergic phenotype and size. Reduced transport of NGF has been proposed to play a role in Alzheimer's disease. Here, we investigated whether chronic and long-term absence of p75(NGFR) (and possibly reduced NGF transport and TrkA binding) would affect the cholinergic septohippocampal system during aging in mice. In young (6-8 months), middle aged (12-18 months), and aged (19-23 months) 129/Sv control mice the total number of choline acetyltransferase-positive medial septum neurons and the mean diameter and cross sectional area of the cholinergic cell bodies were similar. The cholinergic hippocampal innervation, as measured by the density of acetylcholinesterase-positive fibers in the outer molecular layer of the dentate gyrus was also similar across all ages. These parameters also did not change during aging in p75(NGFR) -/- mice and the number and size of the choline acetyltransferase-positive neurons and the cholinergic innervation density were largely similar as in control mice at all ages. These results suggest that p75(NGFR) does not play a major role in the maintenance of the number or morphology of the cholinergic basal forebrain neurons during aging of these mice. Alternatively, p75(NGFR) -/- mice may have developed compensatory mechanisms in response to the absence of p75(NGFR).

  13. Clinical Markers for Identifying Cholinergic Deficits in Parkinson's Disease

    PubMed Central

    Müller, Martijn L.T.M.; Bohnen, Nicolaas I.; Kotagal, Vikas; Scott, Peter J.H.; Koeppe, Robert A.; Frey, Kirk A.; Albin, Roger L.

    2014-01-01

    Background Cholinergic projection systems degeneration is associated with dopamine non-responsive features of Parkinson's disease (PD). Cholinergic deficits are variable in non-demented PD. Identification of cholinergic deficits in PD may help with selection of suitable patients for targeted cholinergic drug treatment in PD. The objective of this retrospective multivariate predictor analysis study was to identify clinical markers indicative of cholinergic deficits in PD patients, as assessed by acetylcholinesterase ([11C]PMP) positron emission tomography. Methods One hundred thirty-seven PD patients (34 female) participated; median modified Hoehn and Yahr score was 2.5 (range 1–4), average age of 65.6 ± 7.4 years, and average duration of motor disease symptoms of 6.0 ± 4.2 years. Subjects were dichotomized as “normocholinergic” or “hypocholinergic” based on a 5th percentile cutoff from normal for the basal forebrain-cortical and pedunculopontine nucleus-thalamic cholinergic projection systems. Previously identified clinical indices of cholinergic denervation were used for statistical prediction of cholinergic deficits. Logistic regression determined which risk factors predicted cholinergic deficits. Sensitivity, specificity, and accuracy were determined for the (combinations of) significant predictor variables. Results There were 49 (35.8%) hypocholinergic PD subjects. The combination of RBD symptoms and fall history showed highest diagnostic accuracy (81.1%) for predicting combined thalamic and cortical cholinergic deficits. A combined assessment of 8.5 meter walk time and lower score on the Montreal cognitive assessment scale provided diagnostic accuracy of 80.7 % for predicting isolated cortical cholinergic denervation. Conclusion Assessment of clinical indices of cholinergic denervation may be useful for identifying suitable subjects for trials of targeted cholinergic drug treatments in PD. PMID:25393613

  14. Impaired rapid eye movement sleep in the Tg2576 APP murine model of Alzheimer's disease with injury to pedunculopontine cholinergic neurons.

    PubMed

    Zhang, Bin; Veasey, Sigrid C; Wood, Marcelo A; Leng, Lewis Z; Kaminski, Christine; Leight, Susan; Abel, Ted; Lee, Virginia M-Y; Trojanowski, John Q

    2005-11-01

    Impaired rapid eye movement sleep (REMS) is commonly observed in Alzheimer's disease, suggesting injury to mesopontine cholinergic neurons. We sought to determine whether abnormal beta-amyloid peptides impair REMS and injure mesopontine cholinergic neurons in transgenic (hAPP695.SWE) mice (Tg2576) that model brain amyloid pathologies. Tg2576 mice and wild-type littermates were studied at 2, 6, and 12 months by using sleep recordings, contextual fear conditioning, and immunohistochemistry. At 2 months of age, REMS was indistinguishable by genotype but was reduced in Tg2576 mice at 6 and 12 months. Choline acetyltransferase-positive neurons in the pedunculopontine tegmentum of Tg2576 mice at 2 months evidenced activated caspase-3 immunoreactivity, and at 6 and 12 months the numbers of pedunculopontine tegmentum choline acetyltransferase-positive neurons were reduced in the Tg2576 mice. Other cholinergic groups involved in REMS were unperturbed. At 12 months, Tg2576 mice demonstrated increased 3-nitrotyrosine immunoreactivity in cholinergic projection sites but not in cholinergic soma. We have identified a population of selectively compromised cholinergic neurons in young Tg2576 mice that manifest early onset REMS impairment. The differential vulnerability of these cholinergic neurons to Abeta injury provides an invaluable tool with which to understand mechanisms of sleep/wake perturbations in Alzheimer's disease.

  15. Involvement of the basolateral amygdala in muscarinic cholinergic modulation of extinction memory consolidation.

    PubMed

    Boccia, Mariano M; Blake, Mariano G; Baratti, Carlos M; McGaugh, James L

    2009-01-01

    Previous studies have reported that drugs affecting neuromodulatory systems within the basolateral amygdala (BLA), including drugs affecting muscarinic cholinergic receptors, modulate the consolidation of many kinds of training, including contextual fear conditioning (CFC). The present experiments investigated the involvement of muscarinic cholinergic influences within the BLA in modulating the consolidation of CFC extinction memory. Male Sprague Dawley rats implanted with unilateral cannula aimed at the BLA were trained on a CFC task, using footshock stimulation, and 24 and 48 h later were given extinction training by replacing them in the apparatus without footshock. Following each extinction session they received intra-BLA infusions of the cholinergic agonist oxotremorine (10 ng). Immediate post-extinction BLA infusions significantly enhanced extinction but infusions administered 180 min after extinction training did not influence extinction. Thus the oxotremorine effects were time-dependent and not attributable to non-specific effects on retention performance. These findings provide evidence that, as previously found with original CFC learning, cholinergic activation within the BLA modulates the consolidation of CFC extinction. PMID:18706510

  16. Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus.

    PubMed

    Teipel, Stefan J; Flatz, Wilhelm; Ackl, Nibal; Grothe, Michel; Kilimann, Ingo; Bokde, Arun L W; Grinberg, Lea; Amaro, Edson; Kljajevic, Vanja; Alho, Eduardo; Knels, Christina; Ebert, Anne; Heinsen, Helmut; Danek, Adrian

    2014-03-30

    Primary progressive aphasia (PPA) is characterized by left hemispheric frontotemporal cortical atrophy. Evidence from anatomical studies suggests that the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal forebrain, may be involved in the pathological process of PPA. Therefore, we studied the pattern of cortical and basal forebrain atrophy in 10 patients with a clinical diagnosis of PPA and 18 healthy age-matched controls using high-resolution magnetic resonance imaging (MRI). We determined the cholinergic basal forebrain nuclei according to Mesulam's nomenclature and the NSP in MRI reference space based on histological sections and the MRI scan of a post-mortem brain in cranio. Using voxel-based analysis, we found left hemispheric cortical atrophy in PPA patients compared with controls, including prefrontal, lateral temporal and medial temporal lobe areas. We detected cholinergic basal forebrain atrophy in left predominant localizations of Ch4p, Ch4am, Ch4al, Ch3 and NSP. For the first time, we have described the pattern of basal forebrain atrophy in PPA and confirmed the involvement of NSP that had been predicted based on theoretical considerations. Our findings may enhance understanding of the role of cholinergic degeneration for the regional specificity of the cortical destruction leading to the syndrome of PPA.

  17. Overexpression of NTRK1 Promotes Differentiation of Neural Stem Cells into Cholinergic Neurons

    PubMed Central

    Wang, Limin; He, Feng; Zhong, Zhuoyuan; Lv, Ruiyan; Xiao, Songhua; Liu, Zhonglin

    2015-01-01

    Neurotrophic tyrosine kinase type 1 (NTRK1) plays critical roles in proliferation, differentiation, and survival of cholinergic neurons; however, it remains unknown whether enhanced expression of NTRK1 in neural stem cells (NSCs) can promote their differentiation into mature neurons. In this study, a plasmid encoding the rat NTRK1 gene was constructed and transfected into C17.2 mouse neural stem cells (NSCs). NTRK1 overexpression in C17.2 cells was confirmed by western blot. The NSCs overexpressing NTRK1 and the C17.2 NSCs transfected by an empty plasmid vector were treated with or without 100 ng/mL nerve growth factor (NGF) for 7 days. Expression of the cholinergic cell marker, choline acetyltransferase (ChAT), was detected by florescent immunocytochemistry (ICC). In the presence of NGF induction, the NSCs overexpressing NTRK1 differentiated into ChAT-immunopositive cells at 3-fold higher than the NSCs transfected by the plasmid vector (26% versus 9%, P < 0.05). The data suggest that elevated NTRK1 expression increases differentiation of NSCs into cholinergic neurons under stimulation of NGF. The approach also represents an efficient strategy for generation of cholinergic neurons. PMID:26509167

  18. Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice.

    PubMed

    Stepanichev, Mikhail; Markov, Daniil; Pasikova, Natalia; Gulyaeva, Natalia

    2016-01-15

    Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats. PMID:26431763

  19. Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice.

    PubMed

    Stepanichev, Mikhail; Markov, Daniil; Pasikova, Natalia; Gulyaeva, Natalia

    2016-01-15

    Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats.

  20. Involvement of the basolateral amygdala in muscarinic cholinergic modulation of extinction memory consolidation.

    PubMed

    Boccia, Mariano M; Blake, Mariano G; Baratti, Carlos M; McGaugh, James L

    2009-01-01

    Previous studies have reported that drugs affecting neuromodulatory systems within the basolateral amygdala (BLA), including drugs affecting muscarinic cholinergic receptors, modulate the consolidation of many kinds of training, including contextual fear conditioning (CFC). The present experiments investigated the involvement of muscarinic cholinergic influences within the BLA in modulating the consolidation of CFC extinction memory. Male Sprague Dawley rats implanted with unilateral cannula aimed at the BLA were trained on a CFC task, using footshock stimulation, and 24 and 48 h later were given extinction training by replacing them in the apparatus without footshock. Following each extinction session they received intra-BLA infusions of the cholinergic agonist oxotremorine (10 ng). Immediate post-extinction BLA infusions significantly enhanced extinction but infusions administered 180 min after extinction training did not influence extinction. Thus the oxotremorine effects were time-dependent and not attributable to non-specific effects on retention performance. These findings provide evidence that, as previously found with original CFC learning, cholinergic activation within the BLA modulates the consolidation of CFC extinction.

  1. Cholinergic and non-cholinergic functions of two acetylcholinesterase genes revealed by gene-silencing in Tribolium castaneum

    PubMed Central

    Lu, Yanhui; Park, Yoonseong; Gao, Xiwu; Zhang, Xin; Yao, Jianxiu; Pang, Yuan-Ping; Jiang, Haobo; Zhu, Kun Yan

    2012-01-01

    We compared biological functions of two acetylcholinesterase genes (TcAce1 and TcAce2) in Tribolium castaneum, a globally distributed major pest of stored grain products and an emerging model organism, by using RNA interference. Although both genes expressed at all developmental stages and mainly in the brain, the transcript level of TcAce1 was 1.2- to 8.7-fold higher than that of TcAce2, depending on developmental stages. Silencing TcAce1 in 20-day larvae led to 100% mortality within two weeks after eclosion and increased larval susceptibilities to anticholinesterase insecticides. In contrast, silencing TcAce2 did not show insect mortality and significantly affect insecticide susceptibility, but delayed insect development and reduced female egg-laying and egg hatching. These results demonstrate for the first time that TcAce1 plays a major role in cholinergic functions and is the target of anticholinesterase insecticides, whereas TcAce2 plays an important, non-cholinergic role in female reproduction, embryo development, and growth of offspring. PMID:22371826

  2. Cholinergic innervation and receptors in the cerebellum.

    PubMed

    Jaarsma, D; Ruigrok, T J; Caffé, R; Cozzari, C; Levey, A I; Mugnaini, E; Voogd, J

    1997-01-01

    We have studied the source and ultrastructural characteristics of ChAT-immunoreactive fibers in the cerebellum of the rat, and the distribution of muscarinic and nicotinic receptors in the cerebellum of the rat, rabbit, cat and monkey, in order to define which of the cerebellar afferents may use ACh as a neurotransmitter, what target structures are they, and which cholinergic receptor mediate the actions of these pathways. Our data confirm and extend previous observations that cholinergic markers occur at relatively low density in the cerebellum and show not only interspecies variability, but also heterogeneity between cerebellar lobules in the same species. As previously demonstrated by Barmack et al. (1992a,b), the predominant fiber system in the cerebellum that might use ACh as a transmitter or a co-transmitter is formed by mossy fibers originating in the vestibular nuclei and innervating the nodulus and ventral uvula. Our results show that these fibers innervate both granule cells and unipolar brush cells, and that the presumed cholinergic action of these fibers most likely is mediated by nicotinic receptors. In addition to cholinergic mossy fibers, the rat cerebellum is innervated by beaded ChAT-immunoreactive fibers. We have demonstrated that these fibers originate in the pedunculopontine tegmental nucleus (PPTg), the lateral paragigantocellular nucleus (LPGi), and to a lesser extent in various raphe nuclei. In both the cerebellar cortex and the cerebellar nuclei these fibers make asymmetric synaptic junctions with small and medium-sized dendritic profiles. Both muscarinic and nicotinic receptor could mediate the action of these diffuse beaded fibers. In the cerebellar nuclei the beaded cholinergic fibers form a moderately dense network, and could in principle have a significant effect on neuronal activity. For instance, the cholinergic fibers arising in the PPTg may modulate the excitability of the cerebellonuclear neurons in relation to sleep and arousal (e

  3. Alzheimer's Disease: Targeting the Cholinergic System

    PubMed Central

    Ferreira-Vieira, Talita H.; Guimaraes, Isabella M.; Silva, Flavia R.; Ribeiro, Fabiola M.

    2016-01-01

    Acetylcholine (ACh) has a crucial role in the peripheral and central nervous systems. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing ACh from acetyl-CoA and choline in the cytoplasm and the vesicular acetylcholine transporter (VAChT) uptakes the neurotransmitter into synaptic vesicles. Following depolarization, ACh undergoes exocytosis reaching the synaptic cleft, where it can bind its receptors, including muscarinic and nicotinic receptors. ACh present at the synaptic cleft is promptly hydrolyzed by the enzyme acetylcholinesterase (AChE), forming acetate and choline, which is recycled into the presynaptic nerve terminal by the high-affinity choline transporter (CHT1). Cholinergic neurons located in the basal forebrain, including the neurons that form the nucleus basalis of Meynert, are severely lost in Alzheimer’s disease (AD). AD is the most ordinary cause of dementia affecting 25 million people worldwide. The hallmarks of the disease are the accumulation of neurofibrillary tangles and amyloid plaques. However, there is no real correlation between levels of cortical plaques and AD-related cognitive impairment. Nevertheless, synaptic loss is the principal correlate of disease progression and loss of cholinergic neurons contributes to memory and attention deficits. Thus, drugs that act on the cholinergic system represent a promising option to treat AD patients. PMID:26813123

  4. Changes in brain cholinergic markers and spatial learning in old galanin-overexpressing mice.

    PubMed

    Pirondi, S; D'Intino, G; Gusciglio, M; Massella, A; Giardino, L; Kuteeva, E; Ogren, S-O; Hökfelt, T; Calzà, L

    2007-03-23

    The cholinergic forebrain system is involved in learning and memory, and its age-dependent decline correlates with a decrease in cognitive performance. Since the neuropeptide galanin participates in cholinergic neuron regulation, we have studied 19- to 23-month-old male mice overexpressing galanin under the platelet-derived growth factor B promoter (GalOE) and wild-type (WT) littermates by monitoring behavioral, neurochemical and morphological/histochemical parameters. In the Morris water maze test, old transgenic animals showed a significant impairment in escape latency in the hidden platform test compared to age-matched WT animals. The morphological/histochemical studies revealed that cholinergic neurons in the basal forebrain display a slight, age- but not genotype-related, alteration in choline acetyltransferase- (ChAT) immunoreactivity. The neurochemical studies showed an age-related decline in ChAT activity in the cerebral cortex of all mice, whereas in the hippocampal formation this effect was seen in GalOE but not WT animals. Expression of BDNF mRNA in the hippocampal formation, as evaluated by RT-PCR, was reduced in old animals; no age- or genotype-induced variations in NGF mRNA expression were observed. These data suggest that galanin overexpression further accentuates the age-related decline of the cholinergic system activity in male mice, resulting in impairment of water maze performance in old animals.

  5. Cholinergic involvement in vascular and glucoregulatory actions of insulin in rats.

    PubMed

    Lévesque, Martin; Santuré, Marta; Pitre, Maryse; Nadeau, André; Bachelard, Hélène

    2006-02-01

    This study was designed to test the glucose metabolic and vasodilator actions of insulin in rats and its relation to cholinergic system-dependent mechanisms. The first group of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique carried out in the absence or presence of atropine. The second group of rats was used to determine the cholinergic contribution to in vivo insulin-mediated glucose utilization in individual muscles. Glucose uptake was examined by using [(3)H]2-deoxy-D-glucose. Muscarinic cholinergic blockade was found to significantly (P = 0.002) reduce insulin sensitivity and to completely abrogate the renal (P = 0.008) and hindquarter (P = 0.02) vasodilator responses to euglycemic infusion of insulin. A significant reduction in insulin-stimulated in vivo glucose uptake was also noted in soleus (P = 0.006), quadriceps (P = 0.03), gastrocnemius (P = 0.02), and extensor digitorum longus (EDL) (P = 0.001) muscles, when insulin was infused at a rate of 4 mU . kg(-1) . min(-1), whereas at the rate of 16 mU . kg(-1) . min(-1), a significant reduction in glucose uptake was only observed in EDL (P = 0.03) and quadriceps (P = 0.01) muscles. Together, these results demonstrate a potential role for cholinergic involvement with physiological insulin actions in glucose clearance and blood flow regulation in rats.

  6. The effects of caffeine on the cholinergic system.

    PubMed

    Pohanka, Miroslav

    2014-01-01

    Caffeine is a secondary metabolite of tea and coffee plants. It is the active psychostimulant ingredient of widely consumed beverages, chocolate and some drugs as well. The major pathways for caffeine including interaction with adenosine receptors have been identified but caffeine has several minor pathways as well that remain poorly understood including the cholinergic system. Given the role of caffeine in the cholinergic system, some molecular targets have been tracked and a mechanism of its action has been proposed in research studies. However, the biological effect of caffeine on the cholinergic system is not completely understood. The present review focuses on the role of caffeine in the cholinergic system.

  7. Central Cholinergic Neurons Are Rapidly Recruited by Reinforcement Feedback.

    PubMed

    Hangya, Balázs; Ranade, Sachin P; Lorenc, Maja; Kepecs, Adam

    2015-08-27

    Basal forebrain cholinergic neurons constitute a major neuromodulatory system implicated in normal cognition and neurodegenerative dementias. Cholinergic projections densely innervate neocortex, releasing acetylcholine to regulate arousal, attention, and learning. However, their precise behavioral function is poorly understood because identified cholinergic neurons have never been recorded during behavior. To determine which aspects of cognition their activity might support, we recorded cholinergic neurons using optogenetic identification in mice performing an auditory detection task requiring sustained attention. We found that a non-cholinergic basal forebrain population-but not cholinergic neurons-were correlated with trial-to-trial measures of attention. Surprisingly, cholinergic neurons responded to reward and punishment with unusual speed and precision (18 ± 3 ms). Cholinergic responses were scaled by the unexpectedness of reinforcement and were highly similar across neurons and two nuclei innervating distinct cortical areas. These results reveal that the cholinergic system broadcasts a rapid and precisely timed reinforcement signal, supporting fast cortical activation and plasticity. PMID:26317475

  8. Attentional Control of Gait and Falls: Is Cholinergic Dysfunction a Common Substrate in the Elderly and Parkinson’s Disease?

    PubMed Central

    Pelosin, Elisa; Ogliastro, Carla; Lagravinese, Giovanna; Bonassi, Gaia; Mirelman, Anat; Hausdorff, Jeffrey M.; Abbruzzese, Giovanni; Avanzino, Laura

    2016-01-01

    The aim of this study was to address whether deficits in the central cholinergic activity may contribute to the increased difficulty to allocate attention during gait in the elderly with heightened risk of falls. We recruited 50 participants with a history of two or more falls (33 patients with Parkinson’s Disease and 17 older adults) and 14 non-fallers age-matched adults. Cholinergic activity was estimated by means of short latency afferent inhibition (SAI), a transcranial magnetic stimulation (TMS) technique that assesses an inhibitory circuit in the sensorimotor cortex and is regarded as a global marker of cholinergic function in the brain. Increased difficulty to allocate attention during gait was evaluated by measuring gait performance under single and dual-task conditions. Global cognition was also assessed. Results showed that SAI was reduced in patients with PD than in the older adults (fallers and non-fallers) and in older adults fallers with respect to non-fallers. Reduction in SAI indicates less inhibition i.e., less cholinergic activity. Gait speed was reduced in the dual task gait compared to normal gait only in our faller population and changes in gait speed under dual task significantly correlated with the mean value of SAI. This association remained significant after adjusting for cognitive status. These findings suggest that central cholinergic activity may be a predictor of change in gait characteristics under dual tasking in older adults and PD fallers independently of cognitive status. PMID:27242515

  9. Defect-induced enhanced photocatalytic activities of reduced α-Fe2O3 nanoblades

    NASA Astrophysics Data System (ADS)

    Feng, Honglei; Wang, Yiqian; Wang, Chao; Diao, Feiyu; Zhu, Wenhui; Mu, Peng; Yuan, Lu; Zhou, Guangwen; Rosei, Federico

    2016-07-01

    Bicrystalline α-Fe2O3 nanoblades (NBs) synthesized by thermal oxidation of iron foils were reduced in vacuum, to study the effect of reduction treatment on microstructural changes and photocatalytic properties. After the vacuum reduction, most bicrystalline α-Fe2O3 NBs transform into single-layered NBs, which contain more defects such as oxygen vacancies, perfect dislocations and dense pores. By comparing the photodegradation capability of non-reduced and reduced α-Fe2O3 NBs over model dye rhodamine B (RhB) in the presence of hydrogen peroxide, we find that vacuum-reduction induced microstructural defects can significantly enhance the photocatalytic efficiency. Even after 10 cycles, the reduced α-Fe2O3 NBs still show a very high photocatalytic activity. Our results demonstrate that defect engineering is a powerful tool to enhance the photocatalytic performance of nanomaterials.

  10. Is the input to a GABAergic or cholinergic synapse the sole asymmetry in rabbit's retinal directional selectivity?

    PubMed

    Grzywacz, N M; Tootle, J S; Amthor, F R

    1997-01-01

    We examined contrast, direction of motion, and concentration dependencies of the effects of GABAergic and cholinergic antagonists, and anticholinesterases on responses to movement of On-Off directionally selective (DS) ganglion cells of the rabbit's retina. The drugs tested were curare and hexamethonium bromide (cholinergic antagonists), physostigmine (anticholinesterase), and picrotoxin (GABAergic antagonist). They all reduced the cells' directional selectivity, while maintaining their preferred-null axis. However, cholinergic antagonists did not block directional selectivity completely even at saturating concentrations. The failure to eliminate directional selectivity was probably not due to an incomplete blockade of cholinergic receptors. In a extension of a Masland and Ames (1976) experiment, saturating concentrations of antagonists blocked the effects of exogenous acetylcholine or nicotine applied during synaptic blockade. Consequently, a noncholinergic pathway may be sufficient to account for at least some directional selectivity. This putative pathway interacts with the cholinergic pathway before spike generation, since physostigmine eliminated directional selectivity at contrasts lower than those saturating responses. This elimination apparently resulted from cholinergic-induced saturation, since reduction of contrast restored directional selectivity. Under picrotoxin, directional selectivity was lost in 33% of the cells regardless of contrast. However, 47% maintained their preferred direction despite saturating concentrations of picrotoxin, and 20% reversed the preferred and null directions. Therefore, models based solely on a GABAergic implementation of Barlow and Levick's asymmetric-inhibition model or solely on a cholinergic implementation of asymmetric-excitation models are not complete models of directional selectivity in the rabbit. We propose an alternate model for this retinal property. PMID:9057267

  11. Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder.

    PubMed

    Silva-Ramos, M; Silva, I; Faria, M; Magalhães-Cardoso, M T; Correia, J; Ferreirinha, F; Correia-de-Sá, P

    2015-12-01

    This study was designed to investigate whether reduced adenosine formation linked to deficits in extracellular ATP hydrolysis by NTPDases contributes to detrusor neuromodulatory changes associated with bladder outlet obstruction in men with benign prostatic hyperplasia (BPH). The kinetics of ATP catabolism and adenosine formation as well as the role of P1 receptor agonists on muscle tension and nerve-evoked [(3)H]ACh release were evaluated in mucosal-denuded detrusor strips from BPH patients (n = 31) and control organ donors (n = 23). The neurogenic release of ATP and [(3)H]ACh was higher (P < 0.05) in detrusor strips from BPH patients. The extracellular hydrolysis of ATP and, subsequent, adenosine formation was slower (t (1/2) 73 vs. 36 min, P < 0.05) in BPH detrusor strips. The A(1) receptor-mediated inhibition of evoked [(3)H]ACh release by adenosine (100 μM), NECA (1 μM), and R-PIA (0.3 μM) was enhanced in BPH bladders. Relaxation of detrusor contractions induced by acetylcholine required 30-fold higher concentrations of adenosine. Despite VAChT-positive cholinergic nerves exhibiting higher A(1) immunoreactivity in BPH bladders, the endogenous adenosine tonus revealed by adenosine deaminase is missing. Restoration of A1 inhibition was achieved by favoring (1) ATP hydrolysis with apyrase (2 U mL(-1)) or (2) extracellular adenosine accumulation with dipyridamole or EHNA, as these drugs inhibit adenosine uptake and deamination, respectively. In conclusion, reduced ATP hydrolysis leads to deficient adenosine formation and A(1) receptor-mediated inhibition of cholinergic nerve activity in the obstructed human bladder. Thus, we propose that pharmacological manipulation of endogenous adenosine levels and/or A(1) receptor activation might be useful to control bladder overactivity in BPH patients.

  12. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology

    PubMed Central

    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S.; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  13. Impact of basal forebrain cholinergic inputs on basolateral amygdala neurons.

    PubMed

    Unal, Cagri T; Pare, Denis; Zaborszky, Laszlo

    2015-01-14

    In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc) neurons send a dense projection to the basolateral nucleus of the amygdala (BLA). In this study, we investigated the effect of near physiological acetylcholine release on BLA neurons using optogenetic tools and in vitro patch-clamp recordings. Adult transgenic mice expressing cre-recombinase under the choline acetyltransferase promoter were used to selectively transduce BFc neurons with channelrhodopsin-2 and a reporter through the injection of an adeno-associated virus. Light-induced stimulation of BFc axons produced different effects depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking interneurons. In principal BLA neurons, two different effects were elicited depending on their activity level. When principal BLA neurons were quiescent or made to fire at low rates by depolarizing current injection, light-induced activation of BFc axons elicited muscarinic IPSPs. In contrast, with stronger depolarizing currents, eliciting firing above ∼ 6-8 Hz, these muscarinic IPSPs lost their efficacy because stimulation of BFc inputs prolonged current-evoked afterdepolarizations. All the effects observed in principal neurons were dependent on muscarinic receptors type 1, engaging different intracellular mechanisms in a state-dependent manner. Overall, our results suggest that acetylcholine enhances the signal-to-noise ratio in principal BLA neurons. Moreover, the cholinergic engagement of afterdepolarizations may contribute to the formation of stimulus associations during fear-conditioning tasks where the timing of conditioned and unconditioned stimuli is not optimal for the induction of synaptic plasticity.

  14. Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

    SciTech Connect

    Winocour, P.D.; Colwell, J.A.

    1985-05-01

    Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, the authors used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. The authors conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis.

  15. Enhanced natural attenuation of BTEX in the nitrate-reducing environment by different electron acceptors.

    PubMed

    Zhao, Yongsheng; Qu, Dan; Hou, Zhimin; Zhou, Rui

    2015-01-01

    Enhancing natural attenuation of benzene, toluene, ethylbenzene, and xylene (BTEX) in groundwater is a potential remediation technology. This study focused on selecting appropriate electron acceptors to promote BTEX degradation in a nitrate-reducing environment. Nitrate-reducing soil was obtained from simulated BTEX-contaminated column. Enhancing experiments were conducted in the microcosm with nitrate-reducing material and simulated BTEX-polluted groundwater to investigate the promoting feasibility of adding dissolved oxygen (DO), nitrate, chelated Fe(III), and sulphate as electron acceptors. The concentrations of BTEX, electron acceptors, and their reducing products were measured. The order of promoting BTEX degradation with four electron acceptors was nitrate>sulphate>chelated Fe(III)>DO, and the first-order decay coefficients were 0.0432, 0.0333, 0.0240, and 0.0155, respectively. Nitrate, sulphate, and chelated Fe(III) enhanced attenuation. Nitrate was the most effective electron acceptor under nitrate-reducing conditions. Selecting proper electron acceptor is significant in promoting BTEX degradation according to the biogeochemical characteristics of local underground environment.

  16. Enhanced Hot-Carrier Luminescence in Multilayer Reduced Graphene Oxide Nanospheres

    PubMed Central

    Chen, Qi; Zhang, Chunfeng; Xue, Fei; Zhou, Yong; Li, Wei; Wang, Ye; Tu, Wenguang; Zou, Zhigang; Wang, Xiaoyong; Xiao, Min

    2013-01-01

    We report a method to promote photoluminescence emission in graphene materials by enhancing carrier scattering instead of directly modifying band structure in multilayer reduced graphene oxide (rGO) nanospheres. We intentionally curl graphene layers to form nanospheres by reducing graphene oxide with spherical polymer templates to manipulate the carrier scattering. These nanospheres produce hot-carrier luminescence with more than ten-fold improvement of emission efficiency as compared to planar nanosheets. With increasing excitation power, hot-carrier luminescence from nanospheres exhibits abnormal spectral redshift with dynamic feature associated to the strengthened electron-phonon coupling. These experimental results can be well understood by considering the screened Coulomb interactions. With increasing carrier density, the reduced screening effect promotes carrier scattering which enhances hot-carrier emission from such multilayer rGO nanospheres. This carrier-scattering scenario is further confirmed by pump-probe measurements. PMID:23897010

  17. Nipecotic acid ethyl ester: a cholinergic agonist that may differentiate muscarinic receptor subtypes

    SciTech Connect

    Zorn, S.H.; Duman, R.S.; Enna, S.J.; Krogsgaard-Larsen, P.; Micheletti, R.; Giraldo, E.; Giachetti, A.

    1986-03-05

    Reports indicate that nipecotic acid ethyl ester (NAEE) displays cholinomimetic properties in vivo. In the present study a series of physiological and biochemical tests were conducted to characterize this action. NAEE had a negative inotropic effect on the guinea pig atrium, and stimulated contraction of the guinea pig ileum and isolated mouse stomach strip at concentrations similar to bethanechol (BCH). The atrial and ilial effects were reversed by atropine. Unlike BCH, NAEE had no effect on basal acid secretion in the isolated mouse stomach at concentrations < 100 ..mu..M. NAEE was more potent than carbachol (CCH) in displacing /sup 3/H-ONB binding from rat brain membranes. The potency of NAEE to inhibit antagonist binding in rat heart membranes was enhanced by Mg/sup + +/ (Hill coefficient < 1.0) and reduced by Gpp(NH)p. Like CCH, NAEE inhibited GTP-stimulated adenylate cyclase in rat brain striatal membranes. As compared to CCH, NAEE had little effect (< 5%) as a stimulator of inositol phosphate (IP) production in rat brain slices. The results indicate that NAEE is a direct-acting muscarinic receptor agonist. Moreover, its differential effects on acid secretion, IP accumulation, and adenylate cyclase suggest that it may be useful for defining cholinergic receptor subclasses.

  18. Pedunculopontine cholinergic cell loss in hallucinating Parkinson disease patients but not in dementia with Lewy bodies patients.

    PubMed

    Hepp, Dagmar Hyacintha; Ruiter, A M; Galis, Y; Voorn, P; Rozemuller, A J M; Berendse, H W; Foncke, E M J; van de Berg, W D J

    2013-12-01

    There is a cholinergic deficit in Parkinson disease (PD) and in dementia with Lewy bodies (DLB) that plays a role in a variety of clinical symptoms, including visual hallucinations (VH). The aim of this study was to assess cholinergic neuronal loss and PD and Alzheimer disease pathology in the pedunculopontine nucleus pars compacta (PPNc) of PD and DLB patients with VH. Postmortem brainstem tissue samples of 9 clinically diagnosed and pathologically confirmed PD patients with VH, 9 DLB patients with VH, and 9 age- and sex-matched nondemented controls were obtained from the Netherlands Brain Bank. Using a morphometric approach, we estimated the density of cholinergic neurons in the PPNc and determined the local load of α-synuclein-immunoreactive Lewy pathology, neurofibrillary tangles, and β-amyloid plaques. Cholinergic cell density in the PPNc was significantly lower in PD compared with DLB patients with VH (-39%, p < 0.001) and controls (-41%, p < 0.001). Alpha-synuclein load was higher in PD, whereas β-amyloid plaque pathology was more pronounced in DLB patients. The mean cell density in DLB patients was not significantly reduced compared with that in controls. These results may indicate different patterns of degeneration of cholinergic output structures in PD and DLB.

  19. Pedunculopontine cholinergic cell loss in hallucinating Parkinson disease patients but not in dementia with Lewy bodies patients.

    PubMed

    Hepp, Dagmar Hyacintha; Ruiter, A M; Galis, Y; Voorn, P; Rozemuller, A J M; Berendse, H W; Foncke, E M J; van de Berg, W D J

    2013-12-01

    There is a cholinergic deficit in Parkinson disease (PD) and in dementia with Lewy bodies (DLB) that plays a role in a variety of clinical symptoms, including visual hallucinations (VH). The aim of this study was to assess cholinergic neuronal loss and PD and Alzheimer disease pathology in the pedunculopontine nucleus pars compacta (PPNc) of PD and DLB patients with VH. Postmortem brainstem tissue samples of 9 clinically diagnosed and pathologically confirmed PD patients with VH, 9 DLB patients with VH, and 9 age- and sex-matched nondemented controls were obtained from the Netherlands Brain Bank. Using a morphometric approach, we estimated the density of cholinergic neurons in the PPNc and determined the local load of α-synuclein-immunoreactive Lewy pathology, neurofibrillary tangles, and β-amyloid plaques. Cholinergic cell density in the PPNc was significantly lower in PD compared with DLB patients with VH (-39%, p < 0.001) and controls (-41%, p < 0.001). Alpha-synuclein load was higher in PD, whereas β-amyloid plaque pathology was more pronounced in DLB patients. The mean cell density in DLB patients was not significantly reduced compared with that in controls. These results may indicate different patterns of degeneration of cholinergic output structures in PD and DLB. PMID:24226265

  20. Cholinergic interneurons control local circuit activity and cocaine conditioning.

    PubMed

    Witten, Ilana B; Lin, Shih-Chun; Brodsky, Matthew; Prakash, Rohit; Diester, Ilka; Anikeeva, Polina; Gradinaru, Viviana; Ramakrishnan, Charu; Deisseroth, Karl

    2010-12-17

    Cholinergic neurons are widespread, and pharmacological modulation of acetylcholine receptors affects numerous brain processes, but such modulation entails side effects due to limitations in specificity for receptor type and target cell. As a result, causal roles of cholinergic neurons in circuits have been unclear. We integrated optogenetics, freely moving mammalian behavior, in vivo electrophysiology, and slice physiology to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of local neurons, these cholinergic cells have dominant control roles, exerting powerful modulation of circuit activity. Furthermore, these neurons could be activated by cocaine, and silencing this drug-induced activity during cocaine exposure (despite the fact that the manipulation of the cholinergic interneurons was not aversive by itself) blocked cocaine conditioning in freely moving mammals.

  1. Manipulation of immunodominant dengue virus E protein epitopes reduces potential antibody-dependent enhancement

    PubMed Central

    2012-01-01

    Background Dengue viruses (DENV) are the most important arboviruses of humans and cause significant disease. Infection with DENV elicits antibody responses to the envelope glycoprotein, predominantly against immunodominant, cross-reactive, weakly-neutralizing epitopes. These weakly-neutralizing antibodies are implicated in enhancing infection via Fcγ receptor bearing cells and can lead to increased viral loads that are associated with severe disease. Here we describe results from the development and testing of cross-reactivity reduced DENV-2 DNA vaccine candidates that contain substitutions in immunodominant B cell epitopes of the fusion peptide and domain III of the envelope protein. Results Cross-reactivity reduced and wild-type vaccine candidates were similarly immunogenic in outbred mice and elicited high levels of neutralizing antibody, however mice immunized with cross-reactivity reduced vaccines produced significantly reduced levels of immunodominant cross-reactive antibodies. Sera from mice immunized with wild-type, fusion peptide-, or domain III- substitution containing vaccines enhanced heterologous DENV infection in vitro, unlike sera from mice immunized with a vaccine containing a combination of both fusion peptide and domain III substitutions. Passive transfer of immune sera from mice immunized with fusion peptide and domain III substitutions also reduced the development of severe DENV disease in AG129 mice when compared to mice receiving wild type immune sera. Conclusions Reducing cross-reactivity in the envelope glycoprotein of DENV may be an approach to improve the quality of the anti-DENV immune response. PMID:22709350

  2. Hypothalamic proopiomelanocortin (POMC) neurons have a cholinergic phenotype.

    PubMed

    Meister, Björn; Gömüç, Burçak; Suarez, Elisabet; Ishii, Yuko; Dürr, Katrin; Gillberg, Linda

    2006-11-01

    Neuronal networks originating in the hypothalamic arcuate nucleus play fundamental roles in the control of energy balance. Neuropeptide Y (NPY)-producing neurons in the arcuate nucleus stimulate food intake, whereas arcuate nucleus neurons that release the proopiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone (alpha-MSH) potently reduce food intake. Relatively little attention has been focused on classical neurotransmitters in regulation of food intake. Here, we have investigated the potential presence of acetylcholine (ACh) in NPY- and POMC-containing neuronal populations of the arcuate nucleus. Antisera to proteins required for cholinergic neurotransmission, including choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT), were employed in double-labeling immunohistochemical experiments. In colchicine-treated rats, ChAT- and VAChT-immunopositive cell bodies were located in the ventral aspect of the arcuate nucleus. ChAT and VAChT immunoreactivities were demonstrated in alpha-MSH- and cocaine- and amphetamine-regulated transcript (CART)-containing cell bodies of the arcuate nucleus, whereas cell bodies containing NPY or agouti-related peptide (AGRP) were distinct from VAChT-immunoreactive neuronal perikarya. VAChT immunoreactivity was also present in a large number of alpha-MSH-containing nerve fiber varicosities throughout the central nervous system. In the commissural part of the nucleus tractus solitarius, no alpha-MSH-containing cell bodies were found to have ChAT or VAChT immunoreactivity. The presence of markers for cholinergic neurotransmission in a subpopulation of hypothalamic POMC/CART neurons suggests co-release of ACh with peptides derived from the POMC precursor and CART. The results indicate a role for ACh in control of energy balance, mediating the effects of peripheral hormones such as leptin and insulin.

  3. Estrogen-Cholinergic Interactions: Implications for Cognitive Aging

    PubMed Central

    Newhouse, Paul; Dumas, Julie

    2015-01-01

    While many studies in humans have investigated the effects of estrogen and hormone therapy on cognition, potential neurobiological correlates of these effects have been less well studied. An important site of action for estrogen in the brain is the cholinergic system. Several decades of research support the critical role of CNS cholinergic systems in cognition in humans, particularly in learning and memory formation and attention. In humans, the cholinergic system has been implicated in many aspects of cognition including the partitioning of attentional resources, working memory, inhibition of irrelevant information, and improved performance on effort-demanding tasks. Studies support the hypothesis that estradiol helps to maintain aspects of attention and verbal and visual memory. Such cognitive domains are exactly those modulated by cholinergic systems and extensive basic and preclinical work over the past several decades has clearly shown that basal forebrain cholinergic systems are dependent on estradiol support for adequate functioning. This paper will review recent human studies from our laboratories and others that have extended preclinical research examining estrogen-cholinergic interactions to humans. Studies examined include estradiol and cholinergic antagonist reversal studies in normal older women, examinations of the neural representations of estrogen-cholinergic interactions using functional brain imaging, and studies of the ability of selective estrogen receptor modulators such as tamoxifen to interact with cholinergic-mediated cognitive performance. We also discuss the implications of these studies for the underlying hypotheses of cholinergic-estrogen interactions and cognitive aging, and indications for prophylactic and therapeutic potential that may exploit these effects. PMID:26187712

  4. Memory improving actions of gabapentin in mice: possible involvement of central muscarinic cholinergic mechanism.

    PubMed

    Boccia, M M; Acosta, G B; Baratti, C M

    2001-10-01

    Male CF-1 mice were tested 48 h after training on a one trial step-through inhibitory avoidance task. Immediately post-training, intraperitoneal (i.p.) injections of the antiepileptic gabapentin (1-(aminomethyl) cyclohexaneacetic acid) (GBP, 10 mg/kg) enhanced retention performance. The effect was prevented by atropine, a central muscarinic cholinergic receptor antagonist (0.5 mg/kg, i.p.) administered after training but 10 min prior to GBP treatment. In contrast, neither methylatropine (0.5 mg/kg, i.p.), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training GBP on retention performance. Low subeffective doses of the central acting anticholinesterase physostigmine (35 mg/kg, i.p.) administered immediately after training, and GBP (5 mg/kg, i.p.), given 10 min after training, significantly enhanced retention performance. The effects of GBP (5 mg/kg, i.p.) were not influenced by the peripherally acting anticholinesterase neostigmine (150 mg/kg, i.p.). Considered together, these findings suggest a disinhibitory action of GBP on the activity of central muscarinic cholinergic mechanisms that are involved in memory consolidation. PMID:11578817

  5. Memory improving actions of gabapentin in mice: possible involvement of central muscarinic cholinergic mechanism.

    PubMed

    Boccia, M M; Acosta, G B; Baratti, C M

    2001-10-01

    Male CF-1 mice were tested 48 h after training on a one trial step-through inhibitory avoidance task. Immediately post-training, intraperitoneal (i.p.) injections of the antiepileptic gabapentin (1-(aminomethyl) cyclohexaneacetic acid) (GBP, 10 mg/kg) enhanced retention performance. The effect was prevented by atropine, a central muscarinic cholinergic receptor antagonist (0.5 mg/kg, i.p.) administered after training but 10 min prior to GBP treatment. In contrast, neither methylatropine (0.5 mg/kg, i.p.), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training GBP on retention performance. Low subeffective doses of the central acting anticholinesterase physostigmine (35 mg/kg, i.p.) administered immediately after training, and GBP (5 mg/kg, i.p.), given 10 min after training, significantly enhanced retention performance. The effects of GBP (5 mg/kg, i.p.) were not influenced by the peripherally acting anticholinesterase neostigmine (150 mg/kg, i.p.). Considered together, these findings suggest a disinhibitory action of GBP on the activity of central muscarinic cholinergic mechanisms that are involved in memory consolidation.

  6. Augmentation of cholinergic-mediated amylase release by forskolin in mouse parotid gland

    SciTech Connect

    Watson, E.L.; Singh, J.C.; Jacobson, K.L.

    1985-12-30

    Cholinergic-mediated amylase release in mouse parotid acini was augmented by forskolin; the potency but not the maximal response to carbachol was altered. Amylase released by carbachol plus forskolin was dependent on extracellular calcium and was mimicked by the calcium ionophore, A23187 plus forskolin. Forskolin was also shown to enhance carbachol-stimulated /sup 45/Ca/sup 2 +/ uptake into isolated acini. Hydroxylamine, nitroprusside, and 8-bromo-c-GMP each in combination with forskolin mimicked the effects of carbachol plus forskolin on amylase release. In the presence of carbachol (10/sup -8/M) forskolin did not augment c-AMP levels. However, in the presence of carbachol (5 x 10/sup -7/ M) or hydroxylamine (50 ..mu..M) forskolin did significantly augment c-AMP accumulation. These results suggest that calcium and c-GMP may mediate the augmentation of cholinergic-mediated amylase release by effects on c-AMP metabolism. 21 references, 1 figure, 3 tables.

  7. Neuropharmacology of memory consolidation and reconsolidation: Insights on central cholinergic mechanisms.

    PubMed

    Blake, M G; Krawczyk, M C; Baratti, C M; Boccia, M M

    2014-01-01

    Central cholinergic system is critically involved in all known memory processes. Endogenous acetylcholine release by cholinergic neurons is necessary for modulation of acquisition, encoding, consolidation, reconsolidation, extinction, retrieval and expression. Experiments from our laboratory are mainly focused on elucidating the mechanisms by which acetylcholine modulates memory processes. Blockade of hippocampal alpha-7-nicotinic receptors (α7-nAChRs) with the antagonist methyllycaconitine impairs memory reconsolidation. However, the administration of a α7-nAChR agonist (choline) produce a paradoxical modulation, causing memory enhancement in mice trained with a weak footshock, but memory impairment in animals trained with a strong footshock. All these effects are long-lasting, and depend on the age of the memory trace. This review summarizes and discusses some of our recent findings, particularly regarding the involvement of α7-nAChRs on memory reconsolidation.

  8. Cholinergic vasodilator mechanism in human fingers

    SciTech Connect

    Coffman, J.D.; Cohen, R.A.

    1987-03-01

    The effect of a cholinergic agonist and antagonist on finger blood flow (FBF) was studied in 10 normal subjects. Total finger blood flow was measured by venous occlusion, air plethysmography, and capillary blood flow (FCF) by the disappearance rate of a radio-isotope from a fingertip injection. Methacholine in doses of 10-80 ..mu..g/min was given by constant infusion via a brachial artery catheter. Average FBF and vascular resistance were not significantly affected. However, the half time (t/sub 1/2/) of the disappearance rate decreased from 50.8 +/- 13.4 to 11.1 +/- 1.5 min; a decrease occurred in all subjects. In seven subjects, atropine (0.2 mg) had no affect alone but inhibited the effect of methacholine on FCF and prevented the redness and sweating of the forearm and hand that occurs with this agent. This study demonstrates a muscarinic cholinergic vasodilator mechanism in the fingertip that uniquely increase capillary blood flow.

  9. Reducing statistics anxiety and enhancing statistics learning achievement: effectiveness of a one-minute strategy.

    PubMed

    Chiou, Chei-Chang; Wang, Yu-Min; Lee, Li-Tze

    2014-08-01

    Statistical knowledge is widely used in academia; however, statistics teachers struggle with the issue of how to reduce students' statistics anxiety and enhance students' statistics learning. This study assesses the effectiveness of a "one-minute paper strategy" in reducing students' statistics-related anxiety and in improving students' statistics-related achievement. Participants were 77 undergraduates from two classes enrolled in applied statistics courses. An experiment was implemented according to a pretest/posttest comparison group design. The quasi-experimental design showed that the one-minute paper strategy significantly reduced students' statistics anxiety and improved students' statistics learning achievement. The strategy was a better instructional tool than the textbook exercise for reducing students' statistics anxiety and improving students' statistics achievement.

  10. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    SciTech Connect

    Srivastava, Pranay; Yadav, Rajesh S.; Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S.; Dwivedi, Hari N.; Pant, Aditiya B.; Khanna, Vinay K.

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  11. Chagas’ disease parasite-derived neurotrophic factor activates cholinergic gene expression in neuronal PC12 cells

    PubMed Central

    Akpan, Nsikan; Caradonna, Kacey; Chuenkova, Marina V.; PereiraPerrin, Mercio

    2008-01-01

    A parasite-derived neurotrophic factor (PDNF) produced by the Chagas’ disease parasite Trypanosoma cruzi binds nerve growth factor (NGF) receptor TrkA, increasing receptor autophosphorylation, activating phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK/Erk) pathways, and transcription factor CREB. The end-result is enhanced survival and neuritogenesis of various types of neurons. PDNF also enhances the expression and activity of tyrosine hydroxylase, a rate limiting enzyme in the synthesis of dopamine and other catecholamine neurotransmitters. It remains unknown, however, if PDNF alters expression and metabolism of acetylcholine (ACh), a neurotransmitter thought to play a role in Chagas’ disease progression. Here we demonstrate that PDNF stimulates mRNA and protein expression of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT), which are critical for synthesis and storage of ACh. Stimulation requires functional TrkA because it did not occur in cell mutants that lack the receptor and in TrkA-expressing wild-type cells treated with K252a, an inhibitor of TrkA kinase activity. It also requires TrkA-dependent PI3K and MAPK/Erk signaling pathways because PDNF stimulation of cholinergic transcripts is abolished by specific pharmacological inhibitors. Furthermore, the cholinergic actions of PDNF were reproduced by PDNF-expressing extracellular T. cruzi trypomastigotes at the start of host cell invasion. In contrast, host cells bearing intracellular T. cruzi showed decreased, rather than increased, cholinergic gene expression. These results suggest that T. cruzi invasion of the nervous system alters cholinergic gene expression and that could play a role in neuropathology, and/or lack thereof, in Chagas’ disease patients. PMID:18502403

  12. Chagas' disease parasite-derived neurotrophic factor activates cholinergic gene expression in neuronal PC12 cells.

    PubMed

    Akpan, Nsikan; Caradonna, Kacey; Chuenkova, Marina V; PereiraPerrin, Mercio

    2008-06-27

    A parasite-derived neurotrophic factor (PDNF) produced by the Chagas' disease parasite Trypanosoma cruzi binds nerve growth factor (NGF) receptor TrkA, increasing receptor autophosphorylation, and activating phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK/Erk) pathways, and transcription factor CREB. The end-result is enhanced survival and neuritogenesis of various types of neurons. PDNF also enhances the expression and activity of tyrosine hydroxylase, a rate limiting enzyme in the synthesis of dopamine and other catecholamine neurotransmitters. It remains unknown, however, if PDNF alters expression and metabolism of acetylcholine (ACh), a neurotransmitter thought to play a role in Chagas' disease progression. Here we demonstrate that PDNF stimulates mRNA and protein expression of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT), which are critical for synthesis and storage of ACh. Stimulation requires functional TrkA because it did not occur in cell mutants that lack the receptor and in TrkA-expressing wild-type cells treated with K252a, an inhibitor of TrkA kinase activity. It also requires TrkA-dependent PI3K and MAPK/Erk signaling pathways because PDNF stimulation of cholinergic transcripts is abolished by specific pharmacological inhibitors. Furthermore, the cholinergic actions of PDNF were reproduced by PDNF-expressing extracellular T. cruzi trypomastigotes at the start of host cell invasion. In contrast, host cells bearing intracellular T. cruzi showed decreased, rather than increased, cholinergic gene expression. These results suggest that T. cruzi invasion of the nervous system alters cholinergic gene expression and that could play a role in neuropathology, and/or lack thereof, in Chagas' disease patients. PMID:18502403

  13. Electrochemically reduced graphene oxide on silicon nanowire arrays for enhanced photoelectrochemical hydrogen evolution.

    PubMed

    Meng, Huan; Fan, Ke; Low, Jingxiang; Yu, Jiaguo

    2016-09-21

    Photoelectrochemical (PEC) water splitting into hydrogen and oxygen by sunlight is a promising approach to solve energy and environmental problems. In this work, silicon nanowire arrays (SiNWs) photocathodes decorated with reduced graphene oxide (rGO) for PEC water splitting were successfully prepared by a flexible and scalable electrochemical reduction method. The SiNWs photocathode with the optimized rGO decoration (SiNWs/rGO20) shows an enhanced activity with a much higher photocurrent density and significantly positive shift of onset potential compared to the bare SiNWs arrays for the hydrogen evolution reaction (HER). The enhanced PEC activity is ascribed to the high electrical conductivity of rGO and improved separation of the photogenerated charge carriers. This work not only demonstrates a facile, rapid and tunable electrochemical reduction method to produce rGO, but also exhibits an efficient protocol to enhance the PEC water splitting of silicon-based materials. PMID:27461187

  14. Electrochemically reduced graphene oxide on silicon nanowire arrays for enhanced photoelectrochemical hydrogen evolution.

    PubMed

    Meng, Huan; Fan, Ke; Low, Jingxiang; Yu, Jiaguo

    2016-09-21

    Photoelectrochemical (PEC) water splitting into hydrogen and oxygen by sunlight is a promising approach to solve energy and environmental problems. In this work, silicon nanowire arrays (SiNWs) photocathodes decorated with reduced graphene oxide (rGO) for PEC water splitting were successfully prepared by a flexible and scalable electrochemical reduction method. The SiNWs photocathode with the optimized rGO decoration (SiNWs/rGO20) shows an enhanced activity with a much higher photocurrent density and significantly positive shift of onset potential compared to the bare SiNWs arrays for the hydrogen evolution reaction (HER). The enhanced PEC activity is ascribed to the high electrical conductivity of rGO and improved separation of the photogenerated charge carriers. This work not only demonstrates a facile, rapid and tunable electrochemical reduction method to produce rGO, but also exhibits an efficient protocol to enhance the PEC water splitting of silicon-based materials.

  15. Enhancing Slow Wave Sleep with Sodium Oxybate Reduces the Behavioral and Physiological Impact of Sleep Loss

    PubMed Central

    Walsh, James K.; Hall-Porter, Janine M.; Griffin, Kara S.; Dodson, Ehren R.; Forst, Elizabeth H.; Curry, Denise T.; Eisenstein, Rhody D.; Schweitzer, Paula K.

    2010-01-01

    Study Objectives: To investigate whether enhancement of slow wave sleep (SWS) with sodium oxybate reduces the impact of sleep deprivation. Design: Double-blind, parallel group, placebo-controlled design Setting: Sleep research laboratory Participants: Fifty-eight healthy adults (28 placebo, 30 sodium oxybate), ages 18-50 years. Interventions: A 5-day protocol included 2 screening/baseline nights and days, 2 sleep deprivation nights, each followed by a 3-h daytime (08:00-11:00) sleep opportunity and a recovery night. Sodium oxybate or placebo was administered prior to each daytime sleep period. Multiple sleep latency test (MSLT), psychomotor vigilance test (PVT), Karolinska Sleepiness Scale (KSS), and Profile of Mood States were administered during waking hours. Measurements and Results: During daytime sleep, the sodium oxybate group had more SWS, more EEG spectral power in the 1-9 Hz range, and less REM. Mean MSLT latency was longer for the sodium oxybate group on the night following the first daytime sleep period and on the day following the second day sleep period. Median PVT reaction time was faster in the sodium oxybate group following the second day sleep period. The change from baseline in SWS was positively correlated with the change in MSLT and KSS. During recovery sleep the sodium oxybate group had less TST, SWS, REM, and slow wave activity (SWA) than the placebo group. Conclusions: Pharmacological enhancement of SWS with sodium oxybate resulted in a reduced response to sleep loss on measures of alertness and attention. In addition, SWS enhancement during sleep restriction appears to result in a reduced homeostatic response to sleep loss. Citation: Walsh JK; Hall-Porter JM; Griffin KS; Dodson ER; Forst EH; Curry DT; Eisenstein RD; Schweitzer PK. Enhancing slow wave sleep with sodium oxybate reduces the behavioral and physiological impact of sleep loss. SLEEP 2010;33(9):1217-1225. PMID:20857869

  16. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    PubMed Central

    Wang, Zhi-Yong; Zhang, Jun-Ai; Wu, Xian-Jin; Liang, Yan-Fang; Lu, Yuan-Bin; Gao, Yu-Chi; Dai, You-Chao; Yu, Shi-Yan; Jia, Yan; Fu, Xiao-Xia; Rao, Xiaoquan; Xu, Jun-Fa

    2016-01-01

    Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents. PMID:27006530

  17. Analgesic and Antineuropathic Drugs Acting Through Central Cholinergic Mechanisms

    PubMed Central

    Bartolini, Alessandro; Cesare Mannelli, Lorenzo Di; Ghelardini, Carla

    2011-01-01

    The role of muscarinic and nicotinic cholinergic receptors in analgesia and neuropathic pain relief is relatively unknown. This review describes how such drugs induce analgesia or alleviate neuropathic pain by acting on the central cholinergic system. Several pharmacological strategies are discussed which increase synthesis and release of acetylcholine (ACh) from cholinergic neurons. The effects of their acute and chronic administration are described. The pharmacological strategies which facilitate the physiological functions of the cholinergic system without altering the normal modulation of cholinergic signals are highlighted. It is proposed that full agonists of muscarinic or nicotinic receptors should be avoided. Their activation is too intense and un-physiological because neuronal signals are distorted when these receptors are constantly activated. Good results can be achieved by using agents that are able to a) increase ACh synthesis, b) partially inhibit cholinesterase activity c) selectively block the autoreceptor or heteroreceptor feedback mechanisms. Activation of M1 subtype muscarinic receptors induces analgesia. Chronic stimulation of nicotinic (N1) receptors has neuronal protective effects. Recent experimental results indicate a relationship between repeated cholinergic stimulation and neurotrophic activation of the glial derived neurotrophic factor (GDNF) family. At least 9 patents covering novel chemicals for cholinergic system modulation and pain control are discussed. PMID:21585331

  18. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

    PubMed Central

    Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai

    2014-01-01

    To date, the effective preventive paradigm against mild cognitive impairment (MCI) is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv). At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism. PMID:24672632

  19. Mangifera indica fruit extract improves memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment.

    PubMed

    Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai

    2014-01-01

    To date, the effective preventive paradigm against mild cognitive impairment (MCI) is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180-200 g, were orally given the extract at doses of 12.5, 50, and 200 mg · kg(-1) BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv). At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg · kg(-1) BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

  20. Local cholinergic and non-cholinergic neural pathways to the rat supraoptic nucleus

    SciTech Connect

    Meeker, M.L.

    1986-01-01

    An estimated two thirds of the input to the supraoptic nucleus of the rat hypothalamus (SON) including a functionally significant cholinergic innervation, arise from local sources of unknown origin. The sources of these inputs were identified utilizing Golgi-Cox, retrograde tracing, choline acetyltransferase immunocytochemistry and anterograde tracing methodologies. Multipolar Golgi impregnated neurons located dorsal and lateral to the SON extend spiney processes into the nucleus. Injections of the retrograde tracers, wheat germ agglutinin or wheat germ agglutinin-horseradish peroxidase, into the SON labeled cells bilaterally in the arcuate nucleus, and ipsilaterally in the lateral hypothalamus, anterior hypothalamus, nucleus of the diagonal band, subfornical organ, medial preoptic area, lateral preoptic area and in the region dorsolateral to the nucleus. Immunocytochemistry for choline acetyltransferase revealed cells within the ventro-caudal portion of cholinergic cell group, Ch4, which cluster dorsolateral to the SON, and extend axon- and dendrite-like processes into the SON. Cells double-labeled by choline acetyltransferase immunocytochemistry and retrograde tracer injections into the SON are localized within the same cholinergic cell group dorsolateral to the SON. Injections of the anterograde tracer, Phaseolus vulgaris-leucoagglutinin, deposited dorsolateral to the SON results in labeled pre-and post-synaptic processes within the SON. The identification and characterization of endogenous immunoglobulin within the SON and other neurons innervating areas lacking a blood-brain barrier established a novel and potentially important system for direct communication of the supraoptic cells with blood-borne constitutents.

  1. Enhanced recovery program for hip and knee replacement reduces death rate

    PubMed Central

    2011-01-01

    Background and purpose Multimodal techniques can aid early rehabilitation and discharge of patients following primary joint replacement. We hypothesized that this not only reduces the economic burden of joint replacement by reducing length of stay, but also helps in reduction of early complications. Patients and methods We evaluated 4,500 consecutive unselected total hip replacements and total knee replacements regarding length of hospital stay, mortality, and perioperative complications. The first 3,000 underwent a traditional protocol while the other 1,500 underwent an enhanced recovery protocol involving behavioral, pharmacological, and procedural modifications. Results There was a reduction in 30-day death rate (0.5% to 0.1%, p = 0.02) and 90-day death rate (0.8% to 0.2%, p = 0.01). The median length of stay decreased from 6 days to 3 days (p < 0.001), resulting in a saving of 5,418 bed days. Requirement for blood transfusion was reduced (23% to 9.8%, p < 0.001). There was a trend of a reduced rate of 30-day myocardial infarction (0.8% to 0.5%. p = 0 .2) and stroke (0.5% to 0.2%, p = 0.2). The 60-day deep vein thrombosis figures (0.8% to 0.6%, p = 0.5) and pulmonary embolism figures (1.2% to 1.1%, p = 0.9) were similar. Re-admission rate remained unchanged during the period of the study (4.7% to 4.8%, p = 0.8). Interpretation This large observational study of unselected consecutive hip and knee arthroplasty patients shows a substantial reduction in death rate, reduced length of stay, and reduced transfusion requirements after the introduction of a multimodal enhanced recovery protocol. PMID:21895500

  2. Basic and modern concepts on cholinergic receptor: A review

    PubMed Central

    Tiwari, Prashant; Dwivedi, Shubhangi; Singh, Mukesh Pratap; Mishra, Rahul; Chandy, Anish

    2013-01-01

    Cholinergic system is an important system and a branch of the autonomic nervous system which plays an important role in memory, digestion, control of heart beat, blood pressure, movement and many other functions. This article serves as both structural and functional sources of information regarding cholinergic receptors and provides a detailed understanding of the determinants governing specificity of muscarinic and nicotinic receptor to researchers. The study helps to give overall information about the fundamentals of the cholinergic system, its receptors and ongoing research in this field.

  3. Protective Role of the Cholinergic Anti-Inflammatory Pathway in a Mouse Model of Viral Myocarditis

    PubMed Central

    Jing-Lin, Zhao; Wen-Wu, Zhang; Xue-Si, Chen; Xing-Xing, Chen; Yue-Chun, Li

    2014-01-01

    Background Activation of the cholinergic anti-inflammatory pathway, which relies on the α7nAchR (alpha 7 nicotinic acetylcholine receptor), has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis. Methodology/Principal Findings In a coxsackievirus B3 murine myocarditis model (Balb/c), nicotine and methyllycaconitine were used to stimulate and block the cholinergic anti-inflammatory pathway, respectively. Relevant signal pathways were studied to compare their effects on myocarditis, survival rate, histopathological changes, ultrastructural changes, and cytokine levels. Nicotine treatments significantly improved survival rate, attenuated myocardial lesions, and downregulated the expression of TNF-α and IL-6. Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and upregulated the expression of TNF-α and IL-6. In addition, levels of the signaling protein phosphorylated STAT3 were higher in the nicotine group and lower in the methyllycaconitine group compared with the untreated myocarditis group. Conclusions/Significance These results show that nicotine protects mice from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral myocarditis in mice. Because nicotine is a α7nAchR agonist and methyllycaconitine is a α7nAchR antagonist, we conclude that α7nAchR activation increases the phosphorylation of STAT3, reduces the expression of TNF-α and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude that blocking α7nAchR reduces the phosphorylation of STAT3, increases

  4. A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.

    PubMed

    Abreu-Villaça, Yael; Correa-Santos, Monique; Dutra-Tavares, Ana C; Paes-Branco, Danielle; Nunes-Freitas, Andre; Manhães, Alex C; Filgueiras, Cláudio C; Ribeiro-Carvalho, Anderson

    2016-08-01

    The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content.

  5. A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.

    PubMed

    Abreu-Villaça, Yael; Correa-Santos, Monique; Dutra-Tavares, Ana C; Paes-Branco, Danielle; Nunes-Freitas, Andre; Manhães, Alex C; Filgueiras, Cláudio C; Ribeiro-Carvalho, Anderson

    2016-08-01

    The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content. PMID:27287270

  6. Cholinergic mechanism in Liriope tetraphylla (Cnidaria, Hydrozoa).

    PubMed

    Scemes, E; Garcia Mendes, E

    1986-01-01

    Crude whole body homogenates of Liriope tetraphylla exhibit a cholinesterase particularly active on acetylthiocholine but not on butyrylthiocholine. The acetylthiocholine hydrolysis is completely blocked by neostigmine. The Michaelis-Menten constant for acetylthiocholine is 0.14 mM. The pharmacological analysis of the responses to the choline esters nicotine and atropine suggests the involvement in Liriope tetraphylla of a cholinergic mechanism in the pointing reflex. Butyrylcholine, nicotine and atropine (but not muscarinic agonists) caused the contraction of the subumbrellar radial muscles. The effects of atropine were dose-dependent and were depressed in competition with muscarinic agonists. MgCl2 interfered with the action of atropine. The results were explained by suggesting the existence, at least at the neuromuscular junction, of excitatory (nicotinic) and inhibitory (muscarinic) pre-synaptic receptors modulating the release of the (unknown) transmitter acting post-synaptically.

  7. Cholinergic manipulations bidirectionally regulate object memory destabilization.

    PubMed

    Stiver, Mikaela L; Jacklin, Derek L; Mitchnick, Krista A; Vicic, Nevena; Carlin, Justine; O'Hara, Matthew; Winters, Boyer D

    2015-04-01

    Consolidated memories can become destabilized and open to modification upon retrieval. Destabilization is most reliably prompted when novel information is present during memory reactivation. We hypothesized that the neurotransmitter acetylcholine (ACh) plays an important role in novelty-induced memory destabilization because of its established involvement in new learning. Accordingly, we investigated the effects of cholinergic manipulations in rats using an object recognition paradigm that requires reactivation novelty to destabilize object memories. The muscarinic receptor antagonist scopolamine, systemically or infused directly into the perirhinal cortex, blocked this novelty-induced memory destabilization. Conversely, systemic oxotremorine or carbachol, muscarinic receptor agonists, administered systemically or intraperirhinally, respectively, mimicked the destabilizing effect of novel information during reactivation. These bidirectional effects suggest a crucial influence of ACh on memory destabilization and the updating functions of reconsolidation. This is a hitherto unappreciated mnemonic role for ACh with implications for its potential involvement in cognitive flexibility and the dynamic process of long-term memory storage.

  8. Somatostatin inhibits cANP-mediated cholinergic transmission in the myenteric plexus

    SciTech Connect

    Wiley, J.; Owyang, C. )

    1987-11-01

    The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study the authors investigated the role of the adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8-bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of ({sup 3}H)ACh in a dose-related manner. Addition of theophylline enhanced the release of ({sup 3}H)ACh stimulated by these cAMP agonists. The observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of ({sup 3}H)ACh evoked by various cAMP agonists in a dose-related manner. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of ({sup 3}H)ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of ({sup 3}H)ACh evoked by 8-bromo-cAMP. This suggests that the principal mechanism by which somatostatin inhibits cAMP-mediated cholinergic transmission is via activation of the inhibitory regulatory protein (N{sub i} subunit) of adenyalte cyclase.

  9. Agonist-induced restoration of hippocampal neurogenesis and cognitive improvement in a model of cholinergic denervation

    PubMed Central

    Van Kampen, Jackalina M.; Eckman, Christopher B.

    2012-01-01

    Loss of basal forebrain cholinergic innervation of the hippocampus and severe neuronal loss within the hippocampal CA1 region are early hallmarks of Alzheimer’s disease, and are strongly correlated with cognitive status. Various therapeutic approaches involve attempts to enhance neurotransmission or to provide some level of neuroprotection for remaining cells. An alternative approach may involve the generation of new cells to replace those lost in AD. Indeed, a simple shift in the balance between cell generation and cell loss may slow disease progression and possibly even reverse existing cognitive deficits. One potential neurogenic regulator might be acetylcholine, itself, which has been shown to play a critical role in hippocampal development. Here, we report the effects of various cholinergic compounds on indices of hippocampal neurogenesis, demonstrating a significant induction following pharmacological activation of muscarinic M1 receptors, located on hippocampal progenitors in the adult brain. This is the first report that a small-molecule agonist may induce neurogenesis in the hippocampal CA1 region. Furthermore, such treatment reversed deficits in markers of neurogenesis and spatial working memory triggered by cholinergic denervation in a rodent model. This study suggests the use of small molecule, receptor agonists may represent a novel means to trigger the restoration of specific neuronal populations lost to a variety of neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, Huntington’s and Amyotrophic Lateral Sclerosis. PMID:20026137

  10. Effectiveness of nootropic drugs with cholinergic activity in treatment of cognitive deficit: a review

    PubMed Central

    Colucci, Luisa; Bosco, Massimiliano; Ziello, Antonio Rosario; Rea, Raffaele; Amenta, Francesco; Fasanaro, Angiola Maria

    2012-01-01

    Nootropics represent probably the first “smart drugs” used for the treatment of cognitive deficits. The aim of this paper is to verify, by a systematic analysis of the literature, the effectiveness of nootropics in this indication. The analysis was limited to nootropics with cholinergic activity, in view of the role played by acetylcholine in learning and memory. Acetylcholine was the first neurotransmitter identified in the history of neuroscience and is the main neurotransmitter of the peripheral, autonomic, and enteric nervous systems. We conducted a systematic review of the literature for the 5-year period 2006–2011. From the data reported in the literature, it emerges that nootropics may be an effective alternative for strengthening and enhancing cognitive performance in patients with a range of pathologies. Although nootropics, and specifically the cholinergic precursors, already have a long history behind them, according to recent renewal of interest, they still seem to have a significant therapeutic role. Drugs with regulatory indications for symptomatic treatment of Alzheimer’s disease, such as cholinesterase inhibitors and memantine, often have transient effects in dementia disorders. Nootropics with a cholinergic profile and documented clinical effectiveness in combination with cognate drugs such as cholinesterase inhibitors or alone in patients who are not suitable for these inhibitors should be taken into account and evaluated further. PMID:27186129

  11. Effectiveness of nootropic drugs with cholinergic activity in treatment of cognitive deficit: a review.

    PubMed

    Colucci, Luisa; Bosco, Massimiliano; Rosario Ziello, Antonio; Rea, Raffaele; Amenta, Francesco; Fasanaro, Angiola Maria

    2012-01-01

    Nootropics represent probably the first "smart drugs" used for the treatment of cognitive deficits. The aim of this paper is to verify, by a systematic analysis of the literature, the effectiveness of nootropics in this indication. The analysis was limited to nootropics with cholinergic activity, in view of the role played by acetylcholine in learning and memory. Acetylcholine was the first neurotransmitter identified in the history of neuroscience and is the main neurotransmitter of the peripheral, autonomic, and enteric nervous systems. We conducted a systematic review of the literature for the 5-year period 2006-2011. From the data reported in the literature, it emerges that nootropics may be an effective alternative for strengthening and enhancing cognitive performance in patients with a range of pathologies. Although nootropics, and specifically the cholinergic precursors, already have a long history behind them, according to recent renewal of interest, they still seem to have a significant therapeutic role. Drugs with regulatory indications for symptomatic treatment of Alzheimer's disease, such as cholinesterase inhibitors and memantine, often have transient effects in dementia disorders. Nootropics with a cholinergic profile and documented clinical effectiveness in combination with cognate drugs such as cholinesterase inhibitors or alone in patients who are not suitable for these inhibitors should be taken into account and evaluated further.

  12. Impairment of basal forebrain cholinergic neurons associated with aging and long-term loss of ovarian function.

    PubMed

    Gibbs, R B

    1998-06-01

    Recent studies suggest that women are at greater risk for Alzheimer's disease than men and that estrogen replacement can help to reduce the risk and severity of Alzheimer's-related dementia in postmenopausal women. We have hypothesized that the increased risk for Alzheimer's-related dementia is due, in part, to the loss of ovarian function in postmenopausal women and to the effects that decreased levels of ovarian hormones have on basal forebrain cholinergic function. In the present study, the effects of aging and ovariectomy on cholinergic neurons in the rat basal forebrain were examined to determine (1) whether aging differentially affects cholinergic neurons in the basal forebrain of males vs females, and (2) whether long-term loss of ovarian function produces deficits in basal forebrain cholinergic function beyond those associated with aging and sex. In part I of the study, gonadally intact male and female rats were sacrificed at 13, 19, and 25 months of age and the effects of aging on cholinergic neurons in the medial septum (MS) and nucleus basalis magnocellularis (NBM) were compared. In part II of the study, female rats were ovariectomized at 13 months of age and then sacrificed 3 and 6 months later along with gonadally intact, age-matched controls. Adjacent sections through the MS and NBM were processed for either immunocytochemical detection of choline acetyltransferase (ChAT) and p75NTR-like immunoreactivity or for in situ hybridization detection and quantification of ChAT and trkA mRNA. Results from part I revealed no significant effects of age on the relative size or density of cholinergic neurons in the MS and NBM of gonadally intact animals. Likewise, no significant effects on the relative numbers of cholinergic neurons expressing p75NTR protein were detected. However, a significant decrease in trkA mRNA was detected in the MS of gonadally intact females, but not males, between 13 and 25 months of age. No significant effects of aging on ChAT mRNA were

  13. Early deprivation reduced anxiety and enhanced memory in adult male rats.

    PubMed

    Zhang, Xuliang; Wang, Bo; Jin, Jing; An, Shuming; Zeng, Qingwen; Duan, Yanhong; Yang, Liguo; Ma, Jing; Cao, Xiaohua

    2014-09-01

    The effects of early deprivation (ED, which involves both dam and littermate deprivation) on anxiety and memory are less investigated in comparison with maternal separation (MS), and it is not yet clear how ED affects long-term potentiation (LTP) in the hippocampal Schaffer collateral pathway. By using a series of behavioral tests, enzyme-linked immunosorbent assay and field potential recording, we explored the effect of pre-weaning daily 3-h ED on anxiety, memory and potential mechanisms in adult male rats. Compared with control, ED rats spent longer time in open arms of elevated plus maze and in light compartment of light-dark transition box. Consistently, stress-induced blood plasma corticosterone level was also lower in ED rats. Moreover, ED rats showed better performance in social recognition and Morris water maze test. In accordance with results in memory tests, the threshold of LTP induction in hippocampal CA3-CA1 pathway of ED rats was also reduced. Our results indicate ED reduced anxiety, but enhanced social recognition and spatial reference memory. We suggest the diminished hypothalamic-pituitary-adrenal axis response and facilitated hippocampal LTP may contribute to the anxiety-reducing and memory-enhancing effects of ED, respectively.

  14. Enhanced strain and temperature sensing by reduced graphene oxide coated etched fiber Bragg gratings.

    PubMed

    S, Sridevi; Vasu, K S; Asokan, S; Sood, A K

    2016-06-01

    This Letter reports on an etched fiber Bragg grating (eFBG) sensor coated with reduced graphene oxide (RGO) having enhanced sensitivity for physical parameters such as strain and temperature. The synergetic effect of the changes in grating pitch and refractive index of RGO with change in temperature or strain enhances the shift in Bragg wavelength (λB). The RGO-coated eFBG sensors exhibit a strain sensitivity of 5.5 pm/μϵ (∼5 times that of bare fiber Bragg gratings) and temperature sensitivity of 33 pm/°C (∼3 times that of bare fiber Bragg gratings). The resolutions of ∼1  μϵ and ∼0.3°C have been obtained for strain and temperature respectively, using RGO-coated eFBG sensors. PMID:27244425

  15. Enhanced strain and temperature sensing by reduced graphene oxide coated etched fiber Bragg gratings.

    PubMed

    S, Sridevi; Vasu, K S; Asokan, S; Sood, A K

    2016-06-01

    This Letter reports on an etched fiber Bragg grating (eFBG) sensor coated with reduced graphene oxide (RGO) having enhanced sensitivity for physical parameters such as strain and temperature. The synergetic effect of the changes in grating pitch and refractive index of RGO with change in temperature or strain enhances the shift in Bragg wavelength (λB). The RGO-coated eFBG sensors exhibit a strain sensitivity of 5.5 pm/μϵ (∼5 times that of bare fiber Bragg gratings) and temperature sensitivity of 33 pm/°C (∼3 times that of bare fiber Bragg gratings). The resolutions of ∼1  μϵ and ∼0.3°C have been obtained for strain and temperature respectively, using RGO-coated eFBG sensors.

  16. Reduced graphene oxide/CeO2 nanocomposite with enhanced photocatalytic performance

    NASA Astrophysics Data System (ADS)

    Kaur, Jasmeet; Anand, Kanika; Anand, Kanica; Singh, Gurpreet; Hastir, Anita; Virpal, Singh, Ravi Chand

    2015-05-01

    In this work, reduced graphene oxide /cerium oxide (RGO/CeO2) nanocomposite was synthesized by in situ reduction of cerium nitrate Ce(NO3)3.6H2O in the presence of graphene oxide by hydrazine hydrate (N2H4.H2O). The intrinsic characteristics of as-prepared nanocomposite were studied using powder x-ray diffraction (XRD), Raman spectroscopy and field-emission scanning electron microscopy (FESEM). The photocatalytic degradation of methylene blue (MB) was employed as a model reaction to evaluate the photocatalytic activity of the RGO/CeO2 nanocomposite. The as-obtained RGO/CeO2 nanocomposite displays a significantly enhanced photocatalytic degradation of MB dye in comparison with bare CeO2 nanoparticles under sunlight irradiation, which can be attributed to the improved separation of electron-hole pairs and enhanced adsorption performance due to presence of RGO.

  17. Enhanced Somatosensory Feedback Reduces Prefrontal Cortical Activity During Walking in Older Adults

    PubMed Central

    Christou, Evangelos A.; Ring, Sarah A.; Williamson, John B.; Doty, Leilani

    2014-01-01

    Background. The coordination of steady state walking is relatively automatic in healthy humans, such that active attention to the details of task execution and performance (controlled processing) is low. Somatosensation is a crucial input to the spinal and brainstem circuits that facilitate this automaticity. Impaired somatosensation in older adults may reduce automaticity and increase controlled processing, thereby contributing to deficits in walking function. The primary objective of this study was to determine if enhancing somatosensory feedback can reduce controlled processing during walking, as assessed by prefrontal cortical activation. Methods. Fourteen older adults (age 77.1±5.56 years) with mild mobility deficits and mild somatosensory deficits participated in this study. Functional near-infrared spectroscopy was used to quantify metabolic activity (tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and gait spatiotemporal data were measured during treadmill walking and overground walking while participants wore normal shoes and under two conditions of enhanced somatosensation: wearing textured insoles and no shoes. Results. Relative to walking with normal shoes, textured insoles yielded a bilateral reduction of prefrontal cortical activity for treadmill walking (ΔTOI = −0.85 and −1.19 for left and right hemispheres, respectively) and for overground walking (ΔTOI = −0.51 and −0.66 for left and right hemispheres, respectively). Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical activity for treadmill walking (ΔTOI = −0.69 and −1.13 for left and right hemispheres, respectively), but not overground walking. Conclusions. Enhanced somatosensation reduces prefrontal activity during walking in older adults. This suggests a less intensive utilization of controlled processing during walking. PMID:25112494

  18. Neocortical morphometry and cholinergic neurochemistry in Pick's disease.

    PubMed Central

    Hansen, L. A.; Deteresa, R.; Tobias, H.; Alford, M.; Terry, R. D.

    1988-01-01

    With a computerized image-analysis apparatus for neocortical morphometry and chemical methods for evaluation of the cholinergic system, five brain specimens of Pick's disease (PD) were studied and the results compared to those from specimens of age-matched normal subjects and Alzheimer's disease (AD). The PD specimens showed major reductions in brain weight, frontal and temporal cortical thickness, and large neuron populations, compared with controls. Lesser reductions were seen in small neurons and thickness of the inferior parietal cortex. The authors found no relationship between age of onset or disease duration and either the degree of cortical thinning or neuron loss or the number of Pick bodies in the neocortex and hippocampus. PD specimens were more atrophic than AD brains, having lower brain weights and more fronto-temporal thinning. Large neurons were comparably reduced in the two conditions in the frontal and temporal lobes, but small neuron losses were greater in the PD midfrontal area. Only the AD cases showed loss of large neurons in the inferior parietal region. Levels of choline acetyltransferase were normal in PD and reduced in AD, whereas muscarinic receptor binding was decreased in both. Images Figure 7 Figure 8 PMID:3381880

  19. Finding the elusive balance between reducing fatigue and enhancing education: perspectives from American residents

    PubMed Central

    2014-01-01

    Duty hour restrictions for residency training were implemented in the United States to improve residents’ educational experience and quality of life, as well as to improve patient care and safety; however, these restrictions are by no means problem-free. In this paper, we discuss the positive and negative aspects of duty hour restrictions, briefly highlighting research on the impact of reduced duty hours and the experiences of American residents. We also consider whether certain specialties (e.g., Emergency Medicine, Radiology) may be more amenable than others (e.g., Surgery) to duty hour restrictions. We conclude that feedback from residents is a crucial element that must be considered in any future attempts to strike a balance between reducing fatigue and enhancing education. PMID:25560226

  20. Cuprous Sulfide/Reduced Graphene Oxide Hybrid Nanomaterials: Solvothermal Synthesis and Enhanced Electrochemical Performance

    NASA Astrophysics Data System (ADS)

    He, Zhanjun; Zhu, Yabo; Xing, Zheng; Wang, Zhengyuan

    2016-01-01

    The cuprous sulfide nanoparticles (CuS NPs)-decorated reduced graphene oxide (rGO) nanocomposites have been successfully prepared via a facile and efficient solvothermal synthesis method. Scanning electron microscopy and transmission electron microscopy images demonstrated that CuS micronspheres composed of nanosheets and distributed on the rGO layer in well-monodispersed form. Fourier-transform infrared spectroscopy analyses and x-ray photoelectron spectroscopy showed that graphene oxide (GO) had been reduced to rGO. The electrochemical performances of CuS/rGO nanocomposites were investigated by cyclic voltammetry and charge/discharge techniques, which showed that the specific capacitance of CuS/rGO nanocomposites was enhanced because of the introduction of rGO.

  1. Effect of tianeptine on the central cholinergic system: involvement of serotonin.

    PubMed

    Bertorelli, R; Amoroso, D; Girotti, P; Consolo, S

    1992-03-01

    The effect of tianeptine on in vivo acetylcholine (ACh) release from brain hemispheric regions of freely moving rats was investigated using the microdialysis technique coupled with a sensitive radioenzymatic method. Tianeptine, at the dose of 30 mg/kg i.p., reduced ACh release from dorsal hippocampi by 40% in 40 min, and induced a 30% decrease of ACh output from frontal cortices while at the doses of 10 and 20 mg/kg it had no effect. In striata the drug did not significantly affect ACh release although it showed a tendency to increase it. The ACh content in the three areas considered was not affected by tianeptine at above doses. The drug did not alter choline-o-acetyltransferase and acetylcholinesterase activities suggesting that it did not influence the cholinergic system through direct action on the ACh metabolism; furthermore, it did not influence the sodium-dependent high-affinity uptake of choline in striatum, cortex and hippocampus. Impairment of serotonergic (5-HT) neurotransmission by chemical lesion of the median raphe nucleus or by metergoline, a blocker of 5-HT receptors, antagonized the cholinergic effect of tianeptine. The involvement of the serotonergic system is specific because lesions of the noradrenergic dorsal bundle failed to prevent the inhibitory action of tianeptine. The present data suggest that 5-HT may mediate the effect of tianeptine on the cholinergic system in dorsal hippocampi.

  2. Altered emotionality, spatial memory and cholinergic function in caveolin-1 knock-out mice.

    PubMed

    Gioiosa, Laura; Raggi, Carla; Ricceri, Laura; Jasmin, Jean-François; Frank, Philippe G; Capozza, Franco; Lisanti, Michael P; Alleva, Enrico; Sargiacomo, Massimo; Laviola, Giovanni

    2008-04-01

    Neurological phenotypes associated with loss of caveolin 1 (cav-1) (the defining structural protein in caveolar vesicles, which regulate signal transduction and cholesterol trafficking in cells) in mice have been reported recently. In brain, cav-1 is highly expressed in neurons and glia. We investigated emotional and cognitive behavioural domains in mice deficient in cav-1 (CavKO mice). CavKO mice were more anxious and spent more time in self-directed grooming behaviour than wild-type (wt) mice. In a spatial/working memory task, CavKO mice failed to recognize the object displacement, thus showing a spatial memory impairment. CavKO mice showed higher locomotor activity than wt mice, thus suggesting reduced inhibitory function by CNS cholinergic systems. Behavioural response to the cholinergic muscarinic antagonist, scopolamine (2 mg/Kg), was decreased in CavKO mice. Few behavioural sex differences emerged in mice; whereas the sex differences were generally attenuated or even reverted in the null genotype. Our data confirm a distinct behavioural phenotype in CavKO mice and indicate a selective alteration in central cholinergic function.

  3. Improving the durability of a drag-reducing nanocoating by enhancing its mechanical stability.

    PubMed

    Cheng, Mengjiao; Zhang, Songsong; Dong, Hongyu; Han, Shihui; Wei, Hao; Shi, Feng

    2015-02-25

    The durability of superhydrophobic surface is a major problem to restrict industrial application of superhydrophobic materials from laboratory research, which can be attributed to a more general issue of mechanical stability for superhydrophobic coatings. Therefore, in order to handle this issue, we have fabricated a mechanically stable drag-reducing coating composed of elastic polydimethylsiloxane (PDMS) and hydrophobic copper particles on model ships, which can resist mechanical abrasion and has displayed a durable drag-reducing effect. In comparison with normal Au superhydrophobic coatings, the as-prepared PDMS/copper coatings showed durable drag reduction performance with a similar drag-reducing rate before (26%) and after (24%) mechanical abrasion. The mechanism for the enhanced mechanical stability and maintained drag reduction of the superhydrophobic surfaces was investigated through characterizations of surface morphology, surface wettability, and water adhesive force evaluation before and after abrasion. This is the first demonstration to realize the application of durable drag reduction by improving the mechanical stability of superhydrophobic coatings. We do believe that superhydrophobic surfaces with good resistance to mechanical abrasion or scratching may draw wide attention and gain significant applications with durable drag-reducing properties.

  4. Corelease of acetylcholine and GABA from cholinergic forebrain neurons

    PubMed Central

    Saunders, Arpiar; Granger, Adam J; Sabatini, Bernardo L

    2015-01-01

    Neurotransmitter corelease is emerging as a common theme of central neuromodulatory systems. Though corelease of glutamate or GABA with acetylcholine has been reported within the cholinergic system, the full extent is unknown. To explore synaptic signaling of cholinergic forebrain neurons, we activated choline acetyltransferase expressing neurons using channelrhodopsin while recording post-synaptic currents (PSCs) in layer 1 interneurons. Surprisingly, we observed PSCs mediated by GABAA receptors in addition to nicotinic acetylcholine receptors. Based on PSC latency and pharmacological sensitivity, our results suggest monosynaptic release of both GABA and ACh. Anatomical analysis showed that forebrain cholinergic neurons express the GABA synthetic enzyme Gad2 and the vesicular GABA transporter (Slc32a1). We confirmed the direct release of GABA by knocking out Slc32a1 from cholinergic neurons. Our results identify GABA as an overlooked fast neurotransmitter utilized throughout the forebrain cholinergic system. GABA/ACh corelease may have major implications for modulation of cortical function by cholinergic neurons. DOI: http://dx.doi.org/10.7554/eLife.06412.001 PMID:25723967

  5. Culture density regulates both the cholinergic phenotype and the expression of the CNTF receptor in P19 neurons.

    PubMed

    Parnas, D; Linial, M

    1997-04-01

    The P19 embryonal carcinoma cells differentiate into neurons, astrocytes, and fibroblast-like cells following induction with retinoic acid. The cells mature into functional neurons, as determined by their ability to release neurotransmitters in a Ca(2+)- and depolarization-dependent manner. P19 neurons in culture represent a mixed population in terms of their neurotransmitter phenotype. The cholinergic phenotype of these neurons is modulated by culture density. Cholinergic markers, such as the vesicular acetylcholine transporter, acetyl cholinesterase, and choline acetyltransferase, are expressed in about 85% of the cells in sparse cultures and are largely suppressed at high cell densities. In contrast, glutamate release is enhanced in dense P19 neuronal cultures. The factor mediating the density effect is concentrated exclusively on the cell membrane of P19 neurons and not on the nonneuronal cells, which also differentiate from P19 embryonal carcinoma cells. This membrane-associated component retains its functionality, even after membrane fixation. The downregulation of the cholinergic properties in dense cultures is paralleled by a downregulation of the alpha subunit of the ciliary neurotrophic factor (CNTF) receptor. Thus, it is suggested that the membrane-associated factor, which mediates the density effect, downregulates the cholinergic phenotype by inhibiting the responsiveness of these neurons to CNTF. We further suggest that the P19 cell line can serve as a model system for the study of neurotransmitter phenotype acquisition and plasticity throughout neuronal differentiation. PMID:9188041

  6. Enhanced transformation of diphenylarsinic acid in soil under sulfate-reducing conditions.

    PubMed

    Guan, Ling; Hisatomi, Shihoko; Fujii, Kunihiko; Nonaka, Masanori; Harada, Naoki

    2012-11-30

    Diphenylarsinic acid (DPAA) is known to be the major contaminant in soils where diphenylchloroarsine and diphenylcyanoarsine were abandoned after World Wars I and II. In this study, experimental model studies were performed to elucidate key factors regulating the transformation of DPAA under anaerobic soil conditions. The elimination of DPAA in Gleysol soils (Qiqihar and Shindori soils) was more rapid than in Mollisol and Regosol soils (Heihe and Ikarashi soils, respectively) during a 5-week incubation. No clear relationship between decreasing rates of DPAA concentrations and soil Eh values was found. The Ikarashi soil showed the slowest decrease in DPAA concentrations among the four soils, but the transformation of DPAA was notably enhanced by addition of exogenous sulfate together with acetate, cellulose or rice straw. Addition of molybdate, a specific inhibitor of sulfate reduction, resulted in the stagnation of DPAA transformation, suggesting that indigenous sulfate reducers play a role in DPAA transformation under anaerobic conditions. Arsenate, phenylarsonic acid, phenylmethylarsinic acid, diphenylmethylarsine oxide and three unknown compounds were detected as metabolites of DPAA. This is the first study to reveal enhancement of DPAA transformation under sulfate-reducing conditions. PMID:23069334

  7. Co-assembly of photosystem II/reduced graphene oxide multilayered biohybrid films for enhanced photocurrent

    NASA Astrophysics Data System (ADS)

    Cai, Peng; Feng, Xiyun; Fei, Jinbo; Li, Guangle; Li, Jiao; Huang, Jianguo; Li, Junbai

    2015-06-01

    A new type of biohybrid photo-electrochemical cell was fabricated by layer-by-layer assembly of photosystem II and reduced graphene oxide. We demonstrate that the photocurrent in the direct electron transfer is enhanced about two fold with improved stability. The assembly strategy without any cross-linker or additional electron mediators makes the cell fabrication and operation much simpler as compared to previous approaches. This work may open new routes for the construction of solar energy conversion systems based on photoactive proteins and graphene materials.A new type of biohybrid photo-electrochemical cell was fabricated by layer-by-layer assembly of photosystem II and reduced graphene oxide. We demonstrate that the photocurrent in the direct electron transfer is enhanced about two fold with improved stability. The assembly strategy without any cross-linker or additional electron mediators makes the cell fabrication and operation much simpler as compared to previous approaches. This work may open new routes for the construction of solar energy conversion systems based on photoactive proteins and graphene materials. Electronic supplementary information (ESI) available: Detailed experimental procedures, XRD patterns, UV-vis spectra, XPS spectra, SDS-PAGE patterns, AFM images and SEM images. See DOI: 10.1039/c5nr02322j

  8. BODIPY-doped silica nanoparticles with reduced dye leakage and enhanced singlet oxygen generation

    PubMed Central

    Wang, Zhuyuan; Hong, Xuehua; Zong, Shenfei; Tang, Changquan; Cui, Yiping; Zheng, Qingdong

    2015-01-01

    Photodynamic therapy (PDT) is a promising modality for cancer treatment. The essential element in PDT is the photosensitizer, which can be excited by light of a specific wavelength to generate cytotoxic oxygen species (ROS) capable of killing tumor cells. The effectiveness of PDT is limited in part by the low yield of ROS from existing photosensitizers and the unwanted side effects induced by the photosensitizers toward normal cells. Thus the design of nanoplatforms with enhanced PDT is highly desirable but remains challenging. Here, we developed a heavy atom (I) containing dipyrromethene boron difluoride (BODIPY) dye with a silylated functional group, which can be covalently incorporated into a silica matrix to form dye-doped nanoparticles. The incorporated heavy atoms can enhance the generation efficiency of ROS. Meanwhile, the covalently dye-encapsulated nanoparticles can significantly reduce dye leakage and subsequently reduce unwanted side effects. The nanoparticles were successfully taken up by various tumor cells and showed salient phototoxicity against these cells upon light irradiation, demonstrating promising applications in PDT. Moreover, the incorporated iodine atom can be replaced by a radiolabeled iodine atom (e.g., I-124, I-125). The resulting nanoparticles will be good contrast agents for positron emission tomography (PET) imaging with their PDT functionality retained. PMID:26211417

  9. Enhanced charge efficiency and reduced energy use in capacitive deionization by increasing the discharge voltage.

    PubMed

    Kim, T; Dykstra, J E; Porada, S; van der Wal, A; Yoon, J; Biesheuvel, P M

    2015-05-15

    Capacitive deionization (CDI) is an electrochemical method for water desalination using porous carbon electrodes. A key parameter in CDI is the charge efficiency, Λ, which is the ratio of salt adsorption over charge in a CDI-cycle. Values for Λ in CDI are typically around 0.5-0.8, significantly less than the theoretical maximum of unity, due to the fact that not only counterions are adsorbed into the pores of the carbon electrodes, but at the same time coions are released. To enhance Λ, ion-exchange membranes (IEMs) can be implemented. With membranes, Λ can be close to unity because the membranes only allow passage for the counterions. Enhancing the value of Λ is advantageous as this implies a lower electrical current and (at a fixed charging voltage) a reduced energy use. We demonstrate how, without the need to include IEMs, the charge efficiency can be increased to values close to the theoretical maximum of unity, by increasing the cell voltage during discharge, with only a small loss of salt adsorption capacity per cycle. In separate constant-current CDI experiments, where after some time the effluent salt concentration reaches a stable value, this value is reached earlier with increased discharge voltage. We compare the experimental results with predictions of porous electrode theory which includes an equilibrium Donnan electrical double layer model for salt adsorption in carbon micropores. Our results highlight the potential of modified operational schemes in CDI to increase charge efficiency and reduce energy use of water desalination.

  10. Pretreatment of microalgal biomass for enhanced recovery/extraction of reducing sugars and proteins.

    PubMed

    Eldalatony, Marwa M; Kabra, Akhil N; Hwang, Jae-Hoon; Govindwar, Sanjay P; Kim, Ki-Hyun; Kim, Hoo; Jeon, Byong-Hun

    2016-01-01

    Microalgae species including Chlamydomonas mexicana, Micractinium reisseri, Scenedesmus obliquus and Tribonema aequale were cultivated in batch cultures, and their biochemical composition was determined. C. mexicana showed the highest carbohydrate content of 52.6% and was selected for further study. Sonication pretreatment under optimum conditions (at 40 kHz, 2.2 Kw, 50 °C for 15 min) released 74 ± 2.7 mg g(-1) of total reducing sugars (TRS) of dry cell weight, while the combined sonication and enzymatic hydrolysis treatment enhanced the TRS yield by fourfold (280.5 ± 4.9 mg g(-1)). The optimal ratio of enzyme [E]:substrate [S] for maximum TRS yield was [1]:[5] at 50 °C and pH 5. Combined sonication and hydrolysis treatment released 7.3% (27.1 ± 0.9 mg g(-1)) soluble protein of dry cell weight, and further fermentation of the dissolved carbohydrate fraction enhanced the soluble protein content up to 56% (228.4 mg g(-1)) of total protein content. Scanning and transmission electron microscopic analyses indicated that microalgae cells were significantly disrupted by the combined sonication and enzyme hydrolysis treatment. This study indicates that pretreatment and subsequent fermentation of the microalgal biomass enhance the recovery of carbohydrates and proteins which can be used as feedstocks for generation of biofuels.

  11. Declining streamflows reveal nonstationary orographic precipitation enhancement driven by reduced westerly flows

    NASA Astrophysics Data System (ADS)

    Luce, Charles; Abatzoglou, John; Holden, Zachary

    2016-04-01

    Although orographic enhancement of precipitation lends mountains an important role in water resources, they are dramatically undersampled by long-term precipitation gages. This has led to the widespread practice of extrapolating trends in low-elevation precipitation gage networks to high elevations via simple climatological precipitation ratios developed from isohyetal maps. An implicit assumption in such a process is non-stationarity in orographic precipitation enhancement, an assumption that can lead to large errors in trend detection and attribution of climate change effects. We show an example from the Northwestern United States where streamflows from mountain watersheds show substantial declines over the last 60 years, even while long-term precipitation gage networks in the region show no trend. We demonstrate that these observed streamflow declines are driven by previously unexplored differential trends in precipitation. November to March westerly winds are strongly correlated with high-elevation precipitation but weakly correlated with low-elevation precipitation. Decreases in winter westerlies across the region from 1950 to 2012 are hypothesized to have reduced orographic precipitation enhancement, yielding differential trends in precipitation across elevations leading to the apparent paradox. Climate projections show continued weakening meridional pressure gradients and westerly flow across the region under greenhouse forcing, highlighting an additional stressor that is relevant for climate change impacts on water resources. This study also reveals the potential of wind speed data from circulation reanalysis products to better inform historical precipitation reconstructions.

  12. Applying lessons learned to enhance human performance and reduce human error for ISS operations

    SciTech Connect

    Nelson, W.R.

    1998-09-01

    A major component of reliability, safety, and mission success for space missions is ensuring that the humans involved (flight crew, ground crew, mission control, etc.) perform their tasks and functions as required. This includes compliance with training and procedures during normal conditions, and successful compensation when malfunctions or unexpected conditions occur. A very significant issue that affects human performance in space flight is human error. Human errors can invalidate carefully designed equipment and procedures. If certain errors combine with equipment failures or design flaws, mission failure or loss of life can occur. The control of human error during operation of the International Space Station (ISS) will be critical to the overall success of the program. As experience from Mir operations has shown, human performance plays a vital role in the success or failure of long duration space missions. The Department of Energy`s Idaho National Engineering and Environmental Laboratory (INEEL) is developed a systematic approach to enhance human performance and reduce human errors for ISS operations. This approach is based on the systematic identification and evaluation of lessons learned from past space missions such as Mir to enhance the design and operation of ISS. This paper describes previous INEEL research on human error sponsored by NASA and how it can be applied to enhance human reliability for ISS.

  13. Thalamic cholinergic innervation and postural sensory integration function in Parkinson’s disease

    PubMed Central

    Albin, Roger L.; Kotagal, Vikas; Koeppe, Robert A.; Scott, Peter J.H.; Frey, Kirk A.; Bohnen, Nicolaas I.

    2013-01-01

    The pathophysiology of postural instability in Parkinson’s disease remains poorly understood. Normal postural function depends in part on the ability of the postural control system to integrate visual, proprioceptive, and vestibular sensory information. Degeneration of cholinergic neurons in the brainstem pedunculopontine nucleus complex and their thalamic efferent terminals has been implicated in postural control deficits in Parkinson’s disease. Our aim was to investigate the relationship of cholinergic terminal loss in thalamus and cortex, and nigrostriatal dopaminergic denervation, on postural sensory integration function in Parkinson’s disease. We studied 124 subjects with Parkinson’s disease (32 female/92 male; 65.5 ± 7.4 years old; 6.0 ± 4.2 years motor disease duration; modified Hoehn and Yahr mean stage 2.4 ± 0.5) and 25 control subjects (10 female/15 male, 66.8 ± 10.1 years old). All subjects underwent 11C-dihydrotetrabenazine vesicular monoaminergic transporter type 2 and 11C-methylpiperidin-4-yl propionate acetylcholinesterase positron emission tomography and the sensory organization test balance platform protocol. Measures of dopaminergic and cholinergic terminal integrity were obtained, i.e. striatal vesicular monoaminergic transporter type 2 binding (distribution volume ratio) and thalamic and cortical acetylcholinesterase hydrolysis rate per minute (k3), respectively. Total centre of pressure excursion (speed), a measure of total sway, and sway variability were determined for individual sensory organization test conditions. Based on normative data, principal component analysis was performed to reduce postural sensory organization functions to robust factors for regression analysis with the dopaminergic and cholinergic terminal data. Factor analysis demonstrated two factors with eigenvalues >2 that explained 52.2% of the variance, mainly reflecting postural sway during sensory organization test Conditions 1–3 and 5, respectively

  14. Utilization of reward-prospect enhances preparatory attention and reduces stimulus conflict.

    PubMed

    van den Berg, Berry; Krebs, Ruth M; Lorist, Monicque M; Woldorff, Marty G

    2014-06-01

    The prospect of gaining money is an incentive widely at play in the real world. Such monetary motivation might have particularly strong influence when the cognitive system is challenged, such as when needing to process conflicting stimulus inputs. Here, we employed manipulations of reward-prospect and attentional-preparation levels in a cued-Stroop stimulus conflict task, along with the high temporal resolution of electrical brain recordings, to provide insight into the mechanisms by which reward-prospect and attention interact and modulate cognitive task performance. In this task, the cue indicated whether or not the participant needed to prepare for an upcoming Stroop stimulus and, if so, whether there was the potential for monetary reward (dependent on performance on that trial). Both cued attention and cued reward-prospect enhanced preparatory neural activity, as reflected by increases in the hallmark attention-related negative-polarity ERP slow wave (contingent negative variation [CNV]) and reductions in oscillatory Alpha activity, which was followed by enhanced processing of the subsequent Stroop stimulus. In addition, similar modulations of preparatory neural activity (larger CNVs and reduced Alpha) predicted shorter versus longer response times (RTs) to the subsequent target stimulus, consistent with such modulations reflecting trial-to-trial variations in attention. Particularly striking were the individual differences in the utilization of reward-prospect information. In particular, the size of the reward effects on the preparatory neural activity correlated across participants with the degree to which reward-prospect both facilitated overall task performance (shorter RTs) and reduced conflict-related behavioral interference. Thus, the prospect of reward appears to recruit attentional preparation circuits to enhance processing of task-relevant target information.

  15. Utilization of reward-prospect enhances preparatory attention and reduces stimulus conflict.

    PubMed

    van den Berg, Berry; Krebs, Ruth M; Lorist, Monicque M; Woldorff, Marty G

    2014-06-01

    The prospect of gaining money is an incentive widely at play in the real world. Such monetary motivation might have particularly strong influence when the cognitive system is challenged, such as when needing to process conflicting stimulus inputs. Here, we employed manipulations of reward-prospect and attentional-preparation levels in a cued-Stroop stimulus conflict task, along with the high temporal resolution of electrical brain recordings, to provide insight into the mechanisms by which reward-prospect and attention interact and modulate cognitive task performance. In this task, the cue indicated whether or not the participant needed to prepare for an upcoming Stroop stimulus and, if so, whether there was the potential for monetary reward (dependent on performance on that trial). Both cued attention and cued reward-prospect enhanced preparatory neural activity, as reflected by increases in the hallmark attention-related negative-polarity ERP slow wave (contingent negative variation [CNV]) and reductions in oscillatory Alpha activity, which was followed by enhanced processing of the subsequent Stroop stimulus. In addition, similar modulations of preparatory neural activity (larger CNVs and reduced Alpha) predicted shorter versus longer response times (RTs) to the subsequent target stimulus, consistent with such modulations reflecting trial-to-trial variations in attention. Particularly striking were the individual differences in the utilization of reward-prospect information. In particular, the size of the reward effects on the preparatory neural activity correlated across participants with the degree to which reward-prospect both facilitated overall task performance (shorter RTs) and reduced conflict-related behavioral interference. Thus, the prospect of reward appears to recruit attentional preparation circuits to enhance processing of task-relevant target information. PMID:24820263

  16. Tetrachloroethene degradation by reducing-agent enhanced Fe(II)/Fe(III) catalyzed percarbonate

    NASA Astrophysics Data System (ADS)

    Miao, Z.; Brusseau, M. L.; Lu, S.; Gu, X.; Yan, N.; Qiu, Z.; Sui, Q.

    2015-12-01

    This project investigated the effect of reducing agents on the degradation of tetrachloroethene(PCE) by Fe(II)/Fe(III) catalyzed sodium percarbonate (SPC). SPC possesses similar function as liquid H2O2, such that free H2O2 is released into solution when percarbonate is mixed with water. The addition of reducing agents, including hydroxylamine hydrochloride, sodium sulfite, ascorbic acid and sodium ascorbate, accelerated the Fe(III)/Fe(II) redoxcycle, leading to a relatively steady Fe(II) concentration and higher production of free radicals. This, in turn, resulted in enhanced PCE oxidation by SPC, with almost complete PCE removal obtained for appropriate Fe and SPC concentrations.The results of chemical probe tests, using nitrobenzene and carbon tetrachloride, demonstrated that HO● was the predominant radical in the system and that O2●-played a minor role. This was further confirmed by the results of electron paramagnetic resonance measurements and salicylic acid hydroxylationanalysis by high performance liquid chromatography(HPLC). PCE degradation decreased significantly with the addition of isopropanol, a strong HO● scavenger, supporting the hypothesis that HO● was primarily responsible for PCE degradation. It should be noted that the release of Cl- was slightly delayed in the first 20 mins, indicating that intermediate products were produced. However, gas chromatography mass spectrometry (GC/MS) analysis did not detect any chlorinated organic compound except PCE, indicating these intermediates were quickly degraded, which resulted in the complete conversion of PCE to CO2. In conclusion, the use of reducing agents to enhance Fe(II)/Fe(III) catalyzed SPC oxidation appears to be a promising approach for the rapid degradation of organic contaminants in groundwater.

  17. Green synthesis of biphasic TiO₂-reduced graphene oxide nanocomposites with highly enhanced photocatalytic activity.

    PubMed

    Sher Shah, Md Selim Arif; Park, A Reum; Zhang, Kan; Park, Jong Hyeok; Yoo, Pil J

    2012-08-01

    A series of TiO(2)-reduced graphene oxide (RGO) nanocomposites were prepared by simple one-step hydrothermal reactions using the titania precursor, TiCl(4) and graphene oxide (GO) without reducing agents. Hydrolysis of TiCl(4) and mild reduction of GO were simultaneously carried out under hydrothermal conditions. While conventional approaches mostly utilize multistep chemical methods wherein strong reducing agents, such as hydrazine, hydroquinone, and sodium borohydride are employed, our method provides the notable advantages of a single step reaction without employing toxic solvents or reducing agents, thereby providing a novel green synthetic route to produce the nanocomposites of RGO and TiO(2). The as-synthesized nanocomposites were characterized by several crystallographic, microscopic, and spectroscopic characterization methods, which enabled confrimation of the robustness of the suggested reaction scheme. Notably, X-ray diffraction and transmission electron micrograph proved that TiO(2) contained both anatase and rutile phases. In addition, the photocatalytic activities of the synthesized composites were measured for the degradation of rhodamine B dye. The catalyst also can degrade a colorless dye such as benzoic acid under visible light. The synthesized nanocomposites of biphasic TiO(2) with RGO showed enhanced catalytic activity compared to conventional TiO(2) photocatalyst, P25. The photocatalytic activity is strongly affected by the concentration of RGO in the nanocomposites, with the best photocatalytic activity observed for the composite of 2.0 wt % RGO. Since the synthesized biphasic TiO(2)-RGO nanocomposites have been shown to effectively reduce the electron-hole recombination rate, it is anticipated that they will be utilized as anode materials in lithium ion batteries. PMID:22788800

  18. Enhanced attachment of Bradyrhizobium japonicum to soybean through reduced root colonization of internally seedborne microorganisms.

    PubMed

    Oehrle, N W; Karr, D B; Kremer, R J; Emerich, D W

    2000-07-01

    Internally seedborne microorganisms are those surviving common surface sterilization procedures. Such microbes often colonize the radicle surface of a germinating soybean (Glycine max) seed, introducing an undefined parameter into studies on attachment and infection by Bradyrhizobium japonicum. Bacterial isolates from surface-sterilized soybean seed, cv. Williams 82 and cv. Maverick, used in our studies, were identified as Agrobacterium radiobacter, Aeromonas sp., Bacillus spp., Chryseomonas luteola, Flavimonas oryzihabitans, and Sphingomonas paucimobilis. Growth of these microbes during seed germination was reduced by treating germinating seeds with 500 micrograms/mL penicillin G. The effects of this antibiotic on seedling development and on B. japonicum 2143 attachment, nodulation, and nitrogen fixation are reported here. Penicillin G treatment of seeds did not reduce seed germination or root tip growth, or affect seedling development. No differences in nodulation kinetics, nitrogen fixation onset or rates were observed. However, the number of B. japonicum attached to treated intact seedlings was enhanced 200-325%, demonstrating that other root-colonizing bacteria can interfere with rhizobial attachment. Penicillin G treatment of soybean seedlings can be used to reduce the root colonizing microbes, which introduce an undefined parameter into studies of attachment of B. japonicum to the soybean root, without affecting plant development.

  19. Reduced linewidth enhancement factor due to excited state transition of quantum dot lasers.

    PubMed

    Xu, Peng-Fei; Ji, Hai-Ming; Xiao, Jin-Long; Gu, Yong-Xian; Huang, Yong-Zhen; Yang, Tao

    2012-04-15

    The carrier induced refractive index change and linewidth enhancement factor α due to ground-state (GS) and excited-state (ES) transitions have been compared by measuring the optical gain spectra from an InAs/GaAs quantum dot (QD) laser structure. It is shown that the ES transition exhibits a reduced α-factor compared to the value due to the GS transition. This result can be explained by the α-factor due to the ES transition having a smaller increase from the non-resonant carriers in the combined state of the wetting layer and InGaAs strain reducing layer than the α-factor increase due to the GS transition, since the relaxation time for carriers from the combined state of the wetting layer and InGaAs strain reducing layer to the ES is shorter than to the GS. The result reported here shows another advantage of using ES QD lasers for optical communication, in addition to their higher modulation speed.

  20. Dual effects of β-cyclodextrin-stabilised silver nanoparticles: enhanced biofilm inhibition and reduced cytotoxicity.

    PubMed

    Jaiswal, Swarna; Bhattacharya, Kunal; McHale, Patrick; Duffy, Brendan

    2015-01-01

    The composition and mode of synthesis of nanoparticles (NPs) can affect interaction with bacterial and human cells differently. The present work describes the ability of β-cyclodextrin (β-CD) capped silver nanoparticles (AgNPs) to inhibit biofilm growth and reduce cytotoxicity. Biofilm formation of Staphylococcus epidermidis CSF 41498 was quantified by a crystal violet assay in the presence of native and capped AgNPs (Ag-10CD and Ag-20CD), and the morphology of the biofilm was observed by scanning electron microscope. The cytotoxicity of the AgNPs against HaCat cells was determined by measuring the increase in intracellular reactive oxygen species and change in mitochondrial membrane potential (ΔΨm). Results indicated that capping AgNPs with β-CD improved their efficacy against S. epidermidis CSF 41498, reduced biofilm formation and their cytotoxicity. The study concluded that β-CD is an effective capping and stabilising agent that reduces toxicity of AgNPs against the mammalian cell while enhancing their antibiofilm activity. PMID:25596861

  1. Non-adrenergic non-cholinergic (NANC) excitatory response of the channel catfish intestine.

    PubMed

    Venugopalan, C S; Holmes, E P; Jarboe, H H; Kleinow, K M

    1994-06-01

    1. Optimal parameters for electrical field stimulation (EFS) of catfish pyloric and middle intestinal segments were determined (15 Hz, 60 V) from a range of frequencies (5-45 Hz) and voltages (40-120 V) using a modified Magnus' method. Contractile responses were produced by EFS which were reproducible and showed no significant difference between the tissues. 2. The contractile cholinergic responses of the tissues to carbachol and acetylcholine (ACh) were blocked by atropine on an equimolar concentration, whereas, these responses were enhanced in the presence of neostigmine, and acetylcholinesterase inhibitor. 3. Adrenergic responses were examined with noradrenaline (NA). NA produced contraction of the segments only, at a concentration of 10(-4) M. Among the various adrenoceptors, beta-adrenoceptor stimulation produced a weak relaxation whereas, both alpha 1- and alpha 2-adrenoceptor stimulation produced contractions, of which alpha 2-induced contraction was of greater magnitude. The beta, alpha 1 and alpha 2 responses were blocked by their respective blocking agents propranolol, prazosin and yohimbine. 4. The autonomic components of the response to EFS were determined by using selected cholinergic and adrenergic antagonists separately or collectively. Cholinergic blockade with atropine did not produce a significant blockade of the EFS-induced response. Similarly, blockade of beta-adrenoceptors with propranolol did not modulate the contractile response to EFS to any significant level. Blockade by prazosin or yohimbine did not significantly change the contractile response to EFS. After a complete blockade of the adrenergic and cholinergic divisions, the intestinal segments still showed a contractile response to EFS which was not significantly different from the control response. This indicated the presence of a non-adrenergic non-cholinergic (NANC) response. 5. Tetrodotoxin, at 10(-6) M, significantly blocked the EFS-induced NANC response suggesting a neurogenic

  2. Subtle learning and memory impairment in an idiopathic rat model of Alzheimer's disease utilizing cholinergic depletions and β-amyloid.

    PubMed

    Deibel, S H; Weishaupt, N; Regis, A M; Hong, N S; Keeley, R J; Balog, R J; Bye, C M; Himmler, S M; Whitehead, S N; McDonald, R J

    2016-09-01

    Alzheimer's disease (AD) is a disease of complex etiology, involving multiple risk factors. When these risk factors are presented concomitantly, cognition and brain pathology are more severely compromised than if those risk factors were presented in isolation. Reduced cholinergic tone and elevated amyloid-beta (Aβ) load are pathological hallmarks of AD. The present study sought to investigate brain pathology and alterations in learning and memory when these two factors were presented together in rats. Rats received either sham surgeries, cholinergic depletions of the medial septum, intracerebroventricular Aβ25-35 injections, or both cholinergic depletion and Aβ25-35 injections (Aβ+ACh group). The Aβ+ACh rats were unimpaired in a striatal dependent visual discrimination task, but had impaired acquisition in the standard version of the Morris water task. However, these rats displayed normal Morris water task retention and no impairment in acquisition of a novel platform location during a single massed training session. Aβ+ACh rats did not have exacerbated brain pathology as indicated by activated astroglia, activated microglia, or accumulation of Aβ. These data suggest that cholinergic depletions and Aβ injections elicit subtle cognitive deficits when behavioural testing is conducted shortly after the presentation of these factors. These factors might have altered hippocampal synaptic plasticity and thus resemble early AD pathology. PMID:27208489

  3. Striatal cholinergic interneuron regulation and circuit effects

    PubMed Central

    Lim, Sean Austin O.; Kang, Un Jung; McGehee, Daniel S.

    2014-01-01

    The striatum plays a central role in motor control and motor learning. Appropriate responses to environmental stimuli, including pursuit of reward or avoidance of aversive experience all require functional striatal circuits. These pathways integrate synaptic inputs from limbic and cortical regions including sensory, motor and motivational information to ultimately connect intention to action. Although many neurotransmitters participate in striatal circuitry, one critically important player is acetylcholine (ACh). Relative to other brain areas, the striatum contains exceptionally high levels of ACh, the enzymes that catalyze its synthesis and breakdown, as well as both nicotinic and muscarinic receptor types that mediate its postsynaptic effects. The principal source of striatal ACh is the cholinergic interneuron (ChI), which comprises only about 1–2% of all striatal cells yet sends dense arbors of projections throughout the striatum. This review summarizes recent advances in our understanding of the factors affecting the excitability of these neurons through acute effects and long term changes in their synaptic inputs. In addition, we discuss the physiological effects of ACh in the striatum, and how changes in ACh levels may contribute to disease states during striatal dysfunction. PMID:25374536

  4. Xenin-25 Potentiates Glucose-dependent Insulinotropic Polypeptide Action via a Novel Cholinergic Relay Mechanism*

    PubMed Central

    Wice, Burton M.; Wang, Songyan; Crimmins, Dan L.; Diggs-Andrews, Kelly A.; Althage, Matthew C.; Ford, Eric L.; Tran, Hung; Ohlendorf, Matthew; Griest, Terry A.; Wang, Qiuling; Fisher, Simon J.; Ladenson, Jack H.; Polonsky, Kenneth S.

    2010-01-01

    The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, “GIP/DT” animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the β-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in β-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM. PMID:20421298

  5. Xenin-25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism.

    PubMed

    Wice, Burton M; Wang, Songyan; Crimmins, Dan L; Diggs-Andrews, Kelly A; Althage, Matthew C; Ford, Eric L; Tran, Hung; Ohlendorf, Matthew; Griest, Terry A; Wang, Qiuling; Fisher, Simon J; Ladenson, Jack H; Polonsky, Kenneth S

    2010-06-25

    The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, "GIP/DT" animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the beta-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in beta-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM. PMID:20421298

  6. Muscarinic and nicotinic cholinergic receptor antagonists differentially mediate acquisition of fructose-conditioned flavor preference and quinine-conditioned flavor avoidance in rats.

    PubMed

    Rotella, Francis M; Olsson, Kerstin; Vig, Vishal; Yenko, Ira; Pagirsky, Jeremy; Kohen, Ilanna; Aminov, Alon; Dindyal, Trisha; Bodnar, Richard J

    2015-09-01

    Rats display both conditioned flavor preference (CFP) for fructose, and conditioned flavor avoidance (CFA) following sweet adulteration with quinine. Previous pharmacological analyses revealed that fructose-CFP expression was significantly reduced by dopamine (DA) D1 or D2 antagonists, but not NMDA or opioid antagonists. Fructose-CFP acquisition was significantly reduced by DA D1, DA D2 or NMDA antagonists, but not opioid antagonists. Quinine-CFA acquisition was significantly enhanced and prolonged by DA D1, NMDA or opioid, but not DA D2 antagonists. Cholinergic interneurons and projections interact with DA systems in the nucleus accumbens and ventral tegmental area. Further, both muscarinic and nicotinic cholinergic receptor signaling have been implicated in sweet intake and development of food-related preferences. Therefore, the present study examined whether systemic administration of muscarinic (scopolamine: SCOP) or nicotinic (mecamylamine: MEC) cholinergic receptor antagonists mediated fructose-CFP expression, fructose-CFP acquisition and quinine-CFA acquisition. For fructose-CFP expression, rats were trained over 10 sessions with a CS+ flavor in 8% fructose and 0.2% saccharin and a CS- flavor in 0.2% saccharin. Two-bottle choice tests with CS+ and CS- flavors mixed in 0.2% saccharin occurred following vehicle, SCOP (0.1-10mg/kg) and MEC (1-8mg/kg). For fructose-CFP acquisition, six groups of rats received vehicle, SCOP (1 or 2.5mg/kg), MEC (4 or 6mg/kg) or a limited intake vehicle control 0.5h prior to 10 CS+ and CS- training sessions followed by six 2-bottle CS+ and CS- choice tests in 0.2% saccharin. For quinine-CFA acquisition, five groups of rats received vehicle, SCOP (1 or 2.5mg/kg) or MEC (4 or 6mg/kg) 0.5h prior to 8 one-bottle CS- (8% fructose+0.2% saccharin: FS) and CS+ (fructose+saccharin+quinine (0.030%: FSQ) training sessions followed by six 2-bottle CS- and CS+ choice tests in fructose-saccharin solutions. Fructose-CFP expression was

  7. Intrinsic Cholinergic Neurons in the Hippocampus: Fact or Artifact?

    PubMed

    Blusztajn, Jan Krzysztof; Rinnofner, Jasmine

    2016-01-01

    It is generally agreed that hippocampal acetylcholine (ACh) is synthesized and released exclusively from the terminals of the long-axon afferents whose cell bodies reside in the medial septum and diagonal band. The search for intrinsic cholinergic neurons in the hippocampus has a long history; however evidence for the existence of these neurons has been inconsistent, with most investigators failing to detect them using in situ hybridization or immunohistochemical staining of the cholinergic markers, choline acetyltransferase (ChAT) or vesicular acetylcholine transporter (VAChT). Advances in the use of bacterial artificial chromosome (BAC) transgenic mice expressing a reporter protein under the control of the genomic elements of the Chat gene (Chat-BAC mice) have facilitated studies of cholinergic neurons. Such mice show robust and faithful expression of the reporter proteins in all known cholinergic cell populations. The availability of the Chat-BAC mice re-ignited interest in hippocampal cholinergic interneurons, because a small number of such reporter-expressing cells is frequently observed in the hippocampus of these mice. However, to date, attempts to confirm that these neurons co-express the endogenous cholinergic marker ChAT, or release ACh, have been unsuccessful. Without such confirmatory evidence it is best to conclude that there are no cholinergic neurons in the hippocampus. Similar considerations apply to other BAC transgenic lines, whose utility as a discovery tool for cell populations heretofore not known to express the genes of interest encoded by the BACs, must be validated by methods that detect expression of the endogenous genes. PMID:27014052

  8. Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function.

    PubMed

    Sussan, Thomas E; Gajghate, Sachin; Chatterjee, Samit; Mandke, Pooja; McCormick, Sarah; Sudini, Kuladeep; Kumar, Sarvesh; Breysse, Patrick N; Diette, Gregory B; Sidhaye, Venkataramana K; Biswal, Shyam

    2015-07-01

    Asthma development and pathogenesis are influenced by the interactions of airway epithelial cells and innate and adaptive immune cells in response to allergens. Oxidative stress is an important mediator of asthmatic phenotypes in these cell types. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and environmental stress. We previously demonstrated that Nrf2-deficient mice have heightened susceptibility to asthma, including elevated oxidative stress, inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. J Exp Med 202: 47-59, 2005). Here we dissected the role of Nrf2 in lung epithelial cells and tested whether genetic or pharmacological activation of Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club cells of the airway epithelium significantly reduced allergen-induced AHR, inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway leakiness and increased airway levels of tight junction proteins zonula occludens-1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial barrier function and increased localization of zonula occludens-1 to the cell surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2'-methoxychalone during the allergen challenge was sufficient to reduce allergic inflammation and AHR. New therapeutic options are needed for asthma, and this study demonstrates that activation of Nrf2 in lung epithelial cells is a novel potential therapeutic target to reduce asthma susceptibility.

  9. Rest Intervals Reduce the Number of Loading Bouts Required to Enhance Bone Formation

    PubMed Central

    Srinivasan, Sundar; Ausk, Brandon J.; Bain, Steven D.; Gardiner, Edith M.; Kwon, Ronald Y.; Gross, Ted S.

    2015-01-01

    Purpose As our society becomes increasingly sedentary, compliance with exercise regimens that require numerous high-energy activities each week become less likely. Alternatively, given an osteogenic exercise intervention that required minimal effort, it is reasonable to presume that participation would be enhanced. Insertion of brief rest-intervals between each cycle of mechanical loading holds potential to achieve this result as substantial osteoblast function is activated by many fewer loading repetitions within each loading bout. Here, we examined the complementary hypothesis that the number of bouts/wk of rest-inserted loading could be reduced from 3/wk without loss of osteogenic efficacy. Methods We conducted a series of 3 wk in vivo experiments that non-invasively exposed the right tibiae of mice to either cyclic (1 Hz) or rest-inserted loading interventions and quantified osteoblast function via dynamic histomorphometry. Results While reducing loading bouts from 3/wk (i.e., 9 total bouts) to 1/wk (3 total bouts) effectively mitigated the osteogenic benefit of cyclic loading, the same reduction did not significantly reduce periosteal bone formation parameters induced by rest-inserted loading. The osteogenic response was robust to the timing of the rest-inserted loading bouts (3 bouts in the first week vs 1 bout/wk for three weeks). However, elimination of any single bout of the three 1/wk bouts mitigated the osteogenic response to rest-inserted loading. Finally, periosteal osteoblast function assessed after the 3 wk intervention was not sensitive to the timing or number of rest-inserted loading bouts. Conclusions We conclude that rest-inserted loading holds potential to retain the osteogenic benefits of mechanical loading with significantly reduced frequency of bouts of activity while also enabling greater flexibility in the timing of the activity. PMID:25207932

  10. Surface modifications of photoanodes in dye sensitized solar cells: enhanced light harvesting and reduced recombination

    NASA Astrophysics Data System (ADS)

    Saxena, Vibha; Aswal, D. K.

    2015-06-01

    In a quest to harvest solar power, dye-sensitized solar cells (DSSCs) have potential for low-cost eco-friendly photovoltaic devices. The major processes which govern the efficiency of a DSSC are photoelectron generation, injection of photo-generated electrons to the conduction band (CB) of the mesoporous nanocrystalline semiconductor (nc-SC); transport of CB electrons through nc-SC and subsequent collection of CB electrons at the counter electrode (CE) through the external circuit; and dye regeneration by redox couple or hole transport layer (HTL). Most of these processes occur at various interfaces of the photoanode. In addition, recombination losses of photo-generated electrons with either dye or redox molecules take place at the interfaces. Therefore, one of the key requirements for high efficiency is to improve light harvesting of the photoanode and to reduce the recombination losses at various interfaces. In this direction, surface modification of the photoanode is the simplest method among the various other approaches available in the literature. In this review, we present a comprehensive discussion on surface modification of the photoanode, which has been adopted in the literature for not only enhancing light harvesting but also reducing recombination. Various approaches towards surface modification of the photoanode discussed are (i) fluorine-doped tin oxide (FTO)/nc-SC interface modified via a compact layer of semiconductor material which blocks exposed sites of FTO to electrolyte (or HTL), (ii) nc-SC/dye interface modification either through acid treatment resulting in enhanced dye loading due to a positively charged surface or by depositing insulating/semiconducting blocking layer on the nc-SC surface, which acts as a tunneling barrier for recombination, (iii) nc-SC/dye interface modified by employing co-adsorbents which helps in reducing the dye aggregation and thereby recombination, and (iv) dye/electrolyte (or dye/HTL) interface modification using

  11. Concanavalin A amplifies both beta-adrenergic and muscarinic cholinergic receptor-adenylate cyclase-linked pathways in cardiac myocytes.

    PubMed Central

    Rocha-Singh, K J; Hines, D K; Honbo, N Y; Karliner, J S

    1991-01-01

    Concanavalin A (Con A) is a tetrameric plant lectin that disrupts plasma membrane-cytoskeletal interactions and alters plasma membrane fluidity. We used Con A as a probe to explore beta-adrenergic and muscarinic cholinergic receptor-mediated regulation of cAMP in intact neonatal rat ventricular myocytes. Preincubation with Con A, 0.5 micrograms/ml, attenuated 1 microM (-)-norepinephrine (NE)-induced downregulation of beta-adrenergic receptors and resulted in a 50% augmentation of cAMP accumulation stimulated by 1 microM NE. Con A also augmented forskolin (1-10 microM)-stimulated cAMP accumulation by an average of 37% (P less than 0.05); however, Con A preincubation had no effect on basal or cholera toxin-stimulated cAMP content. The muscarinic cholinergic agonist carbachol (1-100 microM) decreased 1 microM NE-stimulated cAMP generation by an average of 32% (n = 7, P less than 0.05); preincubation with Con A further enhanced the inhibitory effect of carbachol by 18% (n = 7, P less than 0.05). Carbachol (1 microM) for 2 h decreased muscarinic cholinergic receptor density in whole cells by 33%; preincubation with Con A prevented this receptor downregulation. Con A pretreatment did not affect (-)-isoproterenol- or forskolin-stimulated adenylate cyclase activity in cell homogenates, suggesting that an intact cytoarchitecture is necessary for Con A to augment cAMP formation. We conclude that Con A, through its modulation of beta-adrenergic and muscarinic cholinergic receptor signaling, amplifies both stimulatory and inhibitory adenylate cyclase-linked pathways in intact neonatal ventricular myocytes. These data suggest the possibility that plasma membrane-cytoskeletal interaction is an important regulator of transmembrane signaling because interference with this interaction results in alterations in cAMP accumulation mediated by both beta-adrenergic- and muscarinic cholinergic-adenylate cyclase pathways. PMID:1653274

  12. Hybrid Antibiotic Overcomes Resistance in P. aeruginosa by Enhancing Outer Membrane Penetration and Reducing Efflux.

    PubMed

    Gorityala, Bala Kishan; Guchhait, Goutam; Goswami, Sudeep; Fernando, Dinesh M; Kumar, Ayush; Zhanel, George G; Schweizer, Frank

    2016-09-22

    Therapeutic interventions to treat multidrug-resistant (MDR) Pseudomonas aeruginosa infections are severely limited and often require the use of colistin as drug of last resort. The major challenges impeding the development of novel antipseudomonal agents are the lack of cell penetration and extensive efflux. We have discovered a tobramycin-moxifloxacin hybrid core structure which enhances outer membrane permeability and reduces efflux by dissipating the proton motive force of the cytoplasmic membrane in P. aeruginosa. The optimized hybrid protects Galleria mellonella larvae from the lethal effects of MDR P. aeruginosa. Attempts to select for resistance over a period of 25 days resulted in a 2-fold increase in the minimal inhibitory concentration (MIC) for the hybrid, while moxifloxacin or tobramycin resulted in a 16- and 512-fold increase in MIC. Although the hybrid possesses potent activity against MDR, P. aeruginosa isolates the activity that can be synergized when used in combination with other classes of antibiotics.

  13. Electrochemically Reduced Graphene Oxide on Well-Aligned Titanium Dioxide Nanotube Arrays for Betavoltaic Enhancement.

    PubMed

    Chen, Changsong; Wang, Na; Zhou, Peng; San, Haisheng; Wang, Kaiying; Chen, Xuyuan

    2016-09-21

    We report a novel betavoltaic device with significant conversion efficiency by using electrochemically reduced graphene oxide (ERGO) on TiO2 nanotube arrays (TNTAs) for enhancing the absorption of beta radiation as well as the transportation of carriers. ERGO on TNTAs (G-TNTAs) were prepared by electrochemical anodization and subsequently cyclic voltammetry techniques. A 10 mCi of (63)Ni/Ni source was assembled to G-TNTAs to form the sandwich-type betavoltaic devices (Ni/(63)Ni/G-TNTAs/Ti). By I-V measurements, the optimum betavoltaic device exhibits a significant effective energy conversion efficiency of 26.55% with an open-circuit voltage of 2.38 V and a short-circuit current of 14.69 nAcm(-2). The experimental results indicate that G-TNTAs are a high-potential nanocomposite for developing betavoltaic batteries. PMID:27575802

  14. Electrochemically Reduced Graphene Oxide on Well-Aligned Titanium Dioxide Nanotube Arrays for Betavoltaic Enhancement.

    PubMed

    Chen, Changsong; Wang, Na; Zhou, Peng; San, Haisheng; Wang, Kaiying; Chen, Xuyuan

    2016-09-21

    We report a novel betavoltaic device with significant conversion efficiency by using electrochemically reduced graphene oxide (ERGO) on TiO2 nanotube arrays (TNTAs) for enhancing the absorption of beta radiation as well as the transportation of carriers. ERGO on TNTAs (G-TNTAs) were prepared by electrochemical anodization and subsequently cyclic voltammetry techniques. A 10 mCi of (63)Ni/Ni source was assembled to G-TNTAs to form the sandwich-type betavoltaic devices (Ni/(63)Ni/G-TNTAs/Ti). By I-V measurements, the optimum betavoltaic device exhibits a significant effective energy conversion efficiency of 26.55% with an open-circuit voltage of 2.38 V and a short-circuit current of 14.69 nAcm(-2). The experimental results indicate that G-TNTAs are a high-potential nanocomposite for developing betavoltaic batteries.

  15. Different additives to enhance the gelation of surimi gel with reduced sodium content.

    PubMed

    Cando, Deysi; Herranz, Beatriz; Borderías, A Javier; Moreno, Helena M

    2016-04-01

    This study tested the effect of adding tetra-sodium pyrophosphate, cystine and lysine as surimi gelation enhancers (Alaska Pollock) in order to reduce the sodium content of gels up to 0.3%. These gels were compared with others that contained 3% NaCl content (the amount typically used for surimi processing). To induce protein gelation, gels were first heated and then set at 5 °C/24 h. Once the physicochemical and rheological properties of the gels were determined, cystine and lysine were found to be the most effective additives improving the characteristics of low NaCl surimi gels. The action of these additives is mainly based on the induction of myofibrillar protein unfolding thus facilitating the formation of the types of bonds needed to establish an appropriate network. It was found that a setting period was needed for gel processing to maximize the effect of the additives.

  16. Different additives to enhance the gelation of surimi gel with reduced sodium content.

    PubMed

    Cando, Deysi; Herranz, Beatriz; Borderías, A Javier; Moreno, Helena M

    2016-04-01

    This study tested the effect of adding tetra-sodium pyrophosphate, cystine and lysine as surimi gelation enhancers (Alaska Pollock) in order to reduce the sodium content of gels up to 0.3%. These gels were compared with others that contained 3% NaCl content (the amount typically used for surimi processing). To induce protein gelation, gels were first heated and then set at 5 °C/24 h. Once the physicochemical and rheological properties of the gels were determined, cystine and lysine were found to be the most effective additives improving the characteristics of low NaCl surimi gels. The action of these additives is mainly based on the induction of myofibrillar protein unfolding thus facilitating the formation of the types of bonds needed to establish an appropriate network. It was found that a setting period was needed for gel processing to maximize the effect of the additives. PMID:26593556

  17. Climate change reduces warming potential of nitrous oxide by an enhanced Brewer-Dobson circulation

    NASA Astrophysics Data System (ADS)

    Kracher, Daniela; Reick, Christian H.; Manzini, Elisa; Schultz, Martin G.; Stein, Olaf

    2016-06-01

    The Brewer-Dobson circulation (BDC), which is an important driver of the stratosphere-troposphere exchange, is expected to accelerate with climate change. One particular consequence of this acceleration is the enhanced transport of nitrous oxide (N2O) from its sources at the Earth's surface toward its main sink region in the stratosphere, thus inducing a reduction in its lifetime. N2O is a potent greenhouse gas and the most relevant currently emitted ozone-depleting substance. Here we examine the implications of a reduced N2O lifetime in the context of climate change. We find a decrease in its global warming potential (GWP) and, due to a decline in the atmospheric N2O burden, also a reduction in its total radiative forcing. From the idealized transient global warming simulation we can identify linear regressions for N2O sink, lifetime, and GWP with temperature rise. Our findings are thus not restricted to a particular scenario.

  18. Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity

    PubMed Central

    Takáts, Szabolcs; Varga, Ágnes; Pircs, Karolina; Juhász, Gábor

    2015-01-01

    The HOPS tethering complex facilitates autophagosome-lysosome fusion by binding to Syx17 (Syntaxin 17), the autophagosomal SNARE. Here we show that loss of the core HOPS complex subunit Vps16A enhances autophagosome formation and slows down Drosophila development. Mechanistically, Tor kinase is less active in Vps16A mutants likely due to impaired endocytic and biosynthetic transport to the lysosome, a site of its activation. Tor reactivation by overexpression of Rheb suppresses autophagosome formation and restores growth and developmental timing in these animals. Thus, Vps16A reduces autophagosome numbers both by indirectly restricting their formation rate and by directly promoting their clearance. In contrast, the loss of Syx17 blocks autophagic flux without affecting the induction step in Drosophila. PMID:26061715

  19. [Sodium nitrite reduces lipid accumulation in steatotic cells by enhancing autophagy].

    PubMed

    Zhang, You-jing; Zheng, Nai-rui; Liu, Bin; Ji, Ai-ling; Li, Yan-zhang; Huangfu, Chao-shen

    2015-08-01

    Recent data have revealed that inhibiting autophagy exacerbates lipid accumulation in hepatocytes and nitrite treatment reduces total triglyceride levels in the high-fat diet mice. Therefore, the present study aimed to determine the effects of nitrite on simple hepatic steatosis and the possible role of autophagy. Firstly, steatotic L-02 cells were induced by incubating L-02 cells with 1.2 mmol · L(-1) oleic acid (OA) for 24 h. Secondly, steatotic L-02 cells were treated with 0.2 mmol · L(-1) sodium nitrite (SN) plus 3-methyladenine (3-MA), or chloroquine (CQ) for 24 h, and then lipid accumulation was measured with oil red O staining and triglyceride quantification. The notable steatosis could be observed in L-02 cells following exposure to 1.2 mmol · L(-1) OA for 24 h. Treatment with 0.2 mmol · L(-1) sodium nitrite reduced lipid accumulation in steatotic L-02 cells. 3-MA weakened the ability of sodium nitrite to ameliorate hepatic steatosis. Additionally, the sodium nitrite increased number of LC3-II immunostaining puncta and LC3-II protein expression was confirmed by immunofluorescence or Western blot analysis, and the effects were enhanced by CQ treatment. The number of increased cytoplasm vacuoles and lysosomes increased was confirmed by phase contrast and fluorescence microscope respectively. The increased autolysosome was detected by electron microscopy, this phenomenon could be reversed by CQ treatment. These data demonstrated that sodium nitrite enhanced the autophagic flux and decomposition of triglycerides in steatotic L-02 cells. PMID:26669000

  20. Formation of Random, RIE-Textured Silicon Surfaces with Reduced Reflection and Enhanced Near IR Absorption

    SciTech Connect

    ZAIDI, SALEEM H

    2001-04-01

    The authors have developed novel metal-assisted texturing processes that have led to optically favorable surfaces for solar cells. Large area ({approximately} 200 cm{sup 2}) uniform texturing has been achieved. The physical dimensions of the chamber limited texturing of even larger wafers. Surface contamination and residual RIE-induced damage were removed by incorporation of a complete RCA clean process followed by wet-chemical etching treatments. RIE-textured solar cells with optimized profiles providing performance comparable to the random, wet-chemically etched cells have been demonstrated. A majority of the texture profiles exhibit an enhanced IQE response in the near IR region.using scanning electron microscope measurements, they carried out a detailed analysis of the microstructure of random RIE-textured surfaces. The random microstructure represents a superposition of sub-{micro}m grating structures with a wide distribution of periods, depths, and profiles as determined by the SEM measurements. These structures were modeled using GSOLVER{trademark} software for periodic patterns. The enhanced IR response from random, RIE-textured surfaces is attributed to enhanced coupling of light into the transmitted diffraction orders. These obliquely propagating diffraction orders generate electron-hole pairs closer to the surface, thus, reducing bulk recombination losses relative to a non-scattering, planar surface with identical hemispherical reflection. The optimized texture and damage removal processes have been applied to large area (100--132 cm{sup 2}) multi-crystalline wafers. initial results have demonstrated improved performance relative to planar, control wafers. However, the texture and solar cell fabrication processes require further optimization in the RCA clean, DRE treatments, and emitter formation in order to fully realize the benefits of the low-reflection ({approximately}1-2%) textured surfaces.

  1. Terbium-Doped VO2 Thin Films: Reduced Phase Transition Temperature and Largely Enhanced Luminous Transmittance.

    PubMed

    Wang, Ning; Duchamp, Martial; Dunin-Borkowski, Rafal E; Liu, Shiyu; Zeng, XianTing; Cao, Xun; Long, Yi

    2016-01-26

    Vanadium dioxide (VO2) is a well-known thermochromic material with large IR modulating ability, promising for energy-saving smart windows. The main drawbacks of VO2 are its high phase transition temperature (τ(c) = 68°C), low luminous transmission (T(lum)), and weak solar modulating ability (ΔT(sol)). In this paper, the terbium cation (Tb(3+)) doping was first reported to reduce τ(c) and increase T(lum) of VO2 thin films. Compared with pristine VO2, 2 at. % doping level gives both enhanced T(lum) and ΔT(sol) from 45.8% to 54.0% and 7.7% to 8.3%, respectively. The T(lum) increases with continuous Tb(3+) doping and reaches 79.4% at 6 at. % doping level, representing ∼73.4% relative increment compared with pure VO2. This has surpassed the best reported doped VO2 thin films. The enhanced thermochromic properties is meaningful for smart window applications of VO2 materials. PMID:26729057

  2. Reduced graphene oxide/CeO{sub 2} nanocomposite with enhanced photocatalytic performance

    SciTech Connect

    Kaur, Jasmeet Anand, Kanika; Singh, Gurpreet; Hastir, Anita; Virpal,; Singh, Ravi Chand; Anand, Kanica

    2015-05-15

    In this work, reduced graphene oxide /cerium oxide (RGO/CeO{sub 2}) nanocomposite was synthesized by in situ reduction of cerium nitrate Ce(NO{sub 3}){sub 3}·6H{sub 2}O in the presence of graphene oxide by hydrazine hydrate (N{sub 2}H{sub 4}.H{sub 2}O). The intrinsic characteristics of as-prepared nanocomposite were studied using powder x-ray diffraction (XRD), Raman spectroscopy and field-emission scanning electron microscopy (FESEM). The photocatalytic degradation of methylene blue (MB) was employed as a model reaction to evaluate the photocatalytic activity of the RGO/CeO{sub 2} nanocomposite. The as-obtained RGO/CeO{sub 2} nanocomposite displays a significantly enhanced photocatalytic degradation of MB dye in comparison with bare CeO{sub 2} nanoparticles under sunlight irradiation, which can be attributed to the improved separation of electron-hole pairs and enhanced adsorption performance due to presence of RGO.

  3. Cholinergic afferent stimulation induces axonal function plasticity in adult hippocampal granule cells.

    PubMed

    Martinello, Katiuscia; Huang, Zhuo; Lujan, Rafael; Tran, Baouyen; Watanabe, Masahiko; Cooper, Edward C; Brown, David A; Shah, Mala M

    2015-01-21

    Acetylcholine critically influences hippocampal-dependent learning. Cholinergic fibers innervate hippocampal neuron axons, dendrites, and somata. The effects of acetylcholine on axonal information processing, though, remain unknown. By stimulating cholinergic fibers and making electrophysiological recordings from hippocampal dentate gyrus granule cells, we show that synaptically released acetylcholine preferentially lowered the action potential threshold, enhancing intrinsic excitability and synaptic potential-spike coupling. These effects persisted for at least 30 min after the stimulation paradigm and were due to muscarinic receptor activation. This caused sustained elevation of axonal intracellular Ca(2+) via T-type Ca(2+) channels, as indicated by two-photon imaging. The enhanced Ca(2+) levels inhibited an axonal KV7/M current, decreasing the spike threshold. In support, immunohistochemistry revealed muscarinic M1 receptor, CaV3.2, and KV7.2/7.3 subunit localization in granule cell axons. Since alterations in axonal signaling affect neuronal firing patterns and neurotransmitter release, this is an unreported cellular mechanism by which acetylcholine might, at least partly, enhance cognitive processing. PMID:25578363

  4. Light-responsive threadlike micelles as drag reducing fluids with enhanced heat-transfer capabilities.

    PubMed

    Shi, Haifeng; Wang, Yi; Fang, Bo; Talmon, Yeshayahu; Ge, Wu; Raghavan, Srinivasa R; Zakin, Jacques L

    2011-05-17

    Drag-reducing (DR) surfactant fluids based on threadlike micelles are known to suffer from poor heat-transfer capabilities. Accordingly, the use of these fluids is limited to recirculating systems in which heat exchange is not important. Here, we show for the first time that light-responsive threadlike micelles can offer a potential solution to the above problem. The fluids studied here are composed of the cationic surfactant Ethoquad O/12 PG (EO12) and the sodium salt of trans-ortho-methoxycinnamic acid (OMCA). Initially, these fluids contain numerous threadlike micelles and, in turn, are strongly viscoelastic and effective at reducing drag (up to 75% DR). Upon exposure to UV light, OMCA is photoisomerized from trans to cis. This causes the micelles to shorten considerably, as confirmed by cryo-transmission electron microscopy (cryo-TEM). Because of the absence of long micelles, the UV-irradiated fluid shows lower viscoelasticity and much lower DR properties; however, its heat-transfer properties are considerably superior to the initial fluid. Thus, our study highlights the potential of switching off the DR (and in turn enhancing heat-transfer) at the inlet of a heat exchanger in a recirculating system. While the fluids studied here are not photoreversible, an extension of the above concept would be to subsequently switch on the DR again at the exit of the heat exchanger, thus ensuring an ideal combination of DR and heat-transfer properties.

  5. Enhanced preclinical efficacy of tamoxifen developed as alginate-cysteine/disulfide bond reduced albumin nanoparticles.

    PubMed

    Martínez, A; Muñiz, E; Iglesias, I; Teijón, J M; Blanco, M D

    2012-10-15

    Tamoxifen (TMX) is the most common clinical choice for the treatment of advanced or metastatic estrogen-dependent breast cancer. However, research on new challenging therapies is necessary due to its undesirable side effects and the limitation of the treatment only to the oral route. In this study, the antitumor activity of TMX-loaded nanoparticles based on different mixtures of alginate-cysteine and disulfide bond reduced bovine serum albumin was tested in vivo in MCF-7 nude mice xenograft model. These systems showed an enhancement of the TMX antitumor activity, since lower tumor evolutions and lower tumor growth rates were observed in mice treated with them. Moreover, histological and immunohistochemical studies revealed that treatments with TMX-loaded nanoparticles showed the most regressive and less proliferative tumor tissues. TMX biodistribution studies determined that TMX-loaded nanoparticles caused more accumulation of the drug into the tumor site with undetectable levels of TMX in plasma, reducing the possibility of delivering TMX to other not-targeted organs and, consequently, developing possible side effects. Thus, these TMX nanoparticulate systems are expected to provide a novel approach to the treatment of breast cancer in the future. PMID:22850290

  6. Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution

    PubMed Central

    Kacmarczyk, Thadeous J.; Ishii, Jennifer; Betel, Doron; Alonso, Alicia; Mason, Christopher E.; Figueroa, Maria E.; Melnick, Ari M.

    2015-01-01

    DNA methylation pattern mapping is heavily studied in normal and diseased tissues. A variety of methods have been established to interrogate the cytosine methylation patterns in cells. Reduced representation of whole genome bisulfite sequencing was developed to detect quantitative base pair resolution cytosine methylation patterns at GC-rich genomic loci. This is accomplished by combining the use of a restriction enzyme followed by bisulfite conversion. Enhanced Reduced Representation Bisulfite Sequencing (ERRBS) increases the biologically relevant genomic loci covered and has been used to profile cytosine methylation in DNA from human, mouse and other organisms. ERRBS initiates with restriction enzyme digestion of DNA to generate low molecular weight fragments for use in library preparation. These fragments are subjected to standard library construction for next generation sequencing. Bisulfite conversion of unmethylated cytosines prior to the final amplification step allows for quantitative base resolution of cytosine methylation levels in covered genomic loci. The protocol can be completed within four days. Despite low complexity in the first three bases sequenced, ERRBS libraries yield high quality data when using a designated sequencing control lane. Mapping and bioinformatics analysis is then performed and yields data that can be easily integrated with a variety of genome-wide platforms. ERRBS can utilize small input material quantities making it feasible to process human clinical samples and applicable in a range of research applications. The video produced demonstrates critical steps of the ERRBS protocol. PMID:25742437

  7. Reduced frequency of knowledge of results enhances learning in persons with Parkinson's disease.

    PubMed

    Chiviacowsky, Suzete; Campos, Tiago; Domingues, Marlos Rodrigues

    2010-01-01

    Parkinson's disease (PD) is a progressive neurological disorder, known to cause a large number of motor and non-motor limitations. Research related to factors that affect motor control and learning in people with PD is still relatively limited. The purpose of this study was to compare the effects of different frequencies (100 versus 66%) of knowledge of results (KR) on the learning of a motor skill with spatial demands in participants with PD. Twenty individuals with PD were randomly assigned to one of two groups. The 100% group received KR after each trial, while the 66% group received KR on two thirds of the trials. A linear positioning task with a spatial target was used. Participants carried out the task with the dominant hand while blindfolded. In the acquisition and retention phases, the goal was to position the cursor at a distance of 60 cm from the starting point. The hypothesis was that participants with PD, who practiced with a reduced KR frequency, would demonstrate more effective learning than those who practiced with a 100% KR frequency, similar to previous findings with adults without neurological disorders. The results showed differences between the groups in the retention phase (without KR): The 66% KR group was more accurate and less variable in their performance than the 100% KR group. Thus, reducing KR frequency can enhance motor learning in persons with PD, similar to what has previously been found for unimpaired participants.

  8. Gallium ion implantation greatly reduces thermal conductivity and enhances electronic one of ZnO nanowires

    SciTech Connect

    Xia, Minggang; Cheng, Zhaofang; Han, Jinyun; Zhang, Shengli; Zheng, Minrui; Sow, Chorng-Haur; Thong, John T. L.; Li, Baowen

    2014-05-15

    The electrical and thermal conductivities are measured for individual zinc oxide (ZnO) nanowires with and without gallium ion (Ga{sup +}) implantation at room temperature. Our results show that Ga{sup +} implantation enhances electrical conductivity by one order of magnitude from 1.01 × 10{sup 3} Ω{sup −1}m{sup −1} to 1.46 × 10{sup 4} Ω{sup −1}m{sup −1} and reduces its thermal conductivity by one order of magnitude from 12.7 Wm{sup −1}K{sup −1} to 1.22 Wm{sup −1}K{sup −1} for ZnO nanowires of 100 nm in diameter. The measured thermal conductivities are in good agreement with those in theoretical simulation. The increase of electrical conductivity origins in electron donor doping by Ga{sup +} implantation and the decrease of thermal conductivity is due to the longitudinal and transverse acoustic phonons scattering by Ga{sup +} point scattering. For pristine ZnO nanowires, the thermal conductivity decreases only two times when its diameter reduces from 100 nm to 46 nm. Therefore, Ga{sup +}-implantation may be a more effective method than diameter reduction in improving thermoelectric performance.

  9. Drag-Reducing Polymer Enhances Microvascular Perfusion in the Traumatized Brain with Intracranial Hypertension.

    PubMed

    Bragin, Denis E; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V; Nemoto, Edwin M

    2016-01-01

    Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood-soluble, nontoxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and ischemic limb, but have not yet been studied in the brain. We recently demonstrated that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using in vivo two-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow, and, as a result, reduced tissue hypoxia in both nontraumatized and traumatized rat brains at high intracranial pressure. Our study suggests that DRP could constitute an effective treatment for improving microvascular flow in brain ischemia caused by high intracranial pressure after TBI. PMID:27165871

  10. Navigating the information technology highway: computer solutions to reduce errors and enhance patient safety.

    PubMed

    Koshy, Ranie

    2005-10-01

    Standardized, seamless, integrated information technology in the health-care environment used with other industry tools can markedly decrease preventable errors or adverse events and increase patient safety. According to an Institute of Medicine (IOM) report released in 1999, preventable errors have caused between 44,000 and 98,000 deaths per year. Following the report, President Bill Clinton requested that the Agency of Healthcare Research and Quality, a government agency, look into the issue and fund, at the local or state level, processes that can reduce errors. Funding subsequently was made available for research that utilizes best practice tools in clinical practice to increase patient safety. The Joint Commission on Accreditation of Healthcare Organization has placed a great deal of emphasis on strategies to reduce patient identification errors. Fragmented systems tout the individual as well as enhanced safety applications. These applications, however, are related to prevention in specific conditions and in specific health-care settings. Systems are not integrated with common reference data and common terminology aggregated at a regional or national level to provide access to patient safety risks for timely interventions before errors and adverse events occur. Standardized integrated patient care information systems are not available either on a regional or on a national level. This article examines tangible options to increase patient safety through improved state-of-the-art tools that can be incorporated into the health-care system to prevent errors.

  11. Drag-Reducing Polymer Enhances Microvascular Perfusion in the Traumatized Brain with Intracranial Hypertension.

    PubMed

    Bragin, Denis E; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V; Nemoto, Edwin M

    2016-01-01

    Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood-soluble, nontoxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and ischemic limb, but have not yet been studied in the brain. We recently demonstrated that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using in vivo two-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow, and, as a result, reduced tissue hypoxia in both nontraumatized and traumatized rat brains at high intracranial pressure. Our study suggests that DRP could constitute an effective treatment for improving microvascular flow in brain ischemia caused by high intracranial pressure after TBI.

  12. Enhancement of extracellular cellobiase activity by reducing agents in the filamentous fungus Termitomyces clypeatus.

    PubMed

    Banik, Samudra Prosad; Mukherjee, Soumya; Pal, Swagata; Ghorai, Shakuntala; Majumder, Rajib; Khowala, Suman

    2015-01-01

    Extracellular cellobiase activity of Termitomyces clypeatus increased from 2.9 U ml(-1) to 4.4 and 4.1 in presence of dithiothreitol (DTT) and β-mercaptoethanol (ME), respectively, with a decrease in Km from 0.4 to 0.3 mM (DTT) and 0.35 mM (ME). Catalysis was further enhanced if the reduced enzyme was alkylated and activity increased from 11.4 U ml(-1) (control) to 15.2 (DTT+N-ethylmaleimide) and 15.3 (DTT+iodoacetamide) using p-nitrophenyl-β-D-glucopyranoside and from 14.6 U ml(-1)(control) to 21.9 (DTT+N-ethylmaleimide) and 18.7 (DTT+iodoacetamide) using cellobiose. The reduced enzyme showed 17 % lesser glucose inhibition. CD and tryptophan fluorescence showed no change in secondary structure was caused by DTT up to 50 mM. Cysteine content of the enzyme was 24 %. It is postulated that reduction of disulphide bonds allows better substrate affinity for cellobiase. The studies describe a novel and simple method to increase cellobiase activity for industrial applications.

  13. Nutrient-enhanced diet reduces noise-induced damage to the inner ear and hearing loss.

    PubMed

    Le Prell, Colleen G; Gagnon, Patricia M; Bennett, David C; Ohlemiller, Kevin K

    2011-07-01

    Oxidative stress has been implicated broadly as a cause of cell death and neural degeneration in multiple disease conditions; however, the evidence for successful intervention with dietary antioxidant manipulations has been mixed. In this study, we investigated the potential for protection of cells in the inner ear using a dietary supplement with multiple antioxidant components, which were selected for their potential interactive effectiveness. Protection against permanent threshold shift (PTS) was observed in CBA/J mice maintained on a diet supplemented with a combination of β-carotene, vitamins C and E, and magnesium when compared with PTS in control mice maintained on a nutritionally complete control diet. Although hair cell survival was not enhanced, noise-induced loss of type II fibrocytes in the lateral wall was significantly reduced (P < 0.05), and there was a trend toward less noise-induced loss in strial cell density in animals maintained on the supplemented diet. Taken together, our data suggest that prenoise oral treatment with the high-nutrient diet can protect cells in the inner ear and reduce PTS in mice. The demonstration of functional and morphologic preservation of cells in the inner ear with oral administration of this antioxidant supplemented diet supports the possibility of translation to human patients and suggests an opportunity to evaluate antioxidant protection in mouse models of oxidative stress-related disease and pathology. PMID:21708355

  14. Cholinergic and adrenergic influence on the teleost heart in vivo.

    PubMed

    Axelsson, M; Ehrenström, F; Nilsson, S

    1987-01-01

    The tonical cholinergic and adrenergic influence on the heart rate was investigated in vivo in seven species of marine teleosts (pollack, Pollachius pollachius; cuckoo wrasse, Labrus mixtus; ballan wrasse, Labrus berggylta; five-bearded rockling, Ciliata mustela; tadpole fish, Raniceps raninus; eel-pout, Zoarces viviparus and short-spined sea scorpion, Myoxocephalus scor pius) during rest and, in two of the species (P. pollachius and L. mixtus), also during moderate swimming exercise in a Blazka-type swim tunnel. Ventral aortic blood pressure and heart rate were recorded via a catheter implanted in an afferent branchial artery, and the influence of the cholinergic and adrenergic tonus on the heart rate was assessed by injection of atropine and sotalol respectively. During rest the adrenergic tonus was higher than the cholinergic tonus in all species except L. berggylta, where the reverse was true. In P. pollachius and L. mixtus, exercise appeared to produce a lowering of the cholinergic tonus on the heart and, possibly, a slight increase of the adrenergic tonus. The nature of the adrenergic tonus (humoral or neural) is not clear, but the low plasma concentrations of catecholamines both during rest and exercise could be interpreted in favour of a mainly neural adrenergic tonus on the teleost heart. These experiments are compatible with the view that both a cholinergic inhibitory tonus and an adrenergic excitatory tonus are general features in the control of the teleost heart in vivo, both at rest and during moderate swimming exercise.

  15. Cholinergic functioning in stimulant addiction: implications for medications development.

    PubMed

    Sofuoglu, Mehmet; Mooney, Marc

    2009-11-01

    Acetylcholine, the first neurotransmitter discovered, participates in many CNS functions, including sensory and motor processing, sleep, nociception, mood, stress response, attention, arousal, memory, motivation and reward. These diverse cholinergic effects are mediated by nicotinic- and muscarinic-type cholinergic receptors (nAChR and mAChR, respectively). The goal of this review is to synthesize a growing literature that supports the potential role of acetylcholine as a treatment target for stimulant addiction. Acetylcholine interacts with the dopaminergic reward system in the ventral tegmental area, nucleus accumbens and prefrontal cortex. In the ventral tegmental area, both nAChR and mAChR stimulate the dopaminergic system. In the nucleus accumbens, cholinergic interneurons integrate cortical and subcortical information related to reward. In the prefrontal cortex, the cholinergic system contributes to the cognitive aspects of addiction. Preclinical studies support a facilitative role of nicotinic receptor agonists in the development of stimulant addiction. In contrast, nonselective muscarinic receptor agonists seem to have an inhibitory role. In human studies, acetylcholinesterase inhibitors, which increase synaptic acetylcholine levels, have shown promise for the treatment of stimulant addiction. Further studies testing the efficacy of cholinergic medications for stimulant addiction are warranted. PMID:19845415

  16. Enhanced winter soil frost reduces methane emission during the subsequent growing season in a boreal peatland.

    PubMed

    Zhao, Junbin; Peichl, Matthias; Nilsson, Mats B

    2016-02-01

    Winter climate change may result in reduced snow cover and could, consequently, alter the soil frost regime and biogeochemical processes underlying the exchange of methane (CH4 ) in boreal peatlands. In this study, we investigated the short-term (1-3 years) vs. long-term (11 years) effects of intensified winter soil frost (induced by experimental snow exclusion) on CH4 exchange during the following growing season in a boreal peatland. In the first 3 years (2004-2006), lower CH4 emissions in the treatment plots relative to the control coincided with delayed soil temperature increase in the treatment plots at the beginning of the growing season (May). After 11 treatment years (in 2014), CH4 emissions were lower in the treatment plots relative to the control over the entire growing season, resulting in a reduction in total growing season CH4 emission by 27%. From May to July 2014, reduced sedge leaf area coincided with lower CH4 emissions in the treatment plots compared to the control. From July to August, lower dissolved organic carbon concentrations in the pore water of the treatment plots explained 72% of the differences in CH4 emission between control and treatment. In addition, greater Sphagnum moss growth in the treatment plots resulted in a larger distance between the moss surface and the water table (i.e., increasing the oxic layer) which may have enhanced the CH4 oxidation potential in the treatment plots relative to the control in 2014. The differences in vegetation might also explain the lower temperature sensitivity of CH4 emission observed in the treatment plots relative to the control. Overall, this study suggests that greater soil frost, associated with future winter climate change, might substantially reduce the growing season CH4 emission in boreal peatlands through altering vegetation dynamics and subsequently causing vegetation-mediated effects on CH4 exchange.

  17. Managing tile drainage, subirrigation, and nitrogen fertilization to enhance crop yields and reduce nitrate loss.

    PubMed

    Drury, C F; Tan, C S; Reynolds, W D; Welacky, T W; Oloya, T O; Gaynor, J D

    2009-01-01

    Improving field-crop use of fertilizer nitrogen is essential for protecting water quality and increasing crop yields. The objective of this study was to determine the effectiveness of controlled tile drainage (CD) and controlled tile drainage with subsurface irrigation (CDS) for mitigating off-field nitrate losses and enhancing crop yields. The CD and CDS systems were compared on a clay loam soil to traditional unrestricted tile drainage (UTD) under a corn (Zea Mays L.)-soybean (Glycine Max. (L.) Merr.) rotation at two nitrogen (N) fertilization rates (N1: 150 kg N ha(-1) applied to corn, no N applied to soybean; N2: 200 kg N ha(-1) applied to corn, 50 kg N ha(-1) applied to soybean). The N concentrations in tile flow events with the UTD treatment exceeded the provisional long-term aquatic life limit (LT-ALL) for freshwater (4.7 mg N L(-1)) 72% of the time at the N1 rate and 78% at the N2 rate, whereas only 24% of tile flow events at N1 and 40% at N2 exceeded the LT-ALL for the CDS treatment. Exceedances in N concentration for surface runoff and tile drainage were greater during the growing season than the non-growing season. At the N1 rate, CD and CDS reduced average annual N losses via tile drainage by 44 and 66%, respectively, relative to UTD. At the N2 rate, the average annual decreases in N loss were 31 and 68%, respectively. Crop yields from CDS were increased by an average of 2.8% relative to UTD at the N2 rate but were reduced by an average of 6.5% at the N1 rate. Hence, CD and CDS were effective for reducing average nitrate losses in tile drainage, but CDS increased average crop yields only when additional N fertilizer was applied.

  18. Enhanced winter soil frost reduces methane emission during the subsequent growing season in a boreal peatland.

    PubMed

    Zhao, Junbin; Peichl, Matthias; Nilsson, Mats B

    2016-02-01

    Winter climate change may result in reduced snow cover and could, consequently, alter the soil frost regime and biogeochemical processes underlying the exchange of methane (CH4 ) in boreal peatlands. In this study, we investigated the short-term (1-3 years) vs. long-term (11 years) effects of intensified winter soil frost (induced by experimental snow exclusion) on CH4 exchange during the following growing season in a boreal peatland. In the first 3 years (2004-2006), lower CH4 emissions in the treatment plots relative to the control coincided with delayed soil temperature increase in the treatment plots at the beginning of the growing season (May). After 11 treatment years (in 2014), CH4 emissions were lower in the treatment plots relative to the control over the entire growing season, resulting in a reduction in total growing season CH4 emission by 27%. From May to July 2014, reduced sedge leaf area coincided with lower CH4 emissions in the treatment plots compared to the control. From July to August, lower dissolved organic carbon concentrations in the pore water of the treatment plots explained 72% of the differences in CH4 emission between control and treatment. In addition, greater Sphagnum moss growth in the treatment plots resulted in a larger distance between the moss surface and the water table (i.e., increasing the oxic layer) which may have enhanced the CH4 oxidation potential in the treatment plots relative to the control in 2014. The differences in vegetation might also explain the lower temperature sensitivity of CH4 emission observed in the treatment plots relative to the control. Overall, this study suggests that greater soil frost, associated with future winter climate change, might substantially reduce the growing season CH4 emission in boreal peatlands through altering vegetation dynamics and subsequently causing vegetation-mediated effects on CH4 exchange. PMID:26452333

  19. Enhanced photocatalytic and photoelectrochemical activities of reduced TiO2-x/BiOCl heterojunctions

    NASA Astrophysics Data System (ADS)

    Fu, Rongrong; Zeng, Xiaoqiao; Ma, Lu; Gao, Shanmin; Wang, Qingyao; Wang, Zeyan; Huang, Baibiao; Dai, Ying; Lu, Jun

    2016-04-01

    A key issue to design highly efficient photoelectrodes for hydrogen production is how to prohibit the rapid carrier recombination. In order to use the visible light and reduce the recombination of electrons and holes, reduced TiO2-x/BiOCl heterojunctions are successfully synthesized and the photoelectrodes are assembled in this work. The effects of various Bi/Ti molar ratios on the structural, morphological, optical, photoelectrochemical and photocatalytic activities of the resultant samples are investigated systematically. The TiO2-x nanoparticles contain Ti3+, Ti2+, and oxygen vacancies (Ov), while the BiOCl nanosheets exposed {001} facet. Ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS) results indicate that the existence of Ti3+, Ti2+ and Ov expand the light-response range. Linear scan voltammetry and electrochemical impedance spectroscopy results indicate that more efficient electron transportation is presented in the heterojunctions with the appropriate Bi/Ti molar ratio. Consequently, the reduced TiO2-x/BiOCl heterojunction with the most appropriate Bi/Ti molar ratio exhibits a high photocurrent density of 0.755 mA cm-2 with photoconversion efficiency up to 0.634%, 10.5 and 22.6 times larger than that of pure TiO2 and BiOCl. Furthermore, this heterojunction exhibit 48.38 and 12.54 times enhancement for the visible-light decomposition of rhodamine B compared with pure TiO2 and BiOCl.

  20. Can cholinesterase inhibitors provide additional effects to cholinergic neurotransmission enhancement?

    PubMed

    López, Manuela G; Arias, Esperanza; Sobrado, Mónica; Lorrio, Silvia; Roda, José M; García, Antonio G

    2006-01-01

    The most frequent of the primary degenerative dementias is Alzheimer's disease (AD). The gradual loss of memory and attention in patients suffering from this illness are accompanied by aphasia, apraxia, agnosia, and alterations in visual-spatial perception. This group of symptoms is completed by emotional alterations, psychic instability, and changes in personality that appear in advanced phases of the illness. Different histopathological alterations have been described, like marked atrophy of the cerebral cortex with loss of cortical and subcortical neurons. Other histopathological hallmarks are the formation of senile plaques composed of beta-amyloid (Abeta) and neuro fibrillary tangles composed of hyperphosphorylation of tau protein. PMID:17192661

  1. Cholinergic Enhancement of Frontal Lobe Activity in Mild Cognitive Impairment

    ERIC Educational Resources Information Center

    Saykin, Andrew J.; Wishart, Heather A.; Rabin, Laura A.; Flashman, Laura A.; McHugh, Tara L.; Mamourian, Alexander C.; Santulli, Robert B.

    2004-01-01

    Cholinesterase inhibitors positively affect cognition in Alzheimer's disease (AD) and other conditions, but no controlled functional MRI studies have examined where their effects occur in the brain. We examined the effects of donepezil hydrochloride (Aricept[Registered sign]) on cognition and brain activity in patients with amnestic mild cognitive…

  2. Effects of sustained proNGF blockade on attentional capacities in aged rats with compromised cholinergic system.

    PubMed

    Yegla, B; Parikh, V

    2014-03-01

    Disruption in nerve growth factor (NGF) signaling via tropomyosin-related kinase A (trkA) receptors compromises the integrity of the basal forebrain (BF) cholinergic system, yielding cognitive, specifically attentional, impairments in Alzheimer's disease (AD). Although normal aging is considered a risk factor for AD, the mechanisms underlying the selective vulnerability of the aging cholinergic system to trkA disruption is not clear. The levels of proNGF, a proneurotrophin that possesses higher affinity for p75 receptors, increase in aging. The present study was designed to test the hypothesis that cholinergic and attentional dysfunction in aged rats with reduced BF trkA receptors occurs due to the overactivation of endogenous proNGF signaling. We employed a viral vector that produced trkA shRNA to suppress trkA receptors in the corticopetal cholinergic neurons of aged rats. BF trkA suppression impaired animals' performance on signal trials in both the sustained attention task (SAT) and the cognitively taxing distractor version of SAT (dSAT) and these deficits were normalized by chronic intracerebroventricular administration of proNGF antibody. Moreover, depolarization-evoked acetylcholine (ACh) release and the density of cortical cholinergic fibers were partially restored in these animals. However, SAT/dSAT scores reflecting overall performance did not improve following proNGF blockade in trkA knockdown rats due to impaired performance in non-signal trials. Sustained proNGF blockade alone did not alter baseline attentional performance but produced moderate impairments during challenging conditions. Collectively, our findings indicate that barring proNGF-p75 signaling may exert some beneficial effects on attentional capacities specifically when BF trkA signaling is abrogated. However, endogenous proNGF may also possess neurotrophic effects and blockade of this proneurotrophin may not completely ameliorate attentional impairments in AD and potentially hinder

  3. Enhanced Neural Responses to Imagined Primary Rewards Predict Reduced Monetary Temporal Discounting.

    PubMed

    Hakimi, Shabnam; Hare, Todd A

    2015-09-23

    The pervasive tendency to discount the value of future rewards varies considerably across individuals and has important implications for health and well-being. Here, we used fMRI with human participants to examine whether an individual's neural representation of an imagined primary reward predicts the degree to which the value of delayed monetary payments is discounted. Because future rewards can never be experienced at the time of choice, imagining or simulating the benefits of a future reward may play a critical role in decisions between alternatives with either immediate or delayed benefits. We found that enhanced ventromedial prefrontal cortex response during imagined primary reward receipt was correlated with reduced discounting in a separate monetary intertemporal choice task. Furthermore, activity in enhanced ventromedial prefrontal cortex during reward imagination predicted temporal discounting behavior both between- and within-individual decision makers with 62% and 73% mean balanced accuracy, respectively. These results suggest that the quality of reward imagination may impact the degree to which future outcomes are discounted. Significance statement: We report a novel test of the hypothesis that an important factor influencing the discount rate for future rewards is the quality with which they are imagined or estimated in the present. Previous work has shown that temporal discounting is linked to individual characteristics ranging from general intelligence to the propensity for addiction. We demonstrate that individual differences in a neurobiological measure of primary reward imagination are significantly correlated with discounting rates for future monetary payments. Moreover, our neurobiological measure of imagination can be used to accurately predict choice behavior both between and within individuals. These results suggest that improving reward imagination may be a useful therapeutic target for individuals whose high discount rates promote

  4. A cost analysis of web-enhanced training to reduce alcohol sales to intoxicated bar patrons

    PubMed Central

    Page, Timothy F.; Nederhoff, Dawn M.; Ecklund, Alexandra M.; Horvath, Keith J.; Nelson, Toben F.; Erickson, Darin J.; Toomey, Traci L.

    2016-01-01

    Objective The purpose of this study was to document the development and testing costs of the Enhanced Alcohol Risk Management (eARM) intervention, a web enhanced training program to prevent alcohol sales to intoxicated bar patrons and to estimate its implementation costs in a “real world”, non-research setting. Methods Data for this study were obtained retrospectively from a randomized controlled trial of the eARM intervention, which was conducted across 15 communities in a Midwestern metropolitan area. Inputs and their costs were obtained from records maintained during the randomized controlled trial. Total development and testing costs were computed, and implementation costs were estimated with input from the research team. The average implementation cost per establishment was calculated by dividing the total estimated implementation cost by the number of establishments that participated in the study. This provides an estimate of the resources needed to support a broader dissemination of interventions such as eARM. Results Direct development and testing costs were $484,904. Including the University's overhead cost rate of 51 percent, total development and testing costs were $732,205. Total estimated implementation costs were $179,999 over a 12 month period. The average cost per establishment was $1,588. Conclusions Given the large damage liability awards faced by establishments that serve alcohol to drunk drivers, establishments or their insurance companies may be willing to pay the $1,588 estimated implementation cost in order to limit their exposure to these large damage awards. Therefore, making interventions such as eARM available could be an effective and sustainable policy for reducing alcohol-related incidents. PMID:27087708

  5. The Eng1 β-Glucanase Enhances Histoplasma Virulence by Reducing β-Glucan Exposure

    PubMed Central

    Garfoot, Andrew L.; Shen, Qian; Wüthrich, Marcel; Klein, Bruce S.

    2016-01-01

    ABSTRACT The fungal pathogen Histoplasma capsulatum parasitizes host phagocytes. To avoid antimicrobial immune responses, Histoplasma yeasts must minimize their detection by host receptors while simultaneously interacting with the phagocyte. Pathogenic Histoplasma yeast cells, but not avirulent mycelial cells, secrete the Eng1 protein, which is a member of the glycosylhydrolase 81 (GH81) family. We show that Histoplasma Eng1 is a glucanase that hydrolyzes β-(1,3)-glycosyl linkages but is not required for Histoplasma growth in vitro or for cell separation. However, Histoplasma yeasts lacking Eng1 function have attenuated virulence in vivo, particularly during the cell-mediated immunity stage. Histoplasma yeasts deficient for Eng1 show increased exposure of cell wall β-glucans, which results in enhanced binding to the Dectin-1 β-glucan receptor. Consistent with this, Eng1-deficient yeasts trigger increased tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) cytokine production from macrophages and dendritic cells. While not responsible for large-scale cell wall structure and function, the secreted Eng1 reduces levels of exposed β-glucans at the yeast cell wall, thereby diminishing potential recognition by Dectin-1 and proinflammatory cytokine production by phagocytes. In α-glucan-producing Histoplasma strains, Eng1 acts in concert with α-glucan to minimize β-glucan exposure: α-glucan provides a masking function by covering the β-glucan-rich cell wall, while Eng1 removes any remaining exposed β-glucans. Thus, Histoplasma Eng1 has evolved a specialized pathogenesis function to remove exposed β-glucans, thereby enhancing the ability of yeasts to escape detection by host phagocytes. PMID:27094334

  6. Enhanced monolithic diffraction gratings with high efficiency and reduced polarization sensitivity for remote sensing applications

    NASA Astrophysics Data System (ADS)

    Triebel, Peter; Diehl, Torsten; Moeller, Tobias; Gatto, Alexandre; Pesch, Alexander; Erdmann, Lars H.; Burkhardt, Matthias; Kalies, Alexander

    2015-10-01

    Spectral imaging systems lead to enhanced sensing properties when the sensing system provides sufficient spectral resolution to identify materials from its spectral reflectance signature. The performance of diffraction gratings provides an initial way to improve instrumental resolution. Thus, subsequent manufacturing techniques of high quality gratings are essential to significantly improve the spectral performance. The ZEISS unique technology of manufacturing real-blazed profiles and as well as lamellar profiles comprising transparent substrates is well suited for the production of transmission gratings. In order to reduce high order aberrations, aspherical and free-form surfaces can be alternatively processed to allow more degrees of freedom in the optical design of spectroscopic instruments with less optical elements and therefore size and weight advantages. Prism substrates were used to manufacture monolithic GRISM elements for UV to IR spectral range. Many years of expertise in the research and development of optical coatings enable high transmission anti-reflection coatings from the DUV to the NIR. ZEISS has developed specially adapted coating processes (Ion beam sputtering, ion-assisted deposition and so on) for maintaining the micro-structure of blazed gratings in particular. Besides of transmission gratings, numerous spectrometer setups (e.g. Offner, Rowland circle, Czerny-Turner system layout) working on the optical design principles of reflection gratings. This technology steps can be applied to manufacture high quality reflection gratings from the EUV to the IR applications with an outstanding level of low stray light and ghost diffraction order by employing a combination of holography and reactive ion beam etching together with the in-house coating capabilities. We report on results of transmission gratings on plane and curved substrates and GRISM elements with enhanced efficiency of the grating itself combined with low scattered light in the angular

  7. Spatiotemporal specificity in cholinergic control of neocortical function.

    PubMed

    Muñoz, William; Rudy, Bernardo

    2014-06-01

    Cholinergic actions are critical for normal cortical cognitive functions. The release of acetylcholine (ACh) in neocortex and the impact of this neuromodulator on cortical computations exhibit remarkable spatiotemporal precision, as required for the regulation of behavioral processes underlying attention and learning. We discuss how the organization of the cholinergic projections to the cortex and their release properties might contribute to this specificity. We also review recent studies suggesting that the modulatory influences of ACh on the properties of cortical neurons can have the necessary temporal dynamic range, emphasizing evidence of powerful interneuron subtype-specific effects. We discuss areas that require further investigation and point to technical advances in molecular and genetic manipulations that promise to make headway in understanding the neural bases of cholinergic modulation of cortical cognitive operations. PMID:24637201

  8. Astrocyte Intermediaries of Septal Cholinergic Modulation in the Hippocampus.

    PubMed

    Pabst, Milan; Braganza, Oliver; Dannenberg, Holger; Hu, Wen; Pothmann, Leonie; Rosen, Jurij; Mody, Istvan; van Loo, Karen; Deisseroth, Karl; Becker, Albert J; Schoch, Susanne; Beck, Heinz

    2016-05-18

    The neurotransmitter acetylcholine, derived from the medial septum/diagonal band of Broca complex, has been accorded an important role in hippocampal learning and memory processes. However, the precise mechanisms whereby acetylcholine released from septohippocampal cholinergic neurons acts to modulate hippocampal microcircuits remain unknown. Here, we show that acetylcholine release from cholinergic septohippocampal projections causes a long-lasting GABAergic inhibition of hippocampal dentate granule cells in vivo and in vitro. This inhibition is caused by cholinergic activation of hilar astrocytes, which provide glutamatergic excitation of hilar inhibitory interneurons. These results demonstrate that acetylcholine release can cause slow inhibition of principal neuronal activity via astrocyte intermediaries. PMID:27161528

  9. Coexistence of silver and titanium dioxide nanoparticles: enhancing or reducing environmental risks?

    PubMed

    Zou, Xiaoyan; Shi, Junpeng; Zhang, Hongwu

    2014-09-01

    Due to their bactericidal and photocatalytic characteristics, silver nanoparticles (Ag NPs) and titanium dioxide nanoparticles (TiO2 NPs) are widely used in the fields of environment and physiology. Once these untreated nanoparticles are released into an aquatic environment and encounter one another, there is more uncertainty about their fate and ecotoxicological risks compared with the single nanoparticles. To expand our knowledge of the health and environmental impacts of nanoparticles, we investigated the possible risk of the co-existence of TiO2 NPs and Ag NPs in an aquatic environment using ciliated protozoa (Tetrahymena pyriformis) as an aquatic animal model. In this study, silver ion (Ag(+)) release and physicochemical properties, as well as their effect on oxidative stress biomarkers, were monitored. Continuous illumination (12,000 lx) led to the 20.0% decrease in Ag(+) release in comparison with dark conditions, while TiO2 NPs and continuous illumination resulted in decreasing the Ag(+) concentration to 64.3% in contrast with Ag NPs-only suspensions. Toxicity tests indicated that different illumination modes exerted distinct effects of TiO2 NPs on the toxicity of Ag NPs: no effects, antagonism and synergism in dark, natural light and continuous light, respectively. In the presence of 1.5mg/L (18.8 μM) TiO2 NPs, the toxicity of 1.5 mg/L (13.9 μM) Ag NPs was reduced by 28.7% and increased by 6.93% in natural light and 12,000 lx of continuous light, respectively. After culturing in 12,000 lx continuous light for 24h, SOD activity of the light control surged to 1.96 times compared to the dark control (P<0.001). TiO2 NPs induced a reduction of CAT activity by an average of (36.1±1.7) % in the light. In the natural light reductions in the toxicity of Ag, NPs decrease Ag(+) concentrations via adsorption of Ag(+) onto TiO2 NPs surfaces. The enhancement of Ag NPs toxicity can contribute to the formation of activated TiO2-Ag NPs complexes in continuous light. The

  10. Morphine dependence and withdrawal induced changes in cholinergic signaling

    PubMed Central

    Neugebauer, Nichole M.; Einstein, Emily B.; Lopez, Maria B.; McClure-Begley, Tristan D.; Mineur, Yann S.; Picciotto, Marina R.

    2013-01-01

    Cholinergic signaling is thought to be involved in morphine dependence and withdrawal, but the specific mechanisms involved remain unclear. The current study aimed to identify alterations in the cholinergic system that may contribute to the development of morphine dependence and withdrawal. Acetylcholinesterase (AChE) activity and [3H]-epibatidine binding were evaluated in order to determine if morphine dependence and withdrawal induces alterations in cholinergic signaling or expression of high affinity nicotinic acetylcholine receptors (nAChRs) in the midbrain (MB), medial habenula (MHb) and interpeduncular nucleus (IPN). The effect of cholinergic signaling through nAChRs on morphine-withdrawal induced jumping behavior was then determined. Lastly, the contribution of β4-containing nAChRs receptors in the MHb to morphine-withdrawal induced jumping behavior and neuronal activity as indicated by c-fos expression was assessed. Chronic morphine administration decreased AChE activity in MB and MHb, an effect that was no longer present following precipitated withdrawal. Morphine dependent mice showed increased nicotinic acetylcholine receptor (nAChR) levels in MB. Further, nicotine (0.4 mg/kg) and lobeline (3 mg/kg) decreased jumping behavior while mecamylamine (1 mg/kg) had no effect. Knock-down of β4 subunit-containing nAChRs in the MHb attenuated c-fos activation, but did not decrease morphine withdrawal-induced jumping. Thus, morphine withdrawal induces cholinergic signaling in the MHb, but this does not appear to be responsible for the effects of cholinergic drugs on somatic signs of opiate withdrawal, as measured by jumping behavior. PMID:23651795

  11. Cholinergic excitation from the pedunculopontine tegmental nucleus to the dentate nucleus in the rat.

    PubMed

    Vitale, F; Mattei, C; Capozzo, A; Pietrantoni, I; Mazzone, P; Scarnati, E

    2016-03-11

    In spite of the existence of pedunculopontine tegmental nucleus (PPTg) projections to cerebellar nuclei, their nature and functional role is unknown. These fibers may play a crucial role in postural control and may be involved in the beneficial effects induced by deep-brain stimulation (DBS) of brainstem structures in motor disorders. We investigated the effects of PPTg microstimulation on single-unit activity of dentate, fastigial and interpositus nuclei. The effects of PPTg stimulation were also studied in rats whose PPTg neurons were destroyed by ibotenic acid and subsequently subjected to iontophoretically applied cholinergic antagonists. The main response recorded in cerebellar nuclei was a short-latency (1.5-2 ms) and brief (13-15 ms) orthodromic activation. The dentate nucleus was the most responsive to PPTg stimulation. The destruction of PPTg cells reduced the occurrence of PPTg-evoked activation of dentate neurons, suggesting that the effect was due to stimulation of cell bodies and not due to fibers passing through or close to the PPTg. Application of cholinergic antagonists reduced or eliminated the PPTg-evoked response recorded in the dentate nucleus. The results show that excitation is exerted by the PPTg on the cerebellar nuclei, in particular on the dentate nucleus. Taken together with the reduction of nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in lesioned animals, the iontophoretic experiments suggest that the activation of dentate neurons is due to cholinergic fibers. These data help to explain the effects of DBS of the PPTg on axial motor disabilities in neurodegenerative disorders. PMID:26762800

  12. Regeneration of central cholinergic neurones in the adult rat brain.

    PubMed

    Svendgaard, N A; Björklund, A; Stenevi, U

    1976-01-30

    The regrowth of lesioned central acetylcholinesterase (AChE)-positive axons in the adult rat was studied in irides implanted to two different brain sites: in the caudal diencephalon and hippocampus, and in the hippocampal fimbria. At both implantation sites the cholinergic septo-hippocampal pathways were transected. At 2-4 weeks after lesion, newly formed, probably sprouting fibres could be followed in abundance from the lesioned proximal axon stumps into the iris transplant. Growth of newly formed AChE-positive fibres into the transplant was also observed from lesioned axons in the anterior thalamus, and to a minor extent also from the dorsal and ventral tegmental AChE-positive pathways and the habenulo-interpeduncular tract. The regrowth process of the sprouting AChE-positive, presumed cholinergic fibres into the iris target was studied in further detail in whole-mount preparations of the transplants. For this purpose the irides were removed from the brain, unfolded, spread out on microscope slides, and then stained for AChE. During the first 2-4 weeks after transplantation the sprouting central fibres grew out over large areas of the iris. The new fibres branched profusely into a terminal plexus that covered maximally about half of the iris surface, and in some areas the patterning of the regenerated central fibres mimicked closely that of the normal autonomic cholinergic innervation of the iris. In one series of experiments the AChE-staining was combined with fluorescence histochemical visualization of regenerated adrenergic fibres in the same specimens. In many areas there was a striking congruence in the distributional patterns of the regenerated central cholinergic and adrenergic fibres in the transplant. This indicates that - as in the normal iris - the sprouting cholinergic axons (primarily originating in the lesioned septo-hippocampal pathways) and adrenergic axons (primarily originating in the lesioned axons of the locus neurones) regenerate together

  13. Physiology and immunology of the cholinergic antiinflammatory pathway

    PubMed Central

    Tracey, Kevin J.

    2007-01-01

    Cytokine production by the immune system contributes importantly to both health and disease. The nervous system, via an inflammatory reflex of the vagus nerve, can inhibit cytokine release and thereby prevent tissue injury and death. The efferent neural signaling pathway is termed the cholinergic antiinflammatory pathway. Cholinergic agonists inhibit cytokine synthesis and protect against cytokine-mediated diseases. Stimulation of the vagus nerve prevents the damaging effects of cytokine release in experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, arthritis, and other inflammatory syndromes. Herein is a review of this physiological, functional anatomical mechanism for neurological regulation of cytokine-dependent disease that begins to define an immunological homunculus. PMID:17273548

  14. Enhanced sensitivity in H photofragment detection by two-color reduced-Doppler ion imaging

    SciTech Connect

    Epshtein, Michael; Portnov, Alexander; Kupfer, Rotem; Rosenwaks, Salman; Bar, Ilana

    2013-11-14

    Two-color reduced-Doppler (TCRD) and one-color velocity map imaging (VMI) were used for probing H atom photofragments resulting from the ∼243.1 nm photodissociation of pyrrole. The velocity components of the H photofragments were probed by employing two counterpropagating beams at close and fixed wavelengths of 243.15 and 243.12 nm in TCRD and a single beam at ∼243.1 nm, scanned across the Doppler profile in VMI. The TCRD imaging enabled probing of the entire velocity distribution in a single pulse, resulting in enhanced ionization efficiency, as well as improved sensitivity and signal-to-noise ratio. These advantages were utilized for studying the pyrrole photodissociation at ∼243.1 and 225 nm, where the latter wavelength provided only a slight increase in the H yield over the self-signal from the probe beams. The TCRD imaging enabled obtaining high quality H{sup +} images, even for the low H photofragment yields formed in the 225 nm photolysis process, and allowed determining the velocity distributions and anisotropy parameters and getting insight into pyrrole photodissociation.

  15. Reducing Food Loss and Waste to Enhance Food Security and Environmental Sustainability.

    PubMed

    Shafiee-Jood, Majid; Cai, Ximing

    2016-08-16

    While food shortage remains a big concern in many regions around the world, almost one-third of the total food production is discarded as food loss and waste (FLW). This is associated with about one-quarter of land, water, and fertilizer used for crop production, even though resources and environmental constraints are expected to limit food production around the world. FLW reduction represents a potential opportunity to enhance both food security and environmental sustainability and therefore has received considerable attention recently. By reviewing the recent progress and new developments in the literature, this paper highlights the importance of FLW prevention as a complementary solution to address the Grand Challenge of global food security and environmental sustainability. However, raising awareness only is not enough to realize the expected FLW reduction. We identify the knowledge gaps and opportunities for research by synthesizing the strategies of FLW reduction and the barriers, including (1) filling the data gaps, (2) quantifying the socioeconomic and environmental impacts of FLW reduction strategies, (3) understanding the scale effects, and (4) exploring the impacts of global transitions. It is urgent to take more aggressive yet scientifically based actions to reduce FLW, which require everyone's involvement along the food supply chain, including policy makers, food producers and suppliers, and food consumers. PMID:27428555

  16. Resonant Scanning with Large Field of View Reduces Photobleaching and Enhances Fluorescence Yield in STED Microscopy

    PubMed Central

    Wu, Yong; Wu, Xundong; Lu, Rong; Zhang, Jin; Toro, Ligia; Stefani, Enrico

    2015-01-01

    Photobleaching is a major limitation of superresolution Stimulated Depletion Emission (STED) microscopy. Fast scanning has long been considered an effective means to reduce photobleaching in fluorescence microscopy, but a careful quantitative study of this issue is missing. In this paper, we show that the photobleaching rate in STED microscopy can be slowed down and the fluorescence yield be enhanced by scanning with high speed, enabled by using large field of view in a custom-built resonant-scanning STED microscope. The effect of scanning speed on photobleaching and fluorescence yield is more remarkable at higher levels of depletion laser irradiance, and virtually disappears in conventional confocal microscopy. With ≥6 GW∙cm−2 depletion irradiance, we were able to extend the fluorophore survival time of Atto 647N and Abberior STAR 635P by ~80% with 8-fold wider field of view. We confirm that STED Photobleaching is primarily caused by the depletion light acting upon the excited fluorophores. Experimental data agree with a theoretical model. Our results encourage further increasing the linear scanning speed for photobleaching reduction in STED microscopy. PMID:26424175

  17. Enhanced NH3-Sensitivity of Reduced Graphene Oxide Modified by Tetra-α-Iso-Pentyloxymetallophthalocyanine Derivatives.

    PubMed

    Li, Xiaocheng; Wang, Bin; Wang, Xiaolin; Zhou, Xiaoqing; Chen, Zhimin; He, Chunying; Yu, Zheying; Wu, Yiqun

    2015-12-01

    Three kinds of novel hybrid materials were prepared by noncovalent functionalized reduced graphene oxide (rGO) with tetra-α-iso-pentyloxyphthalocyanine copper (CuPc), tetra-α-iso-pentyloxyphthalocyanine nickel (NiPc) and tetra-α-iso-pentyloxyphthalocyanine lead (PbPc) and characterized by Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-vis), Raman spectra, X-ray photoelectron spectroscopy (XPS), transmission electron microscope (TEM), and atomic force microscope (AFM). The as-synthesized MPc/rGO hybrids show excellent NH3 gas-sensing performance with high response value and fast recovery time compared with bare rGO. The enhancement of the sensing response is mainly attributed to the synergism of gas adsorption of MPc to NH3 gas and conducting network of rGO with greater electron transfer efficiency. Strategies for combining the good properties of rGO and MPc derivatives will open new opportunities for preparing and designing highly efficient rGO chemiresistive gas-sensing hybrid materials for potential applications in gas sensor field. PMID:26403926

  18. Enhanced NH3-Sensitivity of Reduced Graphene Oxide Modified by Tetra-α-Iso-Pentyloxymetallophthalocyanine Derivatives

    NASA Astrophysics Data System (ADS)

    Li, Xiaocheng; Wang, Bin; Wang, Xiaolin; Zhou, Xiaoqing; Chen, Zhimin; He, Chunying; Yu, Zheying; Wu, Yiqun

    2015-09-01

    Three kinds of novel hybrid materials were prepared by noncovalent functionalized reduced graphene oxide (rGO) with tetra-α-iso-pentyloxyphthalocyanine copper (CuPc), tetra-α-iso-pentyloxyphthalocyanine nickel (NiPc) and tetra-α-iso-pentyloxyphthalocyanine lead (PbPc) and characterized by Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-vis), Raman spectra, X-ray photoelectron spectroscopy (XPS), transmission electron microscope (TEM), and atomic force microscope (AFM). The as-synthesized MPc/rGO hybrids show excellent NH3 gas-sensing performance with high response value and fast recovery time compared with bare rGO. The enhancement of the sensing response is mainly attributed to the synergism of gas adsorption of MPc to NH3 gas and conducting network of rGO with greater electron transfer efficiency. Strategies for combining the good properties of rGO and MPc derivatives will open new opportunities for preparing and designing highly efficient rGO chemiresistive gas-sensing hybrid materials for potential applications in gas sensor field.

  19. Reducing Food Loss and Waste to Enhance Food Security and Environmental Sustainability.

    PubMed

    Shafiee-Jood, Majid; Cai, Ximing

    2016-08-16

    While food shortage remains a big concern in many regions around the world, almost one-third of the total food production is discarded as food loss and waste (FLW). This is associated with about one-quarter of land, water, and fertilizer used for crop production, even though resources and environmental constraints are expected to limit food production around the world. FLW reduction represents a potential opportunity to enhance both food security and environmental sustainability and therefore has received considerable attention recently. By reviewing the recent progress and new developments in the literature, this paper highlights the importance of FLW prevention as a complementary solution to address the Grand Challenge of global food security and environmental sustainability. However, raising awareness only is not enough to realize the expected FLW reduction. We identify the knowledge gaps and opportunities for research by synthesizing the strategies of FLW reduction and the barriers, including (1) filling the data gaps, (2) quantifying the socioeconomic and environmental impacts of FLW reduction strategies, (3) understanding the scale effects, and (4) exploring the impacts of global transitions. It is urgent to take more aggressive yet scientifically based actions to reduce FLW, which require everyone's involvement along the food supply chain, including policy makers, food producers and suppliers, and food consumers.

  20. Reduced Graphene Oxide Functionalized with Cobalt Ferrite Nanocomposites for Enhanced Efficient and Lightweight Electromagnetic Wave Absorption.

    PubMed

    Ding, Yi; Liao, Qingliang; Liu, Shuo; Guo, Huijing; Sun, Yihui; Zhang, Guangjie; Zhang, Yue

    2016-01-01

    In this paper, reduced graphene oxide functionalized with cobalt ferrite nanocomposites (CoFe@rGO) as a novel type of electromagnetic wave (EW) absorbing materials was successfully prepared by a three-step chemical method including hydrothermal synthesis, annealing process and mixing with paraffin. The effect of the sample thickness and the amount of paraffin on the EW absorption properties of the composites was studied, revealing that the absorption peaks shifted toward the low frequency regions with the increasing thickness while other conditions had little or no effect. It is found that the CoFe@rGO enhanced both dielectric losses and magnetic losses and had the best EW absorption properties and the wide wavelength coverage of the hole Ku-Band when adding only 5wt% composites to paraffin. Therefore, CoFe@rGO could be used as an efficient and lightweight EW absorber. Compared with the research into traditional absorbing materials, this figures of merit are typically of the same order of magnitude, but given the lightweight nature of the material and the high level of compatibility with mass production standards, making use of CoFe@rGO as an electromagnetic absorber material shows great potential for real product applications. PMID:27587001

  1. Tadalafil enhances working memory, and reduces hippocampal oxidative stress in both young and aged mice.

    PubMed

    Al-Amin, Md Mamun; Hasan, S M Nageeb; Alam, Tanzir; Hasan, Ahmed Tasdid; Hossain, Imran; Didar, Rohini Rowshan; Alam, Md Ashraful; Rahman, Md Mahbubur

    2014-12-15

    Tadalafil, a type-5 phosphodiesterase enzyme inhibitor with long half-life used to treat erectile dysfunction. Recently it has been reported that tadalafil improves cognitive function. Here, we aimed to investigate the age dependent effects of tadalafil on memory, locomotor, behavior, and oxidative stress in the hippocampus. Tadalafil was orally administered everyday (5 mg/kg) to young (2 months) and old (16 months) healthy mice for 4 weeks. Control mice from each group received equal volume of 0.9% normal saline for the same duration. Memory and locomotor activity were tested using radial arm maze and open field test respectively. The level of malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was analyzed and catalase activity was determined from the isolated hippocampus. Treatment with tadalafil in aged mice improves working memory than the corresponding tadalafil treated young mice in radial arm maze test. Tadalafil treated mice traveled less distance in the center and the mean speed of tadalafil treated aged mice was significantly lower than the tadalafil treated young mice in open field test. Tadalafil treatment elicited a decrease of MDA level in the hippocampus of aged mice than that of young mice. APOP level was decreased only in aged mice treated with tadalafil. Treatment with tadalafil decreased NO and increased catalase activity in both young and aged mice. On the basis of previous and our findings, we conclude that tadalafil treatment reduces oxidative stress while increased cGMP level in the hippocampus might be responsible for memory enhancement.

  2. Enhanced sensitivity in H photofragment detection by two-color reduced-Doppler ion imaging

    NASA Astrophysics Data System (ADS)

    Epshtein, Michael; Portnov, Alexander; Kupfer, Rotem; Rosenwaks, Salman; Bar, Ilana

    2013-11-01

    Two-color reduced-Doppler (TCRD) and one-color velocity map imaging (VMI) were used for probing H atom photofragments resulting from the ˜243.1 nm photodissociation of pyrrole. The velocity components of the H photofragments were probed by employing two counterpropagating beams at close and fixed wavelengths of 243.15 and 243.12 nm in TCRD and a single beam at ˜243.1 nm, scanned across the Doppler profile in VMI. The TCRD imaging enabled probing of the entire velocity distribution in a single pulse, resulting in enhanced ionization efficiency, as well as improved sensitivity and signal-to-noise ratio. These advantages were utilized for studying the pyrrole photodissociation at ˜243.1 and 225 nm, where the latter wavelength provided only a slight increase in the H yield over the self-signal from the probe beams. The TCRD imaging enabled obtaining high quality H+ images, even for the low H photofragment yields formed in the 225 nm photolysis process, and allowed determining the velocity distributions and anisotropy parameters and getting insight into pyrrole photodissociation.

  3. Enhanced sensitivity in H photofragment detection by two-color reduced-Doppler ion imaging.

    PubMed

    Epshtein, Michael; Portnov, Alexander; Kupfer, Rotem; Rosenwaks, Salman; Bar, Ilana

    2013-11-14

    Two-color reduced-Doppler (TCRD) and one-color velocity map imaging (VMI) were used for probing H atom photofragments resulting from the ~243.1 nm photodissociation of pyrrole. The velocity components of the H photofragments were probed by employing two counterpropagating beams at close and fixed wavelengths of 243.15 and 243.12 nm in TCRD and a single beam at ~243.1 nm, scanned across the Doppler profile in VMI. The TCRD imaging enabled probing of the entire velocity distribution in a single pulse, resulting in enhanced ionization efficiency, as well as improved sensitivity and signal-to-noise ratio. These advantages were utilized for studying the pyrrole photodissociation at ~243.1 and 225 nm, where the latter wavelength provided only a slight increase in the H yield over the self-signal from the probe beams. The TCRD imaging enabled obtaining high quality H(+) images, even for the low H photofragment yields formed in the 225 nm photolysis process, and allowed determining the velocity distributions and anisotropy parameters and getting insight into pyrrole photodissociation. PMID:24320267

  4. Reduced Graphene Oxide Functionalized with Cobalt Ferrite Nanocomposites for Enhanced Efficient and Lightweight Electromagnetic Wave Absorption

    NASA Astrophysics Data System (ADS)

    Ding, Yi; Liao, Qingliang; Liu, Shuo; Guo, Huijing; Sun, Yihui; Zhang, Guangjie; Zhang, Yue

    2016-09-01

    In this paper, reduced graphene oxide functionalized with cobalt ferrite nanocomposites (CoFe@rGO) as a novel type of electromagnetic wave (EW) absorbing materials was successfully prepared by a three-step chemical method including hydrothermal synthesis, annealing process and mixing with paraffin. The effect of the sample thickness and the amount of paraffin on the EW absorption properties of the composites was studied, revealing that the absorption peaks shifted toward the low frequency regions with the increasing thickness while other conditions had little or no effect. It is found that the CoFe@rGO enhanced both dielectric losses and magnetic losses and had the best EW absorption properties and the wide wavelength coverage of the hole Ku-Band when adding only 5wt% composites to paraffin. Therefore, CoFe@rGO could be used as an efficient and lightweight EW absorber. Compared with the research into traditional absorbing materials, this figures of merit are typically of the same order of magnitude, but given the lightweight nature of the material and the high level of compatibility with mass production standards, making use of CoFe@rGO as an electromagnetic absorber material shows great potential for real product applications.

  5. Swimming Paramecium in magnetically simulated enhanced, reduced, and inverted gravity environments

    PubMed Central

    Guevorkian, Karine; Valles, James M.

    2006-01-01

    Earth's gravity exerts relatively weak forces in the range of 10–100 pN directly on cells in biological systems. Nevertheless, it biases the orientation of swimming unicellular organisms, alters bone cell differentiation, and modifies gene expression in renal cells. A number of methods of simulating different strength gravity environments, such as centrifugation, have been applied for researching the underlying mechanisms. Here, we demonstrate a magnetic force-based technique that is unique in its capability to enhance, reduce, and even invert the effective buoyancy of cells and thus simulate hypergravity, hypogravity, and inverted gravity environments. We apply it to Paramecium caudatum, a single-cell protozoan that varies its swimming propulsion depending on its orientation with respect to gravity, g. In these simulated gravities, denoted by fgm, Paramecium exhibits a linear response up to fgm = 5 g, modifying its swimming as it would in the hypergravity of a centrifuge. Moreover, experiments from fgm = 0 to −5 g show that the response is symmetric, implying that the regulation of the swimming speed is primarily related to the buoyancy of the cell. The response becomes nonlinear for fgm >5 g. At fgm = 10 g, many paramecia “stall” (i.e., swim in place against the force), exerting a maximum propulsion force estimated to be 0.7 nN. These findings establish a general technique for applying continuously variable forces to cells or cell populations suitable for exploring their force transduction mechanisms. PMID:16916937

  6. Reduced Graphene Oxide Functionalized with Cobalt Ferrite Nanocomposites for Enhanced Efficient and Lightweight Electromagnetic Wave Absorption

    PubMed Central

    Ding, Yi; Liao, Qingliang; Liu, Shuo; Guo, Huijing; Sun, Yihui; Zhang, Guangjie; Zhang, Yue

    2016-01-01

    In this paper, reduced graphene oxide functionalized with cobalt ferrite nanocomposites (CoFe@rGO) as a novel type of electromagnetic wave (EW) absorbing materials was successfully prepared by a three-step chemical method including hydrothermal synthesis, annealing process and mixing with paraffin. The effect of the sample thickness and the amount of paraffin on the EW absorption properties of the composites was studied, revealing that the absorption peaks shifted toward the low frequency regions with the increasing thickness while other conditions had little or no effect. It is found that the CoFe@rGO enhanced both dielectric losses and magnetic losses and had the best EW absorption properties and the wide wavelength coverage of the hole Ku-Band when adding only 5wt% composites to paraffin. Therefore, CoFe@rGO could be used as an efficient and lightweight EW absorber. Compared with the research into traditional absorbing materials, this figures of merit are typically of the same order of magnitude, but given the lightweight nature of the material and the high level of compatibility with mass production standards, making use of CoFe@rGO as an electromagnetic absorber material shows great potential for real product applications. PMID:27587001

  7. Nasturtium officinale reduces oxidative stress and enhances antioxidant capacity in hypercholesterolaemic rats.

    PubMed

    Yazdanparast, Razieh; Bahramikia, Seifollah; Ardestani, Amin

    2008-04-15

    Nasturtium officinale R. Br. (Brassicaceae) has been used as a home remedy by the people of south eastern (SE) region of Iran as a medicinal plant. This therapeutical application has been attributed to Nasturtium officinale (N. officinale) antioxidant capacity which is mostly tested by means of cell-free assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). In addition, the antioxidant effect of N. officinale extract has been investigated in hypercholesterolaemic rats in vivo. The results revealed that the extract has notable scavenging activity against DPPH radicals as well as potent reducing power in FRAP assay. Intragastric administration of N. officinale (500 mg/kg body weight per day) to groups of hypercholesterolaemic rats for 30 days lowered their blood total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels by 37, 44 and 48%, respectively. However, the blood high density lipoprotein cholesterol (HDL-C) levels in the same treated rats increased by 16%. To evaluate the mechanism(s) of action, we studied the antioxidative potential of N. officinale extract in terms of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and also the level of reduced glutathione (GSH) in the liver tissues. In addition, hepatic tissue malondialdehyde level (MDA, an index of lipid peroxidation) was also determined. Under hypercholesterolaemic condition, hepatic MDA was increased. Moreover, our data indicated GSH depletion along with significant reduction in the activities of CAT and SOD in rats fed high-fat diet rats. On the other hand, significant elevation in the activities of GPx and GR were seen in the same group of rats. Treatment of hypercholesterolaemic rats with N. officinale extract significantly increased the GSH level along with enhanced CAT and SOD activities in liver tissues. Furthermore, N. officinale extract significantly

  8. Inhibition of cholinergic pathways in Drosophila melanogaster by α-conotoxins

    PubMed Central

    Heghinian, Mari D.; Mejia, Monica; Adams, David J.; Godenschwege, Tanja A.; Marí, Frank

    2015-01-01

    Nicotinic acetylcholine receptors (nAChRs) play a pivotal role in synaptic transmission of neuronal signaling pathways and are fundamentally involved in neuronal disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia. In vertebrates, cholinergic pathways can be selectively inhibited by α-conotoxins; we show that in the model organism Drosophila, the cholinergic component of the giant fiber system is inhibited by α-conotoxins MII, AuIB, BuIA, EI, PeIA, and ImI. The injection of 45 pmol/fly of each toxin dramatically decreases the response of the giant fiber to dorsal longitudinal muscle (GF-DLM) connection to 20 ± 13.9% for MII; 26 ± 13.7% for AuIB, 12 ± 9.9% for BuIA, 30 ± 11.3% for EI, 1 ± 1% for PeIA, and 34 ± 15.4% for ImI. Through bioassay-guided fractionation of the venom of Conus brunneus, we found BruIB, an α-conotoxin that inhibits Drosophila nicotinic receptors but not its vertebrate counterparts. GF-DLM responses decreased to 43.7 ± 8.02% on injection of 45 pmol/fly of BruIB. We manipulated the Dα7 nAChR to mimic the selectivity of its vertebrate counterpart by placing structurally guided point mutations in the conotoxin-binding site. This manipulation rendered vertebrate-like behavior in the Drosophila system, enhancing the suitability of Drosophila as an in vivo tool to carry out studies related to human neuronal diseases.—Heghinian, M. D., Mejia, M., Adams, D. J., Godenschwege, T. A., Marí, F. Inhibition of cholinergic pathways in Drosophila melanogaster by α-conotoxins. PMID:25466886

  9. Cholinergic modulation of fast inhibitory and excitatory transmission to pedunculopontine thalamic projecting neurons.

    PubMed

    Ye, Meijun; Hayar, Abdallah; Strotman, Beau; Garcia-Rill, Edgar

    2010-05-01

    The pedunculopontine nucleus (PPN) is part of the cholinergic arm of the reticular activating system, which is mostly active during waking and rapid-eye movement sleep. The PPN projects to the thalamus and receives cholinergic inputs from the laterodorsal tegmental nucleus and contralateral PPN. We employed retrograde labeling and whole cell recordings to determine the modulation of GABAergic, glycinergic, and glutamatergic transmission to PPN thalamic projecting neurons, and their postsynaptic responses to the nonspecific cholinergic agonist carbachol. M2 and M4 muscarinic receptor-modulated inhibitory postsynaptic responses were observed in 73% of PPN output neurons; in 12.9%, M1 and nicotinic receptor-mediated excitation was detected; and muscarinic and nicotinic-modulated fast inhibitory followed by slow excitatory biphasic responses were evident in 6.7% of cells. A significant increase in the frequency of spontaneous excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents during carbachol application was observed in 66.2% and 65.2% of efferent neurons, respectively. This effect was blocked by a M1 antagonist or nonselective muscarinic blocker, indicating that glutamatergic, GABAergic, and/or glycinergic neurons projecting to PPN output neurons are excited through muscarinic receptors. Decreases in the frequency of miniature EPSCs, and amplitude of electrical stimulation-evoked EPSCs, were blocked by a M2 antagonist, suggesting the presence of M2Rs at terminals of presynaptic glutamatergic neurons. Carbachol-induced multiple types of postsynaptic responses, enhancing both inhibitory and excitatory fast transmission to PPN thalamic projecting neurons through muscarinic receptors. These results provide possible implications for the generation of different frequency oscillations in PPN thalamic projecting neurons during distinct sleep-wake states. PMID:20181729

  10. Cholinergic Modulation of Fast Inhibitory and Excitatory Transmission to Pedunculopontine Thalamic Projecting Neurons

    PubMed Central

    Ye, Meijun; Hayar, Abdallah; Strotman, Beau

    2010-01-01

    The pedunculopontine nucleus (PPN) is part of the cholinergic arm of the reticular activating system, which is mostly active during waking and rapid-eye movement sleep. The PPN projects to the thalamus and receives cholinergic inputs from the laterodorsal tegmental nucleus and contralateral PPN. We employed retrograde labeling and whole cell recordings to determine the modulation of GABAergic, glycinergic, and glutamatergic transmission to PPN thalamic projecting neurons, and their postsynaptic responses to the nonspecific cholinergic agonist carbachol. M2 and M4 muscarinic receptor-modulated inhibitory postsynaptic responses were observed in 73% of PPN output neurons; in 12.9%, M1 and nicotinic receptor-mediated excitation was detected; and muscarinic and nicotinic-modulated fast inhibitory followed by slow excitatory biphasic responses were evident in 6.7% of cells. A significant increase in the frequency of spontaneous excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents during carbachol application was observed in 66.2% and 65.2% of efferent neurons, respectively. This effect was blocked by a M1 antagonist or nonselective muscarinic blocker, indicating that glutamatergic, GABAergic, and/or glycinergic neurons projecting to PPN output neurons are excited through muscarinic receptors. Decreases in the frequency of miniature EPSCs, and amplitude of electrical stimulation-evoked EPSCs, were blocked by a M2 antagonist, suggesting the presence of M2Rs at terminals of presynaptic glutamatergic neurons. Carbachol-induced multiple types of postsynaptic responses, enhancing both inhibitory and excitatory fast transmission to PPN thalamic projecting neurons through muscarinic receptors. These results provide possible implications for the generation of different frequency oscillations in PPN thalamic projecting neurons during distinct sleep-wake states. PMID:20181729

  11. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats.

    PubMed

    Srivastava, Pranay; Yadav, Rajesh S; Chandravanshi, Lalit P; Shukla, Rajendra K; Dhuriya, Yogesh K; Chauhan, Lalit K S; Dwivedi, Hari N; Pant, Aditiya B; Khanna, Vinay K

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20mg/kg body weight, p.o) and curcumin (100mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. PMID:24952339

  12. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats.

    PubMed

    Srivastava, Pranay; Yadav, Rajesh S; Chandravanshi, Lalit P; Shukla, Rajendra K; Dhuriya, Yogesh K; Chauhan, Lalit K S; Dwivedi, Hari N; Pant, Aditiya B; Khanna, Vinay K

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20mg/kg body weight, p.o) and curcumin (100mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin.

  13. Neurotrophin receptor p75 mediates the uptake of the amyloid beta (Aβ) peptide, guiding it to lysosomes for degradation in basal forebrain cholinergic neurons.

    PubMed

    Ovsepian, Saak V; Antyborzec, Inga; O'Leary, Valerie B; Zaborszky, Laszlo; Herms, Jochen; Oliver Dolly, J

    2014-09-01

    A fascinating yet perhaps overlooked trait of the p75 neurotrophin receptor (p75(NTR)) is its ability to bind ligands with no obvious neurotrophic function. Using cultured basal forebrain (BF) neurons, this study demonstrates selective internalization of amyloid β (Aβ) 1-42 in conjunction with p75(NTR) (labelled with IgG192-Cy3) by cholinergic cells. Active under resting conditions, this process was enhanced by high K(+) stimulation and was insensitive to inhibitors of regulated synaptic activity-tetrodotoxin or botulinum neurotoxins (BoNT type/A and/B). Blockade of sarco-endoplasmic reticulum (SERCA) Ca(2+) ATPase with thapsigargin and CPA or chelation of Ca(2+) with EGTA-AM strongly suppressed the endocytosis of p75(NTR), implicating the role of ER released Ca(2+). The uptake of IgG192-Cy3 was also reduced by T-type Ca(2+) channel blocker mibefradil but not Cd(2+), an indiscriminate blocker of high voltage-activated Ca(2+) currents. A strong co-localization of IgG192-Cy3 with late endosome (Rab7) or lysosome (Lamp1) qualifier proteins suggest these compartments as the primary destination for internalized IgG192 and Aβ. Selective uptake and labeling of BF cholinergic cells with IgG192-Cy3 injected into the prefrontal cortex was verified also in vivo. The significance of these findings in relation to Aβ clearance in the cerebral cortex and pathophysiology of Alzheimer's disease is discussed. PMID:23716278

  14. Hepcidin Bound to α2-Macroglobulin Reduces Ferroportin-1 Expression and Enhances Its Activity at Reducing Serum Iron Levels

    PubMed Central

    Huang, Michael Li-Hsuan; Austin, Christopher J. D.; Sari, Marie-Agnès; Suryo Rahmanto, Yohan; Ponka, Prem; Vyoral, Daniel; Richardson, Des R.

    2013-01-01

    Hepcidin regulates iron metabolism by down-regulating ferroportin-1 (Fpn1). We demonstrated that hepcidin is complexed to the blood transport protein, α2-macroglobulin (α2M) (Peslova, G., Petrak, J., Kuzelova, K., Hrdy, I., Halada, P., Kuchel, P. W., Soe-Lin, S., Ponka, P., Sutak, R., Becker, E., Huang, M. L., Suryo Rahmanto, Y., Richardson, D. R., and Vyoral, D. (2009) Blood 113, 6225–6236). However, nothing is known about the mechanism of hepcidin binding to α2M or the effects of the α2M·hepcidin complex in vivo. We show that decreased Fpn1 expression can be mediated by hepcidin bound to native α2M and also, for the first time, hepcidin bound to methylamine-activated α2M (α2M-MA). Passage of high molecular weight α2M·hepcidin or α2M-MA·hepcidin complexes (≈725 kDa) through a Sephadex G-25 size exclusion column retained their ability to decrease Fpn1 expression. Further studies using ultrafiltration indicated that hepcidin binding to α2M and α2M-MA was labile, resulting in some release from the protein, and this may explain its urinary excretion. To determine whether α2M-MA·hepcidin is delivered to cells via the α2M receptor (Lrp1), we assessed α2M uptake and Fpn1 expression in Lrp1−/− and Lrp1+/+ cells. Interestingly, α2M·hepcidin or α2M-MA·hepcidin demonstrated similar activities at decreasing Fpn1 expression in Lrp1−/− and Lrp1+/+ cells, indicating that Lrp1 is not essential for Fpn1 regulation. In vivo, hepcidin bound to α2M or α2M-MA did not affect plasma clearance of α2M/α2M-MA. However, serum iron levels were reduced to a significantly greater extent in mice treated with α2M·hepcidin or α2M-MA·hepcidin relative to unbound hepcidin. This effect could be mediated by the ability of α2M or α2M-MA to retard kidney filtration of bound hepcidin, increasing its half-life. A model is proposed that suggests that unlike proteases, which are irreversibly bound to activated α2M, hepcidin remains labile and available to down

  15. Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG-saporin and 5,7-dihydroxytryptamine: neurochemical and behavioural characterization.

    PubMed

    Lehmann, O; Jeltsch, H; Lehnardt, O; Pain, L; Lazarus, C; Cassel, J C

    2000-01-01

    This study assessed behavioural and neurochemical effects of i.c.v. injections of both the cholinergic toxin 192 IgG-saporin (2 microgram) and the serotonergic toxin 5,7-dihydroxytryptamine (5,7-DHT; 150 microgram) in Long-Evans female rats. Dependent behavioural variables were locomotor activity, forced T-maze alternation, beam walking, Morris water-maze (working and reference memory) and radial-maze performances. After killing by microwave irradiation, the concentrations of acetylcholine, monoamines and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus, frontoparietal cortex and striatum. 192 IgG-saporin reduced the concentration of acetylcholine by approximately 40% in the frontoparietal cortex and hippocampus, but had no effect in the striatum. 5,7-DHT lesions reduced the concentration of serotonin by 60% in the frontoparietal cortex and 80% in the hippocampus and striatum. Noradrenaline was unchanged in all structures except the ventral hippocampus where it was slightly increased in rats given 192 IgG-saporin. Cholinergic lesions induced severe motor deficits but had no other effect. Serotonergic lesions produced diurnal and nocturnal hyperactivity but had no other effect. Rats with combined lesions were more active than those with only serotonergic lesions, showed motor dysfunctions similar to those found in rats with cholinergic lesions alone, and exhibited impaired performances in the T-maze alternation test, the water-maze working memory test and the radial-maze. Taken together and although cholinergic lesions were not maximal, these data show that 192 IgG-saporin and 5,7-DHT lesions can be combined to selectively damage cholinergic and serotonergic neurons, and confirm that cholinergic-serotonergic interactions play an important role in some aspects of memory, particularly in spatial working memory. PMID:10651861

  16. Alcohol and Sleep Restriction Combined Reduces Vigilant Attention, Whereas Sleep Restriction Alone Enhances Distractibility

    PubMed Central

    Lee, James; Manousakis, Jessica; Fielding, Joanne; Anderson, Clare

    2015-01-01

    , Manousakis J, Fielding J, Anderson C. Alcohol and sleep restriction combined reduces vigilant attention, whereas sleep restriction alone enhances distractibility. SLEEP 2015;38(5):765–775. PMID:25515101

  17. Enhanced preventive programme at a beryllium oxide ceramics facility reduces beryllium sensitisation among new workers

    PubMed Central

    Cummings, Kristin J; Deubner, David C; Day, Gregory A; Henneberger, Paul K; Kitt, Margaret M; Kent, Michael S; Kreiss, Kathleen; Schuler, Christine R

    2007-01-01

    Background A 1998 survey at a beryllium oxide ceramics manufacturing facility found that 10% of workers hired in the previous 6 years had beryllium sensitisation as determined by the beryllium lymphocyte proliferation test (BeLPT). In response, the facility implemented an enhanced preventive programme to reduce sensitisation, including increased respiratory and dermal protection and particle migration control. Aim To assess the programme's effectiveness in preventing sensitisation. Methods In 2000, the facility began testing newly hired workers for beryllium sensitisation with the BeLPT at time of hire and during employment. The sensitisation rate and prevalence for workers hired from 2000 to 2004 were compared with that for workers hired from 1993 to 1998, who were tested in the 1998 survey. Facility environmental conditions for both time periods were evaluated. Results Newly hired workers in both cohorts worked for a mean of 16 months. Of the 97 workers hired from 2000 to 2004 with at least one employment BeLPT result, four had abnormal results at time of hire and one became sensitised during employment. Of the 69 workers hired from 1993 to 1998 and tested in 1998, six were found to be sensitised. The sensitisation rate for the 2000–4 workers was 0.7–2.7/1000 person‐months of employment, and that for the 1993–8 workers was 5.6/1000 person‐months, at least 2.1 (95% confidence interval (CI) 0.6 to 8.4) and up to 8.2 (95% CI 1.2 to 188.8) times higher than that for the 2000–4 workers. The sensitisation prevalence for the 2000–4 workers was 1% and that for the 1993–8 workers was 8.7%, 8.4 (95% CI 1.04 to 68.49) times higher than that for the 2000–4 workers. Airborne beryllium levels for production workers for the two time periods were similar. Conclusions A comprehensive preventive programme reduced beryllium sensitisation in new workers during the first years of employment, despite airborne beryllium levels for production workers that were

  18. Nitrogen Limitation is Reducing the Enhancement of NPP by Elevated CO2 in a Deciduous Forest

    SciTech Connect

    Norby, Richard J; Warren, Jeffrey; Iversen, Colleen M; Medlyn, Belinda; McMurtrie, Ross; Hoffman, Forrest M

    2008-01-01

    Accurate model representation of the long-term response of forested ecosystems to elevated atmospheric CO2 concentrations (eCO2) is important for predictions of future concentrations of CO2. For biogeochemical models that predict the response of net primary productivity (NPP) to eCO2, free-air CO2 enrichment (FACE) experiments provide the only source of data for comparison. A synthesis of forest FACE experiments reported a 23% increase in NPP in eCO2, and this result has been used as a model benchmark. Here, we provide new evidence from a FACE experiment in a deciduous forest in Tennessee that N limitation has significantly reduced the stimulation of NPP by eCO2, consistent with predictions from ecosystem and global models that incorporate N feedbacks. The Liquidambar styraciflua stand has been exposed to current ambient atmospheric CO2 or air enriched with CO2 to 550 ppm since 1998. Results from the first 6 years of the experiment indicated that NPP was significantly enhanced by eCO2 and that this was a consistent and sustained response. Now, with 10 years of data, our analysis must be revised. The response of NPP to eCO2 has declined from 24% in 2001-2003 to 9% in 2007. The diminishing response to eCO2 since 2004 coincides with declining NPP in ambient CO2 plots. Productivity of this forest stand is limited by N availability, and the steady decline in forest NPP is closely related to changes in the N economy, as evidenced by declining foliar N concentrations. There is a strong linear relationship between foliar [N] and NPP, and the steeper slope in eCO2 indicates that the NPP response to eCO2 should diminish as foliar N declines. Increased fine-root production and root proliferation deeper in the soil have sustained N uptake, but not to an extent sufficient to benefit aboveground production. The mechanistic basis of the N effect on NPP resides in the photosynthetic machinery. The linear relationships between Jmax and Vcmax with foliar [N] did not change from 1998

  19. Disparate cholinergic currents in rat principal trigeminal sensory nucleus neurons mediated by M1 and M2 receptors: a possible mechanism for selective gating of afferent sensory neurotransmission.

    PubMed

    Kohlmeier, Kristi A; Soja, Peter J; Kristensen, Morten P

    2006-06-01

    Neurons situated in the principal sensory trigeminal nucleus (PSTN) convey orofacial sensory inputs to thalamic relay regions and higher brain centres, and the excitability of these ascending tract cells is modulated across sleep/wakefulness states and during pain conditions. Moreover, acetylcholine release changes profoundly across sleep/wakefulness states and ascending sensory neurotransmission is altered by cholinergic agonists. An intriguing possibility is, therefore, that cholinergic mechanisms mediate such state-dependent modulation of PSTN tract neurons. We tested the hypotheses that cholinergic agonists can modulate PSTN cell excitability and that such effects are mediated by muscarinic receptor subtypes, using patch-clamp methods in rat and mouse. In all examined cells, carbachol elicited an electrophysiological response that was independent of action potential generation as it persisted in the presence of tetrodotoxin. Responses were of three types: depolarization, hyperpolarization or a biphasic response consisting of hyperpolarization followed by depolarization. In voltage-clamp mode, carbachol evoked corresponding inward, outward or biphasic currents. Moreover, immunostaining for the vesicle-associated choline transporter showed cholinergic innervation of the PSTN. Using muscarinic receptor antagonists, we found that carbachol-elicited PSTN neuron hyperpolarization was mediated by M2 receptors and depolarization, in large part, by M1 receptors. These data suggest that acetylcholine acting on M1 and M2 receptors may contribute to selective excitability enhancement or depression in individual, rostrally projecting sensory neurons. Such selective gating effects via cholinergic input may play a functional role in modulation of ascending sensory transmission, including across behavioral states typified by distinct cholinergic tone, e.g. sleep/wakefulness arousal levels or neuropathic pain conditions. PMID:16820015

  20. Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability.

    PubMed

    Greenbury, Sam F; Schaper, Steffen; Ahnert, Sebastian E; Louis, Ard A

    2016-03-01

    Mutational neighbourhoods in genotype-phenotype (GP) maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps-a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure-to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i) If a particular (non-neutral) phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii) If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii) If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i) and ii) reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii) may instead facilitate evolutionary exploration and so

  1. Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability

    PubMed Central

    Greenbury, Sam F.; Schaper, Steffen; Ahnert, Sebastian E.; Louis, Ard A.

    2016-01-01

    Mutational neighbourhoods in genotype-phenotype (GP) maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps—a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure—to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i) If a particular (non-neutral) phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii) If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii) If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i) and ii) reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii) may instead facilitate evolutionary exploration and so

  2. Reduced mobility of fomesafen through enhanced adsorption in biochar-amended soil.

    PubMed

    Khorram, Mahdi Safaei; Wang, Yun; Jin, Xiangxiang; Fang, Hua; Yu, Yunlong

    2015-06-01

    The residual soil material resulting from biomass thermochemical transformation during carbon separation, known as biochar, has been introduced as a soil amendment because of its numerous environmental benefits, including uses for contaminated land management. Adsorption and leaching of fomesafen in soils amended with 3 different rates of rice hull biochar (0.5%, 1%, and 2% w/w) under laboratory conditions were investigated, and studies were performed following a batch equilibration adsorption-desorption procedure and a column experiment for leaching. Adsorption-desorption data fit with the Freundlich equation well. The adsorption coefficient of fomesafen sharply increased from 0.59 to 0.99 to 8.02 to 22.23 when the amount of biochar amendment in the soil increased from 0% to 2% (w/w). In addition, a strong correlation was found between the amount of adsorbed fomesafen and the rate of amended biochar (r > 0.992, p < 0.01). Furthermore, biochar amendments reduced the desorption percentage of fomesafen in the soils. The outcomes of the leaching experiment also illustrated that the lowest fomesafen concentration in the leachate (21.4%) occurred in the soil amended with 2% (w/w) biochar. Moreover, the adsorption coefficients (K(f)(ads)) of the soil were positively correlated with the total amount of adsorbed fomesafen in the corresponding soil columns (r = 0.990, p < 0.01) and negatively correlated with the leachate percentage (r = 0.987, p < 0.05). The results of the present study suggest that biochar amendments in agricultural soils likely alter the fate of herbicides by decreasing their transport through enhanced adsorption.

  3. Enhanced production of human influenza virus in PBS-12SF cells with a reduced interferon response

    PubMed Central

    Carvajal-Yepes, Monica; Sporer, Kelly RB; Carter, Jenna L; Colvin, Christopher J; Coussens, Paul M

    2015-01-01

    Influenza is one of the most important infectious diseases in humans. The best way to prevent severe illness caused by influenza infection is vaccination. Cell culture-derived influenza vaccines are being considered in addition to the widely used egg-based system in order to support the increasing seasonal demand and to be prepared in case of a pandemic. Cell culture based systems offer increased safety, capacity, and flexibility with reduced downstream processing relative to embryonated eggs. We have previously reported a chick embryo cell line, termed PBS-12SF, that supports replication of human and avian influenza A viruses to high titers (>107 PFU/ml) without the need for exogenous proteases or serum proteins. Viral infections in cells are limited by the Interferon (IFN) response typified by production of type I IFNs that bind to the IFNα/β receptor and activate an antiviral state. In this study, we investigated how neutralizing the interferon (IFN) response in PBS-12SF cells, via shRNA-mediated knock-down of IFNAR1 mRNA expression, affects influenza virus production. We were successful in knocking down ∼90% of IFNAR1 protein expression by this method, resulting in a significant decrease in the response to recombinant chIFNα stimulation in PBS-12SF cells as shown by a reduction in expression of interferon-responsive genes when compared to control cells. Additionally; IFNAR1-knock-down cells displayed enhanced viral HA production and released more virus into cell culture supernatants than parental PBS-12SF cells. PMID:26090991

  4. HIPS-GLAD core shell nanorod array photodetectors with enhanced photocurrent and reduced dark current

    NASA Astrophysics Data System (ADS)

    Keles, Filiz; Cansizoglu, Hilal; Badraddin, Emad O.; Brozak, Matthew P.; Watanabe, Fumiya; Karabacak, Tansel

    2016-10-01

    Vertically aligned core/shell nanorod array photodetectors were fabricated by high pressure sputter (HIPS) deposition of copper indium sulfide (CIS) films on glancing angle deposited (GLAD) indium sulfide (In2S3) nanorods. For comparison, we also studied nanorod photodetectors with conventional low pressure sputtered (LPS) CIS film coatings and counterpart thin film devices incorporating HIPS or LPS-CIS on In2S3 films. HIPS-GLAD core/shell photodetectors have shown a superior photocurrent density response along with lowest dark current density. Photoresponsivity defined with the photocurrent density/dark current density ratio γ = |J ph/J dark| was about ∼1820 for HIPS-GLAD nanorod devices, which is several orders of magnitude higher compared to those of LPS-CIS thin film (γ ∼ 2) and HIPS-CIS thin film (γ ∼ 9) devices, and also about four-fold higher than LPS-CIS nanorod devices (γ ∼ 490). Enhanced photoresponsivity is attributed to the porous microstructure and improved conformality of HIPS-CIS film around the In2S3 nanorods confirmed by SEM and EDS measurements. Due to randomization of the sputtered flux at higher working gas pressures, HIPS can provide a more conformal while at the same time a voidy low-density film around nanostructured surfaces. Reduced interelectrode distance and improved p–n junction interface due to the more uniform conformality of HIPS-CIS result in a higher photocurrent in our HIPS-GLAD devices. In addition, the voids in HIPS-CIS film as a result of its porous nature can behave as highly resistive spots that lower the dark current. Therefore, we have demonstrated that by utilizing a simple and low-temperature HIPS-GLAD method, high-photocurrent and low-dark-current photodetectors can be achieved by controlling the conformality and microstructure of a shell layer around nanorod arrays. HIPS shell coating method can be extended to almost any type of nanostructured substrate.

  5. Cholinergic activity correlates with reserve proxies in Alzheimer's disease.

    PubMed

    Garibotto, Valentina; Tettamanti, Marco; Marcone, Alessandra; Florea, Ioana; Panzacchi, Andrea; Moresco, Rosamaria; Virta, Jere R; Rinne, Juha; Cappa, Stefano F; Perani, Daniela

    2013-11-01

    The clinical expression of Alzheimer's disease (AD) occurs as neuropathology exceeds the brain "reserve capacity." A possible association between the cholinergic system and reserve is suggested by preclinical observations that the cholinergic system allows cortical plasticity and by clinical observations of variable responses to cholinergic treatments depending on the patient's educational level. The aim of this study was to investigate the association of reserve proxies, that is, education and occupation, with acetylcholinesterase (AChE) activity, measured voxelwise by [(11)C]-MP4A and positron emission tomography (PET), in 9 healthy controls (HC), 7 patients with early probable AD, and 9 subjects with mild cognitive impairment (MCI) at the time of PET imaging, who progressed to AD at follow-up (prodromal AD). The analysis of prodromal and early AD showed positive correlations between education and AChE activity in the hippocampus, bilaterally, and between occupation and AChE activity in the right posterior cingulate gyrus. The significant correlation between AChE activity in structures belonging to the memory network and reserve proxies suggests that the brain reserve in AD is associated with a preserved/stimulated cholinergic neurotransmission.

  6. Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves.

    PubMed

    Ford, Kevin J; Félix, Aude L; Feller, Marla B

    2012-01-18

    Before vision, a transient network of recurrently connected cholinergic interneurons, called starburst amacrine cells (SACs), generates spontaneous retinal waves. Despite an absence of robust inhibition, cholinergic retinal waves initiate infrequently and propagate within finite boundaries. Here, we combine a variety of electrophysiological and imaging techniques and computational modeling to elucidate the mechanisms underlying these spatial and temporal properties of waves in developing mouse retina. Waves initiate via rare spontaneous depolarizations of SACs. Waves propagate through recurrent cholinergic connections between SACs and volume release of ACh as demonstrated using paired recordings and a cell-based ACh optical sensor. Perforated-patch recordings and two-photon calcium imaging reveal that individual SACs have slow afterhyperpolarizations that induce SACs to have variable depolarizations during sequential waves. Using a computational model in which the properties of SACs are based on these physiological measurements, we reproduce the slow frequency, speed, and finite size of recorded waves. This study represents a detailed description of the circuit that mediates cholinergic retinal waves and indicates that variability of the interneurons that generate this network activity may be critical for the robustness of waves across different species and stages of development.

  7. Physical Chemistry to the Rescue: Differentiating Nicotinic and Cholinergic Agonists

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Researches suggest that two agonists can bind to the same binding site of an important transmembrane protein and elicit a biological response through strikingly different binding interactions. Evidence is provided which suggests two possible types of nicotinic acetylcholine receptor agonist binding like acetlycholine (cholinergic) or like nicotine…

  8. Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves

    PubMed Central

    Ford, Kevin J.; Félix, Aude L.; Feller, Marla B.

    2012-01-01

    Prior to vision, a transient network of recurrently connected cholinergic interneurons, called starburst amacrine cells (SACs), generates spontaneous retinal waves. Despite an absence of robust inhibition, cholinergic retinal waves initiate infrequently and propagate within finite boundaries. Here we combine a variety of electrophysiological and imaging techniques and computational modeling to elucidate the mechanisms underlying these spatial and temporal properties of waves in developing mouse retina. Waves initiate via rare spontaneous depolarizations of SACs. Waves propagate through recurrent cholinergic connections between SACs and volume release of ACh as demonstrated using paired recordings and a cell-based ACh optical sensor. Perforated patch recordings and two-photon calcium imaging reveal that individual SACs have slow afterhyperpolarizations that induce SACs to have variable depolarizations during sequential waves. Using a computational model in which the properties of SACs are based on these physiological measurements, we reproduce the slow frequency, speed, and finite size of recorded waves. This study represents a detailed description of the circuit that mediates cholinergic retinal waves and indicates that variability of the interneurons that generate this network activity may be critical for the robustness of waves across different species and stages of development. PMID:22262883

  9. The cholinergic hypothesis of Alzheimer's disease: a review of progress

    PubMed Central

    Francis, P.; Palmer, A.; Snape, M.; Wilcock, G.

    1999-01-01

    Alzheimer's disease is one of the most common causes of mental deterioration in elderly people, accounting for around 50%-60% of the overall cases of dementia among persons over 65 years of age. The past two decades have witnessed a considerable research effort directed towards discovering the cause of Alzheimer's disease with the ultimate hope of developing safe and effective pharmacological treatments. This article examines the existing scientific applicability of the original cholinergic hypothesis of Alzheimer's disease by describing the biochemical and histopathological changes of neurotransmitter markers that occur in the brains of patients with Alzheimer's disease both at postmortem and neurosurgical cerebral biopsy and the behavioural consequences of cholinomimetic drugs and cholinergic lesions. Such studies have resulted in the discovery of an association between a decline in learning and memory, and a deficit in excitatory amino acid (EAA) neurotransmission, together with important roles for the cholinergic system in attentional processing and as a modulator of EAA neurotransmission. Accordingly, although there is presently no "cure" for Alzheimer's disease, a large number of potential therapeutic interventions have emerged that are designed to correct loss of presynaptic cholinergic function. A few of these compounds have confirmed efficacy in delaying the deterioration of symptoms of Alzheimer's disease, a valuable treatment target considering the progressive nature of the disease. Indeed, three compounds have received European approval for the treatment of the cognitive symptoms of Alzheimer's disease, first tacrine and more recently, donepezil and rivastigmine, all of which are cholinesterase inhibitors.

 PMID:10071091

  10. Autocrine control of angiogenesis by endogenous acetylcholine in an in vitro model using human endothelial cells: evidence for an autocrine cholinergic system in endothelial cells.

    PubMed

    Dhein, Stefan; Wermke, Alice; von Salisch, Sandy; Schlegel, Franziska; Stepan, Holger; Dohmen, Pascal Maria; Kostelka, Martin; Mohr, Friedrich-Wilhelm

    2015-05-01

    We wanted to elucidate whether acetylcholine as the endogenous ligand at cholinoceptors (ChRs) may have effects on angiogenesis and whether they are transduced through muscarinic or nicotinic ChRs. Human umbilical vein endothelial cells were cultured until confluence and thereafter seeded in Matrigel in vitro angiogenesis assays for 18 hours. During the entire cell culture and angiogenesis period, cells were treated with vehicle, eserine (1 μM), in the absence or presence of additional atropine (1 μM) or mecamylamine (1 μM). Finally, the resulting angiogenetic network was investigated histologically. Eserine significantly enhanced acetylcholine formation. When acetylcholine acted through muscarinic ChRs (eserine + mecamylamine), we observed enhanced complexity of the angiogenic network pattern with increased tube length and cell number. In contrast, when acting through nicotinic ChRs (eserine + atropine), we found reduced complexity of pattern with less branches, shorter tubes, and reduced cell number. If acting on both types of ChRs (eserine alone), there were only very small effects. Using α-bungarotoxin, lobeline, and dihydro-β-erythroidine, we also could show that these effects to various degrees involve α7, α3/β2, and α4/β2 n-ChRs. In conclusion, our results support the hypothesis that human umbilical vein endothelial cells possess an autocrine nonneuronal cholinergic system regulating angiogenesic branch formation through the partially opposing effects of n-ChRs and m-ChRs.

  11. Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment

    PubMed Central

    Peter, Jessica; Lahr, Jacob; Minkova, Lora; Lauer, Eliza; Grothe, Michel J.; Teipel, Stefan; Köstering, Lena; Kaller, Christoph P.; Heimbach, Bernhard; Hüll, Michael; Normann, Claus; Nissen, Christoph; Reis, Janine; Klöppel, Stefan

    2016-01-01

    Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer’s disease. We simultaneously assessed the structural and functional integrity of the cholinergic system in 20 patients with MCI and 20 matched healthy controls and examined their effect on verbal episodic memory via multivariate regression analyses. Mediating effects of either cholinergic function or hippocampal volume on the relationship between cholinergic structure and episodic memory were computed. In MCI, a less intact structure and function of the cholinergic system was found. A smaller cholinergic structure was significantly correlated with a functionally more active cholinergic system in patients, but not in controls. This association was not modulated by age or disease severity, arguing against compensational processes. Further analyses indicated that neither functional nor structural changes in the cholinergic system influence verbal episodic memory at the MCI stage. In fact, those associations were fully mediated by hippocampal volume. Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of cholinergic treatment at this disease stage. PMID:27340852

  12. The effect of the augmentation of cholinergic neurotransmission by nicotine on EEG indices of visuospatial attention.

    PubMed

    Logemann, H N A; Böcker, K B E; Deschamps, P K H; Kemner, C; Kenemans, J L

    2014-03-01

    The cholinergic system has been implicated in visuospatial attention but the exact role remains unclear. In visuospatial attention, bias refers to neuronal signals that modulate the sensitivity of sensory cortex, while disengagement refers to the decoupling of attention making reorienting possible. In the current study we investigated the effect of facilitating cholinergic neurotransmission by nicotine (Nicorette Freshmint 2mg, polacrilex chewing gum) on behavioral and electrophysiological indices of bias and disengagement. Sixteen non-smoking participants performed in a Visual Spatial Cueing (VSC) task while EEG was recorded. A randomized, single-blind, crossover design was implemented. Based on the scarce literature, it was expected that nicotine would specifically augment disengagement related processing, especially manifest as an increase of the modulation of the Late Positive Deflection (LPD) by validity of cueing. No effect was expected on bias related components (cue-locked: EDAN, LDAP; target-locked: P1 and N1 modulations). Results show weak indications for a reduction of the reaction time validity effect by nicotine, but only for half of the sample in which the validity effect on the pretest was largest. Nicotine reduced the result of bias as indexed by a reduced P1 modulation by validity, especially in subjects with strong peripheral responses to nicotine. Nicotine did not affect ERP manifestations of the directing of bias (EDAN, LDAP) or disengagement (LPD).

  13. The effect of the augmentation of cholinergic neurotransmission by nicotine on EEG indices of visuospatial attention.

    PubMed

    Logemann, H N A; Böcker, K B E; Deschamps, P K H; Kemner, C; Kenemans, J L

    2014-03-01

    The cholinergic system has been implicated in visuospatial attention but the exact role remains unclear. In visuospatial attention, bias refers to neuronal signals that modulate the sensitivity of sensory cortex, while disengagement refers to the decoupling of attention making reorienting possible. In the current study we investigated the effect of facilitating cholinergic neurotransmission by nicotine (Nicorette Freshmint 2mg, polacrilex chewing gum) on behavioral and electrophysiological indices of bias and disengagement. Sixteen non-smoking participants performed in a Visual Spatial Cueing (VSC) task while EEG was recorded. A randomized, single-blind, crossover design was implemented. Based on the scarce literature, it was expected that nicotine would specifically augment disengagement related processing, especially manifest as an increase of the modulation of the Late Positive Deflection (LPD) by validity of cueing. No effect was expected on bias related components (cue-locked: EDAN, LDAP; target-locked: P1 and N1 modulations). Results show weak indications for a reduction of the reaction time validity effect by nicotine, but only for half of the sample in which the validity effect on the pretest was largest. Nicotine reduced the result of bias as indexed by a reduced P1 modulation by validity, especially in subjects with strong peripheral responses to nicotine. Nicotine did not affect ERP manifestations of the directing of bias (EDAN, LDAP) or disengagement (LPD). PMID:24316088

  14. Positron emission tomography (PET) studies of dopaminergic/cholinergic interactions in the baboon brain

    SciTech Connect

    Dewey, S.L.; Brodie, J.D.; Fowler, J.S.; MacGregor, R.R.; Schlyer, D.J.; King, P.T.; Alexoff, D.L.; Volkow, N.D.; Shiue, C.Y.; Wolf, A.P. )

    1990-01-01

    Interactions between the dopaminergic D2 receptor system and the muscarinic cholinergic system in the corpus striatum of adult female baboons (Papio anubis) were examined using positron emission tomography (PET) combined with (18F)N-methylspiroperidol (( 18F)NMSP) (to probe D2 receptor availability) and (N-11C-methyl)benztropine (to probe muscarinic cholinergic receptor availability). Pretreatment with benztropine, a long-lasting anticholinergic drug, bilaterally reduced the incorporation of radioactivity in the corpus striatum but did not alter that observed in the cerebellum or the rate of metabolism of (18F)NMSP in plasma. Pretreatment with unlabelled NMSP, a potent dopaminergic antagonist, reduced the incorporation of (N-11C-methyl)benztropine in all brain regions, with the greatest effect being in the corpus striatum greater than cortex greater than thalamus greater than cerebellum, but did not alter the rate of metabolism of the labelled benztropine in the plasma. These reductions in the incorporation of either (18F)NMSP or (N-11C-methyl)benztropine exceeded the normal variation in tracer incorporation in repeated studies in the same animal. This study demonstrates that PET can be used as a tool for investigating interactions between neurochemically different yet functionally linked neurotransmitters systems in vivo and provides insight into the consequences of multiple pharmacologic administration.

  15. Cholinergic and perfusion brain networks in Parkinson disease dementia

    PubMed Central

    McKeith, Ian G.; Burn, David J.; Wyper, David J.; O'Brien, John T.; Taylor, John-Paul

    2016-01-01

    Objective: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil. Methods: Forty-nine participants (25 PDD and 24 elderly controls) underwent 123I-QNB and 99mTc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs). Results: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor–naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks. Conclusion: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition. PMID:27306636

  16. Involvement of the cholinergic system in conditioning and perceptual memory.

    PubMed

    Robinson, Lianne; Platt, Bettina; Riedel, Gernot

    2011-08-10

    The cholinergic systems play a pivotal role in learning and memory, and have been the centre of attention when it comes to diseases containing cognitive deficits. It is therefore not surprising, that the cholinergic transmitter system has experienced detailed examination of its role in numerous behavioural situations not least with the perspective that cognition may be rescued with appropriate cholinergic 'boosters'. Here we reviewed the literature on (i) cholinergic lesions, (ii) pharmacological intervention of muscarinic or nicotinic system, or (iii) genetic deletion of selective receptor subtypes with respect to sensory discrimination and conditioning procedures. We consider visual, auditory, olfactory and somatosensory processing first before discussing more complex tasks such as startle responses, latent inhibition, negative patterning, eye blink and fear conditioning, and passive avoidance paradigms. An overarching reoccurring theme is that lesions of the cholinergic projection neurones of the basal forebrain impact negatively on acquisition learning in these paradigms and blockade of muscarinic (and to a lesser extent nicotinic) receptors in the target structures produce similar behavioural deficits. While these pertain mainly to impairments in acquisition learning, some rare cases extend to memory consolidation. Such single case observations warranted replication and more in-depth studies. Intriguingly, receptor blockade or receptor gene knockout repeatedly produced contradictory results (for example in fear conditioning) and combined studies, in which genetically altered mice are pharmacological manipulated, are so far missing. However, they are desperately needed to clarify underlying reasons for these contradictions. Consistently, stimulation of either muscarinic (mainly M(1)) or nicotinic (predominantly α7) receptors was beneficial for learning and memory formation across all paradigms supporting the notion that research into the development and

  17. A Cost Analysis of Web-Enhanced Training to Reduce Alcohol Sales to Intoxicated Bar Patrons

    ERIC Educational Resources Information Center

    Page, Timothy F.; Nederhoff, Dawn M.; Ecklund, Alexandra M.; Horvath, Keith J.; Nelson, Toben F.; Erickson, Darin J.; Toomey, Traci L.

    2015-01-01

    Objective: The purpose of this study was to document the development and testing costs of the Enhanced Alcohol Risk Management (eARM) intervention, a web enhanced training program to prevent alcohol sales to intoxicated bar patrons and to estimate its implementation costs in a "real world", non-research setting. Methods: Data for this…

  18. The memory-ameliorating effects of Artemisia princeps var. orientalis against cholinergic dysfunction in mice.

    PubMed

    Liu, Xiaotong; Kim, Dong Hyun; Kim, Jong Min; Park, Se Jin; Cai, Mudan; Jang, Dae Sik; Ryu, Jong Hoon

    2012-01-01

    Artemisia princeps var. orientalis (Compositae) is widely distributed in China, Japan and Korea and is known to have anti-inflammatory and anti-oxidative activities. The ethyl acetate fraction of ethanolic extract of A. princeps var. orientalis (AEA) was found to inhibit acetylcholinesterase activity in a dose-dependent manner in vitro (IC(50) value: 541.4 ± 67.5 μg/ml). Therefore, we investigated the effects of AEA on scopolamine-induced learning and memory impairment using the passive avoidance, the Y-maze, and the Morris water maze tasks in mice. AEA (100 or 200 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairments in the passive avoidance and Y-maze tasks (p < 0.05). In the Morris water maze task, AEA (200 mg/kg, p.o.) significantly shortened escape latencies in training trials and increased both swimming time spent in the target zone and probe crossing numbers during the probe trial as compared with scopolamine-treated mice (p < 0.05). Additionally, the ameliorating effect of AEA on scopolamine-induced memory impairment was antagonized by a subeffective dose of MK-801. These results suggest that AEA could be an effective treatment against cholinergic dysfunction and its effect is mediated by the enhancement of the cholinergic neurotransmitter system via NMDA receptor signaling or acetylcholinesterase inhibition.

  19. Chronic administration of troxerutin protects mouse brain against D-galactose-induced impairment of cholinergic system.

    PubMed

    Lu, Jun; Wu, Dong-Mei; Hu, Bin; Cheng, Wei; Zheng, Yuan-Lin; Zhang, Zi-Feng; Ye, Qin; Fan, Shao-Hua; Shan, Qun; Wang, Yong-Jian

    2010-02-01

    Previous evidence showed that administration of d-galactose (d-gal) increased ROS production and resulted in impairment of cholinergic system. Troxerutin, a natural bioflavonoid, has been reported to have many benefits and medicinal properties. In this study, we evaluated the protective effect of troxerutin against d-gal-induced impairment of cholinergic system, and explored the potential mechanism of its action. Our results displayed that troxerutin administration significantly improved behavioral performance of d-gal-treated mice in step-through test and morris water maze task. One of the potential mechanisms of this action was decreased AGEs, ROS and protein carbonyl levels in the basal forebrain, hippocampus and front cortex of d-gal-treated mice. Furthermore, our results also showed that troxerutin significantly inhibited cholinesterase (AchE) activity, increased the expression of nicotinic acetylcholine receptor alpha 7 (nAchRalpha7) and enhanced interactions between nAchRalpha7 and either postsynaptic density protein 95 (PSD95) or N-methyl-d-aspartate receptors subunit 1 (NMDAR1) in the basal forebrain, hippocampus and front cortex of d-gal-treated mice, which could help restore impairment of brain function.

  20. Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood.

    PubMed

    Qiao, Dan; Seidler, Frederic J; Abreu-Villaça, Yael; Tate, Charlotte A; Cousins, Mandy M; Slotkin, Theodore A

    2004-01-31

    The developmental neurotoxicity of chlorpyrifos (CPF) involves multiple mechanisms, thus rendering the immature brain susceptible to adverse effects over a wide window of vulnerability. Earlier work indicated that CPF exposure at the neural tube stage elicits apoptosis and disrupts mitotic patterns in the brain primordium but that rapid recovery ensues before birth. In the current study, we assessed whether defects in cholinergic synaptic activity emerge later in development. CPF was given to pregnant rats on gestational days 9-12, using regimens devoid of overt maternal or fetal toxicity. We then examined subsequent development of acetylcholine systems and compared the effects to those on general biomarkers of cell development. Choline acetyltransferase (ChAT), a constitutive marker for cholinergic nerve terminals, was increased in the hippocampus and striatum in adolescence and adulthood. In contrast, hemicholinium-3 (HC-3) binding to the presynaptic choline transporter, an index of nerve impulse activity, was markedly subnormal. Furthermore, m2-muscarinic cholinergic receptor binding was significantly reduced, instead of showing the expected compensatory upregulation for reduced neural input. CPF also elicited delayed-onset alterations in biomarkers of cell packing density, cell number, cell size and neuritic projections, involving brain regions both with and without reductions in indices of cholinergic activity. In combination with earlier results, the current findings indicate that the developing brain, and especially the hippocampus, is adversely affected by CPF regardless of whether exposure occurs early or late in brain development, and that defects emerge in adolescence or adulthood even in situations where normative values are initially restored in the immediate post-exposure period.

  1. An In Vivo Pharmacological Screen Identifies Cholinergic Signaling as a Therapeutic Target in Glial-Based Nervous System Disease

    PubMed Central

    Wang, Liqun; Hagemann, Tracy L.; Messing, Albee

    2016-01-01

    The role that glia play in neurological disease is poorly understood but increasingly acknowledged to be critical in a diverse group of disorders. Here we use a simple genetic model of Alexander disease, a progressive and severe human degenerative nervous system disease caused by a primary astroglial abnormality, to perform an in vivo screen of 1987 compounds, including many FDA-approved drugs and natural products. We identify four compounds capable of dose-dependent inhibition of nervous system toxicity. Focusing on one of these hits, glycopyrrolate, we confirm the role for muscarinic cholinergic signaling in pathogenesis using additional pharmacologic reagents and genetic approaches. We further demonstrate that muscarinic cholinergic signaling works through downstream Gαq to control oxidative stress and death of neurons and glia. Importantly, we document increased muscarinic cholinergic receptor expression in Alexander disease model mice and in postmortem brain tissue from Alexander disease patients, and that blocking muscarinic receptors in Alexander disease model mice reduces oxidative stress, emphasizing the translational significance of our findings. We have therefore identified glial muscarinic signaling as a potential therapeutic target in Alexander disease, and possibly in other gliopathic disorders as well. SIGNIFICANCE STATEMENT Despite the urgent need for better treatments for neurological diseases, drug development for these devastating disorders has been challenging. The effectiveness of traditional large-scale in vitro screens may be limited by the lack of the appropriate molecular, cellular, and structural environment. Using a simple Drosophila model of Alexander disease, we performed a moderate throughput chemical screen of FDA-approved drugs and natural compounds, and found that reducing muscarinic cholinergic signaling ameliorated clinical symptoms and oxidative stress in Alexander disease model flies and mice. Our work demonstrates that small

  2. Does further clean-up reduce the matrix enhancement effect in gas chromatographic analysis of pesticide residues in food?

    PubMed

    Schenck, F J; Lehotay, S J

    2000-01-28

    Sample extracts of apples, peas, green beans, oranges, raspberries, clementines, carrots, and wheat obtained using the Food and Drug Administration (acetone extraction) and Canadian Pest Management Regulatory Agency (acetonitrile extraction) multiresidue methods for pesticides were subjected to clean-up using different solid-phase extraction (SPE) cartridges in an attempt to reduce or eliminate the matrix enhancement effect. The matrix enhancement effect is related to the blocking of active sites on the injector liner by matrix components, thereby increasing signal in the presence of matrix versus standards in solvent in which the pesticides themselves interact with the active sites. Graphitized carbon black (GCB) was often used in combination with various anion-exchange SPE cartridges. The extracts were then spiked with organophosphorus insecticides. These process standards were then compared to standards in acetone of the same concentration using gas chromatography with flame photometric detection or ion trap mass spectrometric detection. Sample matrix enhancement varied from little to no effect for some pesticides (e.g. chlorpyrifos, malathion) to >200% in the case of certain susceptible pesticides. The GCB removed color components but showed little effect in reducing matrix enhancement by itself. The anion-exchange cartridges in combination with GCB or not, substantially reduced the matrix enhancement effect but did not eliminate it. PMID:10677079

  3. Short-term plasticity and modulation of synaptic transmission at mammalian inhibitory cholinergic olivocochlear synapses

    PubMed Central

    Katz, Eleonora; Elgoyhen, Ana Belén

    2014-01-01

    The organ of Corti, the mammalian sensory epithelium of the inner ear, has two types of mechanoreceptor cells, inner hair cells (IHCs) and outer hair cells (OHCs). In this sensory epithelium, vibrations produced by sound waves are transformed into electrical signals. When depolarized by incoming sounds, IHCs release glutamate and activate auditory nerve fibers innervating them and OHCs, by virtue of their electromotile property, increase the amplification and fine tuning of sound signals. The medial olivocochlear (MOC) system, an efferent feedback system, inhibits OHC activity and thereby reduces the sensitivity and sharp tuning of cochlear afferent fibers. During neonatal development, IHCs fire Ca2+ action potentials which evoke glutamate release promoting activity in the immature auditory system in the absence of sensory stimuli. During this period, MOC fibers also innervate IHCs and are thought to modulate their firing rate. Both the MOC-OHC and the MOC-IHC synapses are cholinergic, fast and inhibitory and mediated by the α9α10 nicotinic cholinergic receptor (nAChR) coupled to the activation of calcium-activated potassium channels that hyperpolarize the hair cells. In this review we discuss the biophysical, functional and molecular data which demonstrate that at the synapses between MOC efferent fibers and cochlear hair cells, modulation of transmitter release as well as short term synaptic plasticity mechanisms, operating both at the presynaptic terminal and at the postsynaptic hair-cell, determine the efficacy of these synapses and shape the hair cell response pattern. PMID:25520631

  4. Pre- and neonatal exposure of the Dahl rat to NaCl: development and regional distribution of myocardial alpha 1-adrenergic and cholinergic receptor sites.

    PubMed

    McCaughran, J A; Juno, C J; Friedman, R

    1986-06-01

    The prenatal and/or postweaning effects of a hypertensinogenic high NaCl-containing diet (8.0% NaCl, w/w) on (1) the regional distribution of alpha 1-adrenoceptors and muscarinic cholinergic receptor sites in the heart and (2) the predisposition/resistance to hypertension (HT) were assessed in the inbred Dahl HT-sensitive (S/JR) and HT-resistant (R/JR) rat. The density of alpha 1-adrenoceptors was reduced in the left ventricle but not consistently affected in the ventricular septum, right ventricle, or atria of S/JR offspring with NaCl-induced HT. Both normotensive and hypertensive S/JR rats also displayed a significantly greater density of cholinergic receptor sites in the atria but few consistent alterations in other regions of the heart, compared to R/JR rats. Maternal diet had no effect on the predisposition/resistance to salt-induced HT and little effect on the regional development of alpha 1-adrenoceptors and cholinergic receptor sites. The results of this study suggest that the reduced density of ventricular alpha 1-adrenoceptors in the S/JR strain is a consequence of HT while the elevated density of cholinergic receptors in the atria may be related to the genetic predisposition/resistance to HT.

  5. Forebrain deletion of the dystonia protein torsinA causes dystonic-like movements and loss of striatal cholinergic neurons

    PubMed Central

    Pappas, Samuel S; Darr, Katherine; Holley, Sandra M; Cepeda, Carlos; Mabrouk, Omar S; Wong, Jenny-Marie T; LeWitt, Tessa M; Paudel, Reema; Houlden, Henry; Kennedy, Robert T; Levine, Michael S; Dauer, William T

    2015-01-01

    Striatal dysfunction plays an important role in dystonia, but the striatal cell types that contribute to abnormal movements are poorly defined. We demonstrate that conditional deletion of the DYT1 dystonia protein torsinA in embryonic progenitors of forebrain cholinergic and GABAergic neurons causes dystonic-like twisting movements that emerge during juvenile CNS maturation. The onset of these movements coincides with selective degeneration of dorsal striatal large cholinergic interneurons (LCI), and surviving LCI exhibit morphological, electrophysiological, and connectivity abnormalities. Consistent with the importance of this LCI pathology, murine dystonic-like movements are reduced significantly with an antimuscarinic agent used clinically, and we identify cholinergic abnormalities in postmortem striatal tissue from DYT1 dystonia patients. These findings demonstrate that dorsal LCI have a unique requirement for torsinA function during striatal maturation, and link abnormalities of these cells to dystonic-like movements in an overtly symptomatic animal model. DOI: http://dx.doi.org/10.7554/eLife.08352.001 PMID:26052670

  6. Reduced Burst Release and Enhanced Oral Bioavailability in Shikimic Acid-Loaded Polylactic Acid Submicron Particles by Coaxial Electrospray.

    PubMed

    Wang, Miaomiao; Wang, Yuanwen; Omari-Siaw, Emmanuel; Wang, Shengli; Zhu, Yuan; Xu, Ximing

    2016-08-01

    In this study, using the coaxial electrospray method, we prepared submicron particles of the water-soluble drug shikimic acid (SA) with polylactic acid (PLA) as a polymer, to reduce the burst release and enhance the oral bioavailability. In vitro release study performed in HCl solution (pH 1.2) showed that the coaxial electrospray submicron particles could reduce burst release effect and presented a sustained release profile, compared with free SA and the particles prepared by electrospray method. The absorption of SA in the intestinal tract, studied using an in situ perfusion method in rats, also revealed jejunum as the main absorptive segment followed by duodenum and ileum. Moreover, the SA-loaded particles greatly enhanced the absorption of SA in the tested intestinal segments. The intestinal absorption rate was not enhanced with increasing drug concentration (5-15 μg/mL) which suggested that active transport or facilitated diffusion could play vital role in SA absorption. In addition, the SA-loaded PLA coaxial electrospray particle exhibited a prolonged plasma circulation with enhanced bioavailability after oral administration. In all, the coaxial electrospray technique could provide notable advantages for the oral delivery of SA, thereby enhancing its clinical application.

  7. Component systems enhancement: Reduced girth seam weldments for heavy walled vessels: Final report

    SciTech Connect

    Not Available

    1987-08-01

    Since many coal gasification processes require heavy-wall pressure vessels as an integral part of the process train, new concepts to reduce the cost and schedule for manufacturing and constructing heavy-wall pressure vessels will result in overall plant cost savings. The results of this research demonstrate that it is feasible to use a reduced girth seam weldment design equal to two-thirds of the nominal vessel wall thickness. This reduction in welding thickness greatly reduces the overall cost of heavy-wall vessels. This report summarizes results of nonlinear finite element analysis and scale model testing of various reduced girth seam details demonstrating that the local reduced thickness does not significantly reduce the ultimate pressure capacity of a heavy-wall vessel. The report also summarizes estimated cost and schedule savings for a typical coal gasification vessel that uses a reduced girth seam detail. In addition, estimated overall plant construction cost savings and overall plant operating and maintenance cost savings are presented. 11 refs., 1 fig., 6 tabs.

  8. Interaction of reduced nicotinamide adenine dinucleotide with an antifreeze protein from Dendroides canadensis: mechanistic implication of antifreeze activity enhancement

    PubMed Central

    Wen, Xin; Wang, Sen; Amornwittawat, Natapol; Houghton, Eric A.; Sacco, Michael A.

    2016-01-01

    Antifreeze proteins (AFPs) found in many organisms can noncolligatively lower the freezing point of water without altering the melting point. The difference between the depressed freezing point and the melting point, termed thermal hysteresis (TH), is usually a measure of the antifreeze activity of AFPs. Certain low molecular mass molecules and proteins can further enhance the antifreeze activity of AFPs. Interaction between an enhancer and arginine is known to play an important role in enhancing the antifreeze activity of an AFP from the beetle Dendroides canadensis (DAFP-1). Here, we examined the enhancement effects of several prevalent phosphate-containing coenzymes on the antifreeze activity of DAFP-1. β-Nicotinamide adenine dinucleotide (reduced) (NADH) is identified as the most efficient enhancer of DAFP-1, which increases the antifreeze activity of DAFP-1 by around 10 times. Examination of the enhancement abilities of a series of NADH analogs and various molecular fragments of NADH reveals that the modifications of nicotinamide generate a series of highly efficient enhancers, though none as effective as NADH itself, and the whole molecular structure of NADH is necessary for its highly efficient enhancement effect. We also demonstrated a 1:1 binding between DAFP-1 and NADH. The binding was characterized by high-performance liquid chromatography (HPLC) using the gel filtration method of Hummel and Dreyer. The data analysis suggests binding between DAFP-1 and NADH with a dissociation constant in the micromolar range. Interactions between DAFP-1 and NADH are discussed along with molecular mechanisms of enhancer action. PMID:22038809

  9. Insulin-like growth factor I stimulates lipid oxidation, reduces protein oxidation, and enhances insulin sensitivity in humans.

    PubMed Central

    Hussain, M A; Schmitz, O; Mengel, A; Keller, A; Christiansen, J S; Zapf, J; Froesch, E R

    1993-01-01

    To elucidate the effects of insulin-like growth factor I (IGF-I) on fuel oxidation and insulin sensitivity, eight healthy subjects were treated with saline and recombinant human (IGF-I (10 micrograms/kg.h) during 5 d in a crossover, randomized fashion, while receiving an isocaloric diet (30 kcal/kg.d) throughout the study period. On the third and fourth treatment days, respectively, an L-arginine stimulation test and an intravenous glucose tolerance test were performed. A euglycemic, hyperinsulinemic clamp combined with indirect calorimetry and a glucose tracer infusion were performed on the fifth treatment day. IGF-I treatment led to reduced fasting and stimulated (glucose and/or L-arginine) insulin and growth hormone secretion. Basal and stimulated glucagon secretion remained unchanged. Intravenous glucose tolerance was unaltered despite reduced insulin secretion. Resting energy expenditure and lipid oxidation were both elevated, while protein oxidation was reduced, and glucose turnover rates were unaltered on the fifth treatment day with IGF-I as compared to the control period. Enhanced lipolysis was reflected by elevated circulating free fatty acids. Moreover, insulin-stimulated oxidative and nonoxidative glucose disposal (i.e., insulin sensitivity) were enhanced during IGF-I treatment. Thus, IGF-I treatment leads to marked changes in lipid and protein oxidation, whereas, at the dose used, carbohydrate metabolism remains unaltered in the face of reduced insulin levels and enhanced insulin sensitivity. Images PMID:8227340

  10. Reducing Alcohol Risk in Adjudicated Male College Students: Further Validation of a Group Motivational Enhancement Intervention

    ERIC Educational Resources Information Center

    LaBrie, Joseph W.; Cail, Jessica; Pedersen, Eric R.; Migliuri, Savannah

    2011-01-01

    This study examined the effectiveness of a single-session group motivational enhancement alcohol intervention on adjudicated male college students. Over two sequential academic years, 230 students sanctioned by the university for alcohol-related infractions attended a 60- to 75-minute group intervention. The intervention consisted of a timeline…

  11. Features and Feedback: Enhancing Metamnemonic Knowledge at Retrieval Reduces Source-Monitoring Errors

    ERIC Educational Resources Information Center

    Lane, Sean M.; Roussel, Cristine C.; Villa, Diane; Morita, Shelby K.

    2007-01-01

    Three experiments explored the issue of whether enhanced metamnemonic knowledge at retrieval can improve participants' ability to make difficult source discriminations in the context of the eyewitness suggestibility paradigm. The 1st experiment documented differences in phenomenal experience between veridical and false memories. Experiment 2…

  12. Enhanced Brewer Dobson circulation reduces N2O warming potential under climate change

    NASA Astrophysics Data System (ADS)

    Kracher, Daniela; Reick, Christian; Manzini, Elisa; Schultz, Martin; Stein, Olaf

    2016-04-01

    One implication of climate change is an enhancement of the Brewer Dobson circulation (BDC) triggering the exchange between troposphere and stratosphere. This change in atmospheric dynamics will have effects on atmospheric constituents, especially those with stratospheric sinks such as ozone depleting substances (ODS) including nitrous oxide (N2O). N2O is the most important currently emitted ODS, and the third most important anthropogenic greenhouse gas. Under enhanced BDC, more N2O is transported from the troposphere into the stratosphere, reaching higher altitudes, resulting in an increased N2O sink and a decrease in N2O lifetime. Some aspects of the effect of an enhanced BDC on lifetimes of ODS have already been examined with focus on its implications for ozone. In this study, we examine the effect of a decreasing N2O lifetime in light of climate change. To this end we conduct idealized transient global warming simulations with ECHAM, the atmosphere component of the MPI Earth System Model. As we prescribe surface flux boundary conditions for N2O, we are able to examine further implications of an enhanced N2O sink on atmospheric abundance, which is an important factor for e.g. generating concentration scenarios. Due the idealized simulation setup, we derive findings that are scenario-independent and can easily be extended to other global warming scenarios.

  13. Enhanced and reduced transmission of acoustic waves with bubble meta-screens

    NASA Astrophysics Data System (ADS)

    Bretagne, Alice; Tourin, Arnaud; Leroy, Valentin

    2011-11-01

    We present a class of sonic meta-screens for manipulating air-borne acoustic waves at ultrasonic or audible frequencies. Our screens consist of periodic arrangements of air bubbles in water or possibly embedded in a soft elastic matrix. They can be used for soundproofing but also for exalting transmission at an air/water interface or even to achieve enhanced absorption.

  14. [Probable mechanism of recognition of cholinergic ligands by acetylcholine receptors].

    PubMed

    Demushkin, V P; Kotelevtsev, Iu V; Pliashkevich, Iu G; Khramtsov, N V

    1982-01-01

    Dryding's models were used for the conformational analysis of compounds affecting muscarin-specific acetylcholine receptor and nicotin-specific acetylcholine receptor. Ammonium group and ether oxygen (3.6 A apart from the ammonium group) specifically oriented to each other were shown to be necessary structural elements to reveal muscarin-type cholinergic activity. Ammonium group along with carbonyl oxygen or its substituent (5 A distance) are the necessary structural units providing nicotin-type cholinergic activity. The presence of two hydrophobic substituents (one in the ammonium area and the other neighbouring the second active grouping) is the additional factor. The developed principles were justified by the use of a series of synthetic samples. The compounds were obtained likely favouring affinitive modification of acetylcholine receptor (dissociation constants of acetylcholine receptor complexes equalling to 10(-4)--10(-7) M-1). PMID:7070378

  15. Cholinergic signals in mouse barrel cortex during active whisker sensing.

    PubMed

    Eggermann, Emmanuel; Kremer, Yves; Crochet, Sylvain; Petersen, Carl C H

    2014-12-11

    Internal brain states affect sensory perception, cognition, and learning. Many neocortical areas exhibit changes in the pattern and synchrony of neuronal activity during quiet versus active behaviors. Active behaviors are typically associated with desynchronized cortical dynamics. Increased thalamic firing contributes importantly to desynchronize mouse barrel cortex during active whisker sensing. However, a whisking-related cortical state change persists after thalamic inactivation, which is mediated at least in part by acetylcholine, as we show here by using whole-cell recordings, local pharmacology, axonal calcium imaging, and optogenetic stimulation. During whisking, we find prominent cholinergic signals in the barrel cortex, which suppress spontaneous cortical activity. The desynchronized state of barrel cortex during whisking is therefore driven by at least two distinct signals with opposing functions: increased thalamic activity driving glutamatergic excitation of the cortex and increased cholinergic input suppressing spontaneous cortical activity.

  16. Adenosine Inhibition of Mesopontine Cholinergic Neurons: Implications for EEG Arousal

    PubMed Central

    Rainnie, Donald G.; Grunze, Heinz C. R.; McCarley, Robert W.; Greene, Robert W.

    2013-01-01

    Increased discharge activity of mesopontine cholinergic neurons participates in the production of electroencephalographic (EEG) arousal; such arousal diminishes as a function of the duration of prior wakefulness or of brain hyperthermia. Whole-cell and extracellular recordings in a brainstem slice show that mesopontine cholinergic neurons are under the tonic inhibitory control of endogenous adenosine, a neuromodulator released during brain metabolism. This inhibitory tone is mediated postsynaptically by an inwardly rectifying potassium conductance and by an inhibition of the hyperpolarization-activated current. These data provide a coupling mechanism linking neuronal control of EEG-arousal with the effects of prior wakefulness, brain hyperthermia, and the use of the adenosine receptor blockers caffeine and theophylline. PMID:8303279

  17. Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors.

    PubMed

    de Kloet, Sybren F; Mansvelder, Huibert D; De Vries, Taco J

    2015-10-15

    Nicotine addiction is highly prevalent in current society and is often comorbid with other diseases. In the central nervous system, nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs) and its effects depend on location and receptor composition. Although nicotinic receptors are found in most brain regions, many studies on addiction have focused on the mesolimbic system and its reported behavioral correlates such as reward processing and reinforcement learning. Profound modulatory cholinergic input from the pedunculopontine and laterodorsal tegmentum to dopaminergic midbrain nuclei as well as local cholinergic interneuron projections to dopamine neuron axons in the striatum may play a major role in the effects of nicotine. Moreover, an indirect mesocorticolimbic feedback loop involving the medial prefrontal cortex may be involved in behavioral characteristics of nicotine addiction. Therefore, this review will highlight current understanding of the effects of nicotine on the function of mesolimbic and mesocortical dopamine projections in the mesocorticolimbic circuit. PMID:26208783

  18. Long-lived alphaMUPA transgenic mice show reduced SOD2 expression, enhanced apoptosis and reduced susceptibility to the carcinogen dimethylhydrazine.

    PubMed

    Tirosh, Oren; Pardo, Michal; Schwartz, Betty; Miskin, Ruth

    2005-12-01

    Calorie restriction (CR) extends the life span of various species through mechanisms that are as yet unclear. Recently, we have reported that mitochondrion-mediated apoptosis was enhanced in alphaMUPA transgenic mice that spontaneously eat less and live longer compared with their wild-type (WT) control mice. To understand the molecular mechanisms underlying the increased apoptosis, we compared alphaMUPA and WT mice for parameters associated with SOD2 (MnSOD), a mitochondrial antioxidant enzyme that converts superoxide radicals into H(2)O(2) and is also known to inhibit apoptosis. The SOD2-related parameters included the levels of SOD2 mRNA, immunoreactivity and enzymatic activity in the liver, lipid oxidation and aconitase activity in isolated liver mitochondria, and the sensitivity of the mice to paraquat, an agent that elicits oxidative stress. In addition, we compared the mice for the levels of SOD2 mRNA after treatment with bacterial lipopolysaccharides (LPS), and for the DNA binding activity of NFkappaB as a marker for the inflammatory state. We extended SOD2 determination to the colon, where we also examined the formation of pre-neoplastic aberrant crypt foci (ACF) following treatment with dimethylhydrazine (DMH), a colonic organotypic carcinogen. Overall, alphaMUPA mice showed reduced basal levels of SOD2 gene expression and activity concomitantly with reduced lipid oxidation, increased aconitase activity and enhanced paraquat sensitivity, while maintaining the capacity to produce high levels of SOD2 in response to the inflammatory stimulus. alphaMUPA mice also showed increased resistance to DMH-induced pre-neoplasia. Collectively, these data are consistent with a model, in which an optimal fine-tuning of SOD2 throughout a long-term regimen of reduced eating could contribute to longevity, at least in the alphaMUPA mice. PMID:16139868

  19. Nicotine-Induced Modulation of the Cholinergic Twitch Response in the Ileum of Guinea Pig.

    PubMed

    Donnerer, Josef; Liebmann, Ingrid

    2015-01-01

    In the present study, the direct drug effects of nicotine and its effects on the cholinergic twitch responses of the electrically stimulated longitudinal muscle-myenteric plexus strip from the ileum of guinea pig were investigated. Nicotine dose-dependently (0.3-10 µmol/l) evoked the well-known contractile responses on its own. Whereas the interposed twitch responses remained present without a change in height at 1 µmol/l nicotine, a nicotine concentration of 3 µmol/l slightly and a concentration of 10 µmol/l markedly diminished the twitch during their presence. After the washout of 1-10 µmol/l nicotine, the height of the twitch response was also temporarily and significantly reduced by 30-77%. The P2X purinoceptor agonist αβ-methylene ATP (1-10 µmol/l) dose-dependently induced contractions on its own and reduced the twitch response during its presence in the organ bath; however, it did not diminish the twitch responses after washout of the drug as nicotine did. The P2X antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid, the NMDA channel blocker MK-801 and the inhibitor of small conductance Ca(2+)-activated K(+) (SK) channels apamin reduced the contractile effect of 1 µmol/l nicotine. Apamin also significantly prevented the 'post-nicotine inhibition of the twitch' following the washout of 1-3 µmol/l nicotine. As a conclusion, we provide evidence for a functional interaction between nicotinic receptors and the P2X receptors in the ileum of the guinea pig. The 'post-nicotine inhibition of the twitch' is not due to nicotinic acetylcholine receptor desensitization or transmitter depletion, but most probably the secondary effects of nicotine on SK channels determine the reduced cholinergic motor neuron excitability. PMID:26088942

  20. Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors.

    PubMed

    Shytle, R Douglas; Mori, Takashi; Townsend, Kirk; Vendrame, Martina; Sun, Nan; Zeng, Jin; Ehrhart, Jared; Silver, Archie A; Sanberg, Paul R; Tan, Jun

    2004-04-01

    Almost all degenerative diseases of the CNS are associated with chronic inflammation. A central step in this process is the activation of brain mononuclear phagocyte cells, called microglia. While it is recognized that healthy neurons and astrocytes regulate the magnitude of microglia-mediated innate immune responses and limit excessive CNS inflammation, the endogenous signals governing this process are not fully understood. In the peripheral nervous system, recent studies suggest that an endogenous 'cholinergic anti-inflammatory pathway' regulates systemic inflammatory responses via alpha 7 nicotinic acetylcholinergic receptors (nAChR) found on blood-borne macrophages. These data led us to investigate whether a similar cholinergic pathway exists in the brain that could regulate microglial activation. Here we report for the first time that cultured microglial cells express alpha 7 nAChR subunit as determined by RT-PCR, western blot, immunofluorescent, and immunohistochemistry analyses. Acetylcholine and nicotine pre-treatment inhibit lipopolysaccharide (LPS)-induced TNF-alpha release in murine-derived microglial cells, an effect attenuated by alpha 7 selective nicotinic antagonist, alpha-bungarotoxin. Furthermore, this inhibition appears to be mediated by a reduction in phosphorylation of p44/42 and p38 mitogen-activated protein kinase (MAPK). Though preliminary, our findings suggest the existence of a brain cholinergic pathway that regulates microglial activation through alpha 7 nicotinic receptors. Negative regulation of microglia activation may also represent additional mechanism underlying nicotine's reported neuroprotective properties.

  1. Potential Mechanisms Underlying Intercortical Signal Regulation via Cholinergic Neuromodulators

    PubMed Central

    Whittington, Miles A.; Kopell, Nancy J.

    2015-01-01

    The dynamical behavior of the cortex is extremely complex, with different areas and even different layers of a cortical column displaying different temporal patterns. A major open question is how the signals from different layers and different brain regions are coordinated in a flexible manner to support function. Here, we considered interactions between primary auditory cortex and adjacent association cortex. Using a biophysically based model, we show how top-down signals in the beta and gamma regimes can interact with a bottom-up gamma rhythm to provide regulation of signals between the cortical areas and among layers. The flow of signals depends on cholinergic modulation: with only glutamatergic drive, we show that top-down gamma rhythms may block sensory signals. In the presence of cholinergic drive, top-down beta rhythms can lift this blockade and allow signals to flow reciprocally between primary sensory and parietal cortex. SIGNIFICANCE STATEMENT Flexible coordination of multiple cortical areas is critical for complex cognitive functions, but how this is accomplished is not understood. Using computational models, we studied the interactions between primary auditory cortex (A1) and association cortex (Par2). Our model is capable of replicating interaction patterns observed in vitro and the simulations predict that the coordination between top-down gamma and beta rhythms is central to the gating process regulating bottom-up sensory signaling projected from A1 to Par2 and that cholinergic modulation allows this coordination to occur. PMID:26558772

  2. Results of ENHANCED Implantable Cardioverter Defibrillator Programming to Reduce Therapies and Improve Quality of Life (from the ENHANCED-ICD Study).

    PubMed

    Mastenbroek, Mirjam H; Pedersen, Susanne S; van der Tweel, Ingeborg; Doevendans, Pieter A; Meine, Mathias

    2016-02-15

    Novel implantable cardioverter defibrillator (ICD) discrimination algorithms and programming strategies have significantly reduced the incidence of inappropriate shocks, but there are still gains to be made with respect to reducing appropriate but unnecessary antitachycardia pacing (ATP) and shocks. We examined whether programming a number of intervals to detect (NID) of 60/80 for ventricular tachyarrhythmia (VT)/ventricular fibrillation (VF) detection was safe and the impact of this strategy on (1) adverse events related to ICD shocks and syncopal events; (2) ATPs/shocks; and (3) patient-reported outcomes. The "ENHANCED Implantable Cardioverter Defibrillator programming to reduce therapies and improve quality of life" study (ENHANCED-ICD study) was a prospective, safety-monitoring study enrolling 60 primary and secondary prevention patients at the University Medical Center Utrecht. Patients implanted with any type of ICD with SmartShock technology and aged 18 to 80 years were eligible to participate. In all patients, a prolonged NID 60/80 was programmed. The cycle length for VT/fast VT/VF was 360/330/240 ms, respectively. Programming a NID 60/80 proved safe for ICD patients. Because of the new programming strategy, unnecessary ICD therapy was prevented in 10% of ENHANCED-ICD patients during a median follow-up period of 1.3 years. With respect to patient-reported outcomes, levels of distress were highest and perceived health status lowest at the time of implantation, which both gradually improved during follow-up. In conclusion, the ENHANCED-ICD study demonstrates that programming a NID 60/80 for VT/VF detection is safe for ICD patients and does not negatively impact their quality of life.

  3. Advertising to the enemy: enhanced floral fragrance increases beetle attraction and reduces plant reproduction.

    PubMed

    Theis, Nina; Adler, Lynn S

    2012-02-01

    Many organisms face challenges in avoiding predation while searching for mates. For plants, emitting floral fragrances to advertise reproductive structures could increase the attraction of detrimental insects along with pollinators. Very few studies have experimentally evaluated the costs and benefits of fragrance emission with explicit consideration of how plant fitness is affected by both pollinators and florivores. To determine the reproductive consequences of increasing the apparency of reproductive parts, we manipulated fragrance, pollination, and florivores in the wild Texas gourd, Cucurbita pepo var. texana. With enhanced fragrance we found an increase in the attraction of florivores, rather than pollinators, and a decrease in seed production. This study is the first to demonstrate that enhanced floral fragrance can increase the attraction of detrimental florivores and decrease plant reproduction, suggesting that florivory as well as pollination has shaped the evolution of floral scent. PMID:22624324

  4. The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing

    NASA Astrophysics Data System (ADS)

    Zabner, Joseph; Seiler, Michael P.; Launspach, Janice L.; Karp, Philip H.; Kearney, William R.; Look, Dwight C.; Smith, Jeffrey J.; Welsh, Michael J.

    2000-10-01

    The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.

  5. Metabotropic glutamate 2 receptors modulate synaptic inputs and calcium signals in striatal cholinergic interneurons.

    PubMed

    Pisani, Antonio; Bonsi, Paola; Catania, Maria Vincenza; Giuffrida, Raffaella; Morari, Michele; Marti, Matteo; Centonze, Diego; Bernardi, Giorgio; Kingston, Ann E; Calabresi, Paolo

    2002-07-15

    Striatal cholinergic interneurons were recorded from a rat slice preparation. Synaptic potentials evoked by intrastriatal stimulation revealed three distinct components: a glutamatergic EPSP, a GABA(A)-mediated depolarizing potential, and an acetylcholine (ACh)-mediated IPSP. The responses to group II metabotropic glutamate (mGlu) receptor activation were investigated on the isolated components of the synaptic potentials. Each pharmacologically isolated component was reversibly reduced by bath-applied LY379268 and ((2S,1'R,2'R,3'R)-2-(2,3-dicarboxylcyclopropyl)-glycine, group II agonists. In an attempt to define the relevance of group II mGlu receptor activation on cholinergic transmission, we focused on the inhibitory effect on the IPSP, which was mimicked and occluded by omega-agatoxin IVA (omega-Aga-IVA), suggesting a modulation on P-type high-voltage-activated calcium channels. Spontaneous calcium-dependent plateau-potentials (PPs) were recorded with cesium-filled electrodes plus tetraethylammonium and TTX in the perfusing solution, and measurements of intracellular calcium [Ca2+]i changes were obtained simultaneously. PPs and the concomitant [Ca2+]i elevations were significantly reduced in amplitude and duration by LY379268. The mGlu-mediated inhibitory effect on PPs was mimicked by omega-Aga-IVA, suggesting an involvement of P-type channels. Moreover, electrically induced ACh release from striatal slices was reduced by mGlu2 receptor agonists and occluded by omega-Aga-IVA in a dose-dependent manner. Finally, double-labeling experiments combining mGlu2 receptor in situ hybridization and choline acetyltransferase immunocytochemistry revealed a strong mGlu2 receptor labeling on cholinergic interneurons, whereas single-label isotopic in situ hybridization for mGlu3 receptors did not show any labeling in these large striatal interneurons. These results suggest that the mGlu2 receptor-mediated modulatory action on cell excitability would tune striatal ACh release

  6. Involvement of central cholinergic mechanisms in the effects of oxytocin and an oxytocin receptor antagonist on retention performance in mice.

    PubMed

    Boccia, M M; Baratti, C M

    2000-11-01

    Oxytocin (OT, 0.10 microg/kg, sc) impaired retention of a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 10 min after training, as indicated by retention performance 48 h later. In contrast, the immediate post-training administration of the putative oxytocin receptor antagonist d(CH(2))(5)[Tyr(Me)(2), Thr(4), Thy-NH(9)(2)] OVT (AOT, 0.30 microg/kg, sc) significantly enhanced retention performance. Neither OT nor AOT affected response latencies in mice not given footshock on the training trial, and neither the impairing effects of OT nor the enhancing effects of AOT were seen when the training-treatment interval was 180 min, suggesting that both treatments influenced memory storage. The effects of OT (0.10 microg/kg, sc) on retention were prevented by AOT (0.03 microg/kg, sc) given immediately after training, but 10 min prior to OT treatment. The central acting anticholinesterase physostigmine (35, 70, or 150 microg/kg, i.p.), but not its quaternary analogue neostigmine (150 microg/kg, i.p.), reversed the impairment of retention performance induced by OT, whereas low subeffective doses of the centrally active muscarinic cholinergic antagonist atropine (0.5 mg/kg, i.p.) or the central acting nicotinic cholinergic antagonist mecamylamine (5 mg/kg, i.p.), but not methylatropine (0.5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.) prevented the enhancement of retention performance caused by AOT. We suggest that oxytocin negatively modulates the activity of central cholinergic mechanisms during the posttraining period that follows an aversively motivated learning experience, leading to an impairment of retention performance of the inhibitory avoidance response. PMID:11031128

  7. Involvement of central cholinergic mechanisms in the effects of oxytocin and an oxytocin receptor antagonist on retention performance in mice.

    PubMed

    Boccia, M M; Baratti, C M

    2000-11-01

    Oxytocin (OT, 0.10 microg/kg, sc) impaired retention of a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 10 min after training, as indicated by retention performance 48 h later. In contrast, the immediate post-training administration of the putative oxytocin receptor antagonist d(CH(2))(5)[Tyr(Me)(2), Thr(4), Thy-NH(9)(2)] OVT (AOT, 0.30 microg/kg, sc) significantly enhanced retention performance. Neither OT nor AOT affected response latencies in mice not given footshock on the training trial, and neither the impairing effects of OT nor the enhancing effects of AOT were seen when the training-treatment interval was 180 min, suggesting that both treatments influenced memory storage. The effects of OT (0.10 microg/kg, sc) on retention were prevented by AOT (0.03 microg/kg, sc) given immediately after training, but 10 min prior to OT treatment. The central acting anticholinesterase physostigmine (35, 70, or 150 microg/kg, i.p.), but not its quaternary analogue neostigmine (150 microg/kg, i.p.), reversed the impairment of retention performance induced by OT, whereas low subeffective doses of the centrally active muscarinic cholinergic antagonist atropine (0.5 mg/kg, i.p.) or the central acting nicotinic cholinergic antagonist mecamylamine (5 mg/kg, i.p.), but not methylatropine (0.5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.) prevented the enhancement of retention performance caused by AOT. We suggest that oxytocin negatively modulates the activity of central cholinergic mechanisms during the posttraining period that follows an aversively motivated learning experience, leading to an impairment of retention performance of the inhibitory avoidance response.

  8. Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins.

    PubMed

    Duangjai, Acharaporn; Ingkaninan, Kornkanok; Praputbut, Sakonwun; Limpeanchob, Nanteetip

    2013-04-01

    Black pepper (Piper nigrum L.) lowers blood lipids in vivo and inhibits cholesterol uptake in vitro, and piperine may mediate these effects. To test this, the present study aimed to compare actions of black pepper extract and piperine on (1) cholesterol uptake and efflux in Caco-2 cells, (2) the membrane/cytosol distribution of cholesterol transport proteins in these cells, and (3) the physicochemical properties of cholesterol micelles. Piperine or black pepper extract (containing the same amount of piperine) dose-dependently reduced cholesterol uptake into Caco-2 cells in a similar manner. Both preparations reduced the membrane levels of NPC1L1 and SR-BI proteins but not their overall cellular expression. Micellar cholesterol solubility of lipid micelles was unaffected except by 1 mg/mL concentration of black pepper extract. These data suggest that piperine is the active compound in black pepper and reduces cholesterol uptake by internalizing the cholesterol transporter proteins.

  9. Enhanced and selective ammonia sensing of reduced graphene oxide based chemo resistive sensor at room temperature

    NASA Astrophysics Data System (ADS)

    Kumar, Ramesh; Kaur, Amarjeet

    2016-05-01

    The reduced graphene oxide thin films were fabricated by using the spin coating method. The reduced graphene oxide samples were characterised by Raman studies to obtain corresponding D and G bands at 1360 and 1590 cm-1 respectively. Fourier transform infra-red (FTIR) spectra consists of peak corresponds to sp2 hybridisation of carbon atoms at 1560 cm-1. The reduced graphene oxide based chemoresistive sensor exhibited a p-type semiconductor behaviour in ambient conditions and showed good sensitivity to different concentration of ammonia from 25 ppm to 500 ppm and excellent selectivity at room temperature. The sensor displays selectivity to several hazardous vapours such as methanol, ethanol, acetone and hydrazine hydrate. The sensor demonstrated a sensitivity of 9.8 at 25 ppm concentration of ammonia with response time of 163 seconds.

  10. Enhancing Patient Safety by Reducing Healthcare-Associated Infections: The Role of Discovery and Dissemination

    PubMed Central

    2010-01-01

    Healthcare-associated infections (HAIs) take a major human toll on society and reduce public confidence in the healthcare system. The current convergence of scientific, public, and legislative interest in reducing rates of HAI can provide the necessary momentum to address and answer important questions in HAI research. This position paper outlines priorities for a national approach to HAIs: scrutinizing the science base, developing a prioritized research agenda, conducting studies that address the questions that have been identified, creating and deploying guidelines that are based on the outcomes of these studies, and then initiating new studies that assess the efficacy of the interventions. PMID:20038249

  11. Projections of brainstem core cholinergic and non-cholinergic neurons of cat to intralaminar and reticular thalamic nuclei.

    PubMed

    Paré, D; Smith, Y; Parent, A; Steriade, M

    1988-04-01

    We combined the retrograde transport of wheat germ agglutinin conjugated with horseradish peroxidase with choline acetyltransferase immunohistochemistry to study the projections of cholinergic and non-cholinergic neurons of the upper brainstem core to rostral and caudal intralaminar thalamic nuclei, reticular thalamic complex and zona incerta in the cat. After wheat germ agglutinin-horseradish peroxidase injections in the rostral pole of the reticular thalamic nucleus, the distribution and amount of retrogradely labeled brainstem neurons were similar to those found after tracer injection in thalamic relay nuclei (see preceding paper). After wheat germ agglutinin-horseradish peroxidase injections in the caudal intralaminar centrum medianum-parafascicular complex, rostral intralaminar central lateral-paracentral wing, and zona incerta, the numbers of retrogradely labeled brainstem neurons were more than three times higher than those found after injections in thalamic relay nuclei. The larger numbers of horseradish peroxidase-positive brainstem reticular neurons after tracer injections in intralaminar or zona incerta injections results from a more substantial proportion of labeled neurons in the central tegmental field at rostral midbrain (perirubral) levels and in the ventromedial part of the pontine reticular formation, ipsi- and contralaterally to the injection site. Of all retrogradely labeled neurons in the caudal midbrain core at the level of the cholinergic peribrachial area and laterodorsal tegmental nucleus, 45-50% were also choline acetyltransferase-positive after the injections into central lateral-paracentral and reticular nuclei, while only 25% were also choline acetyltransferase-positive after the injection into the centrum medianum-parafascicular complex. These findings are discussed in the light of physiological evidence of brainstem cholinergic mechanisms involved in the blockade of synchronized oscillations and in activation processes of

  12. Enhanced biological phosphorus removal from wastewater by biomass with different phosphorus contents, Part III: Anaerobic sources of reducing equivalents.

    PubMed

    Schuler, Andrew J; Jenkins, David

    2003-01-01

    Laboratory-scale sequencing batch reactors exhibiting enhanced biological phosphorus removal (EBPR) operated at different influent phosphorus/chemical oxygen demand (COD) ratios were analyzed to evaluate possible anaerobic sources of reducing equivalents. Assuming anaerobic glycogen degradation was the sole anaerobic reducing equivalent source, an anaerobic phase carbon balance showed that glycogen-accumulating metabolism (GAM)-dominated systems were nearly carbon-balanced, but that polyphosphate-accumulating metabolism (PAM)-dominated systems had end-anaerobic phase carbon deficits. An anaerobic-phase reducing equivalent balance showed a reducing equivalent excess for the GAM-dominated systems and a deficit for the PAM-dominated systems, suggesting that glycogen degradation was not the sole reducing equivalent source for PAM. Reducing equivalent balances showed that metabolic models including complete anaerobic tricarboxylic acid (TCA) cycle activity, partial TCA cycle activity, and the glyoxylate bypass could provide the reducing equivalents required in PAM. Metabolic precursors produced in glycolysis, the TCA cycle, or modified versions of the TCA cycle could allow anaerobic growth and account for the PAM carbon deficits. The importance of considering both PAM and GAM activity in evaluating EBPR metabolic models was illustrated.

  13. Extrinsic Sources of Cholinergic Innervation of the Striatal Complex: A Whole-Brain Mapping Analysis

    PubMed Central

    Dautan, Daniel; Hacioğlu Bay, Husniye; Bolam, J. Paul; Gerdjikov, Todor V.; Mena-Segovia, Juan

    2016-01-01

    Acetylcholine in the striatal complex plays an important role in normal behavior and is affected in a number of neurological disorders. Although early studies suggested that acetylcholine in the striatum (STR) is derived almost exclusively from cholinergic interneurons (CIN), recent axonal mapping studies using conditional anterograde tracing have revealed the existence of a prominent direct cholinergic pathway from the pedunculopontine and laterodorsal tegmental nuclei to the dorsal striatum and nucleus accumbens. The identification of the importance of this pathway is essential for creating a complete model of cholinergic modulation in the striatum, and it opens the question as to whether other populations of cholinergic neurons may also contribute to such modulation. Here, using novel viral tracing technologies based on phenotype-specific fluorescent reporter expression in combination with retrograde tracing, we aimed to define other sources of cholinergic innervation of the striatum. Systematic mapping of the projections of all cholinergic structures in the brain (Ch1 to Ch8) by means of conditional tracing of cholinergic axons, revealed that the only extrinsic source of cholinergic innervation arises in the brainstem pedunculopontine and laterodorsal tegmental nuclei. Our results thus place the pedunculopontine and laterodorsal nuclei in a key and exclusive position to provide extrinsic cholinergic modulation of the activity of the striatal systems. PMID:26834571

  14. Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-signaling cytokines in rodents.

    PubMed

    Kanazawa, Hideaki; Ieda, Masaki; Kimura, Kensuke; Arai, Takahide; Kawaguchi-Manabe, Haruko; Matsuhashi, Tomohiro; Endo, Jin; Sano, Motoaki; Kawakami, Takashi; Kimura, Tokuhiro; Monkawa, Toshiaki; Hayashi, Matsuhiko; Iwanami, Akio; Okano, Hideyuki; Okada, Yasunori; Ishibashi-Ueda, Hatsue; Ogawa, Satoshi; Fukuda, Keiichi

    2010-02-01

    Although several cytokines and neurotrophic factors induce sympathetic neurons to transdifferentiate into cholinergic neurons in vitro, the physiological and pathophysiological roles of this remain unknown. During congestive heart failure (CHF), sympathetic neural tone is upregulated, but there is a paradoxical reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic nervous system (SNS). Here we examined whether cholinergic transdifferentiation can occur in the cardiac SNS in rodent models of CHF and investigated the underlying molecular mechanism(s) using genetically modified mice. We used Dahl salt-sensitive rats to model CHF and found that, upon CHF induction, the cardiac SNS clearly acquired cholinergic characteristics. Of the various cholinergic differentiation factors, leukemia inhibitory factor (LIF) and cardiotrophin-1 were strongly upregulated in the ventricles of rats with CHF. Further, LIF and cardiotrophin-1 secreted from cultured failing rat cardiomyocytes induced cholinergic transdifferentiation in cultured sympathetic neurons, and this process was reversed by siRNAs targeting Lif and cardiotrophin-1. Consistent with the data in rats, heart-specific overexpression of LIF in mice caused cholinergic transdifferentiation in the cardiac SNS. Further, SNS-specific targeting of the gene encoding the gp130 subunit of the receptor for LIF and cardiotrophin-1 in mice prevented CHF-induced cholinergic transdifferentiation. Cholinergic transdifferentiation was also observed in the cardiac SNS of autopsied patients with CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of the cardiac SNS via gp130-signaling cytokines secreted from the failing myocardium.

  15. Enhancing antioxidant activity of sesamol at frying temperature by addition of additives through reducing volatility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Additives were evaluated to investigate their effects on volatility of sesamol at frying temperature with the hypothesis that the interaction between an additive and sesamol would reduce sesamol volatility. Twenty-two additive:sesamol combinations were examined by thermogravimetric analysis (TGA) un...

  16. Spaced Learning Enhances Subsequent Recognition Memory by Reducing Neural Repetition Suppression

    ERIC Educational Resources Information Center

    Xue, Gui; Mei, Leilei; Chen, Chuansheng; Lu, Zhong-Lin; Poldrack, Russell; Dong, Qi

    2011-01-01

    Spaced learning usually leads to better recognition memory as compared with massed learning, yet the underlying neural mechanisms remain elusive. One open question is whether the spacing effect is achieved by reducing neural repetition suppression. In this fMRI study, participants were scanned while intentionally memorizing 120 novel faces, half…

  17. Mixed-Mode Surveys: A Strategy to Reduce Costs and Enhance Response Rates

    ERIC Educational Resources Information Center

    Tobin, Daniel; Thomson, Joan; Radhakrishna, Rama; LaBorde, Luke

    2012-01-01

    Mixed-mode surveys present one opportunity for Extension to determine program outcomes at lower costs. In order to conduct a follow-up evaluation, we implemented a mixed-mode survey that relied on communication using the Web, postal mailings, and telephone calls. Using multiple modes conserved costs by reducing the number of postal mailings yet…

  18. Distillers by-product cattle diets enhance reduced sulfur gas fluxes from feedlot soils and manures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Total reduced sulfur (TRS) emissions from animal feeding operations are a concern with increased feeding of high-sulfur distillers by-products. Three feeding trials were conducted to evaluate feeding wet distillers grain plus solubles (WDGS) on TRS fluxes. Fresh manure was collected three times duri...

  19. Enhanced reduced sulfur emission from manures of beef cattle fed distiller's byproducts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reduced sulfur compounds are normal products of manure decomposition which are emitted from confined animal feeding operations (CAFO). These compounds not only contribute to nuisance odors, but with recent EPA regulations, H2S emissions in excess of 100 lbs per day must be reported by the livestock...

  20. Enhancing Cultural and Contextual Intervention Strategies to Reduce HIV/AIDS Among African Americans

    PubMed Central

    2009-01-01

    I describe 4 protective strategies that African Americans employ that may challenge current HIV prevention efforts: (1) an adaptive duality that protects identity, (2) personal control influenced by external factors, (3) long-established indirect communication patterns, and (4) a mistrust of “outsiders.” I propose the Sexual Health Model as a conceptual framework for HIV prevention interventions because it incorporates established adaptive coping strategies into new HIV-related protective skills. The Sexual Health Model promotes interconnectedness, sexual ownership, and body awareness, 3 concepts that represent the context of the African American historical and cultural experience and that enhance rather than contradict future prevention efforts. PMID:19762666

  1. Enhancement of the Musca domestica hytrosavirus infection with orally delivered reducing agents.

    PubMed

    Boucias, D; Baniszewski, J; Prompiboon, P; Lietze, V; Geden, C

    2015-01-01

    House flies (Musca domestica L.) throughout the world are infected with the salivary gland hypertrophy virus MdSGHV (Hytrosaviridae). Although the primary route of infection is thought to be via ingestion, flies that are old enough to feed normally are resistant to infection per os, suggesting that the peritrophic matrix (PM) is a barrier to virus transmission. Histological examination of the peritrophic matrix of healthy flies revealed a multilaminate structure produced by midgut cells located near the proventriculus. SEM revealed the PM to form a confluent sheet surrounding the food bolus with pores/openings less than 10nm in diameter. TEM revealed the PM to be multilayered, varying in width from 350 to 900 nm, and generally thinner in male than in female flies. When flies were fed on the reducing agents dithiothetriol (DTT) or tris (2-caboxyethyl)phosphine hydrochloride (TCEP) for 48 h before per os exposure to the virus, infection rates increased 10- to 20-fold compared with flies that did not receive the reducing agent treatments. PM's from flies treated with DTT and TCEP displayed varying degrees of disruption, particularly in the outer layer, and lacked the electron-dense inner layer facing the ectoperitrophic space. Both drugs were somewhat toxic to the flies, resulting in>40% mortality at doses greater than 10mM (DTT) or 5 mM (TCEP). DTT increased male fly susceptibility (55.1% infected) more than that of females (7.8%), whereas TCEP increased susceptibility of females (42.9%) more than that of males (26.2%). The cause for the sex differences in response to oral exposure the reducing agents is unclear. Exposing flies to food treated with virus and the reducing agents at the same time, rather than pretreating flies with the drugs, had no effect on susceptibility to the virus. Presumably, the reducing agent disrupted the enveloped virus and acted as a viricidal agent. In summary, it is proposed that the reducing agents influence integrity of the PM barrier

  2. Enhanced Mechanical Properties of Graphene (Reduced Graphene Oxide)/Aluminum Composites with a Bioinspired Nanolaminated Structure.

    PubMed

    Li, Zan; Guo, Qiang; Li, Zhiqiang; Fan, Genlian; Xiong, Ding-Bang; Su, Yishi; Zhang, Jie; Zhang, Di

    2015-12-01

    Bulk graphene (reduced graphene oxide)-reinforced Al matrix composites with a bioinspired nanolaminated microstructure were fabricated via a composite powder assembly approach. Compared with the unreinforced Al matrix, these composites were shown to possess significantly improved stiffness and tensile strength, and a similar or even slightly higher total elongation. These observations were interpreted by the facilitated load transfer between graphene and the Al matrix, and the extrinsic toughening effect as a result of the nanolaminated microstructure. PMID:26574873

  3. Reducing readmissions using teach-back: enhancing patient and family education.

    PubMed

    Peter, Debra; Robinson, Paula; Jordan, Marie; Lawrence, Susan; Casey, Krista; Salas-Lopez, Debbie

    2015-01-01

    This article describes a quality improvement initiative, implemented by a patient education workgroup within a tertiary Magnet® facility. The project focused on the association between inadequate care transitions in patients with heart failure and subsequent costly readmissions. The teach-back initiative was piloted with patients hospitalized with heart failure, because of this population's high risk of readmission. Learning outcomes included documented improvements in patients' understanding of their disease and reduced readmission rates.

  4. Control of left ventricular mass by moxonidine involves reduced DNA synthesis and enhanced DNA fragmentation

    PubMed Central

    Paquette, P-A; Duguay, D; Ayoubi, R El-; Menaouar, A; Danalache, B; Gutkowska, J; DeBlois, D; Mukaddam-Daher, S

    2007-01-01

    Background and purpose: Left ventricular hypertrophy (LVH) is a maladaptive process associated with increased cardiovascular risk. Regression of LVH is associated with reduced complications of hypertension. Moxonidine is an antihypertensive imidazoline compound that reduces blood pressure primarily by central inhibition of sympathetic outflow and by direct actions on the heart to release atrial natriuretic peptide, a vasodilator and an antihypertrophic cardiac hormone. This study investigated the effect of moxonidine on LVH and the mechanisms involved in this effect. Experimental approach: Spontaneously hypertensive rats were treated with several doses of moxonidine (s.c.) over 4 weeks. Blood pressure and heart rate were continuously monitored by telemetry. Body weight and water and food intake were measured weekly. Measurements also included left ventricular mass, DNA content, synthesis, fragmentation, and apoptotic/anti-apoptotic pathway proteins. Key results: The decrease in mean arterial pressure stabilized at ∼ −10 mm Hg after 1 week of treatment and thereafter. Compared to vehicle-treated rats (100%), left ventricular mass was dose- and time-dependently reduced by treatment. This reduction remained significantly lower after normalizing to body weight. Moxonidine reduced left ventricular DNA content and inhibited DNA synthesis. DNA fragmentation transiently, but significantly increased at 1 week of moxonidine treatment and was paralleled by elevated active caspase-3 protein. The highest dose significantly decreased the apoptotic protein Bax and all doses stimulated anti-apoptotic Bcl-2 after 4 weeks of treatment. Conclusions and implications: These studies implicate the modulation of cardiac DNA dynamics in the control of left ventricular mass by moxonidine in a rat model of hypertension. PMID:18059325

  5. Characterization of the Conformational Alterations, Reduced Anticoagulant Activity, and Enhanced Antiangiogenic Activity of Prelatent Antithrombin*

    PubMed Central

    Richard, Benjamin; Swanson, Richard; Schedin-Weiss, Sophia; Ramirez, Ben; Izaguirre, Gonzalo; Gettins, Peter G. W.; Olson, Steven T.

    2008-01-01

    A conformationally altered prelatent form of antithrombin that possesses both anticoagulant and antiangiogenic activities is produced during the conversion of native to latent antithrombin (Larsson, H., Akerud, P., Nordling, K., Raub-Segall, E., Claesson-Welsh, L., and Björk, I. (2001) J. Biol. Chem. 276, 11996–12002). Here, we show that the previously characterized prelatent antithrombin is a mixture of native antithrombin and a modified, true prelatent antithrombin that are resolvable by heparin-agarose chromatography. Kinetic analyses revealed that prelatent antithrombin is an intermediate in the conversion of native to latent antithrombin whose formation is favored by stabilizing anions of the Hofmeister series. Purified prelatent antithrombin had reduced anticoagulant function compared with native antithrombin, due to a reduced heparin affinity and consequent impaired ability of heparin to either bridge prelatent antithrombin and coagulation proteases in a ternary complex or to induce full conformational activation of the serpin. Significantly, prelatent antithrombin possessed an antiangiogenic activity more potent than that of latent antithrombin, based on the relative abilities of the two forms to inhibit endothelial cell growth. The prelatent form was conformationally altered from native antithrombin as judged from an attenuation of tryptophan fluorescence changes following heparin activation and a reduced thermal stability. The alterations are consistent with the limited structural changes involving strand 1C observed in a prelatent form of plasminogen activator inhibitor-1 (Dupont, D. M., Blouse, G. E., Hansen, M., Mathiasen, L., Kjelgaard, S., Jensen, J. K., Christensen, A., Gils, A., Declerck, P. J., Andreasen, P. A., and Wind, T. (2006) J. Biol. Chem. 281, 36071–36081), since the 1H NMR spectrum, electrophoretic mobility, and proteolytic susceptibility of prelatent antithrombin most resemble those of native rather than those of latent antithrombin

  6. Reducing readmissions using teach-back: enhancing patient and family education.

    PubMed

    Peter, Debra; Robinson, Paula; Jordan, Marie; Lawrence, Susan; Casey, Krista; Salas-Lopez, Debbie

    2015-01-01

    This article describes a quality improvement initiative, implemented by a patient education workgroup within a tertiary Magnet® facility. The project focused on the association between inadequate care transitions in patients with heart failure and subsequent costly readmissions. The teach-back initiative was piloted with patients hospitalized with heart failure, because of this population's high risk of readmission. Learning outcomes included documented improvements in patients' understanding of their disease and reduced readmission rates. PMID:25479173

  7. A nanoparticle formulation reduces the corneal toxicity of indomethacin eye drops and enhances its corneal permeability.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa; Okamoto, Norio; Shimomura, Yoshikazu

    2014-05-01

    Indomethacin (IMC) has been shown to reduce post-operative inflammation and to decrease intraocular irritation after cataract extraction and in cystoid macular edema; however, the clinical use of its most commonly used eye drops is limited due to topical side-effects that include burning sensation, irritation and epithelial keratitis. It is known that decreasing direct cell stimulation and reducing the amount applied via increasing bioavailability are useful for improving these issues. In this study, we designed ophthalmic formulations containing 0.5% IMC nanoparticles using zirconia beads and Bead Smash 12 (IMCnano eye drops; particle size 76 ± 59 nm, mean ± S.D.), and investigated the corneal toxicity of these IMCnano eye drops. IMCnano eye drops are tolerated better by a human cornea epithelial cell line (HCE-T) than commercially available NDSAIDs preparations (IMC, pranoprofen, diclofenac, bromfenac and nepafenac eye drops), and corneal wound healing in rat eyes with debrided corneal epithelium instilled with IMCnano eye drops is significantly better than that of eyes instilled with commercially available IMC eye drops. In addition, the accumulation of IMC in HCE-T cells treated with the IMCnano eye drops for 30 min was 19.9% that of the accumulation from commercially available IMC eye drops. On the other hand, the corneal penetration of IMC from IMCnano eye drops was significantly greater than in the case of the commercially available IMC eye drops in both in vivo and in vitro studies using rabbit corneas. Taken together, we hypothesize that a nanoparticle formulation reduces the corneal toxicity of IMC eye drops, probably because the accumulation of IMC from IMCnano eye drops in the eye is lower than that from commercially available IMC eye drops. In addition, the nanoparticle formulation may allow a decrease in the amount of IMC used due to the increase in bioavailability, resulting in reduced drug toxicity. These findings provide significant information

  8. Platinum electrodeposition at unsupported electrochemically reduced nanographene oxide for enhanced ammonia oxidation.

    PubMed

    Cunci, Lisandro; Velez, Carlos A; Perez, Ivan; Suleiman, Amal; Larios, Eduardo; José-Yacamán, Miguel; Watkins, James J; Cabrera, Carlos R

    2014-02-12

    The electrochemical reduction of highly oxidized unsupported graphene oxide nanosheets and its platinum electrodeposition was done by the rotating disk slurry electrode technique. Avoiding the use of a solid electrode, graphene oxide was electrochemically reduced in a slurry solution with a scalable process without the use of a reducing agent. Graphene oxide nanosheets were synthesized from carbon platelet nanofibers to obtain highly hydrophilic layers of less than 250 nm in width. The graphene oxide and electrochemically reduced graphene oxide/Pt (erGOx/Pt) hybrid materials were characterized through different spectroscopy and microscopy techniques. Pt nanoparticles with 100 facets, clusters, and atoms at erGOx were identified by high resolution transmission electron microscopy (HRTEM). Cyclic voltammetry was used to characterize the electrocatalytic activity of the highly dispersed erGOx/Pt hybrid material toward the oxidation of ammonia, which showed a 5-fold current density increase when compared with commercially available Vulcan/Pt 20%. This is in agreement with having Pt (100) facets present in the HRTEM images of the erGOx/Pt material.

  9. Platinum Electrodeposition at Unsupported Electrochemically Reduced Nanographene Oxide for Enhanced Ammonia Oxidation

    PubMed Central

    2015-01-01

    The electrochemical reduction of highly oxidized unsupported graphene oxide nanosheets and its platinum electrodeposition was done by the rotating disk slurry electrode technique. Avoiding the use of a solid electrode, graphene oxide was electrochemically reduced in a slurry solution with a scalable process without the use of a reducing agent. Graphene oxide nanosheets were synthesized from carbon platelet nanofibers to obtain highly hydrophilic layers of less than 250 nm in width. The graphene oxide and electrochemically reduced graphene oxide/Pt (erGOx/Pt) hybrid materials were characterized through different spectroscopy and microscopy techniques. Pt nanoparticles with 100 facets, clusters, and atoms at erGOx were identified by high resolution transmission electron microscopy (HRTEM). Cyclic voltammetry was used to characterize the electrocatalytic activity of the highly dispersed erGOx/Pt hybrid material toward the oxidation of ammonia, which showed a 5-fold current density increase when compared with commercially available Vulcan/Pt 20%. This is in agreement with having Pt (100) facets present in the HRTEM images of the erGOx/Pt material. PMID:24417177

  10. The Cholinergic Agonist Carbachol Increases the Frequency of Spontaneous GABAergic Synaptic Currents in Dorsal Raphe Serotonergic Neurons in the Mouse

    PubMed Central

    Yang, Chun; Brown, Ritchie E.

    2013-01-01

    Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative serotonin neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods

  11. The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse.

    PubMed

    Yang, C; Brown, R E

    2014-01-31

    Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods

  12. Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity

    PubMed Central

    Zhang, Peng; Sun, Fang; Tsao, Caroline; Liu, Sijun; Jain, Priyesh; Sinclair, Andrew; Hung, Hsiang-Chieh; Bai, Tao; Wu, Kan; Jiang, Shaoyi

    2015-01-01

    Advances in protein therapy are hindered by the poor stability, inadequate pharmacokinetic (PK) profiles, and immunogenicity of many therapeutic proteins. Polyethylene glycol conjugation (PEGylation) is the most successful strategy to date to overcome these shortcomings, and more than 10 PEGylated proteins have been brought to market. However, anti-PEG antibodies induced by treatment raise serious concerns about the future of PEGylated therapeutics. Here, we demonstrate a zwitterionic polymer network encapsulation technology that effectively enhances protein stability and PK while mitigating the immune response. Uricase modified with a comprehensive zwitterionic polycarboxybetaine (PCB) network exhibited exceptional stability and a greatly prolonged circulation half-life. More importantly, the PK behavior was unchanged, and neither anti-uricase nor anti-PCB antibodies were detected after three weekly injections in a rat model. This technology is applicable to a variety of proteins and unlocks the possibility of adopting highly immunogenic proteins for therapeutic or protective applications. PMID:26371311

  13. Slip knots and unfastening topologies enhance toughness without reducing strength of silk fibroin fibres.

    PubMed

    Berardo, Alice; Pantano, Maria F; Pugno, Nicola M

    2016-02-01

    The combination of high strength and high toughness is a desirable feature that structural materials should display. However, while in the past, engineers had to compromise on either strength or toughness depending on the requested application, nowadays, new toughening strategies are available to provide strong materials with high toughness. In this paper, we focus on one of such strategy, which requires no chemical treatment, but the implementation of slip knots with optimized shape and size in the involved material, which is silkworm silk in this case. In particular, a variety of slip knot topologies with different unfastening mechanisms are investigated, including even complex knots usually used in the textile industry, and their efficiency in enhancing toughness of silk fibres is discussed. PMID:26855750

  14. Slip knots and unfastening topologies enhance toughness without reducing strength of silk fibroin fibres.

    PubMed

    Berardo, Alice; Pantano, Maria F; Pugno, Nicola M

    2016-02-01

    The combination of high strength and high toughness is a desirable feature that structural materials should display. However, while in the past, engineers had to compromise on either strength or toughness depending on the requested application, nowadays, new toughening strategies are available to provide strong materials with high toughness. In this paper, we focus on one of such strategy, which requires no chemical treatment, but the implementation of slip knots with optimized shape and size in the involved material, which is silkworm silk in this case. In particular, a variety of slip knot topologies with different unfastening mechanisms are investigated, including even complex knots usually used in the textile industry, and their efficiency in enhancing toughness of silk fibres is discussed.

  15. Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

    SciTech Connect

    Salem, Tamer Z.; Zhang, Fengrui; Thiem, Suzanne M.

    2013-01-20

    Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

  16. Cholinergic stimulation of pancreatic amylase release and muscarinic receptors: effect of ionophore A23187

    SciTech Connect

    Larose, L.; Morisset, J.

    1985-07-22

    Dispersed rat pancreatic acini were incubated in 0.5 mM calcium medium with increasing concentrations of carbamylcholine, with or without the ionophore A23187 (10/sup -6/M). Addition of the ionophore reduced maximal amylase release, increased the maximal effective concentration of carbamylcholine and dramatically impaired the agonist's capacity to induce enzyme secretion at low concentration. The ionophore also abolished the inhibition of secretion observed at high carbamylcholine concentrations. These effects of the ionophore on the cholinergic secretory response cannot be explained by interaction at the muscarinic receptor since neither the Bmax, the affinity of the receptor for the (/sup 3/H)QNB nor the binding of carbamylcholine were affected by the ionophore. It is suggested that for the conditions studied, the ionophore can interact with the secretory process at one or several points ulterior to the initial recognition site of carbamylcholine on its receptor. 30 references, 3 figures.

  17. Reduced nitrate leaching and enhanced denitrifier activity and efficiency in organically fertilized soils.

    PubMed

    Kramer, Sasha B; Reganold, John P; Glover, Jerry D; Bohannan, Brendan J M; Mooney, Harold A

    2006-03-21

    Conventional agriculture has improved in crop yield but at large costs to the environment, particularly off-site pollution from mineral N fertilizers. In response to environmental concerns, organic agriculture has become an increasingly popular option. One component of organic agriculture that remains in question is whether it can reduce agricultural N losses to groundwater and the atmosphere relative to conventional agriculture. Here we report reduced N pollution from organic and integrated farming systems compared with a conventional farming system. We evaluated differences in denitrification potential and a suite of other soil biological and chemical properties in soil samples taken from organic, integrated, and conventional treatments in an experimental apple orchard. Organically farmed soils exhibited higher potential denitrification rates, greater denitrification efficiency, higher organic matter, and greater microbial activity than conventionally farmed soils. The observed differences in denitrifier function were then assessed under field conditions after fertilization. N(2)O emissions were not significantly different among treatments; however, N(2) emissions were highest in organic plots. Annual nitrate leaching was 4.4-5.6 times higher in conventional plots than in organic plots, with the integrated plots in between. This study demonstrates that organic and integrated fertilization practices support more active and efficient denitrifier communities, shift the balance of N(2) emissions and nitrate losses, and reduce environmentally damaging nitrate losses. Although this study specifically examines a perennial orchard system, the ecological and biogeochemical processes we evaluated are present in all agroecosystems, and the reductions in nitrate loss in this study could also be achievable in other cropping systems. PMID:16537377

  18. Plant diversity affects behavior of generalist root herbivores, reduces crop damage, and enhances crop yield.

    PubMed

    Staudacher, Karin; Schallhart, Nikolaus; Thalinger, Bettina; Wallinger, Corinna; Juen, Anita; Traugott, Michael

    2013-07-01

    Soil-dwelling pests inflict considerable economic damage in agriculture but are hard to control. A promising strategy to reduce pest pressure on crops is to increase the plant diversity in agroecosystems. This approach, however, demands a sound understanding of species' interactions, which is widely lacking for subterranean herbivore-plant systems. Here, we examine the effects of plant diversification on wireworms, the soil-dwelling larvae of click beetles that threaten crops worldwide. We conducted a field experiment employing plant diversification by adding either wheat or a mix of six associated plants (grasses, legumes, and forbs) between rows of maize to protect it from Agriotes wireworms. Wireworm feeding behavior, dispersal between crop and associated plants, as well as maize damage and yield were examined. The former was assessed combining molecular gut content and stable isotope analysis. The pests were strongly attracted by the associated plants in August, when the crop was most vulnerable, whereas in September, shortly before harvest, this effect occurred only in the plant mix. In maize monoculture, the larvae stayed in the principal crop throughout the season. Larval delta13C signatures revealed that maize feeding was reduced up to sevenfold in wireworms of the vegetationally diversified treatments compared to those of the maize monoculture. These findings were confirmed by molecular analysis, which additionally showed a dietary preference of wireworms for specific plants in the associated plant mix. Compared to the monoculture, maize damage was reduced by 38% and 55% in the wheat and plant mix treatment, which translated into a yield increase of 30% and 38%, respectively. The present findings demonstrate that increasing the plant diversity in agroecosystems provides an effective insurance against soil pests. The underlying mechanisms are the diversion of the pest from the principle crop and a changed feeding behavior. The deployment of diverse mixes of

  19. Enhanced photothermal effect of surface oxidized silicon nanocrystals anchored to reduced graphene oxide nanosheets

    NASA Astrophysics Data System (ADS)

    Afshani, Parichehr; Moussa, Sherif; Atkinson, Garrett; Kisurin, Vitaly Y.; Samy El-Shall, M.

    2016-04-01

    We demonstrate the coupling of the photothermal effects of silicon nanocrystals and graphene oxide (GO) dispersed in water. Using laser irradiation (532 nm or 355 nm) of suspended Si nanocrystals in an aqueous solution of GO, the synthesis of surface oxidized Si-reduced GO nanocomposites (SiOx/Si-RGO) is reported. The laser reduction of GO is accompanied by surface oxidation of the Si nanocrystals resulting in the formation of the SiOx/Si-RGO nanocomposites. The SiOx/Si-RGO nanocomposites are proposed as promising materials for photothermal therapy and for the efficient conversion of solar energy into usable heat for a variety of thermal and thermomechanical applications.

  20. Characterization of Channelrhodopsin and Archaerhodopsin in Cholinergic Neurons of Cre-Lox Transgenic Mice

    PubMed Central

    Hedrick, Tristan; Danskin, Bethanny; Larsen, Rylan S.; Ollerenshaw, Doug; Groblewski, Peter; Valley, Matthew; Olsen, Shawn; Waters, Jack

    2016-01-01

    The study of cholinergic signaling in the mammalian CNS has been greatly facilitated by the advent of mouse lines that permit the expression of reporter proteins, such as opsins, in cholinergic neurons. However, the expression of opsins could potentially perturb the physiology of opsin-expressing cholinergic neurons or mouse behavior. Indeed, the published literature includes examples of cellular and behavioral perturbations in preparations designed to drive expression of opsins in cholinergic neurons. Here we investigate expression of opsins, cellular physiology of cholinergic neurons and behavior in two mouse lines, in which channelrhodopsin-2 (ChR2) and archaerhodopsin (Arch) are expressed in cholinergic neurons using the Cre-lox system. The two mouse lines were generated by crossing ChAT-Cre mice with Cre-dependent reporter lines Ai32(ChR2-YFP) and Ai35(Arch-GFP). In most mice from these crosses, we observed expression of ChR2 and Arch in only cholinergic neurons in the basal forebrain and in other putative cholinergic neurons in the forebrain. In small numbers of mice, off-target expression occurred, in which fluorescence did not appear limited to cholinergic neurons. Whole-cell recordings from fluorescently-labeled basal forebrain neurons revealed that both proteins were functional, driving depolarization (ChR2) or hyperpolarization (Arch) upon illumination, with little effect on passive membrane properties, spiking pattern or spike waveform. Finally, performance on a behavioral discrimination task was comparable to that of wild-type mice. Our results indicate that ChAT-Cre x reporter line crosses provide a simple, effective resource for driving indicator and opsin expression in cholinergic neurons with few adverse consequences and are therefore an valuable resource for studying the cholinergic system. PMID:27243816

  1. Enhancing Hematite Photoanode Activity for Water Oxidation by Incorporation of Reduced Graphene Oxide.

    PubMed

    do Amaral Carminati, Saulo; Souza, Flavio L; Nogueira, Ana F

    2016-01-01

    Two effective methods to prepare reduced graphene oxide (rGO)/hematite nanostructured photoanodes and their photoelectrochemical characterization towards water splitting reactions are presented. First, graphene oxide (GO) is reduced to rGO using hydrazine in a basic solution containing tetrabutylammonium hydroxide (TBAOH), and then deposited over the nanostructured hematite photoanodes previously treated at 750 °C for 30 min. The second method follows the deposition of a paste containing a mixture of hematite nanoparticles and rGO sheets by the doctor-blade method, varying the rGO concentration. Since hematite suffers from low electron mobility, a low absorption coefficient, high recombination rates and slow reaction kinetics, the incorporation of rGO in the hematite can overcome such limitations due to graphene's exceptional properties. Using the first method, the rGO incorporation results in a photocurrent density increase from 0.56 to 0.82 mA cm(-2) at 1.23 VRHE. Our results indicate that the rGO incorporation in the hematite photoanodes shows a positive effect in the reduction of the electron-hole recombination rate. PMID:26561385

  2. Immobilized Silver Nanoparticles on Chitosan with Special Surface State-Enhanced Antimicrobial Efficacy and Reduced Cytotoxicity.

    PubMed

    He, Miao; Lu, Liying; Zhang, Jinchi; Li, Danzhen

    2015-09-01

    Immobilized chitosan-Ag nanoparticles (CTS-Ag NPs) with special surface state have been synthesized successfully through immobilizing Ag NPs on the amino-enriched surface of CTS by reducing Ag (I) in situ. The antimicrobial efficiency and potency of CTS-Ag NPs against Escherichia coli and Staphylococcus aureus were studied. Our results reveal that surface-immobilized CTS-Ag NPs show better antimicrobial efficacy than several other reported monodisperse colloidal Ag NPs, because the unique surface state of our CTS-Ag NPs leads to both "contact killing" and "ion mediated killing" functions. Due to the synergetic effect of CTS and Ag NPs, the immobilized CTS-Ag NPs present a broader antimicrobial spectrum and a more effective antifungal activity against Monilia albican. In addition, CTS as an environment friendly dispersant can help to reduce the cytotoxicity of Ag NPs on higher organisms. The immobilized CTS-Ag NPs are stable and can maintain good disinfection potential after 6 months' shelf-time. PMID:26716197

  3. Enhancing global control of alcohol to reduce unsafe sex and HIV in sub-Saharan Africa.

    PubMed

    Chersich, Matthew F; Rees, Helen V; Scorgie, Fiona; Martin, Greg

    2009-01-01

    Sub-Saharan Africa carries a massive dual burden of HIV and alcohol disease, and these pandemics are inextricably linked. Physiological and behavioural research indicates that alcohol independently affects decision-making concerning sex, and skills for negotiating condoms and their correct use. More than 20 studies in Africa have reported higher occurrence of HIV among people with problem drinking; a finding strongly consistent across studies and similar among women and men. Conflation of HIV and alcohol disease in these setting is not surprising given patterns of heavy-episodic drinking and that drinking contexts are often coterminous with opportunities for sexual encounters. HIV and alcohol also share common ground with sexual violence. Both perpetrators and victims of sexual violence have a high likelihood of having drunk alcohol prior to the incident, as with most forms of violence and injury in sub-Saharan Africa. Reducing alcohol harms necessitates multi-level interventions and should be considered a key component of structural interventions to alleviate the burden of HIV and sexual violence. Brief interventions for people with problem drinking (an important component of primary health care), must incorporate specific discussion of links between alcohol and unsafe sex, and consequences thereof. Interventions to reduce alcohol harm among HIV-infected persons are also an important element in positive-prevention initiatives. Most importantly, implementation of known effective interventions could alleviate a large portion of the alcohol-attributable burden of disease, including its effects on unsafe sex, unintended pregnancy and HIV transmission. PMID:19919703

  4. Reduced biological control and enhanced chemical pest management in the evolution of fungus farming in ants.

    PubMed

    Fernández-Marín, Hermógenes; Zimmerman, Jess K; Nash, David R; Boomsma, Jacobus J; Wcislo, William T

    2009-06-22

    To combat disease, most fungus-growing ants (Attini) use antibiotics from mutualistic bacteria (Pseudonocardia) that are cultured on the ants' exoskeletons and chemical cocktails from exocrine glands, especially the metapleural glands (MG). Previous work has hypothesized that (i) Pseudonocardia antibiotics are narrow-spectrum and control a fungus (Escovopsis) that parasitizes the ants' fungal symbiont, and (ii) MG secretions have broad-spectrum activity and protect ants and brood. We assessed the relative importance of these lines of defence, and their activity spectra, by scoring abundance of visible Pseudonocardia for nine species from five genera and measuring rates of MG grooming after challenging ants with disease agents of differing virulence. Atta and Sericomyrmex have lost or greatly reduced the abundance of visible bacteria. When challenged with diverse disease agents, including Escovopsis, they significantly increased MG grooming rates and expanded the range of targets. By contrast, species of Acromyrmex and Trachymyrmex maintain abundant Pseudonocardia. When challenged, these species had lower MG grooming rates, targeted primarily to brood. More elaborate MG defences and reduced reliance on mutualistic Pseudonocardia are correlated with larger colony size among attine genera, raising questions about the efficacy of managing disease in large societies with chemical cocktails versus bacterial antimicrobial metabolites.

  5. Does Enhancing Work-Time Control and Flexibility Reduce Turnover? A Naturally Occurring Experiment

    PubMed Central

    Moen, Phyllis; Kelly, Erin L.; Hill, Rachelle

    2011-01-01

    We investigate the turnover effects of an organizational innovation (ROWE—Results Only Work Environment) aimed at moving away from standard time practices to focus on results rather than time spent at work. To model rates of turnover, we draw on survey data from a sample of employees at a corporate headquarters (N = 775) and institutional records of turnover over eight months following the ROWE implementation. We find the odds of turnover are indeed lower for employees participating in the ROWE initiative, which offers employees greater work-time control and flexibility, and that this is the case regardless of employees’ gender, age, or family life stage. ROWE also moderates the turnover effects of organizational tenure and negative home-to-work spillover, physical symptoms, and job insecurity, with those in ROWE who report these situations generally less likely to leave the organization. Additionally, ROWE reduces turnover intentions among those remaining with the corporation. This research moves the “opting-out” argument from one of private troubles to an issue of greater employee work-time control and flexibility by showing that an organizational policy initiative can reduce turnover. PMID:21532909

  6. Berberine reduces Toll-like receptor-mediated macrophage migration by suppression of Src enhancement.

    PubMed

    Cheng, Wei-Erh; Ying Chang, Miao; Wei, Jyun-Yan; Chen, Yen-Jen; Maa, Ming-Chei; Leu, Tzeng-Horng

    2015-06-15

    Berberine is an isoquinoline with anti-inflammatory activity. We previously demonstrated that there was a loop of signal amplification between nuclear factor kappa B and Src for macrophage mobility triggered by the engagement of Toll-like receptors (TLRs). The simultaneous suppression of lipopolysaccharide (LPS)-mediated upregulation of inducible nitric oxide synthase, cyclooxygenase 2, and cell mobility in berberine-treated macrophages suggested Src might be a target of berberine. Indeed, th reduced migration, greatly suppressed Src induction in both protein and RNA transcript by berberine were observed in macrophages exposed to LPS, peptidoglycan, polyinosinic-polycytidylic acid, and CpG-oligodeoxynucleotides. In addition to Src induction, berberine also inhibited LPS-mediated Src activation in Src overexpressing macrophages and S-nitroso-N-acetylpenicillamine (a nitric oxide donor) could partly restore it. Moreover, berberine suppressed Src activity in fibronectin-stimulated macrophages and in v-Src transformed cells. These results implied that by effectively reducing Src expression and activity, berberine inhibited TLR-mediated cell motility in macrophages.

  7. Evaluation of organic substrates to enhance the sulfate-reducing activity in phosphogypsum.

    PubMed

    Castillo, Julio; Pérez-López, Rafael; Sarmiento, Aguasanta M; Nieto, José M

    2012-11-15

    Several experiments were conducted to evaluate the activity and growth of sulfate-reducing bacteria (SRB) in a metal-rich culture medium (approx. 250 mg/L Fe, 75 mg/L Zn and Cu, 10mg/L Cd) with phosphogypsum as bacterial inoculum. Phosphogypsum was collected from the stack covering the salt-marshes of the Tinto river (SW Spain). Three organic amendments were used as carbon sources, two low-cost wastes (horse manure and legume compost) and one sample of natural soil (vegetal cover). In the experiments, sulfate was reduced to sulfide during the growth of SRB populations, and concentrations were decreased in the solution. Metal concentrations also decreased to values below the detection limit. Metal removal took place by precipitation of newly-formed sulfides. Pyrite-S was the main sulfide component (approx. 200 μmol/g and 80% of pyritization) and occurred mainly as framboidal grains and rarely as isolated polyhedral crystals. Horse manure was the most successful organic substrate to promote SRB activity (sulfate removal of 61%), followed by vegetal cover (49%) and legume compost (31%). These findings propose the possibility of using naturally-occurring SRB in the phosphogypsum for bioremediation strategies based on natural soil covers with organic amendments.

  8. Reducing anxiety and enhancing physical performance by using an advanced version of EMDR: a pilot study

    PubMed Central

    Rathschlag, Marco; Memmert, Daniel

    2014-01-01

    Background The main aim of this pilot study was to investigate an advanced version of eye movement desensitization and reprocessing (EMDR) for reducing anxiety. Methods Fifty participants were asked at two times of measurement (T1 and T2 with a rest of 4 weeks) to generate anxiety via the recall of autobiographical memories according to their anxiety. Furthermore, the participants were randomly assigned to an experimental group and a control group, and the experimental group received an intervention of 1–2 h with the advanced version of EMDR in order to their anxiety 2 weeks after T1. At T1 as well as T2, we measured the intensity of participants' anxiety with a Likert scale (LS) and collected participants' state (temporary) and trait (chronic) anxiety with the State-Trait Anxiety Inventory (STAI). In addition, we measured participants' physical performance in a test for the finger musculature under the induction of their anxiety. Results The results showed that participant's ratings of their perceived intensity of anxiety (measured by a 9-point LS) and the state and trait anxiety decreased significantly in the experimental group but not in the control group from T1 to T2. Moreover, the physical performance under the induction of participants' anxiety increased significantly in the experimental group from T1 to T2 and there were no significant changes in the control group. Conclusions The study could show that the advanced version of EMDR is an appropriate method to reduce anxiety. PMID:24944864

  9. The NLR protein, NLRX1, and its partner, TUFM, reduce type I interferon, and enhance autophagy.

    PubMed

    Lei, Yu; Wen, Haitao; Ting, Jenny P Y

    2013-03-01

    The NLR (nucleotide-binding domain leucine-rich repeat containing) proteins serve as regulators of inflammatory signaling pathways. NLRX1, a mitochondria-localized NLR protein, has been previously shown to negatively regulate inflammatory cytokine production activated via the MAVS-DDX58 (RIG-I) pathway. The literature also indicates that DDX58 has a negative impact upon autophagy. Consistent with the inhibitory role of NLRX1 on DDX58, our recent study indicates a role of NLRX1 in augmenting virus-induced autophagy. This effect is through its interaction with another mitochondrial protein TUFM (Tu translation elongation factor, mitochondrial, also known as EF-TuMT, COXPD4, and P43). TUFM also reduces DDX58-activated cytokines but augments autophagy. Additionally it interacts with ATG12-ATG5-ATG16L1 to form a molecular complex that modulates autophagy. The work shows that both NLRX1 and TUFM work in concert to reduce cytokine response and augment autophagy.

  10. Purinergic and Cholinergic Drugs Mediate Hyperventilation in Zebrafish: Evidence from a Novel Chemical Screen

    PubMed Central

    Rahbar, Saman; Pan, Wen; Jonz, Michael G.

    2016-01-01

    A rapid test to identify drugs that affect autonomic responses to hypoxia holds therapeutic and ecologic value. The zebrafish (Danio rerio) is a convenient animal model for investigating peripheral O2 chemoreceptors and respiratory reflexes in vertebrates; however, the neurotransmitters and receptors involved in this process are not adequately defined. The goals of the present study were to demonstrate purinergic and cholinergic control of the hyperventilatory response to hypoxia in zebrafish, and to develop a procedure for screening of neurochemicals that affect respiration. Zebrafish larvae were screened in multi-well plates for sensitivity to the cholinergic receptor agonist, nicotine, and antagonist, atropine; and to the purinergic receptor antagonists, suramin and A-317491. Nicotine increased ventilation frequency (fV) maximally at 100 μM (EC50 = 24.5 μM). Hypoxia elevated fV from 93.8 to 145.3 breaths min-1. Atropine reduced the hypoxic response only at 100 μM. Suramin and A-317491 maximally reduced fV at 50 μM (EC50 = 30.4 and 10.8 μM) and abolished the hyperventilatory response to hypoxia. Purinergic P2X3 receptors were identified in neurons and O2-chemosensory neuroepithelial cells of the gills using immunohistochemistry and confocal microscopy. These studies suggest a role for purinergic and nicotinic receptors in O2 sensing in fish and implicate ATP and acetylcholine in excitatory neurotransmission, as in the mammalian carotid body. We demonstrate a rapid approach for screening neuroactive chemicals in zebrafish with implications for respiratory medicine and carotid body disease in humans; as well as for preservation of aquatic ecosystems. PMID:27100625

  11. Differential susceptibility of cholinergic and noncholinergic neurogenic responses to calcium channel blockers and low Ca2+ medium in rat urinary bladder.

    PubMed Central

    Bhat, M. B.; Mishra, S. K.; Raviprakash, V.

    1989-01-01

    1. The influence of calcium channel blockers and low Ca2+ medium on the neurogenic responses to single pulse electric field stimulation in rat urinary bladder has been examined. 2. Single pulse stimulation evoked a biphasic contractile response consisting of a fast component with a time to peak of 0.72 +/- 0.05 s and a slow component that reached a maximal tension at 2.8 +/- 0.21 s, possibly mediated by two different neurotransmitters. 3. Atropine (3 x 10(-6) M) selectively inhibited the slow component without altering the fast component, suggesting the involvement of cholinergic and non-cholinergic neurotransmitters, respectively. 4. Reducing Ca2+ in the medium to 1/4 of the normal, abolished the slow component of the neurogenic response while the fast contractile response was not altered which may indicate a relatively greater dependence of the cholinergic component on extracellular Ca2+ than the noncholinergic one. 5. The IC50 values for the fast component with respect to verapamil and diltiazem were 1.08 microM and 1.76 microM, respectively. The greater susceptibility of the slow component to calcium channel blockers (IC50 values of verapamil: 0.07 microM and of diltiazem: 0.25 microM) indicates the differential activation of slow calcium channels by the endogenously released substances. 6. Calcium channel blockers inhibited the ATP-induced contraction which was comparable to that of the non-cholinergic component of the neurogenic response suggesting the involvement of ATP as a possible neurotransmitter. 7. Ach-induced contractions were relatively less susceptible to calcium channel blockers and low Ca2+ medium than was the atropine-sensitive cholinergic component of the neurogenic response. PMID:2743079

  12. Effects of amyloid-beta on cholinergic and acetylcholinesterase-positive cells in cultured basal forebrain neurons of embryonic rat brain.

    PubMed

    Kasa, Peter; Papp, Henrietta; Kasa, Peter; Pakaski, Magdolna; Balaspiri, Lajos

    2004-02-13

    The neurotoxic effects of amyloid-beta(1-42) and amyloid-beta(25-35) (A beta) on cholinergic and acetylcholinesterase-positive neurons were investigated in primary cultures derived from embryonic 18-day-old rat basal forebrain. After various time intervals, the cultures were treated with 1, 5, 10 or 20 microM A beta for different time periods. The cholinergic neurons and their axon terminals were revealed by vesicular acetylcholine transporter immunohistochemistry and the cholinoceptive cells by acetylcholinesterase histochemical staining. To assess the toxic effects of these A beta peptides on the cholinergic neurons, image analysis was applied for quantitative determination of the numbers of axon varicosities/terminals and cells. The results demonstrate that, following treatment with 1 or 5 microM A beta for 5, 10, 30, 60 or 120 min, no changes in vesicular acetylcholine transporter immunohistochemical staining were observed. However, after treatment for 30 min with 10 or 20 microM A beta, the number of stained axon varicosities was reduced, and treatment for 2 h they had disappeared. In contrast, vesicular acetylcholine transporter-positivity could be seen in some of the neuronal perikarya even after 3 days after treatment. The acetylcholinesterase staining was homogeneously distributed in the control neurons. After A beta treatment, the histochemical reaction end-product was detected in some of the neuronal perikarya or in the dendritic processes near to the soma. It is concluded that the neurotoxic effects of A beta appear more rapidly in the cholinergic axon terminals than in the cholinergic and acetylcholinesterase-positive neuronal perikarya. PMID:14725970

  13. Reduced steric hindrance and optimized spatial arrangement of carbohydrate ligands in imprinted monolayers for enhanced protein binding.

    PubMed

    Zheng, Haifu; Du, Xuezhong

    2013-02-01

    Imprinted monolayers provide several advantages over bulk imprinting methods. This is especially important for large templates such as proteins. Concanavalin A (Con A)-imprinted binary monolayers consisting of glycolipids with oligo(ethylene glycol) (OEG) spacers and zwitterionic phospholipids (DPPC) were constructed and investigated. The shorter phosphorylcholine (PC) headgroups with an almost flat-on orientation in the binary monolayers gave rise to reduced steric hindrance favorable to the accommodation of Con A with greater ease and facilitated the access of the OEG-linked mannose moieties for enhanced protein binding. Further enhanced binding resulted from optimized spatial rearrangement of the glycolipids at the air-water interface directed by Con A in the subphase to create bivalent binding sites and to minimize steric crowding of neighboring mannose ligands. The combination of the exposed carbohydrate ligands from biologically inert surfaces and the optimized ligand arrangement is the most reasonable solution to enhancement of protein affinity. The bivalent carbohydrate binding sites protruding from the imprinted monolayers were created to be complementary to the Con A binding pockets. This strategy generates tailor-made surfaces with enhanced protein binding and opens the possibility of controlled assembly of intellectual biomaterials and preparation of biosensors.

  14. Enhanced leavening properties of baker's yeast by reducing sucrase activity in sweet dough.

    PubMed

    Zhang, Cui-Ying; Lin, Xue; Feng, Bing; Liu, Xiao-Er; Bai, Xiao-Wen; Xu, Jia; Pi, Li; Xiao, Dong-Guang

    2016-07-01

    Leavening ability in sweet dough is required for the commercial applications of baker's yeast. This property depends on many factors, such as glycolytic activity, sucrase activity, and osmotolerance. This study explored the importance of sucrase level on the leavening ability of baker's yeast in sweet dough. Furthermore, the baker's yeast strains with varying sucrase activities were constructed by deleting SUC2, which encodes sucrase or replacing the SUC2 promoter with the VPS8/TEF1 promoter. The results verify that the sucrase activity negatively affects the leavening ability of baker's yeast strains under high-sucrose conditions. Based on a certain level of osmotolerance, sucrase level plays a significant role in the fermentation performance of baker's yeast, and appropriate sucrase activity is an important determinant for the leavening property of baker's yeast in sweet dough. Therefore, modification on sucrase activity is an effective method for improving the leavening properties of baker's yeast in sweet dough. This finding provides guidance for the breeding of industrial baker's yeast strains for sweet dough leavening. The transformants BS1 with deleted SUC2 genetic background provided decreased sucrase activity (a decrease of 39.3 %) and exhibited enhanced leavening property (an increase of 12.4 %). Such a strain could be useful for industrial applications.

  15. Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression.

    PubMed

    Hinds, Terry D; Peck, Bailey; Shek, Evan; Stroup, Steven; Hinson, Jennifer; Arthur, Susan; Marino, Joseph S

    2016-01-01

    Unlike the glucocorticoid receptor α (GRα), GR β (GRβ) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C₂C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C₂C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids. PMID:26875982

  16. Enhanced perceptions of control and predictability reduce motion-induced nausea and gastric dysrhythmia.

    PubMed

    Levine, Max E; Stern, Robert M; Koch, Kenneth L

    2014-08-01

    Nausea is a debilitating condition that is typically accompanied by gastric dysrhythmia. The enhancement of perceived control and predictability has generally been found to attenuate the physiological stress response. The aim of the present study was to test the effect of these psychosocial variables in the context of nausea, motion sickness, and gastric dysrhythmia. A 2x2, independent-groups, factorial design was employed in which perceived control and predictability were each provided at high or low levels to 80 participants before exposure to a rotating optokinetic drum. Ratings of nausea were obtained throughout a 6-min baseline period and a 16-min drum rotation period. Noninvasive recordings of the electrical activity of the stomach called electrogastrograms were also obtained throughout the study. Nausea scores were significantly lower among participants with high control than among those with low control, and were significantly lower among participants with high predictability than among those with low predictability. Estimates of gastric dysrhythmia obtained from the EGG during drum rotation were significantly lower among participants with high predictability than among those with low predictability. A significant interaction effect of control and predictability on gastric dysrhythmia was also observed, such that high control was only effective for arresting the development of gastric dysrhythmia when high predictability was also available. Stronger perceptions of control and predictability may temper the development of nausea and gastric dysrhythmia during exposure to provocative motion. Psychosocial interventions in a variety of nausea contexts may represent an alternative means of symptom control. PMID:24748483

  17. Enhanced perceptions of control and predictability reduce motion-induced nausea and gastric dysrhythmia.

    PubMed

    Levine, Max E; Stern, Robert M; Koch, Kenneth L

    2014-08-01

    Nausea is a debilitating condition that is typically accompanied by gastric dysrhythmia. The enhancement of perceived control and predictability has generally been found to attenuate the physiological stress response. The aim of the present study was to test the effect of these psychosocial variables in the context of nausea, motion sickness, and gastric dysrhythmia. A 2x2, independent-groups, factorial design was employed in which perceived control and predictability were each provided at high or low levels to 80 participants before exposure to a rotating optokinetic drum. Ratings of nausea were obtained throughout a 6-min baseline period and a 16-min drum rotation period. Noninvasive recordings of the electrical activity of the stomach called electrogastrograms were also obtained throughout the study. Nausea scores were significantly lower among participants with high control than among those with low control, and were significantly lower among participants with high predictability than among those with low predictability. Estimates of gastric dysrhythmia obtained from the EGG during drum rotation were significantly lower among participants with high predictability than among those with low predictability. A significant interaction effect of control and predictability on gastric dysrhythmia was also observed, such that high control was only effective for arresting the development of gastric dysrhythmia when high predictability was also available. Stronger perceptions of control and predictability may temper the development of nausea and gastric dysrhythmia during exposure to provocative motion. Psychosocial interventions in a variety of nausea contexts may represent an alternative means of symptom control.

  18. MAP training: combining meditation and aerobic exercise reduces depression and rumination while enhancing synchronized brain activity

    PubMed Central

    Alderman, B L; Olson, R L; Brush, C J; Shors, T J

    2016-01-01

    Mental and physical (MAP) training is a novel clinical intervention that combines mental training through meditation and physical training through aerobic exercise. The intervention was translated from neuroscientific studies indicating that MAP training increases neurogenesis in the adult brain. Each session consisted of 30 min of focused-attention (FA) meditation and 30 min of moderate-intensity aerobic exercise. Fifty-two participants completed the 8-week intervention, which consisted of two sessions per week. Following the intervention, individuals with major depressive disorder (MDD; n=22) reported significantly less depressive symptoms and ruminative thoughts. Typical healthy individuals (n=30) also reported less depressive symptoms at follow-up. Behavioral and event-related potential indices of cognitive control were collected at baseline and follow-up during a modified flanker task. Following MAP training, N2 and P3 component amplitudes increased relative to baseline, especially among individuals with MDD. These data indicate enhanced neural responses during the detection and resolution of conflicting stimuli. Although previous research has supported the individual beneficial effects of aerobic exercise and meditation for depression, these findings indicate that a combination of the two may be particularly effective in increasing cognitive control processes and decreasing ruminative thought patterns. PMID:26836414

  19. Magnesium aminoclay enhances lipid production of mixotrophic Chlorella sp. KR-1 while reducing bacterial populations.

    PubMed

    Kim, Bohwa; Praveenkumar, Ramasamy; Lee, Jiye; Nam, Bora; Kim, Dong-Myung; Lee, Kyubock; Lee, Young-Chul; Oh, You-Kwan

    2016-11-01

    Improving lipid productivity and preventing overgrowth of contaminating bacteria are critical issues relevant to the commercialization of the mixotrophic microalgae cultivation process. In this paper, we report the use of magnesium aminoclay (MgAC) nanoparticles for enhanced lipid production from oleaginous Chlorella sp. KR-1 with simultaneous control of KR-1-associated bacterial growth in mixotrophic cultures with glucose as the model substrate. Addition of 0.01-0.1g/L MgAC promoted microalgal biomass production better than the MgAC-less control, via differential biocidal effects on microalgal and bacterial cells (the latter being more sensitive to MgAC's bio-toxicity than the former). The inhibition effect of MgAC on co-existing bacteria was, as based on density-gradient-gel-electrophoresis (DGGE) analysis, largely dosage-dependent and species-specific. MgAC also, by inducing an oxidative stress environment, increased both the cell size and lipid content of KR-1, resulting in a considerable, ∼25% improvement of mixotrophic algal lipid productivity (to ∼410mgFAME/L/d) compared with the untreated control. PMID:27543952

  20. Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression

    PubMed Central

    Hinds, Terry D.; Peck, Bailey; Shek, Evan; Stroup, Steven; Hinson, Jennifer; Arthur, Susan; Marino, Joseph S.

    2016-01-01

    Unlike the glucocorticoid receptor α (GRα), GR β (GRβ) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids. PMID:26875982

  1. MAP training: combining meditation and aerobic exercise reduces depression and rumination while enhancing synchronized brain activity.

    PubMed

    Alderman, B L; Olson, R L; Brush, C J; Shors, T J

    2016-02-02

    Mental and physical (MAP) training is a novel clinical intervention that combines mental training through meditation and physical training through aerobic exercise. The intervention was translated from neuroscientific studies indicating that MAP training increases neurogenesis in the adult brain. Each session consisted of 30 min of focused-attention (FA) meditation and 30 min of moderate-intensity aerobic exercise. Fifty-two participants completed the 8-week intervention, which consisted of two sessions per week. Following the intervention, individuals with major depressive disorder (MDD; n=22) reported significantly less depressive symptoms and ruminative thoughts. Typical healthy individuals (n=30) also reported less depressive symptoms at follow-up. Behavioral and event-related potential indices of cognitive control were collected at baseline and follow-up during a modified flanker task. Following MAP training, N2 and P3 component amplitudes increased relative to baseline, especially among individuals with MDD. These data indicate enhanced neural responses during the detection and resolution of conflicting stimuli. Although previous research has supported the individual beneficial effects of aerobic exercise and meditation for depression, these findings indicate that a combination of the two may be particularly effective in increasing cognitive control processes and decreasing ruminative thought patterns.

  2. Significant enhancement of the thermoelectric figure of merit of polycrystalline Si films by reducing grain size

    NASA Astrophysics Data System (ADS)

    Valalaki, K.; Vouroutzis, N.; Nassiopoulou, A. G.

    2016-08-01

    The thermoelectric properties of p-type polycrystalline silicon thin films deposited by low pressure chemical vapour deposition (LPCVD) were accurately determined at room temperature and the thermoelectric figure of merit was deduced as a function of film thickness, ranging from 100 to 500 nm. The effect of film thickness on their thermoelectric performance is discussed. More than threefold increase in the thermoelectric figure of merit of the 100 nm thick polysilicon film was observed compared to the 500 nm thick film, reaching a value as high as 0.033. This enhancement is mainly the result of the smaller grain size in the thinner films. With the decrease in grain size the resistivity of the films is increased twofold and electrical conductivity decreased, however the Seebeck coefficient is increased by 30% and the thermal conductivity is decreased eightfold, being mainly at the origin of the increased figure of merit of the 100 nm film. Our experimental results were compared to known theoretical models and the possible mechanisms involved are presented and discussed.

  3. Magnesium aminoclay enhances lipid production of mixotrophic Chlorella sp. KR-1 while reducing bacterial populations.

    PubMed

    Kim, Bohwa; Praveenkumar, Ramasamy; Lee, Jiye; Nam, Bora; Kim, Dong-Myung; Lee, Kyubock; Lee, Young-Chul; Oh, You-Kwan

    2016-11-01

    Improving lipid productivity and preventing overgrowth of contaminating bacteria are critical issues relevant to the commercialization of the mixotrophic microalgae cultivation process. In this paper, we report the use of magnesium aminoclay (MgAC) nanoparticles for enhanced lipid production from oleaginous Chlorella sp. KR-1 with simultaneous control of KR-1-associated bacterial growth in mixotrophic cultures with glucose as the model substrate. Addition of 0.01-0.1g/L MgAC promoted microalgal biomass production better than the MgAC-less control, via differential biocidal effects on microalgal and bacterial cells (the latter being more sensitive to MgAC's bio-toxicity than the former). The inhibition effect of MgAC on co-existing bacteria was, as based on density-gradient-gel-electrophoresis (DGGE) analysis, largely dosage-dependent and species-specific. MgAC also, by inducing an oxidative stress environment, increased both the cell size and lipid content of KR-1, resulting in a considerable, ∼25% improvement of mixotrophic algal lipid productivity (to ∼410mgFAME/L/d) compared with the untreated control.

  4. Enhanced leavening properties of baker's yeast by reducing sucrase activity in sweet dough.

    PubMed

    Zhang, Cui-Ying; Lin, Xue; Feng, Bing; Liu, Xiao-Er; Bai, Xiao-Wen; Xu, Jia; Pi, Li; Xiao, Dong-Guang

    2016-07-01

    Leavening ability in sweet dough is required for the commercial applications of baker's yeast. This property depends on many factors, such as glycolytic activity, sucrase activity, and osmotolerance. This study explored the importance of sucrase level on the leavening ability of baker's yeast in sweet dough. Furthermore, the baker's yeast strains with varying sucrase activities were constructed by deleting SUC2, which encodes sucrase or replacing the SUC2 promoter with the VPS8/TEF1 promoter. The results verify that the sucrase activity negatively affects the leavening ability of baker's yeast strains under high-sucrose conditions. Based on a certain level of osmotolerance, sucrase level plays a significant role in the fermentation performance of baker's yeast, and appropriate sucrase activity is an important determinant for the leavening property of baker's yeast in sweet dough. Therefore, modification on sucrase activity is an effective method for improving the leavening properties of baker's yeast in sweet dough. This finding provides guidance for the breeding of industrial baker's yeast strains for sweet dough leavening. The transformants BS1 with deleted SUC2 genetic background provided decreased sucrase activity (a decrease of 39.3 %) and exhibited enhanced leavening property (an increase of 12.4 %). Such a strain could be useful for industrial applications. PMID:27041690

  5. Enhanced ordering reduces electric susceptibility of liquids confined to graphene slit pores

    PubMed Central

    Terrones, Jeronimo; Kiley, Patrick J.; Elliott, James A.

    2016-01-01

    The behaviours of a range of polar and non-polar organic liquids (acetone, ethanol, methanol, N-methyl-2-pyrrolidone (NMP), carbon tetrachloride and water) confined to 2D graphene nanochannels with thicknesses in the range of 4.5 Å to 40 Å were studied using classical molecular dynamics and hybrid density functional theory. All liquids were found to organise spontaneously into ordered layers parallel to the confining surfaces, with those containing polar molecules having their electric dipoles aligned parallel to such surfaces. In particular, monolayers of NMP showed remarkable in-plane ordering and low molecular mobility, suggesting the existence of a previously unknown 2D solid-like phase. Calculations for polar liquids showed dramatically reduced static permittivities normal to the confining surfaces; these changes are expected to improve electron tunnelling across the liquid films, modifying the DC electrical properties of immersed assemblies of carbon nanomaterials. PMID:27265098

  6. Core/shell quantum dot based luminescent solar concentrators with reduced reabsorption and enhanced efficiency.

    PubMed

    Coropceanu, Igor; Bawendi, Moungi G

    2014-07-01

    CdSe/CdS core/shell quantum dots (QDs) have been optimized toward luminescent solar concentration (LSC) applications. Systematically increasing the shell thickness continuously reduced reabsorption up to a factor of 45 for the thickest QDs studied (with ca. 14 monolayers of CdS) compared to the initial CdSe cores. Moreover, an improved synthetic method was developed that retains a high-fluorescence quantum yield, even for particles with the thickest shell volume, for which a quantum yield of 86% was measured in solution. These high quantum yield thick shell quantum dots were embedded in a polymer matrix, yielding highly transparent composites to serve as prototype LSCs, which exhibited an optical efficiency as high as 48%. A Monte Carlo simulation was developed to model LSC performance and to identify the major loss channels for LSCs incorporating the materials developed. The results of the simulation are in excellent agreement with the experimental data. PMID:24902615

  7. Enhanced ordering reduces electric susceptibility of liquids confined to graphene slit pores.

    PubMed

    Terrones, Jeronimo; Kiley, Patrick J; Elliott, James A

    2016-06-06

    The behaviours of a range of polar and non-polar organic liquids (acetone, ethanol, methanol, N-methyl-2-pyrrolidone (NMP), carbon tetrachloride and water) confined to 2D graphene nanochannels with thicknesses in the range of 4.5 Å to 40 Å were studied using classical molecular dynamics and hybrid density functional theory. All liquids were found to organise spontaneously into ordered layers parallel to the confining surfaces, with those containing polar molecules having their electric dipoles aligned parallel to such surfaces. In particular, monolayers of NMP showed remarkable in-plane ordering and low molecular mobility, suggesting the existence of a previously unknown 2D solid-like phase. Calculations for polar liquids showed dramatically reduced static permittivities normal to the confining surfaces; these changes are expected to improve electron tunnelling across the liquid films, modifying the DC electrical properties of immersed assemblies of carbon nanomaterials.

  8. Customization of user interfaces to reduce errors and enhance user acceptance.

    PubMed

    Burkolter, Dina; Weyers, Benjamin; Kluge, Annette; Luther, Wolfram

    2014-03-01

    Customization is assumed to reduce error and increase user acceptance in the human-machine relation. Reconfiguration gives the operator the option to customize a user interface according to his or her own preferences. An experimental study with 72 computer science students using a simulated process control task was conducted. The reconfiguration group (RG) interactively reconfigured their user interfaces and used the reconfigured user interface in the subsequent test whereas the control group (CG) used a default user interface. Results showed significantly lower error rates and higher acceptance of the RG compared to the CG while there were no significant differences between the groups regarding situation awareness and mental workload. Reconfiguration seems to be promising and therefore warrants further exploration.

  9. Enhanced ordering reduces electric susceptibility of liquids confined to graphene slit pores.

    PubMed

    Terrones, Jeronimo; Kiley, Patrick J; Elliott, James A

    2016-01-01

    The behaviours of a range of polar and non-polar organic liquids (acetone, ethanol, methanol, N-methyl-2-pyrrolidone (NMP), carbon tetrachloride and water) confined to 2D graphene nanochannels with thicknesses in the range of 4.5 Å to 40 Å were studied using classical molecular dynamics and hybrid density functional theory. All liquids were found to organise spontaneously into ordered layers parallel to the confining surfaces, with those containing polar molecules having their electric dipoles aligned parallel to such surfaces. In particular, monolayers of NMP showed remarkable in-plane ordering and low molecular mobility, suggesting the existence of a previously unknown 2D solid-like phase. Calculations for polar liquids showed dramatically reduced static permittivities normal to the confining surfaces; these changes are expected to improve electron tunnelling across the liquid films, modifying the DC electrical properties of immersed assemblies of carbon nanomaterials. PMID:27265098

  10. Enhanced ordering reduces electric susceptibility of liquids confined to graphene slit pores

    NASA Astrophysics Data System (ADS)

    Terrones, Jeronimo; Kiley, Patrick J.; Elliott, James A.

    2016-06-01

    The behaviours of a range of polar and non-polar organic liquids (acetone, ethanol, methanol, N-methyl-2-pyrrolidone (NMP), carbon tetrachloride and water) confined to 2D graphene nanochannels with thicknesses in the range of 4.5 Å to 40 Å were studied using classical molecular dynamics and hybrid density functional theory. All liquids were found to organise spontaneously into ordered layers parallel to the confining surfaces, with those containing polar molecules having their electric dipoles aligned parallel to such surfaces. In particular, monolayers of NMP showed remarkable in-plane ordering and low molecular mobility, suggesting the existence of a previously unknown 2D solid-like phase. Calculations for polar liquids showed dramatically reduced static permittivities normal to the confining surfaces; these changes are expected to improve electron tunnelling across the liquid films, modifying the DC electrical properties of immersed assemblies of carbon nanomaterials.

  11. Reduced graphene oxide-yttria nanocomposite modified electrode for enhancing the sensitivity of electrochemical genosensor.

    PubMed

    Rasheed, P Abdul; Radhakrishnan, Thulasi; Shihabudeen, P K; Sandhyarani, N

    2016-09-15

    Reduced graphene oxide-yttria nanocomposite (rGO:Y) is applied as electrochemical genosensor platform for ultrahigh sensitive detection of breast cancer 1 (BRCA1) gene for the first time. The sensor is based on the sandwich assay in which gold nanoparticle cluster labeled reporter DNA hybridize to the target DNA. Glassy carbon electrode modified with rGO-yttria serves as the immobilization platform for capture probe DNA. The sensor exhibited a fine capability of sensing BRCA1 gene with linear range of 10attomolar (aM) to 1nanomolar (nM) and a detection limit of 5.95attomolar. The minimum distinguishable response concentration is down to the attomolar level with a high sensitivity and selectivity. We demonstrated that the use of rGO:Y modified electrode along with gold nanoparticle cluster (AuNPC) label leads to the highly sensitive electrochemical detection of BRCA1 gene. PMID:27153526

  12. Enhancing Motivation to Reduce the Risk of HIV Infection for Economically Disadvantaged Urban Women

    PubMed Central

    Carey, Michael P.; Maisto, Stephen A.; Kalichman, Seth C.; Forsyth, Andrew D.; Wright, Ednita M.; Johnson, Blair T.

    2008-01-01

    This research evaluated a motivation-based HIV-risk-reduction intervention for economically disadvantaged urban women. Participants completed a survey that assessed HIV-related knowledge, risk perceptions, behavioral intentions, sexual communication, substance use, and risk behavior. A total of 102 at-risk women (76% African-American) were randomly assigned to either the risk-reduction intervention or to a waiting list. Women were reassessed at three and twelve weeks. Results indicated that treated women increased their knowledge and risk awareness, strengthened their intentions to adopt safer sexual practices, communicated their intentions with partners, reduced substance use proximal to sexual activities, and engaged in fewer acts of unprotected vaginal intercourse. These effects were observed immediately and most were maintained at follow-up. PMID:9256553

  13. Reduced graphene oxide-yttria nanocomposite modified electrode for enhancing the sensitivity of electrochemical genosensor.

    PubMed

    Rasheed, P Abdul; Radhakrishnan, Thulasi; Shihabudeen, P K; Sandhyarani, N

    2016-09-15

    Reduced graphene oxide-yttria nanocomposite (rGO:Y) is applied as electrochemical genosensor platform for ultrahigh sensitive detection of breast cancer 1 (BRCA1) gene for the first time. The sensor is based on the sandwich assay in which gold nanoparticle cluster labeled reporter DNA hybridize to the target DNA. Glassy carbon electrode modified with rGO-yttria serves as the immobilization platform for capture probe DNA. The sensor exhibited a fine capability of sensing BRCA1 gene with linear range of 10attomolar (aM) to 1nanomolar (nM) and a detection limit of 5.95attomolar. The minimum distinguishable response concentration is down to the attomolar level with a high sensitivity and selectivity. We demonstrated that the use of rGO:Y modified electrode along with gold nanoparticle cluster (AuNPC) label leads to the highly sensitive electrochemical detection of BRCA1 gene.

  14. Regulatory risk assessments: Is there a need to reduce uncertainty and enhance robustness?

    PubMed

    Snodin, D J

    2015-12-01

    A critical evaluation of several recent regulatory risk assessments has been undertaken. These relate to propyl paraben (as a food additive, cosmetic ingredient or pharmaceutical excipient), cobalt (in terms of a safety-based limit for pharmaceuticals) and the cancer Threshold of Toxicological Concern as applied to food contaminants and pharmaceutical impurities. In all cases, a number of concerns can be raised regarding the reliability of the current assessments, some examples being absence of data audits, use of single-dose and/or non-good laboratory practice studies to determine safety metrics, use of a biased data set and questionable methodology and lack of consistency with precedents and regulatory guidance. Drawing on these findings, a set of recommendations is provided to reduce uncertainty and improve the quality and robustness of future regulatory risk assessments. PMID:26614814

  15. Modulated surface nanostructures for enhanced light trapping and reduced surface reflection of crystalline silicon solar cells

    NASA Astrophysics Data System (ADS)

    Tayagaki, Takeshi; Hoshi, Yusuke; Hirai, Yuji; Matsuo, Yasutaka; Usami, Noritaka

    2016-05-01

    We demonstrated the fabrication of modulated surface nanostructures as a new surface texture design for thin wafer solar cells. Using a combination of conventional alkali etching and colloidal lithography, we fabricated surface textures with micrometer and nanometre scales on a Si substrate. These modulated surface nanostructures exhibit reduced surface reflection in a broad spectral range, compared with conventional micrometer textures. We investigated optical absorption using a rigorous coupled wave analysis simulation, which revealed a significant reduction in surface reflection over a broad spectral range and efficient light trapping (comparable to that of conventional micrometer-scale textures) for the modulated nanostructures. We found that the modulated surface nanostructures have a high potential of improving the performance of thin wafer crystalline Si solar cells.

  16. Reduced graphene oxide and Ag wrapped TiO2 photocatalyst for enhanced visible light photocatalysis

    NASA Astrophysics Data System (ADS)

    Leong, Kah Hon; Sim, Lan Ching; Bahnemann, Detlef; Jang, Min; Ibrahim, Shaliza; Saravanan, Pichiah

    2015-10-01

    A well-organised reduced graphene oxide (RGO) and silver (Ag) wrapped TiO2 nano-hybrid was successfully achieved through a facile and easy route. The inherent characteristics of the synthesized RGO-Ag/TiO2 were revealed through crystalline phase, morphology, chemical composition, Raman scattering, UV-visible absorption, and photoluminescence analyses. The adopted synthesis route significantly controlled the uniform formation of silver nanoparticles and contributed for the absorption of light in the visible spectrum through localized surface plasmon resonance effects. The wrapped RGO nanosheets triggered the electron mobility and promoted visible light shift towards red spectrum. The accomplishment of synergised effect of RGO and Ag well degraded Bisphenol A under visible light irradiation with a removal efficiency of 61.9%.

  17. Topical Mitomycin-C enhances subbasal nerve regeneration and reduces erosion frequency in the debridement wounded mouse cornea.

    PubMed

    Pal-Ghosh, Sonali; Pajoohesh-Ganji, Ahdeah; Tadvalkar, Gauri; Kyne, Briana M; Guo, Xiaoqing; Zieske, James D; Stepp, Mary Ann

    2016-05-01

    Corneal epithelial basement membrane dystrophies and superficial injuries caused by scratches can lead to recurrent corneal erosion syndrome (RCES). Patients and animals with reduced corneal sensory nerve innervation can also develop recurrent erosions. Multiple wild-type mouse strains will spontaneously develop recurrent corneal erosions after single 1.5 mm debridement wounds. Here we show that this wound is accompanied by an increase in corneal epithelial cell proliferation after wound closure but without a commensurate increase in corneal epithelial thickness. We investigated whether excess corneal epithelial cell proliferation contributes to erosion formation. We found that topical application of Mitomycin C (MMC), a drug used clinically to improve healing after glaucoma and refractive surgery, reduces erosion frequency, enhances subbasal axon density to levels seen in unwounded corneas, and prevents excess epithelial cell proliferation after debridement wounding. These results suggest that topically applied MMC, which successfully reduces corneal haze and scarring after PRK, may also function to enhance subbasal nerve regeneration and epithelial adhesion when used to treat RCES.

  18. Enhancement effects of reducing agents on the degradation of tetrachloroethene in the Fe(II)/Fe(III) catalyzed percarbonate system.

    PubMed

    Miao, Zhouwei; Gu, Xiaogang; Lu, Shuguang; Brusseau, Mark L; Yan, Ni; Qiu, Zhaofu; Sui, Qian

    2015-12-30

    In this study, the effects of reducing agents on the degradation of tetrachloroethene (PCE) were investigated in the Fe(II)/Fe(III) catalyzed sodium percarbonate (SPC) system. The addition of reducing agents, including hydroxylamine hydrochloride, sodium sulfite, ascorbic acid and sodium ascorbate, accelerated the Fe(III)/Fe(II) redox cycle, leading to a relatively steady Fe(II) concentration and higher production of free radicals. This, in turn, resulted in enhanced PCE oxidation by SPC, with almost complete PCE removal obtained for appropriate Fe and SPC concentrations. The chemical probe tests, using nitrobenzene and carbon tetrachloride, demonstrated that HO was the predominant radical in the system and that O2(-) played a minor role, which was further confirmed by the results of electron spin resonance measurements. PCE degradation decreased significantly with the addition of isopropanol, a HO scavenger, supporting the hypothesis that HO was primarily responsible for PCE degradation. It is noteworthy that Cl(-) release was slightly delayed in the first 20 min, indicating that intermediate products were produced. However, these intermediates were further degraded, resulting in the complete conversion of PCE to CO2. In conclusion, the use of reducing agents to enhance Fe(II)/Fe(III) catalyzed SPC oxidation appears to be a promising approach for the rapid degradation of organic contaminants in groundwater. PMID:26257094

  19. Enhancement effects of reducing agents on the degradation of tetrachloroethene in the Fe(II)/Fe(III) catalyzed percarbonate system.

    PubMed

    Miao, Zhouwei; Gu, Xiaogang; Lu, Shuguang; Brusseau, Mark L; Yan, Ni; Qiu, Zhaofu; Sui, Qian

    2015-12-30

    In this study, the effects of reducing agents on the degradation of tetrachloroethene (PCE) were investigated in the Fe(II)/Fe(III) catalyzed sodium percarbonate (SPC) system. The addition of reducing agents, including hydroxylamine hydrochloride, sodium sulfite, ascorbic acid and sodium ascorbate, accelerated the Fe(III)/Fe(II) redox cycle, leading to a relatively steady Fe(II) concentration and higher production of free radicals. This, in turn, resulted in enhanced PCE oxidation by SPC, with almost complete PCE removal obtained for appropriate Fe and SPC concentrations. The chemical probe tests, using nitrobenzene and carbon tetrachloride, demonstrated that HO was the predominant radical in the system and that O2(-) played a minor role, which was further confirmed by the results of electron spin resonance measurements. PCE degradation decreased significantly with the addition of isopropanol, a HO scavenger, supporting the hypothesis that HO was primarily responsible for PCE degradation. It is noteworthy that Cl(-) release was slightly delayed in the first 20 min, indicating that intermediate products were produced. However, these intermediates were further degraded, resulting in the complete conversion of PCE to CO2. In conclusion, the use of reducing agents to enhance Fe(II)/Fe(III) catalyzed SPC oxidation appears to be a promising approach for the rapid degradation of organic contaminants in groundwater.

  20. Reduced GABAA Receptor α6 Expression in The Trigeminal Ganglion Enhanced Myofascial Nociceptive Response

    PubMed Central

    Kramer, P. R.; Bellinger, L. L.

    2013-01-01

    Activation of the GABAA receptor results in inhibition of neuronal activity. One subunit of this multi-subunit receptor termed alpha 6 (Gabrα6) contributed to inflammatory temporomandibular joint (TMJ) nociception but TMJ disorders often include myofascial pain. To address Gabrα6 role in myofascial pain we hypothesized that Gabrα6 has an inhibitory role in myofascial nociceptive responses similar to inflammatory TMJ arthritis. To test this hypothesis a, myofascial nociceptive response was induced by placing a ligature bilaterally on the tendon attachment of the anterior superficial part of a male rat's masseter muscle. Four days after ligature placement Gabrα6 expression was reduced by infusing the trigeminal ganglia (TG) with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabra6 siRNA) or no known gene (control siRNA). After siRNA infusion nociceptive behavioral responses were measured, i.e., feeding behavior and head withdrawal after pressing upon the region above the ligature with von Frey filaments. Neuronal activity in the TG and trigeminal nucleus caudalis and upper cervical region (Vc–C1) was measured by quantitating the amount of phosphorylated extracellular signalregulated kinase (p-ERK). Total Gabrα6 and GABAA receptor contents in the TG and Vc–C1 were determined. Gabrα6 siRNA infusion reduced Gabrα6 and GABAA receptor expression and significantly increased the nociceptive response in both nociceptive assays. Gabra6 siRNA infusion also significantly increased TG p-ERK expression of the ligated rats. From these results we conclude GABAA receptors consisting of the Gabrα6 subunit inhibit TG nociceptive sensory afferents in the trigeminal pathway and have an important role in the regulation of myofascial nociception. PMID:23602886

  1. Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats.

    PubMed

    Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-01-01

    This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly (P < 0.05) increased bladder capacity from 58.0 ± 4.7% to 85.8 ± 10.3% and 96.5 ± 10.7%, respectively, of saline control capacity, while TNS failed to inhibit spinal reflex bladder contractions. After administering propranolol (3 mg/kg iv, a β₁/β₂-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (P < 0.05) reduced to 64.5 ± 9.5% and 64.7 ± 7.3%, respectively, of the saline control capacity. However, the residual PNS inhibition (about 10% increase in capacity) was still statistically significant (P < 0.05). Propranolol treatment also significantly (P = 0.0019) increased the amplitude of bladder contractions but did not change the control bladder capacity. Naloxone (1 mg/kg iv, an opioid receptor antagonist) had no effect on either spinal reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the amplitude of the reflex bladder contractions. This study indicates an important role of β₁/β₂-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity.

  2. Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats.

    PubMed

    Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-01-01

    This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly (P < 0.05) increased bladder capacity from 58.0 ± 4.7% to 85.8 ± 10.3% and 96.5 ± 10.7%, respectively, of saline control capacity, while TNS failed to inhibit spinal reflex bladder contractions. After administering propranolol (3 mg/kg iv, a β₁/β₂-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (P < 0.05) reduced to 64.5 ± 9.5% and 64.7 ± 7.3%, respectively, of the saline control capacity. However, the residual PNS inhibition (about 10% increase in capacity) was still statistically significant (P < 0.05). Propranolol treatment also significantly (P = 0.0019) increased the amplitude of bladder contractions but did not change the control bladder capacity. Naloxone (1 mg/kg iv, an opioid receptor antagonist) had no effect on either spinal reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the amplitude of the reflex bladder contractions. This study indicates an important role of β₁/β₂-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity. PMID:25394827

  3. Integrative training for children and adolescents: techniques and practices for reducing sports-related injuries and enhancing athletic performance.

    PubMed

    Myer, Gregory D; Faigenbaum, Avery D; Chu, Donald A; Falkel, Jeff; Ford, Kevin R; Best, Thomas M; Hewett, Timothy E

    2011-02-01

    As more children and adolescents participate in sports and conditioning activities (sometimes without consideration for cumulative workload), it is important to establish age-appropriate training guidelines that may reduce the risk of sports-related injury and enhance athletic performance. The purpose of this article is to review the scientific evidence on youth strength and conditioning and to provide age-appropriate recommendations for integrating different strength and conditioning activities into a well-designed program that is safe, effective, and enjoyable. Integrative training is defined as a program or plan that incorporates general and specific strength and conditioning activities that enhance both health- and skill-related components of physical fitness. The cornerstone of integrative training is age-appropriate education and instruction by qualified professionals who understand the physical and psychosocial uniqueness of children and adolescents.

  4. Direct observation of enhanced plasmon-driven catalytic reaction activity of Au nanoparticles supported on reduced graphene oxides by SERS.

    PubMed

    Liang, Xiu; You, Tingting; Liu, Dapeng; Lang, Xiufeng; Tan, Enzhong; Shi, Jihua; Yin, Penggang; Guo, Lin

    2015-04-21

    Graphene-based nanocomposites have recently attracted tremendous research interest in the field of catalysis due to their unique optical and electronic properties. However, direct observation of enhanced plasmon-driven catalytic activity of Au nanoparticles (NPs) supported on reduced graphene oxides (Au/rGO) has rarely been reported. Herein, based on the reduction from 4-nitrobenzenethiol (4-NBT) to p,p'-dimercaptoazobenzene (DMAB), the catalytic property of Au/rGO nanocomposites was investigated and compared with corresponding Au NP samples with similar size distribution. Our results show that Au/rGO nanocomposites could serve as a good catalytic and analytic platform for plasmon-driven chemical reactions. In addition, systematic comparisons were conducted during power- and time-dependent surface-enhanced Raman scattering (SERS) experiments, which exhibited a lower power threshold and higher catalytic efficiency for Au/rGO as compared to Au NPs toward the reaction. PMID:25793752

  5. Enhanced strength in reduced graphene oxide/nickel composites prepared by molecular-level mixing for structural applications

    NASA Astrophysics Data System (ADS)

    Zhao, Chao

    2015-02-01

    An effective molecular-level mixing approach was used to prepare reduced graphene oxide (rGO)/Ni powders, which were directly consolidated into rGO/Ni composites by spark plasma sintering. The rGO/Ni composites were found to exhibit a homogeneous dispersion of rGO and a strong interfacial bonding between the rGO and the Ni matrix. The enhanced interfacial bonding was attributed to the oxygen-mediated bonding generated from the interactions between the residue functional groups of rGO and the Ni atoms. Tensile test revealed that 1.5 wt% rGO/Ni composites demonstrated a 95.2 % increase in tensile strength and a 327.6 % increase in yield strength, while simultaneously retained a 12.1 % of elongation. This study thus proposed an effective way to fabricate rGO/Ni composites with enhanced tensile properties.

  6. Sodium chloride enhances cadmium tolerance through reducing cadmium accumulation and increasing anti-oxidative enzyme activity in tobacco.

    PubMed

    Zhang, Bing-Lin; Shang, Sheng-Hua; Zhang, Hai-Tao; Jabeen, Zahra; Zhang, Guo-Ping

    2013-06-01

    The effect of sodium chloride (NaCl) on cadmium (Cd) uptake, translocation, and oxidative stress was investigated using 2 tobacco cultivars differing in Cd tolerance. The growth inhibition of the tobacco plants exposed to Cd toxicity was in part alleviated by moderate addition of NaCl in the culture solution. Cadmium concentration of shoots and roots in the 2 cultivars increased with increasing Cd levels in the solution and decreased with the addition of NaCl. The addition of NaCl could alleviate the oxidative stress caused by Cd toxicity, as reflected by reduced production of malondialdehyde and recovered or enhanced activities of antioxidative enzymes catalase and glutathione peroxidase. The results also showed that the enhancement of antioxidative enzyme activity by NaCl for the tobacco plants exposed to Cd stress is related to induced Ca signaling.

  7. Memory-improving actions of glucose: involvement of a central cholinergic muscarinic mechanism.

    PubMed

    Kopf, S R; Baratti, C M

    1994-11-01

    Post-training intraperitoneal administration of alpha-D[+]-glucose (10-300 mg/kg) facilitated 24-h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. Glucose did not increase the retention latencies of mice that had not received a footshock during training. The effect of glucose (30 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by glucose (30 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to glucose treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training glucose on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and glucose (10 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of glucose (10 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the memory facilitation induced by post-training administration of glucose could result from an enhancement of brain acetylcholine synthesis and/or its release that, in turn, might modulate the activity of muscarinic cholinergic mechanisms that are critically involved in memory storage. PMID:7857246

  8. Inhibition of cholinergic pathways in Drosophila melanogaster by α-conotoxins.

    PubMed

    Heghinian, Mari D; Mejia, Monica; Adams, David J; Godenschwege, Tanja A; Marí, Frank

    2015-03-01

    Nicotinic acetylcholine receptors (nAChRs) play a pivotal role in synaptic transmission of neuronal signaling pathways and are fundamentally involved in neuronal disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia. In vertebrates, cholinergic pathways can be selectively inhibited by α-conotoxins; we show that in the model organism Drosophila, the cholinergic component of the giant fiber system is inhibited by α-conotoxins MII, AuIB, BuIA, EI, PeIA, and ImI. The injection of 45 pmol/fly of each toxin dramatically decreases the response of the giant fiber to dorsal longitudinal muscle (GF-DLM) connection to 20 ± 13.9% for MII; 26 ± 13.7% for AuIB, 12 ± 9.9% for BuIA, 30 ± 11.3% for EI, 1 ± 1% for PeIA, and 34 ± 15.4% for ImI. Through bioassay-guided fractionation of the venom of Conus brunneus, we found BruIB, an α-conotoxin that inhibits Drosophila nicotinic receptors but not its vertebrate counterparts. GF-DLM responses decreased to 43.7 ± 8.02% on injection of 45 pmol/fly of BruIB. We manipulated the Dα7 nAChR to mimic the selectivity of its vertebrate counterpart by placing structurally guided point mutations in the conotoxin-binding site. This manipulation rendered vertebrate-like behavior in the Drosophila system, enhancing the suitability of Drosophila as an in vivo tool to carry out studies related to human neuronal diseases. . PMID:25466886

  9. Alleviating Effects of Bushen-Yizhi Formula on Ibotenic Acid-Induced Cholinergic Impairments in Rat

    PubMed Central

    Hou, Xue-Qin; Zhang, Lei; Yang, Cong; Rong, Cui-Ping; He, Wen-Qing; Zhang, Chun-Xia; Li, Shi; Su, Ru-Yu; Chang, Xiang; Qin, Ji-Huan; Chen, Yun-Bo

    2015-01-01

    Abstract This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases. PMID:25482164

  10. Memory-improving actions of glucose: involvement of a central cholinergic muscarinic mechanism.

    PubMed

    Kopf, S R; Baratti, C M

    1994-11-01

    Post-training intraperitoneal administration of alpha-D[+]-glucose (10-300 mg/kg) facilitated 24-h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. Glucose did not increase the retention latencies of mice that had not received a footshock during training. The effect of glucose (30 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by glucose (30 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to glucose treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training glucose on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and glucose (10 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of glucose (10 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the memory facilitation induced by post-training administration of glucose could result from an enhancement of brain acetylcholine synthesis and/or its release that, in turn, might modulate the activity of muscarinic cholinergic mechanisms that are critically involved in memory storage.

  11. Enhanced Lapidus arthrodesis: crossed screw technique with middle cuneiform fixation further reduces sagittal mobility.

    PubMed

    Galli, Melissa M; McAlister, Jeffrey E; Berlet, Gregory C; Hyer, Christopher F

    2015-01-01

    Persistent medial column sagittal mobility can be encountered despite successful first tarsometatarsal stabilization if fixation has been limited to the first tarsometatarsal joint. The purpose of the present cadaveric research was to quantify the effect of a third point of fixation from the base of the first metatarsal to the middle cuneiform compared with the traditional isolated first tarsometatarsal fixation. Ten matched pairs of below-the-knee specimens, with a known cause of death, sex, ethnicity, and age, height, weight, and body mass index at death, were used for our examination. Portable fluoroscopy aided with the accurate placement of all points of fixation. Measurements of movement were obtained using the validated Klaue device. The 20 matched below-the-knee specimens were from 10 cadavers (2 female and 8 male donors, aged 72.8 ± 9.3 years, body mass index 21.1 ± 4.2 kg/m(2)). The sagittal plane motion of the first ray was 7.45 ± 1.82 mm before fixation. With isolated first tarsometatarsal fixation, the sagittal motion decreased to 4.41 ± 1.51 mm and decreased further to 3.12 ± 1.06 mm, with the addition of middle cuneiform fixation. Statistically significant enhancement of the stability of sagittal first ray motion was noted with the addition of the first metatarsal to middle cuneiform pin, even after simulated Lapidus fixation. Our findings suggest that first metatarsal to middle cuneiform fixation can be beneficial if excessive sagittal motion is present after standard 2-point fixation and can play a role in the prevention of recurrence and complications. PMID:25456344

  12. Reduced PMA enhances the responsiveness of transfected THP-1 macrophages to polarizing stimuli.

    PubMed

    Maeß, Marten B; Wittig, Berith; Cignarella, Andrea; Lorkowski, Stefan

    2014-01-15

    Macrophages are versatile cells of the immune system which react to various external stimuli through different polarization patterns which adjust the cells to the required function whether it is removal of pathogens or necrotic cells, tissue repair or propagation of inflammation. As much of macrophage behavior is determined by their polarization, appropriate models to study macrophage polarization are required. Previously we have published a protocol for transfection of THP-1 macrophages, which in brief pre-differentiates THP-1 monocytes for 48h using 100ng/ml PMA, followed by detachment of the cells and eletroporation using Lonza nucleofector technology and finally includes further 48h of differentiation with 100ng/ml PMA. When we applied this protocol to study interleukin (IL) 10 dependent polarization, the cells were inert to the IL10 stimulus, as indicated by a failure to induce IL10 target genes such as SOCS3. Further investigation revealed that the cells were classically activated by the differentiation agent phorbol 12-myristate 13-acetate (PMA) as shown by induction of chemokine receptor CCR7. Subsequent reduction of PMA concentration during THP-1 macrophage differentiation significantly improved their response to IL10 as SOCS3 increased more than 40-fold. This increased responsiveness of the THP-1 macrophages was also confirmed for polarization with LPS and IFNγ. Up-regulation of classical activation markers CCL3, CCR7 and TNFα was enhanced from 18-, 21- and 70-fold, respectively, to 48-, 222- and 951-fold, respectively. Reduction of PMA concentration did not negatively affect macrophage differentiation or transfection efficiency. Expression of macrophage differentiation markers CD11b and CD68 as well as cell morphology remained unchanged. In addition transfection efficiency and rates of apoptosis and necrosis remained unaffected. Thus our revised protocol combines high transfection efficiency and cell vitality with a strong response to polarizing

  13. Growth and production of buckwheat (Fagopyrum esculentum) treated with reduced, ambient, and enhanced UV-B radiation.

    PubMed

    Gaberscik, Alenka; Voncina, Meta; Trost, Tadeja; Germ, Mateja; Olof Björn, Lars

    2002-02-01

    The effect of enhanced UV-B radiation on buckwheat (Fagopyrum esculentum Moench. variety 'Darja'), an important high elevation crop, was studied in order to estimate its vulnerability in changing UV-B environment. Plants were grown in outdoor experiments from July to October under reduced and ambient UV-B levels, and an UV-B level simulating 17% ozone depletion in Ljubljana. During the development the following parameters were monitored: light saturated photosynthetic activity, transpiration, potential and effective photochemical efficiencies of photosystem II, the contents of photosynthetic pigments and methanol soluble UV-B absorbing compounds. At the end of the experiment, growth rate and production of seeds were estimated. In the following growth season the seeds collected from plants exposed to different UV-B treatments were tested for germination capacity. Total UV-B absorbing compounds during plant development were increased by UV-B radiation, photosynthetic pigments (chlorophyll a and b and carotenoids) decreased. Photosynthetic rate was lowered in an early stage of development. UV-B treatment resulted in the increase in the transpiration rate and consequently the decrease in water use efficiency (WUE). The disturbances in water economy and in photosynthesis affected the reproduction potential negatively; the production of seeds in plants cultivated under ambient and enhanced UV-B was 57 and 39% of the production of specimens treated with reduced UV-B, respectively. The germination of seeds collected from treated plants revealed on average about 95% success, independently of the treatment, but the time needed for germination was the shortest for seeds developed under enhanced UV-B level treatment. Enhanced UV-B radiation affected water relations and production of buckwheat, but not the potential of seeds for germination.

  14. Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

    PubMed Central

    Dobrovinskaya, Oxana; Valencia-Cruz, Georgina; Castro-Sánchez, Luis; Bonales-Alatorre, Edgar O.; Liñan-Rico, Liliana; Pottosin, Igor

    2016-01-01

    Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca2+ signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options. PMID:27630569

  15. Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

    PubMed Central

    Dobrovinskaya, Oxana; Valencia-Cruz, Georgina; Castro-Sánchez, Luis; Bonales-Alatorre, Edgar O.; Liñan-Rico, Liliana; Pottosin, Igor

    2016-01-01

    Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca2+ signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options.

  16. Purinergic and cholinergic components of bladder contractility and flow.

    PubMed

    Theobald, R J

    1995-01-01

    The role of ATP as a neurotransmitter/neuromodulator in the urinary tract has been the subject of much study, particularly whether ATP has a functional role in producing urine flow. Recent studies suggested significant species variation, specifically a variation between cat and other species. This study was performed to determine the in vivo response of cat urinary bladder to pelvic nerve stimulation (PNS) and to the exogenous administration of cholinergic and purinergic agents. In anesthetized cats, bladder contractions and fluid expulsion was measured in response to PNS and to the exogenous administration of cholinergic and purinergic agents. Fluid was instilled into the bladder and any fluid expelled by bladder contractions induced by PNS or exogenous agents was collected in a beaker. The volume was measured in a graduated cylinder and recorded. PNS, carbachol and APPCP produced sustained contractions with significant expulsion of fluid. ATP, ACh and hypogastric nerve stimulation did not produce any significant expulsion of fluid. Atropine, a cholinergic antagonist, inhibited PNS contractions and fluid expulsion with no effect on purinergic actions. There was a significant relationship between the magnitude of the contraction, duration of the contractions and volume of fluid expelled. The data and information from other studies, strongly suggests a functional role for ATP as a cotransmitter in the lower urinary tract different from ACh's role. ATP stimulation of a specific purinergic receptor plays a role in initiation of bladder contractions and perhaps in the initiation of urine flow from the bladder. ACh's role is functionally different and appears to be more involved in maintenance of contractile activity and flow. PMID:7830505

  17. Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia.

    PubMed

    Dobrovinskaya, Oxana; Valencia-Cruz, Georgina; Castro-Sánchez, Luis; Bonales-Alatorre, Edgar O; Liñan-Rico, Liliana; Pottosin, Igor

    2016-01-01

    Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca(2+) signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options. PMID:27630569

  18. Novel aspects of cholinergic regulation of colonic ion transport

    PubMed Central

    Bader, Sandra; Diener, Martin

    2015-01-01

    Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (Isc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on Isc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport – up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors – is more complex than previously assumed. PMID:26236483

  19. Cholinergic Interneurons Are Differentially Distributed in the Human Striatum

    PubMed Central

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel

    2007-01-01

    Background The striatum (caudate nucleus, CN, and putamen, Put) is a group of subcortical nuclei involved in planning and executing voluntary movements as well as in cognitive processes. Its neuronal composition includes projection neurons, which connect the striatum with other structures, and interneurons, whose main roles are maintaining the striatal organization and the regulation of the projection neurons. The unique electrophysiological and functional properties of the cholinergic interneurons give them a crucial modulating function on the overall striatal response. Methodology/Principle Findings This study was carried out using stereological methods to examine the volume and density (cells/mm3) of these interneurons, as visualized by choline acetyltransferase (ChAT) immunoreactivity, in the following territories of the CN and Put of nine normal human brains: 1) precommissural head; 2) postcommissural head; 3) body; 4) gyrus and 5) tail of the CN; 6) precommissural and 7) postcommissural Put. The distribution of ChAT interneurons was analyzed with respect to the topographical, functional and chemical territories of the dorsal striatum. The CN was more densely populated by cholinergic neurons than the Put, and their density increased along the anteroposterior axis of the striatum with the CN body having the highest neuronal density. The associative territory of the dorsal striatum was by far the most densely populated. The striosomes of the CN precommissural head and the postcommissural Put contained the greatest number of ChAT-ir interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery of the striosomes throughout the striatum. Conclusions/Significance All these data reveal that cholinergic interneurons are differentially distributed in the distinct topographical and functional territories of the human dorsal striatum, as well as in its chemical compartments. This heterogeneity may indicate that the posterior aspects of the CN require a

  20. Effects of single or repeated administration of a carbamate, propoxur, and an organophosphate, DDVP, on jejunal cholinergic activities and contractile responses in rats.

    PubMed

    Kobayashi, H; Sato, I; Akatsu, Y; Fujii, S; Suzuki, T; Matsusaka, N; Yuyama, A

    1994-01-01

    Wistar rats were injected once or repeatedly for 10 days with dichlorvos (DDVP, 5 mg kg-1), propoxur (10 mg kg-1), oxotremorine (0.1 mg kg-1) or atropine (5 mg kg-1). Animals were killed 20 min or 24 h after single or consecutive injections, respectively, for determinations of cholinergic activities and contractile responses to acetylcholine (ACh) of the jejunum. Single treatments: while DDVP and propoxur decreased acetylcholinesterase (AChE) activity, oxotremorine and atropine did not. Although DDVP, propoxur and oxotremorine increased levels of ACh, atropine decreased them. Contractile responses to ACh were enhanced by DDVP and reduced by oxotremorine and atropine. The Bmax value of binding of [3H]quinuclidinyl benzylate (QNB) to muscarinic ACh receptors was decreased by atropine. Consecutive treatments: DDVP and oxotremorine decreased AChE activity markedly and slightly, respectively. Although DDVP and oxotremorine increased levels of ACh, propoxur decreased them. Without affecting the contractile responses, DDVP caused a reduction and propoxur and atropine caused an increase in the Bmax value for binding of [3H]QNB. Both the contractile responses and the value of Bmax for binding of [3H]-QNB were decreased by oxotremorine. In summary, propoxur and DDVP showed similar effects mainly through their anticholinesterase properties in the case of single injection, but DDVP had similar effects to those of oxotremorine and propoxur had similar effects to those of atropine in the case of repeated injection.

  1. Decoration of BiOI quantum size nanoparticles with reduced graphene oxide in enhanced visible-light-driven photocatalytic studies

    NASA Astrophysics Data System (ADS)

    Liu, Zhang; Xu, Weicheng; Fang, Jianzhang; Xu, Xiaoxin; Wu, Shuxing; Zhu, Ximiao; Chen, Zehua

    2012-10-01

    Herein, a reverse microemulsion route was developed to synthesize bismuth oxyiodide (BiOI) nanocrystals and reduced graphene oxide (RGO) nanocomposites as a highly efficient photocatalyst, and both the formation of BiOI and the reduction of RGO were achieved in situ in microemulsions simultaneously at low temperature (60 °C). The uniform nanocrystal size and structure were indicated by XRD, TEM, and the reduction of GO by ascorbic acid was evidenced by FTIR, XPS, and Raman spectra techniques. The enhanced photoactivity of RGO/BiOI nanocomposites under visible light was attributed to improved light absorption and efficient charge separation and transportation.

  2. Enhanced photocatalytic performance of ZnO-reduced graphene oxide hybrid synthesized via ultrasonic probe-assisted study

    SciTech Connect

    Prakash, A.; Sahu, N. K.; Bahadur, D.

    2013-02-05

    A facile ultrasonic horn-assisted reaction has been used to synthesize zinc oxide-reduced graphene oxide (ZnO-RGO) hybrids in dimethylformamide. The incorporation of graphene oxide prevents the cluster formation of ZnO nanoparticles. The photocatalytic performance in degradation of methylene blue has been investigated with ZnO and ZnO-RGO hybrids and the results show that the RGO plays an important role in the enhancement of photocatalytic performance of ZnO-RGO. A direct evidence of electron exchange between ZnO and RGO is confirmed by zeta potentials measurements, which is an established reason for photocatalytic degradation of organic dyes.

  3. Dietary polyunsaturated fatty acids improve cholinergic transmission in the aged brain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cholinergic theory of aging states that dysfunction of cholinergic neurons arising from the basal forebrain and terminating in the cortex and hippocampus may be involved in the cognitive decline that occurs during aging and Alzheimer’s disease. Despite years of research, pharmacological interven...

  4. Modeling Parkinson’s Disease Falls Associated With Brainstem Cholinergic Systems Decline

    PubMed Central

    Kucinski, Aaron; Sarter, Martin

    2015-01-01

    In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson’s disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from the pedunculopontine nucleus (PPN) also contributes to impaired gait and falls, here we assessed the effects of selective cholinergic PPN lesions in combination with striatal DA loss or BF cholinergic cells loss as well as losses in all 3 regions. Results indicate that all combination losses that included the BF cholinergic system slowed traversal and increased slips and falls. However, the performance of rats with losses in all 3 regions (PPN, BF, and DA) was not more severely impaired than following combined BF cholinergic and striatal DA lesions. These results confirm the hypothesis that BF cholinergic-striatal disruption of attentional-motor interactions is a primary source of falls. Additional losses of PPN cholinergic neurons may worsen posture and gait control in situations not captured by the current testing conditions. PMID:25798629

  5. Muscle Relaxation of the Foot Reduces Corticospinal Excitability of Hand Muscles and Enhances Intracortical Inhibition.

    PubMed

    Kato, Kouki; Muraoka, Tetsuro; Mizuguchi, Nobuaki; Nakagawa, Kento; Nakata, Hiroki; Kanosue, Kazuyuki

    2016-01-01

    The object of this study was to clarify the effects of foot muscle relaxation on activity in the primary motor cortex (M1) of the hand area. Subjects were asked to volitionally relax the right foot from sustained contraction of either the dorsiflexor (tibialis anterior; TA relaxation) or plantarflexor (soleus; SOL relaxation) in response to an auditory stimulus. Single- and paired-pulse transcranial magnetic stimulation (TMS) was delivered to the hand area of the left M1 at different time intervals before and after the onset of TA or SOL relaxation. Motor evoked potentials (MEPs) were recorded from the right extensor carpi radialis (ECR) and flexor carpi radialis (FCR). MEP amplitudes of ECR and FCR caused by single-pulse TMS temporarily decreased after TA and SOL relaxation onset, respectively, as compared with those of the resting control. Furthermore, short-interval intracortical inhibition (SICI) of ECR evaluated with paired-pulse TMS temporarily increased after TA relaxation onset. Our findings indicate that muscle relaxation of the dorsiflexor reduced corticospinal excitability of the ipsilateral hand muscles. This is most likely caused by an increase in intracortical inhibition. PMID:27242482

  6. Reduced ventilation and enhanced magnitude of the deep Pacific carbon pool during the last glacial period

    NASA Astrophysics Data System (ADS)

    Skinner, L.; McCave, I. N.; Carter, L.; Fallon, S.; Scrivner, A. E.; Primeau, F.

    2015-02-01

    It has been proposed that the ventilation of the deep Pacific carbon pool was not significantly reduced during the last glacial period, posing a problem for canonical theories of glacial-interglacial CO2 change. However, using radiocarbon dates of marine tephra deposited off New Zealand, we show that deep- (> 2000 m) and shallow sub-surface ocean-atmosphere 14C age offsets (i.e. "reservoir-" or "ventilation" ages) in the southwest Pacific increased by ˜1089 and 337 yrs respectively, reaching ˜2689 and ˜1037 yrs during the late glacial. A comparison with other radiocarbon data from the southern high-latitudes suggests that broadly similar changes were experienced right across the Southern Ocean. If, like today, the Southern Ocean was the main source of water to the glacial ocean interior, these observations would imply a significant change in the global radiocarbon inventory during the last glacial period, possibly equivalent to an increase in the average radiocarbon age > 2 km of ˜ 700 yrs. Simple mass balance arguments and numerical model sensitivity tests suggest that such a change in the ocean's mean radiocarbon age would have had a major impact on the marine carbon inventory and atmospheric CO2, possibly accounting for nearly half of the glacial-interglacial CO2 change. If confirmed, these findings would underline the special role of high latitude shallow sub-surface mixing and air-sea gas exchange in regulating atmospheric CO2 during the late Pleistocene.

  7. Muscle Relaxation of the Foot Reduces Corticospinal Excitability of Hand Muscles and Enhances Intracortical Inhibition

    PubMed Central

    Kato, Kouki; Muraoka, Tetsuro; Mizuguchi, Nobuaki; Nakagawa, Kento; Nakata, Hiroki; Kanosue, Kazuyuki

    2016-01-01

    The object of this study was to clarify the effects of foot muscle relaxation on activity in the primary motor cortex (M1) of the hand area. Subjects were asked to volitionally relax the right foot from sustained contraction of either the dorsiflexor (tibialis anterior; TA relaxation) or plantarflexor (soleus; SOL relaxation) in response to an auditory stimulus. Single- and paired-pulse transcranial magnetic stimulation (TMS) was delivered to the hand area of the left M1 at different time intervals before and after the onset of TA or SOL relaxation. Motor evoked potentials (MEPs) were recorded from the right extensor carpi radialis (ECR) and flexor carpi radialis (FCR). MEP amplitudes of ECR and FCR caused by single-pulse TMS temporarily decreased after TA and SOL relaxation onset, respectively, as compared with those of the resting control. Furthermore, short-interval intracortical inhibition (SICI) of ECR evaluated with paired-pulse TMS temporarily increased after TA relaxation onset. Our findings indicate that muscle relaxation of the dorsiflexor reduced corticospinal excitability of the ipsilateral hand muscles. This is most likely caused by an increase in intracortical inhibition. PMID:27242482

  8. Digestibility of gluten proteins is reduced by baking and enhanced by starch digestion

    PubMed Central

    Pan, Xiaoyan; Bellido, Vincent; Toole, Geraldine A.; Gates, Fred K.; Wickham, Martin S. J.; Shewry, Peter R.; Bakalis, Serafim; Padfield, Philip; Mills, E. N. Clare

    2015-01-01

    Scope Resistance of proteins to gastrointestinal digestion may play a role in determining immune‐mediated adverse reactions to foods. However, digestion studies have largely been restricted to purified proteins and the impact of food processing and food matrices on protein digestibility is poorly understood. Methods and results Digestibility of a total gliadin fraction (TGF), flour (cv Hereward), and bread was assessed using in vitro batch digestion with simulated oral, gastric, and duodenal phases. Protein digestion was monitored by SDS‐PAGE and immunoblotting using monoclonal antibodies specific for celiac‐toxic sequences (QQSF, QPFP) and starch digestion by measuring undigested starch. Whereas the TGF was rapidly digested during the gastric phase the gluten proteins in bread were virtually undigested and digested rapidly during the duodenal phase only if amylase was included. Duodenal starch digestion was also slower in the absence of duodenal proteases. Conclusion The baking process reduces the digestibility of wheat gluten proteins, including those containing sequences active in celiac disease. Starch digestion affects the extent of protein digestion, probably because of gluten‐starch complex formation during baking. Digestion studies using purified protein fractions alone are therefore not predictive of digestion in complex food matrices. PMID:26202208

  9. Physical and chemical activation of reduced graphene oxide for enhanced adsorption and catalytic oxidation.

    PubMed

    Liu, Shizhen; Peng, Wenchao; Sun, Hongqi; Wang, Shaobin

    2014-01-21

    Physical and chemical activation of reduced graphene oxide (RGO) using different reagents, CO2, ZnCl2 and CO2/ZnCl2, to obtain highly porous and metal-free carbonaceous materials was carried out and their adsorption and catalytic behavior were investigated. Physical activation using CO2 was proved to be much more effective than chemical ZnCl2 activation, and increased the specific surface area (SSA) of RGO from ~200 to higher than 600 m(2) g(-1). Methylene blue (MB) was then used to evaluate the adsorption and catalytic activity of the activated RGO (A-RGO) materials with peroxymonosulfate (PMS) as an oxidant. It was found that the SSA and oxygen containing groups are two important factors determining the adsorptive and catalytic performance of the A-RGO materials. RGO by physicochemical CO2/ZnCl2 activation presented the best adsorption and RGO by physical CO2 activation exhibited the highest catalytic degradation of MB.

  10. Synergistic effect of titanium dioxide nanocrystal/reduced graphene oxide hybrid on enhancement of microbial electrocatalysis

    NASA Astrophysics Data System (ADS)

    Zou, Long; Qiao, Yan; Wu, Xiao-Shuai; Ma, Cai-Xia; Li, Xin; Li, Chang Ming

    2015-02-01

    A small sized TiO2 nanocrystal (˜10 nm)/reduced graphene oxide (TiO2/rGO) hybrid is synthesized through a sol-gel process for hybrid TiO2/GO followed by solvothermal reduction of GO to rGO and is further used as a microbial fuel cell (MFC) anode. The strong synergistic effect from a large surface area produced by uniformly deposited TiO2 nanocrystals, good hydrophilicity of TiO2 nanocrystals and superior conductivity of rGO leads to significantly improved electrocatalysis. In particular, a direct electrochemistry is realized by generating endogenous flavins from a large amount of microbes grown on the highly biocompatible TiO2 nanocrystals to mediate fast electron transfer between microbes and conductive rGO for a high performance anode. The TiO2/rGO hybrid anode delivers a maximum power density of 3169 mW m-2 in Shewanella putrefaciens CN32 MFC, which is much large than that of the conventional carbon cloth anode and reported TiO2/carbon hybrid anode, thus offering great potential for practical applications of MFC. This work is for the first time to report that the synergistic effect from tailoring the physical structure to achieve small sized TiO2 nanocrystals while rationally designing chemistry to introduce highly conductive rGO and superior biocompatible TiO2 is able to significantly boost the MFC performance.

  11. Consequences for Ground Level Enhancements (GLEs) from a Reduced Heliomagnetic Field

    NASA Astrophysics Data System (ADS)

    Kahler, S.

    2007-12-01

    A recent assessment of the long-term records of solar energetic particle (SEP) events by McCracken (Space Weather, 2007) has concluded that the frequency of occurrence of large SEP events is smallest for the most active solar cycles. In particular, the E > 4 GeV fluences were ~ 10 times larger and 4 times more frequent in the 20 years preceding the onset of the space era in 1958. A return in the near future to the solar activity level characteristic of the Gleissberg minima of 1800-1820 and 1875-1910 could introduce an era of much more energetic SEP events with longer fluences than those observed since 1958. The working explanation of this variation of SEP event intensity is that the lower solar activity produces weaker magnetic fields, which decrease the coronal Alfven speeds, which reduce the compression ratios of shocks driven by coronal mass ejections (CMEs). This explanation implicitly assumes not only that other variables such as solar wind density and CME speeds are unchanged through a declining heliospheric magnetic field, but also assumes the existence of the controversial long-term increase in the heliospheric field. We examine these assumptions from two points of view: 1) the relationship of solar magnetic fields to CME and solar wind characteristics, and 2) our best knowledge of the long-term variations in solar wind properties.

  12. Early life adversity reduces stress reactivity and enhances impulsive behavior: Implications for health behaviors

    PubMed Central

    Lovallo, William R.

    2012-01-01

    Altered reactivity to stress, either in the direction of exaggerated reactivity or diminished reactivity, may signal a dysregulation of systems intended to maintain homeostasis and a state of good health. Evidence has accumulated that diminished reactivity to psychosocial stress may signal poor health outcomes. One source of diminished cortisol and autonomic reactivity is the experience of adverse rearing during childhood and adolescence. The Oklahoma Family Health Patterns Project has examined a cohort of 426 healthy young adults with and without a family history of alcoholism. Regardless of family history, persons who had experienced high degrees of adversity prior to age 16 had a constellation of changes including reduced cortisol and heart rate reactivity, diminished cognitive capacity, and unstable regulation of affect, leading to behavioral impulsivity and antisocial tendencies. We present a model whereby this constellation of physiological, cognitive, and affective tendencies is consistent with altered central dopaminergic activity leading to changes in brain function that may foster impulsive and risky behaviors. These in turn may promote greater use of alcohol other drugs along with adopting poor health behaviors. This model provides a pathway from early life adversity to low stress reactivity that forms a basis for risky behaviors and poor health outcomes. PMID:23085387

  13. Traumatic Acid Reduces Oxidative Stress and Enhances Collagen Biosynthesis in Cultured Human Skin Fibroblasts.

    PubMed

    Jabłońska-Trypuć, Agata; Pankiewicz, Walentyn; Czerpak, Romuald

    2016-09-01

    Traumatic acid (TA) is a plant hormone (cytokinin) that in terms of chemical structure belongs to the group of fatty acids derivatives. It was isolated from Phaseolus vulgaris. TA activity and its influence on human cells and organism has not previously been the subject of research. The aim of this study was to examine the effects of TA on collagen content and basic oxidative stress parameters, such as antioxidative enzyme activity, reduced glutathione, thiol group content, and lipid peroxidation in physiological conditions. The results show a stimulatory effect of TA on tested parameters. TA caused a decrease in membrane phospholipid peroxidation and exhibited protective properties against ROS production. It also increases protein and collagen biosynthesis and its secretion into the culture medium. The present findings reveal that TA exhibits multiple and complex activity in fibroblast cells in vitro. TA, with its activity similar to unsaturated fatty acids, shows antioxidant and stimulatory effects on collagen biosynthesis. It is a potentially powerful agent with applications in the treatment of many skin diseases connected with oxidative stress and collagen biosynthesis disorders. PMID:27423205

  14. Enhanced dielectric performance in polymer composite films with carbon nanotube-reduced graphene oxide hybrid filler.

    PubMed

    Kim, Jin-Young; Kim, TaeYoung; Suk, Ji Won; Chou, Harry; Jang, Ji-Hoon; Lee, Jong Ho; Kholmanov, Iskandar N; Akinwande, Deji; Ruoff, Rodney S

    2014-08-27

    The electrical conductivity and the specific surface area of conductive fillers in conductor-insulator composite films can drastically improve the dielectric performance of those films through changing their polarization density by interfacial polarization. We have made a polymer composite film with a hybrid conductive filler material made of carbon nanotubes grown onto reduced graphene oxide platelets (rG-O/CNT). We report the effect of the rG-O/CNT hybrid filler on the dielectric performance of the composite film. The composite film had a dielectric constant of 32 with a dielectric loss of 0.051 at 0.062 wt% rG-O/CNT filler and 100 Hz, while the neat polymer film gave a dielectric constant of 15 with a dielectric loss of 0.036. This is attributed to the increased electrical conductivity and specific surface area of the rG-O/CNT hybrid filler, which results in an increase in interfacial polarization density between the hybrid filler and the polymer.

  15. Reduced graphene oxide supported platinum nanocubes composites: one-pot hydrothermal synthesis and enhanced catalytic activity

    NASA Astrophysics Data System (ADS)

    Li, Fumin; Gao, Xueqing; Xue, Qi; Li, Shuni; Chen, Yu; Lee, Jong-Min

    2015-02-01

    Reduced graphene oxide (rGO) supported platinum nanocubes (Pt-NCs) composites (Pt-NCs/rGO) were synthesized successfully by a water-based co-chemical reduction method, in which polyallylamine hydrochloride acted as a multi-functional molecule for the functionalization of graphene oxide, anchorage of PtII precursor, and control of Pt crystal facets. The morphology, structure, composition, and catalytic property of Pt-NCs/rGO composites were characterized in detail by various spectroscopic techniques. Transmission electron microscopy images showed well-defined Pt-NCs with an average size of 9 nm uniformly distributed on the rGO surface. The as-prepared Pt-NCs/rGO composites had excellent colloidal stability in the aqueous solution, and exhibited superior catalytic activity towards the hydrogenation reduction of nitro groups compared to commercial Pt black. The improved catalytic activity originated from the abundant exposed Pt{100} facets of Pt-NCs, excellent dispersion of Pt-NCs on the rGO surface, and synergistic effect between Pt-NCs and rGO.

  16. Sprinkler irrigation of rice fields reduces grain arsenic but enhances cadmium.

    PubMed

    Moreno-Jiménez, Eduardo; Meharg, Andrew A; Smolders, Erik; Manzano, Rebeca; Becerra, Daniel; Sánchez-Llerena, Javier; Albarrán, Ángel; López-Piñero, Antonio

    2014-07-01

    Previous studies have demonstrated that rice cultivated under flooded conditions has higher concentrations of arsenic (As) but lower cadmium (Cd) compared to rice grown in unsaturated soils. To validate such effects over long terms under Mediterranean conditions a field experiment, conducted over 7 successive years was established in SW Spain. The impact of water management on rice production and grain arsenic (As) and cadmium (Cd) was measured, and As speciation was determined to inform toxicity evaluation. Sprinkler irrigation was compared to traditional flooding. Both irrigation techniques resulted in similar grain yields (~3000 kg grain ha(-1)). Successive sprinkler irrigation over 7 years decreased grain total As to one-sixth its initial concentration in the flooded system (0.55 to 0.09 mg As kg(-1)), while one cycle of sprinkler irrigation also reduced grain total As by one-third (0.20 mg kg(-1)). Grain inorganic As concentration increased up to 2 folds under flooded conditions compared to sprinkler irrigated fields while organic As was also lower in sprinkler system treatments, but to a lesser extent. This suggests that methylation is favored under water logging. However, sprinkler irrigation increased Cd transfer to grain by a factor of 10, reaching 0.05 mg Cd kg(-1) in 7 years. Sprinkler systems in paddy fields seem particularly suited for Mediterranean climates and are able to mitigate against excessive As accumulation, but our evidence shows that an increased Cd load in rice grain may result. PMID:24742557

  17. Torsion angle dynamics: reduced variable conformational sampling enhances crystallographic structure refinement.

    PubMed

    Rice, L M; Brünger, A T

    1994-08-01

    A reduced variable conformational sampling strategy for macromolecules based on molecular dynamics in torsion angle space is evaluated using crystallographic refinement as a prototypical search problem. Bae and Haug's algorithm for constrained dynamics [Bae, D.S., Haug, E.J. A recursive formulation for constrained mechanical system dynamics. Mech. Struct. Mach. 15:359-382, 1987], originally developed for robotics, was used. Their formulation solves the equations of motion exactly for arbitrary holonomic constraints, and hence differs from commonly used approximation algorithms. It uses gradients calculated in Cartesian coordinates, and thus also differs from internal coordinate formulations. Molecular dynamics can be carried out at significantly higher temperatures due to the elimination of the high frequency bond and angle vibrations. The sampling strategy presented here combines high temperature torsion angle dynamics with repeated trajectories using different initial velocities. The best solutions can be identified by the free R value, or the R value if experimental phase information is appropriately included in the refinement. Applications to crystallographic refinement. Applications to crystallographic refinement show a significantly increased radius of convergence over conventional techniques. For a test system with diffraction data to 2 A resolution, slow-cooling protocols fail to converge if the backbone atom root mean square (rms) coordinate deviation from the crystal structure is greater than 1.25 A, but torsion angle refinement can correct backbone atom rms coordinate deviations up to approximately 1.7 A.

  18. Multilayer super-short carbon nanotube/reduced graphene oxide architecture for enhanced supercapacitor properties

    NASA Astrophysics Data System (ADS)

    Zeng, Fanyan; Kuang, Yafei; Zhang, Ningshuang; Huang, Zhongyuan; Pan, Yang; Hou, Zhaohui; Zhou, Haihui; Yan, Chenglin; Schmidt, Oliver G.

    2014-02-01

    Zero-dimension super-short carbon nanotubes (SSCNTs) with aspect ratio of less than 5 could be synthesized by tailoring the raw multi-walled carbon nanotubes (MWCNTs) with a simple ultrasonic oxidation-cut method. The introduction of SSCNTs adequately increases the utilization of closed pore volumes of MWCNTs and effectively inhibits the stacking of reduced graphene oxides (RGOs). Thus an RGO/SSCNT is prepared by a wet-chemical route for supercapacitors. The topography and structure of the as-prepared materials are characterized by scanning electron microscope and nitrogen sorption isotherms, and their supercapacitor properties are also investigated. The results show that the SSCNTs could cross the gaps of RGO layers to form a three-dimensional (3D) multilayer architecture, with a much higher specific capacitance (244 F g-1 at 50 mV s-1) than that of RGO (136 F g-1) and RGO/MWCNTs (91 F g-1). Furthermore, the RGO/SSCNTs displays a high specific capacitance of 210 F g-1 at the ultrahigh scan rate of 1000 mV s-1 (85% capacity retention compared to 50 mV s-1). These attractive results indicate that RGO/SSCNT with 3D multilayer architecture is a promising graphene-based material for high power supercapacitors.

  19. Graphenol defects induced blue emission enhancement in chemically reduced graphene quantum dots.

    PubMed

    Zhang, Wenkai; Liu, Yingqiu; Meng, Xianrui; Ding, Tao; Xu, Yuanqing; Xu, Hao; Ren, Yanrong; Liu, Baoying; Huang, Jiajia; Yang, Jinghe; Fang, Xiaomin

    2015-09-14

    In this work, few layer graphene quantum dots (GQDs) with a size of 3-5 nm are purposely treated with highly concentrated aqueous NaBH4 solutions to obtain the reduced graphene quantum dots (rGQDs). Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy demonstrate that the number of carbonyl groups decreases but -OH related defects increase during chemical reduction. Green and weak emissions of original GQDs originate from carrier recombination in the disorder-induced localized state (mainly including carbonyl and carboxyl and epoxy groups). As the reduction degree increases, the photoluminescence (PL) quantum efficiency of GQDs increases dramatically from 2.6% to 10.1%. In the meantime, the PL peak position blue shifts rapidly, and full width at half maximum (FWHM) becomes narrower. Thus we can infer that graphenol topological defects (hydroxyl functionalized graphene) are gradually formed during reduction. Besides, graphenol defect related PL features a longer fluorescence lifetime, excitation wavelength dependence but less pH sensitivity. PMID:26247890

  20. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis.

    PubMed

    Wilkins, Heather M; Harris, Janna L; Carl, Steven M; E, Lezi; Lu, Jianghua; Eva Selfridge, J; Roy, Nairita; Hutfles, Lewis; Koppel, Scott; Morris, Jill; Burns, Jeffrey M; Michaelis, Mary L; Michaelis, Elias K; Brooks, William M; Swerdlow, Russell H

    2014-12-15

    Brain bioenergetic function declines in some neurodegenerative diseases, this may influence other pathologies and administering bioenergetic intermediates could have therapeutic value. To test how one intermediate, oxaloacetate (OAA) affects brain bioenergetics, insulin signaling, inflammation and neurogenesis, we administered intraperitoneal OAA, 1-2 g/kg once per day for 1-2 weeks, to C57Bl/6 mice. OAA altered levels, distributions or post-translational modifications of mRNA and proteins (proliferator-activated receptor-gamma coactivator 1α, PGC1 related co-activator, nuclear respiratory factor 1, transcription factor A of the mitochondria, cytochrome oxidase subunit 4 isoform 1, cAMP-response element binding, p38 MAPK and adenosine monophosphate-activated protein kinase) in ways that should promote mitochondrial biogenesis. OAA increased Akt, mammalian target of rapamycin and P70S6K phosphorylation. OAA lowered nuclear factor κB nucleus-to-cytoplasm ratios and CCL11 mRNA. Hippocampal vascular endothelial growth factor mRNA, doublecortin mRNA, doublecortin protein, doublecortin-positive neuron counts and neurite length increased in OAA-treated mice. (1)H-MRS showed OAA increased brain lactate, GABA and glutathione thereby demonstrating metabolic changes are detectable in vivo. In mice, OAA promotes brain mitochondrial biogenesis, activates the insulin signaling pathway, reduces neuroinflammation and activates hippocampal neurogenesis.

  1. Conductivity enhancement and resistance changes in polymer films filled with reduced graphene oxide

    NASA Astrophysics Data System (ADS)

    Okhay, O.; Krishna, R.; Salimian, M.; Titus, E.; Gracio, J.; Guerra, L. M.; Ventura, J.

    2013-02-01

    The electrical properties of polymer composites based on polycarbonate (PC) and panipol CXM (CX), filled with reduced graphene oxide (rGO), were investigated. The composite preparation conditions allowed good dispersion of rGO in the polymer matrix. We show here that when used as a nanofiller in polymers, rGO offers an appreciable improvement of the electrical current in 3 orders of magnitude (from 10-10 A to 10-7 A at 10 V), as observed in current-voltage (I-V) data for both PC and CX polymers with rGO. The suggested mechanism for the observed switching effects is the migration of oxygen groups aided by both the electrical field and Joule heating. Moreover, some reset- and set- like changes similar to resistive switching were observed in the I-V data of PC and CX-based films upon the addition of rGO. Clockwise (resembling a memristive system type II) and counter-clockwise (resembling a memristive system type I) directions were detected in the I-V data of the analyzed films. According to the obtained results, rGO can be a good filler for PC and CX polymer-based films for application in electronic and photonic areas, due to the significant improvement of the electrical conductivity of these polymers.

  2. Low-level laser therapy (LLLT) reduces inflammatory infiltrate and enhances skeletal muscle repair: Histomorphometric parameters

    NASA Astrophysics Data System (ADS)

    Paiva-Oliveira, E. L.; Lima, N. C.; Silva, P. H.; Sousa, N. T. A.; Barbosa, F. S.; Orsini, M.; Silva, J. G.

    2012-09-01

    Low level laser therapy (LLLT) has been suggested as an effective therapeutics in inflammatory processes modulation and tissue repairing. However, there is a lack of studies that analyze the anti-inflammatory effects of the infrared lasers in muscular skeletal injury. The aim of this study was to investigate the effects of low-level laser therapy 904 nm in the repair process of skeletal muscle tissue. Swiss mice were submitted to cryoinjury and divided in test (LLLT-treated) and control groups. Histological sections were stained with hematoxylin-eosin to assess general morphology and inflammatory influx, and Picrossirus to quantify collagen fibers deposition. Our results showed significant reduction in inflammatory infiltrated in irradiated mice after 4 days of treatment compared to control ( p = 0.01). After 8 days, the irradiated group showed high levels at regenerating myofibers with significant statistically differences in relation at control group ( p < 0.01). Collagen deposition was significantly increased in the final stages of regeneration at test group, when compared with control group ( p = 0.05). Our data suggests that LLLT reduces the inflammatory response in the initial stages of injury and accelerates the process of muscular tissue repair.

  3. Central cholinergic control of vasopressin release in conscious rats

    SciTech Connect

    Iitake, K.; Share, L.; Ouchi, Y.; Crofton, J.T.; Brooks, D.P.

    1986-08-01

    Intracerebroventricular (icv) administration of carbachol into conscious rats evoked a substantial increase in vasopressin secretion and blood pressure in a dose-dependent manner. These effects were blocked by pretreatment with the muscarinic blocker, atropine (10 g icv), but not by the nicotinic blocker, hexamethonium (10 g icv). Hexamethonium did, however, block the increase in blood pressure, the decrease in heart rate, and they very small elevation in the plasma vasopressin concentration induced by nicotine (10 g icv). These results indicate that stimulation of either central nicotinic or muscarinic receptors can affect the cardiovascular system and suggest that the cholinergic stimulation of vasopressin secretion may involve primarily muscarinic receptors in the conscious rat.

  4. Enhanced Antitumor Efficacy and Reduced Toxicity of Docetaxel Loaded Estradiol Functionalized Stealth Polymeric Nanoparticles.

    PubMed

    Jain, Sanyog; Spandana, Gollapalli; Agrawal, Ashish Kumar; Kushwah, Varun; Thanki, Kaushik

    2015-11-01

    In spite of extensive research over the decades, breast cancer treatment is still a major challenge due to nonspecific distribution of the chemotherapeutics. This void can be filled by restricting the distribution of chemotherapeutics toward the cancerous cells. In the present report estradiol (E2) functionalization of docetaxel (DTX) loaded PLGA nanoparticles was supposed to have specific distribution of DTX to cancerous cells simultaneously avoiding the nonspecific distribution toward the normal cells. In line, E2-PEG-PLGA conjugate was synthesized and characterized by FTIR and NMR spectroscopy. Extensive optimization of different process variables resulted in the formation of spherical E2-PEG-PLGA NPs in the size range of 228.5 ± 11.8 nm and entrapment efficiency of 94.25 ± 2.49. Trehalose (5% w/v) resulted in the formation of a fluffy, easy to redisperse freeze-dried cake of nanoparticles. PXRD analysis revealed the amorphous nature of DTX encapsulated within the nanoparticles. X-ray photoelectron spectroscopy confirmed the presence of E2 over the surface of nanoparticles. In line with our hypothesis, cellular uptake studies on ER positive MCF-7 cells revealed relatively higher uptake and efficient localization into the nuclear region of E2-PEG-PLGA NPs in comparison with plain counterparts, while in the case of ER negative HeLa cells E2-PEG-PLGA NPs showed no difference in fluorescence pattern as compared to MCF-7 cells incubated with unmodified nanoformulation, indicating nonspecific delivery of DTX. Moreover, MTT assay revealed relatively higher cytotoxicity of E2-PEG-PLGA NPs in comparison with free DTX. Furthermore, in vivo pharmacokinetic studies revealed 9.36- and 4.79-fold enhancement in circulation half-life and AUC(0-∞), respectively, of E2-PEG-PLGA NPs in comparison with Taxotere. In vivo antitumor efficacy in DMBA induced rat model demonstrated significant reduction in tumor volume in comparison with the plain counterpart (PLGA-NPs) and a

  5. Cholinergic receptor activation induces a relative facilitation of synaptic responses in the entorhinal cortex during theta- and gamma-frequency stimulation of parasubicular inputs.

    PubMed

    Sparks, D W; Chapman, C A

    2013-01-29

    The parasubiculum sends its single major output to layer II of the entorhinal cortex, and it may therefore interact with inputs to the entorhinal cortex from other cortical areas, and help to shape the activity of layer II entorhinal cells that project to the hippocampal formation. Cholinergic inputs are thought to contribute to the generation of theta- and gamma-frequency activities in the parasubiculum and entorhinal cortex, and the present study assessed how cholinergic receptor activation affects synaptic responses of the entorhinal cortex to theta- and gamma-frequency stimulation. Depth profiles of field excitatory postsynaptic potentials (fEPSPs) in acute brain slices showed a short-latency negative fEPSP in layer II, consistent with the activation of excitatory synaptic inputs to layer II. Application of the cholinergic agonist carbachol (CCh) suppressed synaptic responses and enhanced paired-pulse facilitation. CCh also resulted in a marked relative facilitation of synaptic responses evoked during short 5-pulse trains of stimulation at both theta- and gamma-frequencies. Application of the M(1) antagonist pirenzepine, but not the M(2) antagonist methoctramine, blocked the facilitation of responses. Inhibition of the M-current or block of GABA(B) receptors had no effect, but the facilitation effect was partially blocked by the N-methyl-d-aspartate (NMDA) antagonist APV, indicating that NMDA receptors play a role. Application of ZD7288, a selective inhibitor of the hyperpolarization-activated cationic current I(h), almost completely blocked the relative facilitation of responses, and the less potent I(h)-blocker Cs(+) also resulted in a partial block. The relative facilitation of synaptic responses induced by CCh is therefore likely mediated by multiple mechanisms including the cholinergic suppression of transmitter release that enhances transmitter availability during repetitive stimulation, NMDA receptor-mediated effects on pre- or postsynaptic function, and

  6. One-pot synthesis of cuprous oxide-reduced graphene oxide nanocomposite with enhanced photocatalytic and electrocatalytic performance

    NASA Astrophysics Data System (ADS)

    Han, Fugui; Li, Heping; Yang, Jun; Cai, Xiaodong; Fu, Li

    2016-03-01

    We report on the facile one-step synthesis of porous cuprous oxide nanoparticles on reduced graphene oxide (Cu2O-RGO) by synchronously reducing Cu2+ ions and GO with ethylene glycol. The basic chemical components, crystal structure and surface morphology of prepared nanocomposite was carefully characterized. The photocatalytic activities of the as-prepared nanocomposite was investigated by photodegrading methylene blue (MB) under visible light. The electrocatalytic property of the nanocomposite was investigated by electrocatalytic determination of acetaminophen. The results indicate that the corporation of RGO with Cu2O nanoparticles could high enhance the both photocatalytic and electrocatalytic properties. Moreover, we found that the content of RGO introduced into nanocomposite could highly affect the product properties.

  7. Identification of reducing and nonreducing neutral carbohydrates by laser-enhanced in-source decay (LEISD) MALDI MS.

    PubMed

    Yang, Hongmei; Li, Zong-Jun; Wan, Debin; Lian, Wenhui; Liu, Shuying

    2013-05-01

    In this work, laser-enhanced in-source decay (LEISD) technique of matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FT-ICR-MS) was used to distinguish reducing and nonreducing carbohydrates. Interestingly, easier cleavage of (1 → 2)-linked glycosidic bonds for nonreducing carbohydrates containing D-fructofuranosyl units was observed in MALDI-FT-ICR-MS, which was in agreement with the result of theoretical calculation by the software package Gaussian 09. Importantly, no cross-ring cleavage of fructofuranosyl residues was detected in the LEISD spectra of nonreducing carbohydrates. LEISD method therefore offers an attractive alternative for fast and efficient differentiation of reducing and nonreducing carbohydrates, and the positions of nonreducing monosaccharide residues in a carbohydrate chain could be easily speculated.

  8. Abiotic stresses sequentially applied enhance natural resistance and reduce postharvest decay.

    PubMed

    D'Hallewin, G; Molinu, G M; Dore, A; Venditti, T; Rodov, V

    2009-01-01

    The feasibility to restrain citrus green mould (Penicillium digitatum Sacc.) during storage, by means of induced natural resistance, was investigated following combined heat and ultravioLet light C (254 nm, UV-C) treatments. Heat treatment (HT) was performed by keeping Citrus fruits in a humid saturated room at 36 degrees C for 36 h while, the UV-C light treatment (254 nm) was carried out by illuminating the fruits with 3 or 6 kJm(-2). Physical treatments were sequential and reversely applied to un-inoculated or to 24 h-old inoculated lemons or oranges. Then, fruits were stored for 30 days at 8 or 5 degrees C with 95% relative humidity (RH) followed by a 6 day simulated marketing period at 20 degrees C and 75% RH. Constitutive (cuticle and epicuticular wax) and induced resistance (scoparone biosynthesis) were monitored and the variation in natural resistance was correlated to the decay development. HT influenced positively the constitutive factors of resistance by reducing or delaying cuticular cracking and by remodelling the epicuticular wax layer. Following HT the synthesis of scoparone took place only in the albedo of wounds and was greater when fruits were inoculated. Following UV-C illumination, scoparone accumulated rapidly in the outer rind (flavedo) but, particularly with 6 kJm(-2), favoured cuticular fracturing during storage. Sequential treatments resulted significantly more effective in controlling decay on either, inoculated and non inoculated fruit. The best control of green mould during storage of lemons and oranges was obtained when HT preceded 6 kJm(-2) UV-C illumination with 52 and 45% reduction of natural decay in fruit stored at 8 degrees C compared to the control, respectively. PMID:20222548

  9. Reducing Health Disparities and Enhancing the Responsible Conduct of Research Involving LGBT Youth.

    PubMed

    Fisher, Celia B; Mustanski, Brian

    2014-09-01

    Although there is clearly a need for evidenced-based behavioral or biomedical prevention or treatment programs for suicide, substance abuse, and sexual health targeted to members of the LGBT population under the age of eighteen, few such programs exist, due in substantial part to limited research knowledge. Ambiguities in regulations that govern human subjects protections and the related inconsistencies in institutional review board (IRB) interpretations of regulatory language are the key reason for the lack of rigorous clinical trial evidence to support treatment choices and prevention approaches to reducing health disparities for this population. Gi