Science.gov

Sample records for neurochemical profile quantification

  1. Reproducibility of Neurochemical Profile Quantification in Pregenual Cingulate, Anterior Midcingulate, and Bilateral Posterior Insular Subdivisions Measured at 3 Tesla

    PubMed Central

    de Matos, Nuno M. P.; Meier, Lukas; Wyss, Michael; Meier, Dieter; Gutzeit, Andreas; Ettlin, Dominik A.; Brügger, Mike

    2016-01-01

    The current report assessed measurement reproducibility of proton magnetic resonance spectroscopy at 3 Tesla in the left and right posterior insular, pregenual anterior cingulate, and anterior midcingulate cortices. Ten healthy male volunteers aged 21–30 years were tested at four different days, of which nine were included in the data analysis. Intra- and inter-subject variability of myo-inositol, creatine, glutamate, total-choline, total-N-acetylaspartate, and combined glutamine–glutamate were calculated considering the influence of movement parameters, age, daytime of measurements, and tissue composition. Overall mean intra-/inter-subject variability for all neurochemicals combined revealed small mean coefficients of variation across the four regions: 5.3/9.05% in anterior midcingulate, 6.6/8.84% in pregenual anterior cingulate, 7.3/10.00% in left posterior and 8.2/10.55% in right posterior insula. Head movement, tissue composition and day time revealed no significant explanatory variance contribution suggesting a negligible influence on the data. A strong correlation between Cramer–Rao Lower Bounds (a measure of fitting errors) and the mean intra-subject coefficients of variation (r = 0.799, p < 0.001) outlined the importance of low fitting errors in order to obtain robust and finally meaningful measurements. The present findings confirm proton magnetic resonance spectroscopy as a reliable tool to measure brain neurochemistry in small subregions of the human brain. PMID:27445745

  2. Reproducibility of Neurochemical Profile Quantification in Pregenual Cingulate, Anterior Midcingulate, and Bilateral Posterior Insular Subdivisions Measured at 3 Tesla.

    PubMed

    de Matos, Nuno M P; Meier, Lukas; Wyss, Michael; Meier, Dieter; Gutzeit, Andreas; Ettlin, Dominik A; Brügger, Mike

    2016-01-01

    The current report assessed measurement reproducibility of proton magnetic resonance spectroscopy at 3 Tesla in the left and right posterior insular, pregenual anterior cingulate, and anterior midcingulate cortices. Ten healthy male volunteers aged 21-30 years were tested at four different days, of which nine were included in the data analysis. Intra- and inter-subject variability of myo-inositol, creatine, glutamate, total-choline, total-N-acetylaspartate, and combined glutamine-glutamate were calculated considering the influence of movement parameters, age, daytime of measurements, and tissue composition. Overall mean intra-/inter-subject variability for all neurochemicals combined revealed small mean coefficients of variation across the four regions: 5.3/9.05% in anterior midcingulate, 6.6/8.84% in pregenual anterior cingulate, 7.3/10.00% in left posterior and 8.2/10.55% in right posterior insula. Head movement, tissue composition and day time revealed no significant explanatory variance contribution suggesting a negligible influence on the data. A strong correlation between Cramer-Rao Lower Bounds (a measure of fitting errors) and the mean intra-subject coefficients of variation (r = 0.799, p < 0.001) outlined the importance of low fitting errors in order to obtain robust and finally meaningful measurements. The present findings confirm proton magnetic resonance spectroscopy as a reliable tool to measure brain neurochemistry in small subregions of the human brain. PMID:27445745

  3. Toward an in Vivo Neurochemical Profile: Quantification of 18 Metabolites in Short-Echo-Time 1H NMR Spectra of the Rat Brain

    NASA Astrophysics Data System (ADS)

    Pfeuffer, Josef; Tkáč , Ivan; Provencher, Stephen W.; Gruetter, Rolf

    1999-11-01

    Localized in vivo1H NMR spectroscopy was performed with 2-ms echo time in the rat brain at 9.4 T. Frequency domain analysis with LCModel showed that the in vivo spectra can be explained by 18 metabolite model solution spectra and a highly structured background, which was attributed to resonances with fivefold shorter in vivo T1 than metabolites. The high spectral resolution (full width at half maximum approximately 0.025 ppm) and sensitivity (signal-to-noise ratio approximately 45 from a 63-μL volume, 512 scans) was used for the simultaneous measurement of the concentrations of metabolites previously difficult to quantify in 1H spectra. The strongly represented signals of N-acetylaspartate, glutamate, taurine, myo-inositol, creatine, phosphocreatine, glutamine, and lactate were quantified with Cramér-Rao lower bounds below 4%. Choline groups, phosphorylethanolamine, glucose, glutathione, γ-aminobutyric acid, N-acetylaspartylglutamate, and alanine were below 13%, whereas aspartate and scyllo-inositol were below 22%. Intra-assay variation was assessed from a time series of 3-min spectra, and the coefficient of variation was similar to the calculated Cramér-Rao lower bounds. Interassay variation was determined from 31 pooled spectra, and the coefficient of variation for total creatine was 7%. Tissue concentrations were found to be in very good agreement with neurochemical data from the literature.

  4. Light-Induced Alterations in Striatal Neurochemical Profiles

    NASA Technical Reports Server (NTRS)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.

    1997-01-01

    Much of our present knowledge regarding circadian rhythms and biological activity during space flight has been derived from those missions orbiting the Earth. During space missions, astronauts can become exposed to bright/dark cycles that vary considerably from those that entrain the mammalian biological timing system to the 24-hour cycle found on Earth. As a spacecraft orbits the Earth, the duration of the light/dark period experienced becomes a function of the time it takes to circumnavigate the planet which in turn depends upon the altitude of the craft. Orbiting the Earth at an altitude of 200-800 km provides a light/dark cycle lasting between 80 and 140 minutes, whereas a voyage to the moon or even another planet would provide a light condition of constant light. Currently, little is known regarding the effects of altered light/dark cycles on neurochemical levels within the central nervous system (CNS). Many biochemical, physiological and behavioral phenomena are under circadian control, governed primarily by the hypothalamic suprachiasmatic nucleus. As such, these phenomena are subject to influence by the environmental light/dark cycle. Circadian variations in locomotor and behavioral activities have been correlated to both the environmental light/dark cycle and to dopamine (DA) levels within the CNS. It has been postulated by Martin-Iverson et al. that DA's role in the control of motor activity is subject to modulation by circadian rhythms (CR), environmental lighting and excitatory amino acids (EAAs). In addition, DA and EAA receptor regulated pathways are involved in both the photic entrainment of CR and the control of motor activity. The cellular mechanisms by which DA and EAA-receptor ligands execute these functions, is still unclear. In order to help elucidate these mechanisms, we set out to determine the effects of altered environmental light/dark cycles on CNS neurotransmitter levels. In this study, we focused on the striatum, a region of the brain

  5. Comparison of T1 relaxation times of the neurochemical profile in rat brain at 9.4 tesla and 14.1 tesla.

    PubMed

    Cudalbu, Cristina; Mlynárik, Vladimír; Xin, Lijing; Gruetter, Rolf

    2009-10-01

    Knowledge of T(1) relaxation times can be important for accurate relative and absolute quantification of brain metabolites, for sensitivity optimizations, for characterizing molecular dynamics, and for studying changes induced by various pathological conditions. (1)H T(1) relaxation times of a series of brain metabolites, including J-coupled ones, were determined using a progressive saturation (PS) technique that was validated with an adiabatic inversion-recovery (IR) method. The (1)H T(1) relaxation times of 16 functional groups of the neurochemical profile were measured at 14.1T and 9.4T. Overall, the T(1) relaxation times found at 14.1T were, within the experimental error, identical to those at 9.4T. The T(1)s of some coupled spin resonances of the neurochemical profile were measured for the first time (e.g., those of gamma-aminobutyrate [GABA], aspartate [Asp], alanine [Ala], phosphoethanolamine [PE], glutathione [GSH], N-acetylaspartylglutamate [NAAG], and glutamine [Gln]). Our results suggest that T(1) does not increase substantially beyond 9.4T. Furthermore, the similarity of T(1) among the metabolites (approximately 1.5 s) suggests that T(1) relaxation time corrections for metabolite quantification are likely to be similar when using rapid pulsing conditions. We therefore conclude that the putative T(1) increase of metabolites has a minimal impact on sensitivity when increasing B(0) beyond 9.4T. PMID:19645007

  6. Multi-center reproducibility of neurochemical profiles in the human brain at 7 T.

    PubMed

    van de Bank, B L; Emir, U E; Boer, V O; van Asten, J J A; Maas, M C; Wijnen, J P; Kan, H E; Oz, G; Klomp, D W J; Scheenen, T W J

    2015-03-01

    The purpose of this work was to harmonize data acquisition and post-processing of single voxel proton MRS ((1) H-MRS) at 7 T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7 T MR systems from two different vendors using an identical semi-localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations ('subject', 'institute' and 'random') were identified with a variance component analysis. Concentrations of 10-11 metabolites, which were corrected for T1 , T2 , magnetization transfer effects and partial volume effects, were obtained with mean Cramér-Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within-subject and system noise, except for total N-acetylaspartate, glutamine and glutathione, which were related to differences in signal-to-noise ratio and in shimming performance between vendors. After multi-center harmonization of acquisition and post-processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7 T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with (1) H-MRS at ultra-high magnetic field. PMID:25581510

  7. Effect of manganese chloride on the neurochemical profile of the rat hypothalamus

    PubMed Central

    Just, Nathalie; Cudalbu, Cristina; Lei, Hongxia; Gruetter, Rolf

    2011-01-01

    Manganese (Mn2+)-enhanced magnetic resonance imaging studies of the neuronal pathways of the hypothalamus showed that information about the regulation of food intake and energy balance circulate through specific hypothalamic nuclei. The dehydration-induced anorexia (DIA) model demonstrated to be appropriate for studying the hypothalamus with Mn2+-enhanced magnetic resonance imaging. Manganese is involved in the normal functioning of a variety of physiological processes and is associated with enzymes contributing to neurotransmitter synthesis and metabolism. It also induces psychiatric and motor disturbances. The molecular mechanisms by which Mn2+ produces alterations of the hypothalamic physiological processes are not well understood. 1H-magnetic resonance spectroscopy measurements of the rodent hypothalamus are challenging due to the distant location of the hypothalamus resulting in limited measurement sensitivity. The present study proposed to investigate the effects of Mn2+ on the neurochemical profile of the hypothalamus in normal, DIA, and overnight fasted female rats at 14.1 T. Results provide evidence that γ-aminobutyric acid has an essential role in the maintenance of energy homeostasis in the hypothalamus but is not condition specific. On the contrary, glutamine, glutamate, and taurine appear to respond more accurately to Mn2+ exposure. An increase in glutamine levels could also be a characteristic response of the hypothalamus to DIA. PMID:21712832

  8. NMR-Based Metabolic Profiling Reveals Neurochemical Alterations in the Brain of Rats Treated with Sorafenib.

    PubMed

    Du, Changman; Shao, Xue; Zhu, Ruiming; Li, Yan; Zhao, Qian; Fu, Dengqi; Gu, Hui; Kong, Jueying; Luo, Li; Long, Hailei; Deng, Pengchi; Wang, Huijuan; Hu, Chunyan; Zhao, Yinglan; Cen, Xiaobo

    2015-11-01

    Sorafenib, an active multi-kinase inhibitor, has been widely used as a chemotherapy drug to treat advanced clear-cell renal cell carcinoma patients. In spite of the relative safety, sorafenib has been shown to exert a negative impact on cognitive functioning in cancer patients, specifically on learning and memory; however, the underlying mechanism remains unclear. In this study, an NMR-based metabolomics approach was applied to investigate the neurochemical effects of sorafenib in rats. Male rats were once daily administrated with 120 mg/kg sorafenib by gavage for 3, 7, and 28 days, respectively. NMR-based metabolomics coupled with histopathology examinations for hippocampus, prefrontal cortex (PFC), and striatum were performed. The (1)H NMR spectra data were analyzed by using multivariate pattern recognition techniques to show the time-dependent biochemical variations induced by sorafenib. Excellent separation was obtained and distinguishing metabolites were observed between sorafenib-treated and control rats. A total of 36 differential metabolites in hippocampus of rats treated with sorafenib were identified, some of which were significantly changed. Furthermore, these modified metabolites mainly reflected the disturbances in neurotransmitters, energy metabolism, membrane, and amino acids. However, only a few metabolites in PFC and striatum were altered by sorafenib. Additionally, no apparent histological changes in these three brain regions were observed in sorafenib-treated rats. Together, our findings demonstrate the disturbed metabonomics pathways, especially, in hippocampus, which may underlie the sorafenib-induced cognitive deficits in patients. This work also shows the advantage of NMR-based metabolomics over traditional approach on the study of biochemical effects of drugs. PMID:26233726

  9. Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats

    SciTech Connect

    Trabace, L.; Zotti, M.; Morgese, M.G.; Tucci, P.; Colaianna, M.; Schiavone, S.; Avato, P.; Cuomo, V.

    2011-09-01

    Carvacrol is the major constituent of essential oils from aromatic plants. It showed antimicrobial, anticancer and antioxidant properties. Although it was approved for food use and included in the chemical flavorings list, no indication on its safety has been estimated. Since the use of plant extracts is relatively high among women, aim of this study was to evaluate carvacrol effects on female physiology and endocrine profiles by using female rats in proestrus and diestrus phases. Serotonin and metabolite tissue content in prefrontal cortex and nucleus accumbens, after carvacrol administration (0.15 and 0.45 g/kg p.o.), was measured. Drug effects in behavioral tests for alterations in motor activity, depression, anxiety-related behaviors and endocrine alterations were also investigated. While in proestrus carvacrol reduced serotonin and metabolite levels in both brain areas, no effects were observed in diestrus phase. Only in proestrus phase, carvacrol induced a depressive-like behavior in forced swimming test, without accompanying changes in ambulation. The improvement of performance in FST after subchronic treatment with fluoxetine (20 mg/kg) suggested a specific involvement of serotonergic system. No differences were found across the groups with regard to self-grooming behavior. Moreover, in proestrus phase, carvacrol reduced only estradiol levels without binding hypothalamic estradiol receptors. Our study showed an estrous-stage specific effect of carvacrol on depressive behaviors and endocrine parameters, involving serotonergic system. Given the wide carvacrol use not only as feed additive, but also as cosmetic essence and herbal remedy, our results suggest that an accurate investigation on the effects of its chronic exposure is warranted. - Highlights: > Carvacrol induced a depressive-like phenotype in rats, depending on ovarian cyclicity. > Carvacrol selectively reduced serotonin content in female rats in proestrus phase. > Carvacrol reduced serotonin levels

  10. Simultaneous profiling of multiple neurochemical pathways from a single cerebrospinal fluid sample using GC/MS/MS with electron capture detection.

    PubMed

    Eckstein, James A; Ammerman, Gina M; Reveles, Jessica M; Ackermann, Bradley L

    2008-06-01

    Biogenic amines and amino acids are widely characterized in the pathways representing neurotransmission. Although several analytical methodologies have been used to detect specific target molecules in relevant fluids such as cerebrospinal fluid (CSF), multiple assays must be used to survey the primary pathways involved. This article describes the development of a GC/MS/MS method capable of analyzing up to 43 analytes (representing 20 amino acids and more than seven neurochemical pathways) from a single 50 microl CSF sample. In this procedure, a CSF sample is first treated with acetonitrile to precipitate proteins. The dried sample is then derivatized with a mixture of 2,2,3,3,3-pentafluoro-1-propanol and pentafluoropropionic acetic anhydride to replace all active hydrogen atoms with fluorine-containing groups. Due to the concentration difference between amino acids and neurotransmitters, these two compound classes are analyzed in separate injections of the same derivatized extract. The total run time for each injection is approximately 15-20 min. An essential feature of the method is the use of argon as a reagent gas for electron capture chemical ionization (ECCI), as the use of the more traditional gas (methane) lacked sufficient durability to be considered for use with the present instrumentation. This article describes the development of this method including a detailed investigation of the chemical ionization conditions used. The resultant conditions allow for the profiling of biogenic amines (e.g. serotonin, norepinephrine, and dopamine) in the low picogram per milliliter range. PMID:18286669

  11. Differences in the neurochemical and behavioural profiles of lisdexamfetamine methylphenidate and modafinil revealed by simultaneous dual-probe microdialysis and locomotor activity measurements in freely-moving rats.

    PubMed

    Rowley, Helen L; Kulkarni, Rajiv S; Gosden, Jane; Brammer, Richard J; Hackett, David; Heal, David J

    2014-03-01

    Lisdexamfetamine dimesylate is a novel prodrug approved in North America, Europe and Brazil for treating attention deficit hyperactivity disorder (ADHD). It undergoes rate-limited hydrolysis by red blood cells to yield d-amphetamine. Following our previous work comparing lisdexamfetamine with d-amphetamine, the neurochemical and behavioural profiles of lisdexamfetamine, methylphenidate and modafinil were compared by dual-probe microdialysis in the prefrontal cortex (PFC) and striatum of conscious rats with simultaneous locomotor activity measurement. We employed pharmacologically equivalent doses of all compounds and those that spanned the therapeutically relevant and psychostimulant range. Lisdexamfetamine (0.5, 1.5, 4.5 mg/kg d-amphetamine base, per os (po)), methylphenidate (3, 10, 30 mg/kg base, po) and modafinil (100, 300, 600 mg/kg base, po) increased efflux of dopamine and noradrenaline in PFC, and dopamine in striatum. Only lisdexamfetamine increased 5-hydroxytryptamine (5-HT) efflux in PFC and striatum. Lisdexamfetamine had larger and more sustained effects on catecholaminergic neurotransmission than methylphenidate or modafinil. Linear correlations were observed between striatal dopamine efflux and locomotor activity for lisdexamfetamine and methylphenidate, but not modafinil. Regression slopes revealed greater increases in extracellular dopamine could be elicited without producing locomotor activation by lisdexamfetamine than methylphenidate. These results are consistent with clinical findings showing that lisdexamfetamine is an effective ADHD medication with prolonged duration of action and good separation between its therapeutic actions and stimulant side-effects. PMID:24327450

  12. Neurochemical Profile of Dementia Pugilistica

    PubMed Central

    Kokjohn, Tyler A.; Maarouf, Chera L.; Daugs, Ian D.; Hunter, Jesse M.; Whiteside, Charisse M.; Malek-Ahmadi, Michael; Rodriguez, Emma; Kalback, Walter; Jacobson, Sandra A.; Sabbagh, Marwan N.; Beach, Thomas G.

    2013-01-01

    Abstract Dementia pugilistica (DP), a suite of neuropathological and cognitive function declines after chronic traumatic brain injury (TBI), is present in approximately 20% of retired boxers. Epidemiological studies indicate TBI is a risk factor for neurodegenerative disorders including Alzheimer disease (AD) and Parkinson disease (PD). Some biochemical alterations observed in AD and PD may be recapitulated in DP and other TBI persons. In this report, we investigate long-term biochemical changes in the brains of former boxers with neuropathologically confirmed DP. Our experiments revealed biochemical and cellular alterations in DP that are complementary to and extend information already provided by histological methods. ELISA and one-dimensional and two dimensional Western blot techniques revealed differential expression of select molecules between three patients with DP and three age-matched non-demented control (NDC) persons without a history of TBI. Structural changes such as disturbances in the expression and processing of glial fibrillary acidic protein, tau, and α-synuclein were evident. The levels of the Aβ–degrading enzyme neprilysin were reduced in the patients with DP. Amyloid-β levels were elevated in the DP participant with the concomitant diagnosis of AD. In addition, the levels of brain-derived neurotrophic factor and the axonal transport proteins kinesin and dynein were substantially decreased in DP relative to NDC participants. Traumatic brain injury is a risk factor for dementia development, and our findings are consistent with permanent structural and functional damage in the cerebral cortex and white matter of boxers. Understanding the precise threshold of damage needed for the induction of pathology in DP and TBI is vital. PMID:23268705

  13. Neurochemical profile of dementia pugilistica.

    PubMed

    Kokjohn, Tyler A; Maarouf, Chera L; Daugs, Ian D; Hunter, Jesse M; Whiteside, Charisse M; Malek-Ahmadi, Michael; Rodriguez, Emma; Kalback, Walter; Jacobson, Sandra A; Sabbagh, Marwan N; Beach, Thomas G; Roher, Alex E

    2013-06-01

    Dementia pugilistica (DP), a suite of neuropathological and cognitive function declines after chronic traumatic brain injury (TBI), is present in approximately 20% of retired boxers. Epidemiological studies indicate TBI is a risk factor for neurodegenerative disorders including Alzheimer disease (AD) and Parkinson disease (PD). Some biochemical alterations observed in AD and PD may be recapitulated in DP and other TBI persons. In this report, we investigate long-term biochemical changes in the brains of former boxers with neuropathologically confirmed DP. Our experiments revealed biochemical and cellular alterations in DP that are complementary to and extend information already provided by histological methods. ELISA and one-dimensional and two dimensional Western blot techniques revealed differential expression of select molecules between three patients with DP and three age-matched non-demented control (NDC) persons without a history of TBI. Structural changes such as disturbances in the expression and processing of glial fibrillary acidic protein, tau, and α-synuclein were evident. The levels of the Aβ-degrading enzyme neprilysin were reduced in the patients with DP. Amyloid-β levels were elevated in the DP participant with the concomitant diagnosis of AD. In addition, the levels of brain-derived neurotrophic factor and the axonal transport proteins kinesin and dynein were substantially decreased in DP relative to NDC participants. Traumatic brain injury is a risk factor for dementia development, and our findings are consistent with permanent structural and functional damage in the cerebral cortex and white matter of boxers. Understanding the precise threshold of damage needed for the induction of pathology in DP and TBI is vital. PMID:23268705

  14. Quantitative autoradiography of neurochemicals

    SciTech Connect

    Rainbow, T.C.; Biegon, A.; Bleisch, W.V.

    1982-05-24

    Several new methods have been developed that apply quantitative autoradiography to neurochemistry. These methods are derived from the 2-deoxyglucose (2DG) technique of Sokoloff (1), which uses quantitative autoradiography to measure the rate of glucose utilization in brain structures. The new methods allow the measurement of the rate of cerbral protein synthesis and the levels of particular neurotransmitter receptors by quantitative autoradiography. As with the 2DG method, the new techniques can measure molecular levels in micron-sized brain structures; and can be used in conjunction with computerized systems of image processing. It is possible that many neurochemical measurements could be made by computerized analysis of quantitative autoradiograms.

  15. Acquiring local field potential information from amperometric neurochemical recordings

    PubMed Central

    Zhang, Hao; Lin, Shih-Chieh; Nicolelis, Miguel A.L.

    2009-01-01

    Simultaneous acquisition of in vivo electrophysiological and neurochemical information is essential for understanding how endogenous neurochemicals modulate the dynamics of brain activity. However, up to now such a task has rarely been accomplished due to the major technical challenge of operating two independent recording systems simultaneously in real-time. Here we propose a simpler solution for achieving this goal by using only a standard electrochemical technique - amperometry. To demonstrate its feasibility, we compared amperometric signals with simultaneously recorded local field potential (LFP) signals. We found that the high frequency component (HFC) of the amperometric signals did not reflect neurochemical fluctuations, but instead it resembled LFPs in several aspects, including: (1) coherent spectral fluctuations; (2) clear characterization of different brain states; (3) identical hippocampal theta depth profile. As such, our findings provide the first demonstration that both LFP and local neurochemical information can be simultaneously acquired from electrochemical sensors alone. PMID:19428527

  16. Leveraging transcript quantification for fast computation of alternative splicing profiles.

    PubMed

    Alamancos, Gael P; Pagès, Amadís; Trincado, Juan L; Bellora, Nicolás; Eyras, Eduardo

    2015-09-01

    Alternative splicing plays an essential role in many cellular processes and bears major relevance in the understanding of multiple diseases, including cancer. High-throughput RNA sequencing allows genome-wide analyses of splicing across multiple conditions. However, the increasing number of available data sets represents a major challenge in terms of computation time and storage requirements. We describe SUPPA, a computational tool to calculate relative inclusion values of alternative splicing events, exploiting fast transcript quantification. SUPPA accuracy is comparable and sometimes superior to standard methods using simulated as well as real RNA-sequencing data compared with experimentally validated events. We assess the variability in terms of the choice of annotation and provide evidence that using complete transcripts rather than more transcripts per gene provides better estimates. Moreover, SUPPA coupled with de novo transcript reconstruction methods does not achieve accuracies as high as using quantification of known transcripts, but remains comparable to existing methods. Finally, we show that SUPPA is more than 1000 times faster than standard methods. Coupled with fast transcript quantification, SUPPA provides inclusion values at a much higher speed than existing methods without compromising accuracy, thereby facilitating the systematic splicing analysis of large data sets with limited computational resources. The software is implemented in Python 2.7 and is available under the MIT license at https://bitbucket.org/regulatorygenomicsupf/suppa. PMID:26179515

  17. Quantification of AES depth profiles by the MRI model

    NASA Astrophysics Data System (ADS)

    Kovač, Janez; Zalar, Anton; Praček, Borut

    2003-02-01

    The main physical effects that contribute to interface broadening in the sputter depth profiles of polycrystalline metallic multilayer structures were studied by comparison of measured and simulated AES depth profiles. An algorithm based on the so-called mixing-roughness-information depth (MRI) model was used to simulate AES depth profiles of Ni/Cr multilayer structures with different roughnesses of the initial surfaces. The simulated depth profiles were compared with measurements performed at two different depth profiling parameters on the Ni/Cr and Al/Ni/Cr multilayer structures with an initial surface roughness of about 1.0 and 21.5 nm, respectively. The comparison of simulated and measured depth profiles enabled us to separate and estimate different contributions to the interface broadening, as well as their dependence on the sputter depth. We found that roughness was the dominant factor related to depth resolution with respect to the information depth and atomic mixing contribution. The values of roughness introduced into the simulation algorithm coincided well with the values measured by AFM at the initial surface and after depth profiling. The results showed the capability of the simulation procedure based on the MRI model to separate and evaluate different contributions to the depth resolution.

  18. Profiling and Quantification of Phenolics in Stevia rebaudiana Leaves.

    PubMed

    Karaköse, Hande; Müller, Anja; Kuhnert, Nikolai

    2015-10-21

    Stevia rebaudiana (Bertoni) is a plant from the Asteraceae family with significant economic value because of the steviol glycoside sweeteners in its leaves. Chlorogenic acids and flavonoid glycosides of S. rebaudiana from seven different botanical varieties cultivated over two years and harvested three times a year in eight European locations were profiled and quantified in a total of 166 samples. Compounds quantified include chlorogenic acids as well as flavonoid glycosides and aglycons. All phenolic concentration profiles show a perfect Gaussian distribution. Principal component analyses allow distinction between varieties of different geographical origin and distinction between different plant varieties. Although concentrations of all chlorogenic acids showed a positive correlation, no correlation was observed for flavonoid glycosides. Conclusions from these findings with respect to the biosynthesis and functional role of phenolics in S. rebaudiana are discussed. PMID:26333998

  19. Recent Advances in Mass Spectrometry for the Identification of Neuro-chemicals and their Metabolites in Biofluids

    PubMed Central

    Kailasa, Suresh Kumar; Wu, Hui-Fen

    2013-01-01

    Recently, mass spectrometric related techniques have been widely applied for the identification and quantification of neurochemicals and their metabolites in biofluids. This article presents an overview of mass spectrometric techniques applied in the detection of neurological substances and their metabolites from biological samples. In addition, the advances of chromatographic methods (LC, GC and CE) coupled with mass spectrometric techniques for analysis of neurochemicals in pharmaceutical and biological samples are also discussed. PMID:24381533

  20. NLX-112, a novel 5-HT1A receptor agonist for the treatment of L-DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat.

    PubMed

    Iderberg, H; McCreary, A C; Varney, M A; Kleven, M S; Koek, W; Bardin, L; Depoortère, R; Cenci, M A; Newman-Tancredi, A

    2015-09-01

    , probably due to induction of flat body posture and forepaw treading which are typical of 5-HT1A agonists upon acute administration. However, upon repeated administration of NLX-112 (0.63 mg/kg, i.p., twice a day), flat body posture and forepaw treading subsided within 4 days of treatment. Taken together, these observations suggest that NLX-112 could exhibit a novel therapeutic profile, combining robust anti-dyskinetic properties without impairing the therapeutic properties of L-DOPA, and with additional beneficial effects on non-motor (affective) symptoms. PMID:26037043

  1. Effects of acute and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo 1H MR spectroscopy at 9.4 T

    PubMed Central

    Wang, Wen-Tung; Lee, Phil; Yeh, Hung-Wen; Smirnova, Irina V.; Choi, In-Young

    2012-01-01

    Chronic hyperglycemia could lead to cerebral metabolic alterations and CNS injury. However, findings of metabolic alterations in poorly managed diabetes in humans and animal models are rather inconsistent. We have characterized the cerebral metabolic consequences of untreated hyperglycemia from the onset to the chronic stage in a streptozotocin-induced rat model of diabetes. In vivo 1H magnetic resonance spectroscopy (MRS) was used to measure over 20 neurochemicals longitudinally. Upon the onset of hyperglycemia (acute state), increases in brain glucose levels were accompanied by increases in osmolytes and ketone bodies, all of which remained consistently high through the chronic state of over 10 weeks of hyperglycemia. Only after over 4 weeks of hyperglycemia, the levels of other neurochemicals including N-acetylaspartate and glutathione were significantly reduced and these alterations persisted into the chronic stage. However, glucose transport was not altered in chronic hyperglycemia of over 10 weeks. When glucose levels were acutely restored to euglycemia, some neurochemical changes were irreversible, indicating the impact of prolonged uncontrolled hyperglycemia on the CNS. Furthermore, progressive changes in neurochemical levels from control to acute and chronic conditions demonstrated the utility of 1H MRS as a noninvasive tool in monitoring the disease progression in diabetes. PMID:22353009

  2. Quantification problems in depth profiling of pwr steels using Ar+ ion sputtering and XPS analysis.

    PubMed

    Ignatova, Velislava A; Van Den Berghe, Sven; Van Dyck, Steven; Popok, Vladimir N

    2006-10-01

    The oxide scales of AISI 304 formed in boric acid solutions at 300 degrees C and pH = 4.5 have been studied using X-ray photoelectron spectroscopy (XPS) depth profiling. The present focus is depth profile quantification both in depth and chemical composition on a molecular level. The roughness of the samples is studied by atomic force microscopy before and after sputtering, and the erosion rate is determined by measuring the crater depth with a surface profilometer and vertical scanning interferometry. The resulting roughness (20-30 nm), being an order of magnitude lower than the crater depth (0.2-0.5 microm), allows layer-by-layer profiling, although the ion-induced effects result in an uncertainty of the depth calibration of a factor of 2. The XPS spectrum deconvolution and data evaluation applying target factor analysis allows chemical speciation on a molecular level. The elemental distribution as a function of the sputtering time is obtained, and the formation of two layers is observed-one hydroxide (mainly iron-nickel based) on top and a second one deeper, mainly consisting of iron-chromium oxides. PMID:16984670

  3. Neurochemical Profiles of some novel psychoactive substances

    PubMed Central

    Iversen, Les; Gibbons, Simon; Treble, Ric; Setola, Vincent; Huang, Xi-Ping; Roth, Bryan L.

    2013-01-01

    Fourteen substances from the class of drugs sometimes known as “legal highs” were screened against a battery of human receptors in binding assays, and their potencies as inhibitors of monoamine uptake determined in functional in vitro assays. Thirteen of the test substances acted as inhibitors of monoamine uptake at submicromolar concentrations, including 9 potent inhibitors of the dopamine transporter (DAT), 12 potent inhibitors of the norepinephrine transporter (NET) and 4 potent inhibitors of the serotonin transporter (SERT). Seven compounds acted as submicromolar inhibitors of both DAT and NET, and three substances 1-(benzofuran-5-yl)propan-2-amine (5-APB),1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one hydrochloride, (“naphyrone”) and 1-naphthalen-1-yl-2-pyrrolidin-1-ylpentan-1-one hydrochloride, (“1-naphyrone”) were submicromolar inhibitors of all three monoamine transporters. There was a lack of correlation between results of functional uptake experiments and in vitro binding assays for the monoamine transporters. There was also no correlation between the human behavioural effects of the substances and the results of bindings assays for a range of receptor targets, although 1-(benzofuran-5-yl)propan-2-amine(5-APB), 1-(benzofuran-6-yl)propan-2-amine hydrochloride(6-APB) and 5-iodo-2,3-dihydro-1H-inden-2-amine hydrochloride,(5-iodo-aminoindane) exhibited <100nM affinities for 5HT2B and α2C receptors. Functional assays revealed that 5-APB and 6-APB were potent full agonists at 5HT2B receptors. PMID:23261499

  4. Quantification and size-profiling of extracellular vesicles using tunable resistive pulse sensing.

    PubMed

    Maas, Sybren L N; De Vrij, Jeroen; Broekman, Marike L D

    2014-01-01

    Extracellular vesicles (EVs), including 'microvesicles' and 'exosomes', are highly abundant in bodily fluids. Recent years have witnessed a tremendous increase in interest in EVs. EVs have been shown to play important roles in various physiological and pathological processes, including coagulation, immune responses, and cancer. In addition, EVs have potential as therapeutic agents, for instance as drug delivery vehicles or as regenerative medicine. Because of their small size (50 to 1,000 nm) accurate quantification and size profiling of EVs is technically challenging. This protocol describes how tunable resistive pulse sensing (tRPS) technology, using the qNano system, can be used to determine the concentration and size of EVs. The method, which relies on the detection of EVs upon their transfer through a nano sized pore, is relatively fast, suffices the use of small sample volumes and does not require the purification and concentration of EVs. Next to the regular operation protocol an alternative approach is described using samples spiked with polystyrene beads of known size and concentration. This real-time calibration technique can be used to overcome technical hurdles encountered when measuring EVs directly in biological fluids. PMID:25350417

  5. Significance of multiple neurochemicals that regulate respiration.

    PubMed

    Pilowsky, Paul M; Sun, Qi-Jian; Lonergan, Tina; Makeham, John M; Seyedabadi, Maryam; Verner, Todd A; Goodchild, Ann K

    2008-01-01

    Current efforts to characterize the neuronal mechanisms that underlie automatic breathing generally adopt a 'minimalist' approach. In this review, we survey three of the many neurochemicals that are known to be present in raphe neurons and may be involved in respiration. Specifically, we ask the question, 'Is the minimalist approach consistent with the large number of neuronal types and neurochemicals found in respiratory centres'? PMID:18085284

  6. In Vivo Neurochemical Characterization of Developing Guinea Pigs and the Effect of Chronic Fetal Hypoxia.

    PubMed

    Wang, Wen-Tung; Lee, Phil; Dong, Yafeng; Yeh, Hung-Wen; Kim, Jieun; Weiner, Carl P; Brooks, William M; Choi, In-Young

    2016-07-01

    The guinea pig is a frequently used animal model for human pregnancy complications, such as oxygen deprivation or hypoxia, which result in altered brain development. To investigate the impact of in utero chronic hypoxia on brain development, pregnant guinea pigs underwent either normoxic or hypoxic conditions at about 70 % of 65-day term gestation. After delivery, neurochemical profiles consisting of 19 metabolites and macromolecules were obtained from the neonatal cortex, hippocampus, and striatum from birth to 12 weeks postpartum using in vivo (1)H MR spectroscopy at 9.4 T. The effects of chronic fetal hypoxia on the neurochemical profiles were particularly significant at birth. However, the overall developmental trends of neurochemical concentration changes were similar between normoxic and hypoxic animals. Alterations of neurochemicals including N-acetylaspartate (NAA), phosphorylethanolamine, creatine, phosphocreatine, and myo-inositol indicate neuronal loss, delayed myelination, and altered brain energetics due to chronic fetal hypoxia. These observed neurochemical alterations in the developing brain may provide insights into hypoxia-induced brain pathology, neurodevelopmental compromise, and potential neuroprotective measures. PMID:27233245

  7. The Impact of Neurochemical Mediators on Antidepressant Effectiveness

    PubMed Central

    2013-01-01

    Despite marked differences in the psychobiological profiles of depressed patients, clinical research has not supported selection of antidepressant (AD) medications based on neurochemistry. Prescribers have been advised to start all patients on the same class of ADs and then switch or combine them until benefit is achieved. New research may transform this practice. By matching clinical moderators to neurochemical mediators, health professionals may finally be able to overcome the disappointing remission rates associated with initial AD treatments and avoid the progressively worsening results associated with current trial and error approaches. PMID:24047106

  8. Simultaneous wireless electrophysiological and neurochemical monitoring

    NASA Astrophysics Data System (ADS)

    Murari, Kartikeya; Mollazadeh, Mohsen; Thakor, Nitish; Cauwenberghs, Gert

    2008-08-01

    Information processing and propagation in the central nervous system is mostly electrical in nature. At synapses, electrical signals cause the release of neurotransmitters like dopamine, glutamate etc., that are sensed by post-synaptic neurons resulting in signal propagation or inhibition. It can be very informative to monitor electrical and neurochemical signals simultaneously to understand the mechanisms underlying normal or abnormal brain function. We present an integrated system for the simultaneous wireless acquisition of neurophysiological and neurochemical activity. Applications of the system to neuroscience include monitoring EEG and glutamate in rat somatosensory cortex following global ischemia.

  9. Detection and Quantification of Rotenoids from Clitoria fairchildiana and its Lipids Profile.

    PubMed

    Santos, Rauldenis A F; David, Jorge M; David, Juceni P

    2016-05-01

    This work describes the isolation and quantification of rotenoids from crude organic extracts of different parts of Clitoria fairchildiana R. A. Howard (Leguminosae) by HPLC-DAD. The lipid composition and the Artemia salina cytotoxic activities of the isolates were also conducted. Clitoriacetal (1), 6-deoxyclitoriacetal (2), stemonal and stemonone were isolated by chromatographic procedures and identified by usual spectroscopic and spectrometric techniques. Clitoriacetal and 6-deoxyclitoriacetal were not found in all parts of the plant, such as leaves and petals, but in the roots they occur in higher concentration. The activity against brine shrimp revealed that the root extract (LD50 = 158 ppm) was the more active. PMID:27319136

  10. Neurochemical measurements in the zebrafish brain

    PubMed Central

    Jones, Lauren J.; McCutcheon, James E.; Young, Andrew M. J.; Norton, William H. J.

    2015-01-01

    The zebrafish is an ideal model organism for behavioral genetics and neuroscience. The high conservation of genes and neurotransmitter pathways between zebrafish and other vertebrates permits the translation of research between species. Zebrafish behavior can be studied at both larval and adult stages and recent research has begun to establish zebrafish models for human disease. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique that permits the detection of neurotransmitter release and reuptake. In this study we have used in vitro FSCV to measure the release of analytes in the adult zebrafish telencephalon. We compare different stimulation methods and present a characterization of neurochemical changes in the wild-type zebrafish brain. This study represents the first FSCV recordings in zebrafish, thus paving the way for neurochemical analysis of the fish brain. PMID:26441575

  11. Metabolic Profiling and Quantification of Neurotransmitters in Mouse Brain by Gas Chromatography-Mass Spectrometry.

    PubMed

    Jäger, Christian; Hiller, Karsten; Buttini, Manuel

    2016-01-01

    Metabolites are key mediators of cellular functions, and have emerged as important modulators in a variety of diseases. Recent developments in translational biomedicine have highlighted the importance of not looking at just one disease marker or disease inducing molecule, but at populations thereof to gain a global understanding of cellular function in health and disease. The goal of metabolomics is the systematic identification and quantification of metabolite populations. One of the most pressing issues of our times is the understanding of normal and diseased nervous tissue functions. To ensure high quality data, proper sample processing is crucial. Here, we present a method for the extraction of metabolites from brain tissue, their subsequent preparation for non-targeted gas chromatography-mass spectrometry (GC-MS) measurement, as well as giving some guidelines for processing of raw data. In addition, we present a sensitive screening method for neurotransmitters based on GC-MS in selected ion monitoring mode. The precise multi-analyte detection and quantification of amino acid and monoamine neurotransmitters can be used for further studies such as metabolic modeling. Our protocol can be applied to shed light on nervous tissue function in health, as well as neurodegenerative disease mechanisms and the effect of experimental therapeutics at the metabolic level. © 2016 by John Wiley & Sons, Inc. PMID:27584556

  12. Quantification and profiling of lipophilic marine toxins in microalgae by UHPLC coupled to high-resolution orbitrap mass spectrometry.

    PubMed

    Orellana, Gabriel; Van Meulebroek, Lieven; Van Vooren, Sarah; De Rijcke, Maarten; Vandegehuchte, Michiel; Janssen, Colin R; Vanhaecke, Lynn

    2015-08-01

    During the last decade, a significant increase in the occurrence of harmful algal blooms (HABs), linked to repetitive cases of shellfish contamination has become a public health concern and therefore, accurate methods to detect marine toxins in different matrices are required. In this study, we developed a method for profiling lipophilic marine microalgal toxins based on ultra-high-performance liquid chromatography coupled to high-resolution Orbitrap mass spectrometry (UHPLC-HR-Orbitrap MS). Extraction of selected toxins (okadaic acid (OA), dinophysistoxin-1 (DTX-1), pectenotoxin-2 (PTX-2), azaspiracid-1 (AZA-1), yessotoxin (YTX) and 13-desmethyl spirolide C (SPX-1)) was optimized using a Plackett-Burman design. Three key algal species, i.e., Prorocentrum lima, Protoceratium reticulatum and Alexandrium ostenfeldii were used to test the extraction efficiency of OA, YTXs and SPXs, respectively. Prorocentrum micans, fortified with certified reference solutions, was used for recovery studies. The quantitative and confirmatory performance of the method was evaluated according to CD 2002/657/EC. Limits of detection and quantification ranged between 0.006 and 0.050 ng mL(-1) and 0.018 to 0.227 ng mL(-1), respectively. The intra-laboratory reproducibility ranged from 6.8 to 11.7 %, repeatability from 6.41 to 11.5 % and mean corrected recoveries from 81.9 to 119.6 %. In addition, algae cultures were retrospectively screened for analogues and metabolites through a homemade database. Using the ToxID software programme, 18 toxin derivates were detected in the extract of three toxin producing microalgae species. In conclusion, the generic extraction and full-scan HRMS approach offers an excellent quantitative performance and simultaneously allows to profile analogues and metabolites of marine toxins in microalgae. Graphical Abstract Optimization of extraction, detection and quantification of lipophilic marine toxins in microalgae by UHPLC-HR Orbitrap MS. PMID:25893798

  13. Deuterium depth profile quantification in a ASDEX Upgrade divertor tile using secondary ion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Ghezzi, F.; Caniello, R.; Giubertoni, D.; Bersani, M.; Hakola, A.; Mayer, M.; Rohde, V.; Anderle, M.

    2014-10-01

    We present the results of a study where secondary ion mass spectrometry (SIMS) has been used to obtain depth profiles of deuterium concentration on plasma facing components of the first wall of the ASDEX Upgrade tokamak. The method uses primary and secondary standards to quantify the amount of deuterium retained. Samples of bulk graphite coated with tungsten or tantalum-doped tungsten are independently profiled with three different SIMS instruments. Their deuterium concentration profiles are compared showing good agreement. In order to assess the validity of the method, the integrated deuterium concentrations in the coatings given by one of the SIMS devices is compared with nuclear reaction analysis (NRA) data. Although in the case of tungsten the agreement between NRA and SIMS is satisfactory, for tantalum-doped tungsten samples the discrepancy is significant because of matrix effect induced by tantalum and differently eroded surface (W + Ta always exposed to plasma, W largely shadowed). A further comparison where the SIMS deuterium concentration is obtained by calibrating the measurements against NRA values is also presented. For the tungsten samples, where no Ta induced matrix effects are present, the two methods are almost equivalent.The results presented show the potential of the method provided that the standards used for the calibration reproduce faithfully the matrix nature of the samples.

  14. Profiling and relative quantification of phosphatidylethanolamine based on acetone stable isotope derivatization.

    PubMed

    Wang, Xiang; Wei, Fang; Xu, Ji-qu; Lv, Xin; Dong, Xu-yan; Han, Xianlin; Quek, Siew-young; Huang, Feng-hong; Chen, Hong

    2016-01-01

    Phosphatidylethanolamine (PE) is considered to be one of the pivotal lipids for normal cellular function as well as disease initiation and progression. In this study, a simple, efficient, reliable, and inexpensive method for the qualitative analysis and relative quantification of PE, based on acetone stable isotope derivatization combined with double neutral loss scan-shotgun electrospray ionization tandem-quadrupole mass spectrometry analysis (ASID-DNLS-Shotgun ESI-MS/MS), was developed. The ASID method led to alkylation of the primary amino groups of PE with an isopropyl moiety. The use of acetone (d0-acetone) and deuterium-labeled acetone (d6-acetone) introduced a 6 Da mass shift that was ideally suited for relative quantitative analysis, and enhanced sensitivity for mass analysis. The DNLS model was introduced to simultaneously analyze the differential derivatized PEs by shotgun ESI-MS/MS with high selectivity and accuracy. The reaction specificity, labeling efficiency, and linearity of the ASID method were thoroughly evaluated in this study. Its excellent applicability was validated by qualitative and relative quantitative analysis of PE species presented in liver samples from rats fed different diets. Using the ASID-DNLS-Shotgun ESI-MS/MS method, 45 PE species from rat livers have been identified and quantified in an efficient manner. The level of total PEs tended to decrease in the livers of rats on high fat diets compared with controls. The levels of PE 32:1, 34:3, 34:2, 36:3, 36:2, 42:10, plasmalogen PE 36:1 and lyso PE 22:6 were significantly reduced, while levels of PE 36:1 and lyso PE 16:0 increased. PMID:26703264

  15. Molecular Detection, Quantification, and Toxigenicity Profiling of Aeromonas spp. in Source- and Drinking-Water.

    PubMed

    Robertson, Boakai K; Harden, Carol; Selvaraju, Suresh B; Pradhan, Suman; Yadav, Jagjit S

    2014-01-01

    Aeromonas is ubiquitous in aquatic environments and has been associated with a number of extra-gastrointestinal and gastrointestinal illnesses. This warrants monitoring of raw and processed water sources for pathogenic and toxigenic species of this human pathogen. In this study, a total of 17 different water samples [9 raw and 8 treated samples including 4 basin water (partial sand filtration) and 4 finished water samples] were screened for Aeromonas using selective culturing and a genus-specific real-time quantitative PCR assay. The selective culturing yielded Aeromonas counts ranging 0 - 2 x 10(3)CFU/ml and 15 Aeromonas isolates from both raw and treated water samples. The qPCR analysis indicated presence of a considerable nonculturable population (3.4 x 10(1) - 2.4 x 10(4) cells/ml) of Aeromonas in drinking water samples. Virulence potential of the Aeromonas isolates was assessed by multiplex/singleplex PCR-based profiling of the hemolysin and enterotoxin genes viz cytotoxic heat-labile enterotoxin (act), heat-labile cytotonic enterotoxin (alt), heat-stable cytotonic enterotoxin (ast), and aerolysin (aerA) genes. The water isolates yielded five distinct toxigenicity profiles, viz. act, alt, act+alt, aerA+alt, and aerA+alt+act. The alt gene showed the highest frequency of occurrence (40%), followed by the aerA (20%), act (13%), and ast (0%) genes. Taken together, the study demonstrated the occurrence of a considerable population of nonculturable Aeromonads in water and prevalence of toxigenic Aeromonas spp. potentially pathogenic to humans. This emphasizes the importance of routine monitoring of both source and drinking water for this human pathogen and role of the developed molecular approaches in improving the Aeromonas monitoring scheme for water. PMID:24949108

  16. Attomole quantification and global profile of RNA modifications: Epitranscriptome of human neural stem cells

    PubMed Central

    Basanta-Sanchez, Maria; Temple, Sally; Ansari, Suraiya A.; D'Amico, Anna; Agris, Paul F.

    2016-01-01

    Exploration of the epitranscriptome requires the development of highly sensitive and accurate technologies in order to elucidate the contributions of the more than 100 RNA modifications to cell processes. A highly sensitive and accurate ultra-high performance liquid chromatography—tandem mass spectrometry method was developed to simultaneously detect and quantify 28 modified and four major nucleosides in less than 20 min. Absolute concentrations were calculated using extinction coefficients of each of the RNA modifications studied. A comprehensive RNA modifications database of UV profiles and extinction coefficient is reported within a 2.3–5.2 % relative standard deviation. Excellent linearity was observed 0.99227–0.99999 and limit of detection values ranged from 63.75 attomoles to 1.21 femtomoles. The analytical performance was evaluated by analyzing RNA modifications from 100 ng of RNA from human pluripotent stem cell-derived neural cells. Modifications were detected at concentrations four orders of magnitude lower than the corresponding parental nucleosides, and as low as 23.01 femtograms, 64.09 attomoles. Direct and global quantitative analysis of RNA modifications are among the advantages of this new approach. PMID:26438536

  17. Neurochemical mechanisms underlying responses to psychostimulants

    SciTech Connect

    Volkow, N.D.; Fowler, J.S.; Hitzemann, R.; Wang, G.J. |

    1994-11-01

    This study employed positron emission tomography (PET) to investigate biochemical and metabolic characteristics of the brain of individuals which could put them at risk for drug addiction. It takes advantage of the normal variability between individuals in response to psychoactive drugs to investigate relation between mental state, brain neurochemistry and metabolism and the behavioral response to drugs. We discuss its use to assess if there is an association between mental state and dompaminergic reactivity in response to the psychostimulant drug methylphenidate (MP). Changes in synaptic dopamine induced by MP were evaluated with PET and [11C]raclopride, a D{sub 2} receptor radioligand that is sensitive to endogenous dopamine. Methylpphenidate significantly decreased striatal [11C]raclopride binding. The study showed a correlation between the magnitude of the dopamine-induced changes by methylphenidate, and the mental state of the subjects. Subjects reporting high levels of anxiety and restlessness at baseline had larger changes in MP-induced dopamine changes than those that did not. Further investigations on the relation between an individual`s response to a drug and his/her mental state and personality as well as his neurochemical brain composition may enable to understand better differences in drug addiction vulnerability.

  18. Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence

    SciTech Connect

    Chou, D.T.; Khan, S.; Forde, J.; Hirsh, K.R.

    1985-06-17

    The development of tolerance to the stimulatory action of caffeine upon mesencephalic reticular neurons and upon spontaneous locomotor activity was evaluated in rats after two weeks of chronic exposure to low doses of caffeine (5-10 mg/kg/day via their drinking water). These doses are achievable through dietary intake of caffeine-containing beverages in man. Concomitant measurement of (/sup 3/H)-CHA binding in the mesencephalic reticular formation was also carried out in order to explore the neurochemical basis of the development of tolerance. Caffeine, 2.5 mg/kg i.v., markedly increased the firing rate of reticular neurons in caffeine naive rats but failed to modify the neuronal activity in a group exposed chronically to low doses of caffeine. In addition, in spontaneous locomotor activity studies, the data show a distinct shift to the right of the caffeine dose-response curve in caffeine pretreated rats. These results clearly indicate that tolerance develops to the stimulatory action of caffeine upon the reticular formation at the single neuronal activity level as well as upon spontaneous locomotor activity. Furthermore, in chronically caffeine exposed rats, an increase in the number of binding sites for (/sup 3/H)-CHA was observed in reticular formation membranes without any change in receptor affinity. 28 references, 4 figures.

  19. Metabolic and neurochemical profiles in insulin-treated diabetic rats.

    PubMed

    Bellush, L L; Reid, S G

    1994-01-01

    Plasma glucose concentration was measured at 3-h intervals in streptozotocin-induced diabetic rats placed on various insulin replacement regimens using three different kinds of insulin. High insulin dosages produced at least periodic hypoglycemia, even though there were no overt signs of insulin overdose. Low- and single-dose regimens produced periods of hyperglycemia. Both high and low doses of protamine zinc insulin normalized diabetes-induced reductions in 5-hydroxyindole-3-acetic acid [5-HIAA; the principal metabolite of 5-hydroxytryptamine (5-HT)] and 5-HT turnover (5-HIAA/5-HT), despite the failure of the low-dose regimen to normalize plasma glucose. Diabetic rats evidenced continued hyperphagia and hyperdipsia during insulin treatment, and insulin treatment also induced hyperphagia and excessive weight gain in nondiabetic rats. Insulin treatment only partially normalized diabetes-induced adrenal hypertrophy. Adrenal hypertrophy is an indication of a continued stresslike physiological state in diabetes even during insulin therapy. This state may be involved in the enhanced risk in diabetic humans for development of anxiety disorders and clinical depression. PMID:7508209

  20. Neurochemical characteristics of the ventromedial hypothalamus in mediating the antiaversive effects of anxiolytics in different models of anxiety.

    PubMed

    Talalaenko, A N; Pankrat'ev, D V; Goncharenko, N V

    2003-03-01

    In experiments on rats using an "illuminated area" avoidance test and a "threatening situation" avoidance test, preliminary i.p. administration and subsequent microinjection into the ventromedial hypothalamus of various combinations of monoamines, transmitter amino acids, and their agonists and antagonists demonstrated differences in the functional importance of the neurochemical profile of this limbic formation in mediating anxiety states of different origins. The neurochemical analysis with local intrahypothalamic administration of anxiosedative and anxioselective substances showed that the antiaversive actions of Campirone are obtained only in conditions in which the dominant motivation is fear, while chlordiazepoxide, Phenibut, and Indoter are also active in anxiety induced by negatively stressful zoosocial influences; these actions are mediated respectively by serotoninergic and GABAergic types of synaptic switching in the ventromedial hypothalamus. PMID:12762592

  1. A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.

    PubMed

    Grahn, Peter J; Mallory, Grant W; Khurram, Obaid U; Berry, B Michael; Hachmann, Jan T; Bieber, Allan J; Bennet, Kevin E; Min, Hoon-Ki; Chang, Su-Youne; Lee, Kendall H; Lujan, J L

    2014-01-01

    Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS. Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a "smart" neuroprosthetic system for treatment of neurologic and psychiatric disorders

  2. Neurochemical, morphologic, and laminar characterization of cortical projection neurons in the cingulate motor areas of the macaque monkey

    NASA Technical Reports Server (NTRS)

    Nimchinsky, E. A.; Hof, P. R.; Young, W. G.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1996-01-01

    The primate cingulate gyrus contains multiple cortical areas that can be distinguished by several neurochemical features, including the distribution of neurofilament protein-enriched pyramidal neurons. In addition, connectivity and functional properties indicate that there are multiple motor areas in the cortex lining the cingulate sulcus. These motor areas were targeted for analysis of potential interactions among regional specialization, connectivity, and cellular characteristics such as neurochemical profile and morphology. Specifically, intracortical injections of retrogradely transported dyes and intracellular injection were combined with immunocytochemistry to investigate neurons projecting from the cingulate motor areas to the putative forelimb region of the primary motor cortex, area M1. Two separate groups of neurons projecting to area M1 emanated from the cingulate sulcus, one anterior and one posterior, both of which furnished commissural and ipsilateral connections with area M1. The primary difference between the two populations was laminar origin, with the anterior projection originating largely in deep layers, and the posterior projection taking origin equally in superficial and deep layers. With regard to cellular morphology, the anterior projection exhibited more morphologic diversity than the posterior projection. Commissural projections from both anterior and posterior fields originated largely in layer VI. Neurofilament protein distribution was a reliable tool for localizing the two projections and for discriminating between them. Comparable proportions of the two sets of projection neurons contained neurofilament protein, although the density and distribution of the total population of neurofilament protein-enriched neurons was very different in the two subareas of origin. Within a projection, the participating neurons exhibited a high degree of morphologic heterogeneity, and no correlation was observed between somatodendritic morphology and

  3. BEHAVIORAL AND NEUROCHEMICAL CONSEQUENCES OF DEVELOPMENTAL ORGANOTIN EXPOSURE IN RATS.

    EPA Science Inventory

    Behavioral and Neurochemical Consequences of Developmental Organotin Exposure in Rats.
    Ehman, K.,1 Jenkins, S.,2 Barone Jr., S.2 and Moser, V.2 1Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, 2Neurotoxicology Division, U.S. Environmental Protection ...

  4. Neurochemical Correlates of Autistic Disorder: A Review of the Literature

    ERIC Educational Resources Information Center

    Lam, Kristen S. L.; Aman, Michael G.; Arnold, L. Eugene

    2006-01-01

    Review of neurochemical investigations in autistic disorder revealed that a wide array of transmitter systems have been studied, including serotonin, dopamine, norepinephrine, acetylcholine, oxytocin, endogenous opioids, cortisol, glutamate, and gamma-aminobutyric acid (GABA). These studies have been complicated by the fact that autism is a very…

  5. Development of the Neurochemical Architecture of the Central Complex

    PubMed Central

    Boyan, George S.; Liu, Yu

    2016-01-01

    The central complex represents one of the most conspicuous neuroarchitectures to be found in the insect brain and regulates a wide repertoire of behaviors including locomotion, stridulation, spatial orientation and spatial memory. In this review article, we show that in the grasshopper, a model insect system, the intricate wiring of the fan-shaped body (FB) begins early in embryogenesis when axons from the first progeny of four protocerebral stem cells (called W, X, Y, Z, respectively) in each brain hemisphere establish a set of tracts to the primary commissural system. Decussation of subsets of commissural neurons at stereotypic locations across the brain midline then establishes a columnar neuroarchitecture in the FB which is completed during embryogenesis. Examination of the expression patterns of various neurochemicals in the central complex including neuropeptides, a neurotransmitter and the gas nitric oxide (NO), show that these appear progressively and in a substance-specific manner during embryogenesis. Each neuroactive substance is expressed by neurons located at stereotypic locations in a given central complex lineage, confirming that the stem cells are biochemically multipotent. The organization of axons expressing the various neurochemicals within the central complex is topologically related to the location, and hence birthdate, of the neurons within the lineages. The neurochemical expression patterns within the FB are layered, and so reflect the temporal topology present in the lineages. This principle relates the neuroanatomical to the neurochemical architecture of the central complex and so may provide insights into the development of adaptive behaviors.

  6. Improved profile fitting and quantification of uncertainty in experimental measurements of impurity transport coefficients using Gaussian process regression

    NASA Astrophysics Data System (ADS)

    Chilenski, M. A.; Greenwald, M.; Marzouk, Y.; Howard, N. T.; White, A. E.; Rice, J. E.; Walk, J. R.

    2015-02-01

    The need to fit smooth temperature and density profiles to discrete observations is ubiquitous in plasma physics, but the prevailing techniques for this have many shortcomings that cast doubt on the statistical validity of the results. This issue is amplified in the context of validation of gyrokinetic transport models (Holland et al 2009 Phys. Plasmas 16 052301), where the strong sensitivity of the code outputs to input gradients means that inadequacies in the profile fitting technique can easily lead to an incorrect assessment of the degree of agreement with experimental measurements. In order to rectify the shortcomings of standard approaches to profile fitting, we have applied Gaussian process regression (GPR), a powerful non-parametric regression technique, to analyse an Alcator C-Mod L-mode discharge used for past gyrokinetic validation work (Howard et al 2012 Nucl. Fusion 52 063002). We show that the GPR techniques can reproduce the previous results while delivering more statistically rigorous fits and uncertainty estimates for both the value and the gradient of plasma profiles with an improved level of automation. We also discuss how the use of GPR can allow for dramatic increases in the rate of convergence of uncertainty propagation for any code that takes experimental profiles as inputs. The new GPR techniques for profile fitting and uncertainty propagation are quite useful and general, and we describe the steps to implementation in detail in this paper. These techniques have the potential to substantially improve the quality of uncertainty estimates on profile fits and the rate of convergence of uncertainty propagation, making them of great interest for wider use in fusion experiments and modelling efforts.

  7. Novel methods for the quantification of changes in actin organization in chondrocytes using fluorescent imaging and linear profiling.

    PubMed

    Qusous, Ala; Parker, Eleanor; Geewan, Corinne; Kapasi, Arva; Getting, Stephen J; Hucklebridge, Frank; Keshavarz, Tajalli; Kerrigan, Mark J P

    2012-07-01

    We present three novel reproducible methodologies for the quantification of changes in actin organization from microscope images. Striation and integrative analysis were devised for the investigation of trans-cellular filaments and F-actin localization, respectively, in response to physiological or mechanical actin-modulatory conditions. Additionally, the Parker-Qusous (PQ) formula was developed as a measure of total quantity of F-actin, independent of cell volume changes, whereby fluorescence intensity was divided by the cube root of cell volume, squared. Values obtained were quantified in Mauricean Units (Mu; pixel/μm(3)). Upon isolation, there was a 49% decrease in total F-actin fluorescence from 1.91 ± 0.16 pixel/μm(3) (Mu) to 0.95 ± 0.55 Mu, whereas upon culture, an apparent increase in total fluorescence was deemed insignificant due to an increase in average cell volume, with a rise, however, in striation units (StU) from 1 ± 1 to 5 ± 1 StU/cell, and a decrease in percentage cortical fluorescence to 30.45% ± 1.52% (P = 7.8 × 10(-5)). Freshly isolated chondrocytes exhibited a decrease in total F-actin fluorescence to 0.61 ± 0.05 Mu and 0.32 ± 0.02 Mu, 10 min posthypertonic and hypotonic challenges, respectively. Regulatory volume decrease was inhibited in the presence of REV5901 with maintenance of actin levels at 1.15 Mu. Following mechanical impact in situ, there was a reduction in total F-actin fluorescence to 0.95 ± 0.08 Mu and 0.74 ± 0.06 Mu under isotonic and hypotonic conditions, respectively, but not under hypertonic conditions. We report simple methodologies for quantification of changes in actin organization, which will further our understanding of the role of actin in various cellular stress responses. These techniques can be applied to better quantify changes in localization of various proteins using fluorescent labeling. PMID:22514026

  8. Age-Related Neurochemical Changes in the Vestibular Nuclei

    PubMed Central

    Smith, Paul F.

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics. PMID:26973593

  9. Age-Related Neurochemical Changes in the Vestibular Nuclei.

    PubMed

    Smith, Paul F

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa's ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics. PMID:26973593

  10. Linking Essential Tremor to the Cerebellum: Neurochemical Evidence.

    PubMed

    Marin-Lahoz, Juan; Gironell, Alexandre

    2016-06-01

    The pathophysiology and the exact anatomy of essential tremor (ET) is not well known. One of the pillars that support the cerebellum as the main anatomical locus in ET is neurochemistry. This review examines the link between neurochemical abnormalities found in ET and cerebellum. The review is based on published data about neurochemical abnormalities described in ET both in human and in animal studies. We try to link those findings with cerebellum. γ-aminobutyric acid (GABA) is the main neurotransmitter involved in the pathophysiology of ET. There are several studies about GABA that clearly points to a main role of the cerebellum. There are few data about other neurochemical abnormalities in ET. These include studies with noradrenaline, glutamate, adenosine, proteins, and T-type calcium channels. One single study reveals high levels of noradrenaline in the cerebellar cortex. Another study about serotonin neurotransmitter results negative for cerebellum involvement. Finally, studies on T-type calcium channels yield positive results linking the rhythmicity of ET and cerebellum. Neurochemistry supports the cerebellum as the main anatomical locus in ET. The main neurotransmitter involved is GABA, and the GABA hypothesis remains the most robust pathophysiological theory of ET to date. However, this hypothesis does not rule out other mechanisms and may be seen as the main scaffold to support findings in other systems. We clearly need to perform more studies about neurochemistry in ET to better understand the relations among the diverse systems implied in ET. This is mandatory to develop more effective pharmacological therapies. PMID:26498765

  11. HUMAN METHAMPHETAMINE PHARMACOKINETICS SIMULATED IN THE RAT: BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF A 72- HOUR BINGE

    PubMed Central

    Kuczenski, Ronald; Segal, David S.; Melega, William P.; Lacan, Goran; McCunney, Stanley J.

    2009-01-01

    Bingeing is one pattern of high dose methamphetamine (METH) abuse which involves continuous drug taking over several days and can result in psychotic behaviors for which the brain pathology remains poorly-defined. A corresponding animal model of this type of METH exposure may provide novel insights into the neurochemical and behavioral sequelae associated with this condition. Accordingly, to simulate the pharmacokinetic profile of a human METH binge exposure in rats we used a computer-controlled, intravenous METH procedure (dynamic infusion) to overcome species differences in METH pharmacokinetics and to replicate the human 12-h plasma METH half-life. Animals were treated over 13 weeks with escalating METH doses, using dynamic infusion, and then exposed to a binge in which drug was administered every 3 h for 72h. Throughout the binge, behavioral effects included unabated intense oral stereotypies in the absence of locomotion and in the absence of sleep. Decrements in regional brain dopamine, norepinephrine and serotonin levels, measured at 1 and 10 h after the last injection of the binge, had, with the exception of caudate-putamen dopamine and frontal cortex serotonin, recovered by 48 h. At 10 h after the last injection of the binge, [3H]ligand binding to dopamine and vesicular monoamine transporters in caudate-putamen were reduced by 35% and 13%, respectively. In a separate METH binge treated cohort, post-binge behavioral alterations were apparent in an attenuated locomotor response to a METH challenge infusion at 24h after the last injection of the binge. Collectively, the changes we characterized during and following a METH binge suggest that for humans under similar exposure conditions, multiple time-dependent neurochemical deficits contribute to their behavioral profiles. PMID:19571794

  12. Qualitative profiling and quantification of neonicotinoid metabolites in human urine by liquid chromatography coupled with mass spectrometry.

    PubMed

    Taira, Kumiko; Fujioka, Kazutoshi; Aoyama, Yoshiko

    2013-01-01

    Neonicotinoid pesticides have been widely applied for the production of fruits and vegetables, and occasionally detected in conventionally grown produce. Thus oral exposure to neonicotinoid pesticides may exist in the general population; however, neonicotinoid metabolites in human body fluids have not been investigated comprehensively. The purpose of this study is the qualitative profiling and quantitative analysis of neonicotinoid metabolites in the human spot urine by liquid chromatography coupled with mass spectrometry (LC/MS). Human urine samples were collected from three patients suspected of subacute exposure to neonicotinoid pesticides. A qualitative profiling of urinary metabolites was performed using liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) with a database of nominal molecular weights of 57 known metabolites of three neonicotinoid pesticides (acetamiprid, Imidacloprid, and clothianidin), as well as the parent compounds. Then a quantitative analysis of selected urinary metabolites was performed using liquid chromatography/tandem mass spectrometry (LC/MS/MS) with a standard pesticide and metabolite, which were detected by the qualitative profiling. The result of qualitative profiling showed that seven metabolites, i.e. an acetamiprid metabolite, N-desmethyl-acetamiprid; three Imidacloprid metabolites, 5-hydroxy-Imidacloprid, 4,5-dihydroxy-imidacloprid, 4,5-dehydro-Imidacloprid; a common metabolite of acetamiprid and Imidacloprid, N-(6-chloronicotinoyl)-glycine; and two clothianidin metabolites, N-desmethyl-clothianidin, N-(2-(methylsulfanyl)thiazole-5-carboxyl)-glycine, as well as acetamiprid, were detected in the urine of three cases. The result of the quantitative analysis showed N-desmethyl-acetamiprid was determined in the urine of one case, which had been collected on the first visit, at a concentration of 3.2 ng/mL. This is the first report on the qualitative and quantitative detection of N-desmethyl-acetamiprid in the human

  13. Qualitative Profiling and Quantification of Neonicotinoid Metabolites in Human Urine by Liquid Chromatography Coupled with Mass Spectrometry

    PubMed Central

    Taira, Kumiko; Fujioka, Kazutoshi; Aoyama, Yoshiko

    2013-01-01

    Neonicotinoid pesticides have been widely applied for the production of fruits and vegetables, and occasionally detected in conventionally grown produce. Thus oral exposure to neonicotinoid pesticides may exist in the general population; however, neonicotinoid metabolites in human body fluids have not been investigated comprehensively. The purpose of this study is the qualitative profiling and quantitative analysis of neonicotinoid metabolites in the human spot urine by liquid chromatography coupled with mass spectrometry (LC/MS). Human urine samples were collected from three patients suspected of subacute exposure to neonicotinoid pesticides. A qualitative profiling of urinary metabolites was performed using liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) with a database of nominal molecular weights of 57 known metabolites of three neonicotinoid pesticides (acetamiprid, Imidacloprid, and clothianidin), as well as the parent compounds. Then a quantitative analysis of selected urinary metabolites was performed using liquid chromatography/tandem mass spectrometry (LC/MS/MS) with a standard pesticide and metabolite, which were detected by the qualitative profiling. The result of qualitative profiling showed that seven metabolites, i.e. an acetamiprid metabolite, N-desmethyl-acetamiprid; three Imidacloprid metabolites, 5-hydroxy-Imidacloprid, 4,5-dihydroxy-imidacloprid, 4,5-dehydro-Imidacloprid; a common metabolite of acetamiprid and Imidacloprid, N-(6-chloronicotinoyl)-glycine; and two clothianidin metabolites, N-desmethyl-clothianidin, N-(2-(methylsulfanyl)thiazole-5-carboxyl)-glycine, as well as acetamiprid, were detected in the urine of three cases. The result of the quantitative analysis showed N-desmethyl-acetamiprid was determined in the urine of one case, which had been collected on the first visit, at a concentration of 3.2 ng/mL. This is the first report on the qualitative and quantitative detection of N-desmethyl-acetamiprid in the human

  14. A novel Whole Air Sample Profiler (WASP) for the quantification of volatile organic compounds in the boundary layer

    SciTech Connect

    Mak, J. E.; Su, L.; Guenther, Alex B.; Karl, Thomas G.

    2013-10-16

    The emission and fate of reactive VOCs is of inherent interest to those studying chemical biosphere-atmosphere interactions. In-canopy VOC observations are obtainable using tower-based samplers, but the lack of suitable sampling systems for the full boundary 5 layer has limited the data characterizing the vertical structure of such gases above the canopy height and still in the boundary layer. This is the important region where many reactive VOCs are oxidized or otherwise removed. Here we describe an airborne sampling system designed to collect a vertical profile of air into a 3/800 OD tube 150m in length. The inlet ram air pressure is used to flow sampled air through the 10 tube, which results in a varying flow rate based on aircraft speed and altitude. Since aircraft velocity decreases during ascent, it is necessary to account for the variable flow rate into the tube. This is accomplished using a reference gas that is pulsed into the air stream so that the precise altitude of the collected air can be reconstructed post-collection. The pulsed injections are also used to determine any significant effect 15 from diffusion/mixing within the sampling tube, either during collection or subsequent extraction for gas analysis. This system has been successfully deployed, and we show some measured vertical profiles of isoprene and its oxidation products methacrolein and methyl vinyl ketone from a mixed canopy near Columbia, Missouri.

  15. Integrated identification, qualification and quantification strategy for pharmacokinetic profile study of Guizhi Fuling capsule in healthy volunteers

    PubMed Central

    Zhong, Yun-Xi; Jin, Xiao-Liang; Gu, Shi-Yin; Peng, Ying; Zhang, Ke-Rong; Ou-Yang, Bing-Chen; Wang, Yu; Xiao, Wei; Wang, Zhen-Zhong; Aa, Ji-Ye; Wang, Guang-Ji; Sun, Jian-Guo

    2016-01-01

    Guizhi Fuling capsule (GZFL), a traditional Chinese medicine formulation, is widely used in China to relieve pain from dysmenorrhea and is now in a Phase II clinical trial in the USA. Due to the low exposure of the five main medicative ingredients (amygdalin, cinnamic acid, gallic acid, paeoniflorin and paeonol) of GZFL in human, a strategy was built to qualitatively and quantitatively identify the possible metabolites of GZFL and to describe the pharmacokinetic profiles of GZFL in human. In this strategy, LC-Q-TOF/MS was used to identify and structurally elucidate the possible metabolites of GZFL in vivo; and a time-based metabolite-confirming step (TBMCs) was used to confirm uncertain metabolites. The simultaneously quantitation results by LC-MS/MS showed low exposure of the five medicative ingredients. According to the strategy we built, a total of 36 metabolites were found and structurally elucidated. The simultaneously semi-quantitative analysis by LC-MS/MS showed that obvious time-concentration curves could be established for 12 of the metabolites, and most of them showed a relatively higher exposure. This study provides a better understanding of the metabolic processes of GZFL in human. PMID:27527657

  16. Integrated identification, qualification and quantification strategy for pharmacokinetic profile study of Guizhi Fuling capsule in healthy volunteers.

    PubMed

    Zhong, Yun-Xi; Jin, Xiao-Liang; Gu, Shi-Yin; Peng, Ying; Zhang, Ke-Rong; Ou-Yang, Bing-Chen; Wang, Yu; Xiao, Wei; Wang, Zhen-Zhong; Aa, Ji-Ye; Wang, Guang-Ji; Sun, Jian-Guo

    2016-01-01

    Guizhi Fuling capsule (GZFL), a traditional Chinese medicine formulation, is widely used in China to relieve pain from dysmenorrhea and is now in a Phase II clinical trial in the USA. Due to the low exposure of the five main medicative ingredients (amygdalin, cinnamic acid, gallic acid, paeoniflorin and paeonol) of GZFL in human, a strategy was built to qualitatively and quantitatively identify the possible metabolites of GZFL and to describe the pharmacokinetic profiles of GZFL in human. In this strategy, LC-Q-TOF/MS was used to identify and structurally elucidate the possible metabolites of GZFL in vivo; and a time-based metabolite-confirming step (TBMCs) was used to confirm uncertain metabolites. The simultaneously quantitation results by LC-MS/MS showed low exposure of the five medicative ingredients. According to the strategy we built, a total of 36 metabolites were found and structurally elucidated. The simultaneously semi-quantitative analysis by LC-MS/MS showed that obvious time-concentration curves could be established for 12 of the metabolites, and most of them showed a relatively higher exposure. This study provides a better understanding of the metabolic processes of GZFL in human. PMID:27527657

  17. Quantification of mid and late evoked sinks in laminar current source density profiles of columns in the primary auditory cortex

    PubMed Central

    Schaefer, Markus K.; Hechavarría, Julio C.; Kössl, Manfred

    2015-01-01

    Current source density (CSD) analysis assesses spatiotemporal synaptic activations at somatic and/or dendritic levels in the form of depolarizing current sinks. Whereas many studies have focused on the short (<50 ms) latency sinks, associated with thalamocortical projections, sinks with longer latencies have received less attention. Here, we analyzed laminar CSD patterns for the first 600 ms after stimulus onset in the primary auditory cortex of Mongolian gerbils. By applying an algorithm for contour calculation, three distinct mid and four late evoked sinks were identified in layers I, III, Va, VIa, and VIb. Our results further showed that the patterns of intracortical information-flow remained qualitatively similar for low and for high sound pressure level stimuli at the characteristic frequency (CF) as well as for stimuli ± 1 octave from CF. There were, however, differences associated with the strength, vertical extent, onset latency, and duration of the sinks for the four stimulation paradigms used. Stimuli one octave above the most sensitive frequency evoked a new, and quite reliable, sink in layer Va whereas low level stimulation led to the disappearance of the layer VIb sink. These data indicate the presence of input sources specifically activated in response to level and/or frequency parameters. Furthermore, spectral integration above vs. below the CF of neurons is asymmetric as illustrated by CSD profiles. These results are important because synaptic feedback associated with mid and late sinks—beginning at 50 ms post stimulus latency—is likely crucial for response modulation resulting from higher order processes like memory, learning or cognitive control. PMID:26557058

  18. Quantification of Hydrogen Concentrations in Surface and Interface Layers and Bulk Materials through Depth Profiling with Nuclear Reaction Analysis.

    PubMed

    Wilde, Markus; Ohno, Satoshi; Ogura, Shohei; Fukutani, Katsuyuki; Matsuzaki, Hiroyuki

    2016-01-01

    Nuclear reaction analysis (NRA) via the resonant (1)H((15)N,αγ)(12)C reaction is a highly effective method of depth profiling that quantitatively and non-destructively reveals the hydrogen density distribution at surfaces, at interfaces, and in the volume of solid materials with high depth resolution. The technique applies a (15)N ion beam of 6.385 MeV provided by an electrostatic accelerator and specifically detects the (1)H isotope in depths up to about 2 μm from the target surface. Surface H coverages are measured with a sensitivity in the order of ~10(13) cm(-2) (~1% of a typical atomic monolayer density) and H volume concentrations with a detection limit of ~10(18) cm(-3) (~100 at. ppm). The near-surface depth resolution is 2-5 nm for surface-normal (15)N ion incidence onto the target and can be enhanced to values below 1 nm for very flat targets by adopting a surface-grazing incidence geometry. The method is versatile and readily applied to any high vacuum compatible homogeneous material with a smooth surface (no pores). Electrically conductive targets usually tolerate the ion beam irradiation with negligible degradation. Hydrogen quantitation and correct depth analysis require knowledge of the elementary composition (besides hydrogen) and mass density of the target material. Especially in combination with ultra-high vacuum methods for in-situ target preparation and characterization, (1)H((15)N,αγ)(12)C NRA is ideally suited for hydrogen analysis at atomically controlled surfaces and nanostructured interfaces. We exemplarily demonstrate here the application of (15)N NRA at the MALT Tandem accelerator facility of the University of Tokyo to (1) quantitatively measure the surface coverage and the bulk concentration of hydrogen in the near-surface region of a H2 exposed Pd(110) single crystal, and (2) to determine the depth location and layer density of hydrogen near the interfaces of thin SiO2 films on Si(100). PMID:27077920

  19. Thiamine deficiency induced neurochemical, neuroanatomical, and neuropsychological alterations: a reappraisal.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Storti, Monica; Christova, Monica; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen; Brigo, Francesco

    2013-01-01

    Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans. PMID:24235882

  20. Probing the neurochemical basis of synaesthesia using psychophysics

    PubMed Central

    Terhune, Devin B.; Song, Seoho M.; Duta, Mihaela D.; Kadosh, Roi Cohen

    2014-01-01

    The neurochemical mechanisms that contribute to synaesthesia are poorly understood, but multiple models implicate serotonin and GABA in the development of this condition. Here we used psychophysical tasks to test the predictions that synaesthetes would display behavioral performance consistent with reduced GABA and elevated serotonin in primary visual cortex. Controls and synaesthetes completed the orientation-specific surround suppression (OSSS) and tilt-after effect (TAE) tasks, previously shown to relate to GABA and serotonin levels, respectively. Controls and synaesthetes did not differ in the performance parameter previously associated with GABA or in the magnitude of the TAE. However, synaesthetes did display lower contrast difference thresholds in the OSSS task than controls when no surround (NS) was present. These results are inconsistent with the hypothesized roles of GABA and serotonin in this condition, but provide preliminary evidence that synaesthetes exhibit enhanced contrast discrimination. PMID:24600378

  1. Thiamine Deficiency Induced Neurochemical, Neuroanatomical, and Neuropsychological Alterations: A Reappraisal

    PubMed Central

    Höller, Yvonne; Storti, Monica; Christova, Monica; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen

    2013-01-01

    Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans. PMID:24235882

  2. Neurobehavioral and neurochemical effects of prenatal ethanol administration in rats

    SciTech Connect

    Pradhan, S.; Briggs, F. )

    1992-01-01

    Effects of prenatal ethanol exposure in rats on the behavior and on the levels of multiple neurotransmitters in the brain have been investigated. Timed pregnant Sprague-Dawley rats were divided into three groups: ethanol-exposed, pair-fed control and nutritional control. Ethanol was administered through Leiber-DeCarli liquid diet containing 6% ethanol (v/v) throughout the gestation period in ethanol-exposed rats. Male offspring were tested for alternations in neurobehavioral and neurochemical parameters. Animals exposed to ethanol in utero exhibited lower birth weights, delayed motor development, delayed learning and no catch-up growth, as well as significant alterations in levels of dopamine, norepinephrine, serotonin and GABA in discrete brain areas.

  3. Tourette's syndrome: a neurochemical analysis of postmortem cortical brain tissue.

    PubMed

    Singer, H S; Hahn, I H; Krowiak, E; Nelson, E; Moran, T

    1990-04-01

    Postmortem frontal, temporal, and occipital regions of the brain from adult patients who had a diagnosis of Tourette's syndrome were analyzed for neurochemical alterations. In 3 of 4 TS-affected brains, the concentration of adenosine 3',5'-monophosphate (cyclic AMP) was reduced in all brain regions evaluated. This diminution in cyclic AMP was not associated with a significant change in the activity of the synthesizing enzyme, adenylate cyclase. No significant differences were identified for the neurotransmitter-synthesizing enzymes choline acetyltransferase and glutamate decarboxylase. Concentrations of dopamine, norepinephrine, and the serotonin metabolite 5-hydroxyindoleacetic acid were not altered. Postsynaptic receptor-binding activity for muscarinic cholinergic ([3H]quinuclidinyl benzilate) and beta receptors ([125I]iodocyanopindolol) showed no generalized impairment. It is suggested that symptoms of Tourette's syndrome might be related to an abnormality within a second messenger system. PMID:1972320

  4. Profiles.

    ERIC Educational Resources Information Center

    School Arts, 1979

    1979-01-01

    Profiles seven Black, Native American, and Chicano artists and art teachers: Hale A. Woodruff, Allan Houser, Luis Jimenez, Betrand D. Phillips, James E. Pate, I, and Fernando Navarro. This article is part of a theme issue on multicultural art. (SJL)

  5. LONG-TERM BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF INTRADENTATE ADMINISTRATION OF COLCHICINE IN RATS

    EPA Science Inventory

    Previous work has shown that the intradentate administration of colchicine produces time-dependent behavioral and neurochemical changes. eficits in learning and memory and alterations In the signal transduction process for the cholinergic muscarinic receptor have been observed up...

  6. Noninvasive Quantification of 2-Hydroxyglutarate in Human Gliomas with IDH1 and IDH2 Mutations.

    PubMed

    Emir, Uzay E; Larkin, Sarah J; de Pennington, Nick; Voets, Natalie; Plaha, Puneet; Stacey, Richard; Al-Qahtani, Khalid; Mccullagh, James; Schofield, Christopher J; Clare, Stuart; Jezzard, Peter; Cadoux-Hudson, Tom; Ansorge, Olaf

    2016-01-01

    Mutations in the isocitrate dehydrogenase genes (IDH1/2) occur often in diffuse gliomas, where they are associated with abnormal accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). Monitoring 2-HG levels could provide prognostic information in this disease, but detection strategies that are noninvasive and sufficiently quantitative have yet to be developed. In this study, we address this need by presenting a proton magnetic resonance spectroscopy ((1)H-MRS) acquisition scheme that uses an ultrahigh magnetic field (≥ 7T) capable of noninvasively detecting 2-HG with quantitative measurements sufficient to differentiate mutant cytosolic IDH1 and mitochondrial IDH2 in human brain tumors. Untargeted metabolomics analysis of in vivo (1)H-MRS spectra discriminated between IDH-mutant tumors and healthy tissue, and separated IDH1 from IDH2 mutations. High-quality spectra enabled the quantification of neurochemical profiles consisting of at least eight metabolites, including 2-HG, glutamate, lactate, and glutathione in both tumor and healthy tissue voxels. Notably, IDH2 mutation produced more 2-HG than IDH1 mutation, consistent with previous findings in cell culture. By offering enhanced sensitivity and specificity, this scheme can quantitatively detect 2-HG and associated metabolites that may accumulate during tumor progression, with implications to better monitor patient responses to therapy. PMID:26669865

  7. [Neurochemical features of the ventral pallidum in realization of the antiaversive effects of anxiolytics in different models of anxiety].

    PubMed

    Talalaenko, A N; Pankrat'ev, D V; Bulgakova, N P

    2006-01-01

    Preliminary intraperitoneal injections of some combinations of adreno- and dopaminomimetics, monoamines, and mediator amino acids (as well as of their agonists and antagonists) followed by microinjections of the same combinations into the ventral pallidum reveal differences in the functional significance of the neurochemical profile of this paleostriatum formation in realization of the anxiety states of different genesis, as manifested in the "illuminated site avoidance" and the "threatening situation" tests in rats. The pharmacological analysis based on the local injection of anxiosedative and anxioselective agents into the ventral paleostriatum showed that the antiaversive action of campirone is revealed under the conditions of dominating fear motivation, while that analogous action of chlordiazepoxide, phenibut and indoter is revealed under negative stressful zoosocial impacts and is realized by serotonin- and GABA-ergic (rather than by cathecholamine- and glutaminergic) aversive systems of the ventral pallidum. PMID:16579051

  8. Hormonal and neurochemical correlates of various forms of animal "aggression".

    PubMed

    Brain, P F; Haug, M

    1992-11-01

    The majority of studies attempting to evaluate the roles of hormones and neurochemicals in "aggression" concern laboratory rodents, notably rats and mice, with fewer investigations on infrahuman primates. Studies suggest that situations used to assess aggression (e.g., social conflict tests, parental attack, predatory behavior, use of unavoidable electroshock) actually tap a diverse range of motivations whose functions include offense, defense and predation. It is also apparent that ethoexperimental techniques, i.e., those applying ethological methodologies and concepts to laboratory situations, have advantages in assessing the direct and indirect consequences of chemical treatments. In this review, the impacts of hormonal manipulation (by surgery and/or application) and varying neurotransmitters (studied in terms of regional changes and as consequences of drug treatments) on a variety of forms of behavior are assessed. Different tests do show varying responses to common treatments, confirming the heterogeneity of the available paradigms. A brief discussion is provided of which tests are likely to prove most relevant to clinical studies. PMID:1363136

  9. Effect of Artificial Gravity: Central Nervous System Neurochemical Studies

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.; D'Amelio, Fernando; Eng, Lawrence F.

    1997-01-01

    The major objective of this project was to assess chemical and morphological modifications occurring in muscle receptors and the central nervous system of animals subjected to altered gravity (2 x Earth gravity produced by centrifugation and simulated micro gravity produced by hindlimb suspension). The underlying hypothesis for the studies was that afferent (sensory) information sent to the central nervous system by muscle receptors would be changed in conditions of altered gravity and that these changes, in turn, would instigate a process of adaptation involving altered chemical activity of neurons and glial cells of the projection areas of the cerebral cortex that are related to inputs from those muscle receptors (e.g., cells in the limb projection areas). The central objective of this research was to expand understanding of how chronic exposure to altered gravity, through effects on the vestibular system, influences neuromuscular systems that control posture and gait. The project used an approach in which molecular changes in the neuromuscular system were related to the development of effective motor control by characterizing neurochemical changes in sensory and motor systems and relating those changes to motor behavior as animals adapted to altered gravity. Thus, the objective was to identify changes in central and peripheral neuromuscular mechanisms that are associated with the re-establishment of motor control which is disrupted by chronic exposure to altered gravity.

  10. Wireless Amperometric Neurochemical Monitoring Using an Integrated Telemetry Circuit

    PubMed Central

    Roham, Masoud; Halpern, Jeffrey M.; Martin, Heidi B.; Chiel, Hillel J.

    2015-01-01

    An integrated circuit for wireless real-time monitoring of neurochemical activity in the nervous system is described. The chip is capable of conducting high-resolution amperometric measurements in four settings of the input current. The chip architecture includes a first-order ΔΣ modulator (ΔΣM) and a frequency-shift-keyed (FSK) voltage-controlled oscillator (VCO) operating near 433 MHz. It is fabricated using the AMI 0.5 μm double-poly triple-metal n-well CMOS process, and requires only one off-chip component for operation. Measured dc current resolutions of ~250 fA, ~1.5 pA, ~4.5 pA, and ~17 pA were achieved for input currents in the range of ±5, ±37, ±150, and ±600 nA, respectively. The chip has been interfaced with a diamond-coated, quartz-insulated, microneedle, tungsten electrode, and successfully recorded dopamine concentration levels as low as 0.5 μM wirelessly over a transmission distance of ~0.5 m in flow injection analysis experiments. PMID:18990633

  11. Neurochemical targets and behavioral effects of organohalogen compounds: an update.

    PubMed

    Mariussen, E; Fonnum, F

    2006-03-01

    Organohalogen compounds (OHCs) have been used and still are used extensively as pesticides, flame retardants, hydraulic fluids, and in other industrial applications. These compounds are stable, most often lipophilic, and may therefore easily biomagnify. Today these compounds are found distributed both in human tissue, including breast milk, and in wildlife animals. In the late 1960s and early 1970s, high levels of the polychlorinated biphenyls (PCBs) and the pesticide dichlorodiphenyl trichloroethane (DDT) were detected in the environment. In the 1970s it was discovered that PCBs and some chlorinated pesticides, such as lindane, have neurotoxic potentials after both acute and chronic exposure. Although the use of PCBs, DDT, and other halogenated pesticides has been reduced, and environmental levels of these compounds are slowly diminishing, other halogenated compounds with potential of toxic effects are being found in the environment. These include the brominated flame retardants, chlorinated paraffins (PCAs), and perfluorinated compounds, whose levels are increasing. It is now established that several OHCs have neurobehavioral effects, indicating adverse effects on the central nervous system (CNS). For instance, several reports have shown that OHCs alter neurotransmitter functions in CNS and Ca2+ homeostatic processes, induce protein kinase C (PKC) and phospholipase A2 (PLA2) mobilization, and induce oxidative stress. In this review we summarize the findings of the neurobehavioral and neurochemical effects of some of the major OHCs with our main focus on the PCBs. Further, we try to elucidate, on the basis of available literature, the possible implications of these findings on human health. PMID:16686424

  12. Neurochemical effects of the enantiomers of mirtazapine in normal rats.

    PubMed

    McGrath, C; Burrows, G D; Norman, T R

    1998-09-01

    The present study was designed to examine the neurochemical effects of (+/-)-mirtazapine (10 mg kg(-1) i.p.) and its enantiomers in rats. Male Sprague-Dawley rats received either (+)-mirtazapine, (-)-mirtazapine, (+/-)-mirtazapine or vehicle, by intraperitoneal injection for two weeks. Maximum change in temperature from baseline, following a single dose of the 5-HT1A receptor agonist 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.15 mg kg(-1) s.c.), was used to assess the function of the 5-HT1A receptors. Chronic drug treatment potentiated this response, with (+/-)-mirtazapine > (-)-mirtazapine > (+)-mirtazapine. Receptor changes were also observed with a slight decrease in beta1-adrenoceptor density, although this failed to reach significance. A significant decrease in beta1-adrenoceptor affinity was observed following (-)-mirtazapine treatment. All drugs tested significantly reduced the density of the 5-HT2 receptors. Results of the present study suggest that in so far as alterations in these receptor populations are important for the therapeutic action of antidepressants, neither of the enantiomers appear to be more active than the racemic mixture. PMID:9774241

  13. Neurochemical Effects of Chronic Administration of Calcitriol in Rats

    PubMed Central

    Jiang, Pei; Zhang, Li-Hong; Cai, Hua-Lin; Li, Huan-De; Liu, Yi-Ping; Tang, Mi-Mi; Dang, Rui-Li; Zhu, Wen-Ye; Xue, Ying; He, Xin

    2014-01-01

    Despite accumulating data showing the various neurological actions of vitamin D (VD), its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D) administration (50 ng/kg/day or 100 ng/kg/day). Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA) status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD) 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS) expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA) expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function. PMID:25533012

  14. Neurochemical background and approaches in the understanding of motion sickness

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.

    1982-01-01

    The problems and nature of space motion sickness were defined. The neurochemical and neurophysiological bases of vestibular system function and of the expression of motion sickness wre reviewed. Emphasis was given to the elucidation of the neuropharmacological mechanisms underlying the effects of scopolamine and amphetamine on motion sickness. Characterization of the ascending reticular activating system and the limbic system provided clues to the etiology of the side effects of scopolamine. The interrelationship between central cholinergic pathways and the peripheral (autonomic) expression of motion sickness was described. A correlation between the stress of excessive motion and a variety of hormonal responses to that stress was also detailed. The cholinergic system is involved in the efferent modulation of the vestibular hair cells, as an afferent modulator of the vestibular nuclei, in the activation of cortical and limbic structures, in the expression of motion sickness symptoms and most likely underscores a number of the hormonal changes that occur in stressful motion environments. The role of lecithin in the regulation of the levels of neurotransmitters was characterized as a possible means by which cholinergic neurochemistry can be modulated.

  15. The neurochemical basis of photic entrainment of the circadian pacemaker

    NASA Technical Reports Server (NTRS)

    Rea, Michael A.; Buckley, Becky; Lutton, Lewis M.

    1992-01-01

    Circadian rhythmicity in mammals is controlled by the action of a light-entrainable hypothalamus, in association with two cell clusters known as the supra chiasmatic nuclei (SCN). In the absence of temporal environmental clues, this pacemaker continues to measure time by an endogenous mechanism (clock), driving biochemical, physiological, and behavioral rhythms that reflect the natural period of the pacemaker oscillation. This endogenous period usually differs slightly from 24 hours (i.e., circadian). When mammals are maintained under a 24 hour light-dark (LD) cycle, the pacemaker becomes entrained such that the period of the pacemaker oscillation matches that of the LD cycle. Potentially entraining photic information is conveyed to the SCN via a direct retinal projection, the retinohypothalamic tract (RHT). RHT neurotransmission is thought to be mediated by the release of excitatory amino acids (EAA) in the SCN. In support of this hypothesis, recent experiments using nocturnal rodents have shown that EAA antagonists block the effects of light on pacemaker-driven behavioral rhythms, and attenuate light induced gene expression in SCN cells. An understanding of the neurochemical basis of the photic entrainment process would facilitate the development of pharmacological strategies for maintaining synchrony among shift workers in environments, such as the Space Station, which provide unreliable or conflicting temporal photic clues.

  16. Neurochemical Changes Associated with Stress-Induced Sleep Disturbance in Rats: In Vivo and In Vitro Measurements.

    PubMed

    Lee, Do-Wan; Chung, Seockhoon; Yoo, Hyun Ju; Kim, Su Jung; Woo, Chul-Woong; Kim, Sang-Tae; Lee, Dong-Hoon; Kim, Kyung Won; Kim, Jeong-Kon; Lee, Jin Seong; Choi, Choong Gon; Shim, Woo Hyun; Choi, Yoonseok; Woo, Dong-Cheol

    2016-01-01

    The goal of this study was to quantitatively assess the changes in the cerebral neurochemical profile and to identify those factors that contribute to the alteration of endogenous biomolecules when rats are subjected to stress-induced sleep disturbance. We exposed Sprague-Dawley rats (controls: n = 9; stress-induced sleep perturbation rats: n = 11) to a psychological stressor (cage exchange method) to achieve stress-induced sleep perturbation. In vivo magnetic resonance imaging assessments were carried out using a high-resolution 9.4 T system. For in vivo neurochemical analysis, a single voxel was localized in the right dorsal hippocampal region, and in vivo spectra were quantified for 17 cerebral neurochemical signals. Rats were sacrificed upon completion of the magnetic resonance spectroscopy protocol, and whole-brain tissue was harvested from twenty subjects. The dopamine and serotonin signals were obtained by performing in vitro liquid chromatography-tandem mass spectrometry on the harvested tissue. In the right dorsal hippocampal region, the gamma-aminobutyric-acid (GABA) and glutamine (Gln) concentrations were significantly higher in the sleep-perturbed rats than in the sham controls. The ratios of Gln/Glu (glutamate), Gln/tCr (total-creatine), and GABA/Glu were also significantly higher in the sleep-perturbed group, while serotonin concentrations were significantly lower in the sleep-perturbed rats. Pearson correlation results among individual rat data indicate that concentrations of dopamine (DA) and serotonin (5-HT) were significantly higher in SSP rats. A larger correlation coefficient was also observed for the SSP rats. Analysis of the correlation between the in vivo and in vitro signals indicated that the concentrations of Gln, 5-HT, and DA exhibited a significant negative correlation in the SSP rat data but not in that of control rats. The authors propose that the altered and correlated GABA, Gln, 5-HT, and DA concentrations/ratios could be considered

  17. Neurochemical Changes Associated with Stress-Induced Sleep Disturbance in Rats: In Vivo and In Vitro Measurements

    PubMed Central

    Lee, Do-Wan; Chung, Seockhoon; Yoo, Hyun Ju; Kim, Su Jung; Woo, Chul-Woong; Kim, Sang-Tae; Lee, Dong-Hoon; Kim, Kyung Won; Kim, Jeong-Kon; Lee, Jin Seong; Choi, Choong Gon; Shim, Woo Hyun; Choi, Yoonseok; Woo, Dong-Cheol

    2016-01-01

    The goal of this study was to quantitatively assess the changes in the cerebral neurochemical profile and to identify those factors that contribute to the alteration of endogenous biomolecules when rats are subjected to stress-induced sleep disturbance. We exposed Sprague-Dawley rats (controls: n = 9; stress-induced sleep perturbation rats: n = 11) to a psychological stressor (cage exchange method) to achieve stress-induced sleep perturbation. In vivo magnetic resonance imaging assessments were carried out using a high-resolution 9.4 T system. For in vivo neurochemical analysis, a single voxel was localized in the right dorsal hippocampal region, and in vivo spectra were quantified for 17 cerebral neurochemical signals. Rats were sacrificed upon completion of the magnetic resonance spectroscopy protocol, and whole-brain tissue was harvested from twenty subjects. The dopamine and serotonin signals were obtained by performing in vitro liquid chromatography-tandem mass spectrometry on the harvested tissue. In the right dorsal hippocampal region, the gamma-aminobutyric-acid (GABA) and glutamine (Gln) concentrations were significantly higher in the sleep-perturbed rats than in the sham controls. The ratios of Gln/Glu (glutamate), Gln/tCr (total-creatine), and GABA/Glu were also significantly higher in the sleep-perturbed group, while serotonin concentrations were significantly lower in the sleep-perturbed rats. Pearson correlation results among individual rat data indicate that concentrations of dopamine (DA) and serotonin (5-HT) were significantly higher in SSP rats. A larger correlation coefficient was also observed for the SSP rats. Analysis of the correlation between the in vivo and in vitro signals indicated that the concentrations of Gln, 5-HT, and DA exhibited a significant negative correlation in the SSP rat data but not in that of control rats. The authors propose that the altered and correlated GABA, Gln, 5-HT, and DA concentrations/ratios could be considered

  18. Caffeine triggers behavioral and neurochemical alterations in adolescent rats.

    PubMed

    Ardais, A P; Borges, M F; Rocha, A S; Sallaberry, C; Cunha, R A; Porciúncula, L O

    2014-06-13

    Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions. PMID:24726984

  19. Neurochemical Characterization of the Tree Shrew Dorsal Striatum

    PubMed Central

    Rice, Matthew W.; Roberts, Rosalinda C.; Melendez-Ferro, Miguel; Perez-Costas, Emma

    2011-01-01

    The striatum is a major component of the basal ganglia and is associated with motor and cognitive functions. Striatal pathologies have been linked to several disorders, including Huntington’s, Tourette’s syndrome, obsessive–compulsive disorders, and schizophrenia. For the study of these striatal pathologies different animal models have been used, including rodents and non-human primates. Rodents lack on morphological complexity (for example, the lack of well defined caudate and putamen nuclei), which makes it difficult to translate data to the human paradigm. Primates, and especially higher primates, are the closest model to humans, but there are ever-increasing restrictions to the use of these animals for research. In our search for a non-primate animal model with a striatum that anatomically (and perhaps functionally) can resemble that of humans, we turned our attention to the tree shrew. Evolutionary genetic studies have provided strong data supporting that the tree shrews (Scadentia) are one of the closest groups to primates, although their brain anatomy has only been studied in detail for specific brain areas. Morphologically, the tree shrew striatum resembles the primate striatum with the presence of an internal capsule separating the caudate and putamen, but little is known about its neurochemical composition. Here we analyzed the expression of calcium-binding proteins, the presence and distribution of the striosome and matrix compartments (by the use of calbindin, tyrosine hydroxylase, and acetylcholinesterase immunohistochemistry), and the GABAergic system by immunohistochemistry against glutamic acid decarboxylase and Golgi impregnation. In summary, our results show that when compared to primates, the tree shrew dorsal striatum presents striking similarities in the distribution of most of the markers studied, while presenting some marked divergences when compared to the rodent striatum. PMID:21887131

  20. Neurochemical Evidence of Potential Neurotoxicity After Prophylactic Cranial Irradiation

    SciTech Connect

    Kalm, Marie; Abel, Edvard; Wasling, Pontus; Nyman, Jan; Hietala, Max Albert; Bremell, Daniel; Hagberg, Lars; Elam, Mikael; Blennow, Kaj; Björk-Eriksson, Thomas; Zetterberg, Henrik

    2014-07-01

    Purpose: To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid β–related processes could characterize the neurochemical response to cranial radiation. Methods and Materials: Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation. Results: The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -β were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies. Conclusion: In conclusion, we were able to detect radiation therapy–induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid β metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.

  1. Quantification of 4-hydroxy-2-nonenal-protein adducts in the in vivo gastric digesta of mini-pigs using a GC-MS/MS method with accuracy profile validation.

    PubMed

    Delosière, Mylène; Santé-Lhoutellier, Véronique; Chantelauze, Céline; Durand, Denys; Thomas, Agnès; Joly, Charlotte; Pujos-Guillot, Estelle; Rémond, Didier; Comte, Blandine; Gladine, Cécile; Guy, Alexandre; Durand, Thierry; Laurentie, Michel; Dufour, Claire

    2016-08-10

    Hydroxyalkenals are lipid oxidation end-products resulting from the oxidation of polyunsaturated fatty acids (PUFA). This study aimed at quantifying the production of 4-hydroxy-2-nonenal-protein adducts (HNE-P) via Michael addition from n-6 PUFA oxidation in the gastric digesta of mini-pigs after the consumption of meat-based meals with different plant antioxidant contents. Using the accuracy profile procedure, we validated an extraction protocol for the quantification of HNE-P by GC-MS/MS in gastric contents. The formation of HNE-P in the gastric compartment was observed for the first time, with concentrations ranging from less than 0.52 to 1.33 nmol HNE-P per 500 mg digesta. Nevertheless, most gastric HNE-P levels were below the limit of quantification of 0.52 nmol HNE-P per 500 mg digesta. In this animal study, the protective effect of plant antioxidant sources on HNE-P formation was not evidenced contrasting with the results using TBARS as markers. PMID:27418316

  2. Chemical profiling and quantification of Gua-Lou-Gui-Zhi decoction by high performance liquid chromatography/quadrupole-time-of-flight mass spectrometry and ultra-performance liquid chromatography/triple quadrupole mass spectrometry.

    PubMed

    Xu, Wen; Huang, Mingqing; Li, Huang; Chen, Xianwen; Zhang, Yuqin; Liu, Jie; Xu, Wei; Chu, Kedan; Chen, Lidian

    2015-04-01

    Gua-Lou-Gui-Zhi decoction (GLGZD) is a classical formula of traditional Chinese medicine, which has been commonly used to treat dysfunction after stroke, epilepsy and spinal cord injury. In this study, a systematic method was established for chemical profiling and quantification analysis of the major constituents in GLGZD. For qualitative analysis, a method of high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (Q-TOF MS) was developed. 106 compounds, including monoterpene glycosides, galloyl glucoses, phenolic acids, flavonoids, gingerols and triterpene saponins were identified or tentatively presumed by comparison with reference standards or literature data. According to the qualitative results, a new quantitative analysis method of ultra-performance liquid chromatography/triple quadrupole mass spectrometry (QqQ-MS) was established. 24 representative compounds were simultaneously detected in 10 batches of GLGZD samples in 7.5 min. The calibration curves for all analytes showed good linearity (r>0.9959) within the test ranges. The LODs and the LOQs were less than 30.6 and 70.9 ng/mL, respectively. The RSDs of intra- and inter-day precision, repeatability and stability were below 3.64%, 4.85%, 4.84% and 3.87%, respectively. The overall recoveries ranged from 94.94% to 103.66%, with the RSDs within 5.12%. This study established a high sensitive and efficient method for the integrating quality control, including identification and quantification of Chinese medicinal preparation. PMID:25710597

  3. Stereochemistry of mephedrone neuropharmacology: enantiomer-specific behavioural and neurochemical effects in rats

    PubMed Central

    Gregg, Ryan A; Baumann, Michael H; Partilla, John S; Bonano, Julie S; Vouga, Alexandre; Tallarida, Christopher S; Velvadapu, Venkata; Smith, Garry R; Peet, M Melissa; Reitz, Allen B; Negus, S Stevens; Rawls, Scott M

    2015-01-01

    Background and Purpose Synthetic cathinones, commonly referred to as ‘bath salts’, are a group of amphetamine-like drugs gaining popularity worldwide. 4-Methylmethcathinone (mephedrone, MEPH) is the most commonly abused synthetic cathinone in the UK, and exerts its effects by acting as a substrate-type releaser at monoamine transporters. Similar to other cathinone-related compounds, MEPH has a chiral centre and exists stably as two enantiomers: R-mephedrone (R-MEPH) and S-mephedrone (S-MEPH). Experimental Approach Here, we provide the first investigation into the neurochemical and behavioural effects of R-MEPH and S-MEPH. We analysed both enantiomers in rat brain synaptosome neurotransmitter release assays and also investigated their effects on locomotor activity (e.g. ambulatory activity and repetitive movements), behavioural sensitization and reward. Key Results Both enantiomers displayed similar potency as substrates (i.e. releasers) at dopamine transporters, but R-MEPH was much less potent than S-MEPH as a substrate at 5-HT transporters. Locomotor activity was evaluated in acute and repeated administration paradigms, with R-MEPH producing greater repetitive movements than S-MEPH across multiple doses. After repeated drug exposure, only R-MEPH produced sensitization of repetitive movements. R-MEPH produced a conditioned place preference whereas S-MEPH did not. Lastly, R-MEPH and S-MEPH produced biphasic profiles in an assay of intracranial self-stimulation (ICSS), but R-MEPH produced greater ICSS facilitation than S-MEPH. Conclusions and Implications Our data are the first to demonstrate stereospecific effects of MEPH enantiomers and suggest that the predominant dopaminergic actions of R-MEPH (i.e. the lack of serotonergic actions) render this stereoisomer more stimulant-like when compared with S-MEPH. This hypothesis warrants further study. PMID:25255824

  4. Dystrophin quantification

    PubMed Central

    Anthony, Karen; Arechavala-Gomeza, Virginia; Taylor, Laura E.; Vulin, Adeline; Kaminoh, Yuuki; Torelli, Silvia; Feng, Lucy; Janghra, Narinder; Bonne, Gisèle; Beuvin, Maud; Barresi, Rita; Henderson, Matt; Laval, Steven; Lourbakos, Afrodite; Campion, Giles; Straub, Volker; Voit, Thomas; Sewry, Caroline A.; Morgan, Jennifer E.; Flanigan, Kevin M.

    2014-01-01

    Objective: We formed a multi-institution collaboration in order to compare dystrophin quantification methods, reach a consensus on the most reliable method, and report its biological significance in the context of clinical trials. Methods: Five laboratories with expertise in dystrophin quantification performed a data-driven comparative analysis of a single reference set of normal and dystrophinopathy muscle biopsies using quantitative immunohistochemistry and Western blotting. We developed standardized protocols and assessed inter- and intralaboratory variability over a wide range of dystrophin expression levels. Results: Results from the different laboratories were highly concordant with minimal inter- and intralaboratory variability, particularly with quantitative immunohistochemistry. There was a good level of agreement between data generated by immunohistochemistry and Western blotting, although immunohistochemistry was more sensitive. Furthermore, mean dystrophin levels determined by alternative quantitative immunohistochemistry methods were highly comparable. Conclusions: Considering the biological function of dystrophin at the sarcolemma, our data indicate that the combined use of quantitative immunohistochemistry and Western blotting are reliable biochemical outcome measures for Duchenne muscular dystrophy clinical trials, and that standardized protocols can be comparable between competent laboratories. The methodology validated in our study will facilitate the development of experimental therapies focused on dystrophin production and their regulatory approval. PMID:25355828

  5. Physiological, Morphological and Neurochemical Characterization of Neurons Modulated by Movement

    PubMed Central

    Dessem, Dean

    2011-01-01

    The role of individual neurons and their function in neuronal circuits is fundamental to understanding the neuronal mechanisms of sensory and motor functions. Most investigations of sensorimotor mechanisms rely on either examination of neurons while an animal is static1,2 or record extracellular neuronal activity during a movement.3,4 While these studies have provided the fundamental background for sensorimotor function, they either do not evaluate functional information which occurs during a movement or are limited in their ability to fully characterize the anatomy, physiology and neurochemical phenotype of the neuron. A technique is shown here which allows extensive characterization of individual neurons during an in vivo movement. This technique can be used not only to study primary afferent neurons but also to characterize motoneurons and sensorimotor interneurons. Initially the response of a single neuron is recorded using electrophysiological methods during various movements of the mandible followed by determination of the receptive field for the neuron. A neuronal tracer is then intracellularly injected into the neuron and the brain is processed so that the neuron can be visualized with light, electron or confocal microscopy (Fig. 1). The detailed morphology of the characterized neuron is then reconstructed so that neuronal morphology can be correlated with the physiological response of the neuron (Figs. 2,3). In this communication important key details and tips for successful implementation of this technique are provided. Valuable additional information can be determined for the neuron under study by combining this method with other techniques. Retrograde neuronal labeling can be used to determine neurons with which the labeled neuron synapses; thus allowing detailed determination of neuronal circuitry. Immunocytochemistry can be combined with this method to examine neurotransmitters within the labeled neuron and to determine the chemical phenotypes of

  6. Eating disorder and obsessive-compulsive disorder: neurochemical and phenomenological commonalities.

    PubMed Central

    Jarry, J L; Vaccarino, F J

    1996-01-01

    This paper explores a possible connection between neurochemistry and cognitions in eating disorders (ED). Cognitions play an important role in ED. However, a possible neurochemical origin of these cognitions has not been explored. Obsessive-compulsive disorder (OCD) is known as a disorder of thinking. Extensive neurochemical research conducted on this disorder indicates a connection between serotonin (5-HT) dysregulation and cognitions in OCD. This study used research done on OCD as a template to interpret the available research findings in ED and their possible meaning in terms of neurochemical origin of cognitions in ED. This paper suggests that the neurochemical and behavioral expression of both ED and OCD occur on a continuum. At one end of the continuum, ED and OCD are expressed through constrained behaviors of an avoidant quality. This pole is also characterized by high levels of serotonin markers. At the other end, both disorders are characterized by disinhibited approach behavior. This end of the continuum is characterized by low levels of 5-HT markers. It is suggested that these levels of 5-HT generate cognitions that may in turn promote specific behaviors. PMID:8580116

  7. Immunohistochemical screening for neurochemical markers in uremic patients on maintenance hemodialysis.

    PubMed

    Johansson, O; Hilliges, M; Han, S W; Ståhle-Bäckdahl, M; Hägermark, O

    1988-01-01

    The epidermis and dermis of 12 uremic patients on maintenance hemodialysis were investigated utilizing the indirect immunofluorescence technique as a tool to study the distribution of neurochemical markers, such as neuropeptides. No differences between controls and the patients were revealed. PMID:3078417

  8. Compulsive Behavior and Eye Blink in Prader-Willi Syndrome: Neurochemical Implications

    ERIC Educational Resources Information Center

    Holsen, Laura; Thompson, Travis

    2004-01-01

    Compulsive behavior in Prader-Willi syndrome is well-documented, though the neurochemical basis of these behaviors remains unknown. We studied a group of 16 people with Prader-Willi syndrome and a comparison group of 19 people with intellectual disability. Using eye-blink rate as an indirect measure of central nervous system dopamine, we found a…

  9. CHARACTERIZATION OF DISULFOTON-INDUCED BEHAVIORAL AND NEUROCHEMICAL EFFECTS FOLLOWING REPEATED EXPOSURE

    EPA Science Inventory

    These experiments examined the relationship between behavioral alterations and neurochemical changes in rats exposed repeatedly to disulfoton, an organophosphate cholinesterase inhibitor. Long-Evans rats were injected i.p. for 30 days with 0, 0.5,1, or 2 mg/kg of disulfoton in co...

  10. Examining Neurochemical Determinants of Inspection Time: Development of a Biological Model.

    ERIC Educational Resources Information Center

    Stough, Con; Thompson, J. C.; Bates, T. C.; Nathan, P. J.

    2001-01-01

    Describes results of several studies of the neurochemical determinants of inspection time (IT), outlining the significance of several studies in which performance on the IT task is measured before and after modulating key human central nervous system neurotransmitters and receptor systems. Results of these studies suggest a primarily cholinergic…

  11. Simultaneous quantification of eight bioactive secondary metabolites from Codonopsis ovata by validated high performance thin layer chromatography and their antioxidant profile.

    PubMed

    Dar, Alamgir A; Sangwan, Payare L; Khan, Imran; Gupta, Nidhi; Qaudri, Afnan; Tasduq, Sheikh A; Kitchlu, Surinder; Kumar, Anil; Koul, Surrinder

    2014-11-01

    Chemical investigation of Codonopsis ovata resulted in the isolation and identification of β-sitosterol-3-O-glycoside, luteolin, apigenin, gentiacaulein, swertiaperenine, β-sitosterol, taraxeryl-3-acetate, and 3β-acetoxyoleanane-12-one. A rapid, precise, sensitive and validated HPTLC method for simultaneous quantification of these natural products (NPs) was developed on silica-gel 60F254 plate using ternary solvent system, n-hexane:ethyl acetate:formic acid (10.5:3.5:0.43, v/v/v). Markers were quantified after post chromatographic derivatization with cerric ammonium sulfate reagent. The method was validated for accuracy, precision, LOD, LOQ and all calibration curves showed a good linear relationship (r>0.9924) within test range. Precision was evaluated by intra- and inter-day tests with RSDs <2.59%, accuracy validation recovery 92.43-99.50% with RSDs <1.00%. Apigenin was found major component (natural abundance: 1.103%) and β-sitosterol the least (0.0263%). The NPs displayed antioxidant activity with luteolin exhibiting maximum effect at 1μg/mL concentration (75.9% for DPPH and 43.7% for ABTS) and others at 10 and 25μg/mL, suggesting thereby their apparent potential use for the prevention of free radical induced diseases or as an additive element to food and pharmaceutical industry. PMID:25194343

  12. Ultrastructural and neurochemical architecture of the pituitary neural lobe of Xenopus laevis.

    PubMed

    van Wijk, Diane C W A; Meijer, Kari H; Roubos, Eric W

    2010-09-01

    The melanotrope cell in the amphibian pituitary pars intermedia is a model to study fundamental aspects of neuroendocrine integration. They release alpha-melanophore-stimulating hormone (alphaMSH), under the control of a large number of neurochemical signals derived from various brain centers. In Xenopus laevis, most of these signals are produced in the hypothalamic magnocellular nucleus (Mg) and are probably released from neurohemal axon terminals in the pituitary neural lobe, to stimulate alphaMSH-release, causing skin darkening. The presence in the neural lobe of at least eight stimulatory factors implicated in melanotrope cell control has led us to investigate the ultrastructural architecture of this neurohemal organ, with particular attention to the diversity of neurohemal axon terminals and their neurochemical contents. Using regular electron microscopy, we here distinguish six types of neurohemal axon terminal, on the basis of the size, shape and electron-density of their secretory granule contents. Subsequently, we have identified the neurochemical contents of these terminal types by immuno-electron microscopy and antisera raised against not only the 'classical' neurohormones vasotocin and mesotocin but also brain-derived neurotrophic factor, cocaine- and amphetamine-regulated transcript peptide, corticotropin-releasing factor, metenkephalin, pituitary adenylyl cyclase-activating polypeptide, thyrotropin-releasing hormone and urocortin-1. This has revealed that each terminal type possesses a unique set of neurochemical messengers, containing at least four, but in some cases up to eight messengers. These results reveal the potential of the Mg/neural lobe system to release a wide variety of neurochemical messengers in a partly co-ordinated and partly differential way to control melanotrope cell activity as well as ion and water balance regulatory organs, in response to various, continuously changing, environmental stimuli. PMID:20067800

  13. Quantification of ammonia oxidation rates and the distribution of ammonia-oxidizing Archaea and Bacteria in marine sediment depth profiles from Catalina Island, California

    PubMed Central

    Beman, J. M.; Bertics, Victoria J.; Braunschweiler, Thomas; Wilson, Jesse M.

    2012-01-01

    Microbial communities present in marine sediments play a central role in nitrogen biogeochemistry at local to global scales. Along the oxidation–reduction gradients present in sediment profiles, multiple nitrogen cycling processes (such as nitrification, denitrification, nitrogen fixation, and anaerobic ammonium oxidation) are active and actively coupled to one another – yet the microbial communities responsible for these transformations and the rates at which they occur are still poorly understood. We report pore water geochemical (O2, NH4+, and NO3−) profiles, quantitative profiles of archaeal and bacterial amoA genes, and ammonia oxidation rate measurements, from bioturbated marine sediments of Catalina Island, California. Across triplicate sediment cores collected offshore at Bird Rock (BR) and within Catalina Harbor (CH), oxygen penetration (0.24–0.5 cm depth) and the abundance of amoA genes (up to 9.30 × 107 genes g–1) varied with depth and between cores. Bacterial amoA genes were consistently present at depths of up to 10 cm, and archaeal amoA was readily detected in BR cores, and CH cores from 2008, but not 2007. Although detection of DNA is not necessarily indicative of active growth and metabolism, ammonia oxidation rate measurements made in 2008 (using isotope tracer) demonstrated the production of oxidized nitrogen at depths where amoA was present. Rates varied with depth and between cores, but indicate that active ammonia oxidation occurs at up to 10 cm depth in bioturbated CH sediments, where it may be carried out by either or both ammonia-oxidizing archaea and bacteria. PMID:22837756

  14. The neurochemical profile of the hippocampus in isoflurane-treated and unanesthetized rat pups

    PubMed Central

    Akulov, Andrey E.

    2015-01-01

    In vivo study of cerebral metabolism in neonatal animals by high-resolution magnetic resonance spectroscopy (MRS) is an important tool for deciphering the developmental origins of adult diseases. Up to date, all in vivo spectrum acquisition procedures have been performed in neonatal rodents under anesthesia. However, it is still unknown if the inhaled anesthetic isoflurane, which is commonly used in magnetic resonance imaging studies, could affect metabolite levels in the brain of neonatal rats. Moreover, the unanesthetized MRS preparation that uses neonatal rodent pups is still lacking. Here, a novel restraint protocol was developed for neonatal rats in accordance with the European Directive 2010/63/EU. This protocol shares the same gradation of severity as the protocol for non-invasive magnetic resonance imaging of animals with appropriate sedation or anesthesia. Such immobilization of neonatal rats without anesthesia can be implemented for MRS studies when an interaction between anesthetic and target drugs is expected. Short-term isoflurane treatment did not affect the levels of key metabolites in the hippocampi of anesthetized pups and, in contrast to juvenile and adult rodents, it is suitable for MRS studies in neonatal rats when the interaction between anesthetic and target drugs is not expected. PMID:27486369

  15. Prenatal Restraint Stress Generates Two Distinct Behavioral and Neurochemical Profiles in Male and Female Rats

    PubMed Central

    Casolini, Paola; Cinque, Carlo; Alemà, Giovanni Sebastiano; Morley-Fletcher, Sara; Chiodi, Valentina; Spagnoli, Luigi Giusto; Gradini, Roberto; Catalani, Assia; Nicoletti, Ferdinando; Maccari, Stefania

    2008-01-01

    Prenatal Restraint Stress (PRS) in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy) on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS (“PRS rats”) showed increased anxiety-like behavior in the elevated plus maze (EPM), a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females. PMID:18478112

  16. Specific targeted quantification combined with non-targeted metabolite profiling for quality evaluation of Gastrodia elata tubers from different geographical origins and cultivars.

    PubMed

    Ma, Xiao-Dong; Fan, Ya-Xi; Jin, Can-Can; Wang, Fei; Xin, Gui-Zhong; Li, Ping; Li, Hui-Jun

    2016-06-10

    Gastrodia elata tuber (GET) has been widely used as a famous herbal medicine in China and other East Asian countries. In this work, we developed a comprehensive strategy integrating targeted and non-targeted analyses for quality evaluation and discrimination of GET from different geographical origins and cultivars. Firstly, 43 batches of GET samples of five cultivars from three regions in China were efficiently quantified by a "single standard to determine multi-components" (SSDMC) method. Six marker compounds were simultaneously determined within 11min using gastrodin as the internal standard. It showed that samples from different regions and cultivars could not be differentiated by the contents of six marker compounds. Secondly, a non-targeted metabolite profiling analysis was performed by ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Samples from different geographical origins and cultivars were clearly discriminated by principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). 147 discriminant ions contributing to the group separation were selected from 1194 aligned variables. Furthermore, based on the relative intensities of discriminant ions, support vector machines (SVM) was employed to predict the geographical origins of GET. The obtained SVM model showed excellent prediction performance with an average prediction accuracy of 100%. These results demonstrated that the UHPLC-QTOF/MS-based non-targeted metabolite profiling analysis, as a vital supplement to targeted analysis, can be used to discriminate the geographical origins and cultivars of GET. PMID:27157425

  17. Neurochemical changes in Huntington R6/2 mouse striatum detected by in vivo 1H NMR spectroscopy

    PubMed Central

    Tkac, Ivan; Dubinsky, Janet M.; Keene, C. Dirk; Gruetter, Rolf; Low, Walter C.

    2009-01-01

    The neurochemical profile of the striatum of R6/2 Huntington's disease mice was examined at different stages of pathogenesis using in vivo 1H NMR spectroscopy at 9.4 T. Between 8 and 12 weeks, R6/2 mice exhibited distinct changes in a set of 17 quantifiable metabolites compared with littermate controls. Concentrations of creatine, glycerophosphorylcholine, glutamine and glutathione increased and N-acetylaspartate decreased at 8 weeks. By 12 weeks, concentrations of phosphocreatine, taurine, ascorbate, glutamate, and myo-inositol increased and phophorylethanolamine decreased. These metabolic changes probably reflected multiple processes, including compensatory processes to maintain homeostasis, active at different stages in the development of HD. The observed changes in concentrations suggested impairment of neurotransmission, neuronal integrity and energy demand, and increased membrane breakdown, gliosis, and osmotic and oxidative stress. Comparisons between metabolite concentrations from individual animals clearly distinguished HD transgenics from non-diseased littermates and identified possible markers of disease progression. Metabolic changes in R6/2 striata were distinctly different from those observed previously in the quinolinic acid and 3NP models of HD. Longitudinal monitoring of changes in these metabolites may provide quantifiable measures of disease progression and treatment effects in both mouse models of HD and patients. PMID:17217418

  18. The neurochemical effects of anxiolytic drugs are dependent on rearing conditions in Fawn-Hooded rats.

    PubMed

    Lodge, Daniel J; Lawrence, Andrew J

    2003-05-01

    There is a vast literature examining the neurochemical effects of anxiolytics throughout the rat brain; however, although the behavioural actions of anxiolytic drugs are routinely assessed in animal models of anxiety, the majority of neurochemical studies have been performed in rats with relatively 'normal' behavioural phenotypes. Since there is significant evidence that an anxious phenotype is associated with numerous neurochemical alterations, it is feasible that the central effects of anxiolytics may vary depending on the underlying behavioural state (and corresponding neuropathology) of the experimental animal. For this reason, the aim of the present study was to examine the effect of chronic anxiolytic drug administration on the central CCK and dopamine systems in anxious (isolated from weaning) and nonanxious (group-housed) Fawn-Hooded (FH) rats. It is important to note that these studies were performed in rats with continued access to ethanol, which may affect the responses to anxiolytic treatment. Chronic anxiolytic treatment with the selective CCK-B (CCK(2)) receptor antagonist, Ci-988 (0.3 mg/kg/day ip) or diazepam (2 mg/kg/day ip), induced numerous effects throughout the central nervous system (CNS), with Ci-988 inducing significant changes in the density of dopamine D(2) receptors, and diazepam producing marked changes in both dopamine D(2) and CCK-B receptor binding density as well as preproCCK mRNA expression. Interestingly, the neurochemical effects of these anxiolytic drugs varied significantly depending on the rearing conditions of the rats, demonstrating the importance of using adequate animal models when correlating the behavioural and central effects of drugs acting throughout the CNS. PMID:12691780

  19. Efficient quantification of the health-relevant anthocyanin and phenolic acid profiles in commercial cultivars and breeding selections of blueberries ( Vaccinium spp.).

    PubMed

    Yousef, Gad G; Brown, Allan F; Funakoshi, Yayoi; Mbeunkui, Flaubert; Grace, Mary H; Ballington, James R; Loraine, Ann; Lila, Mary A

    2013-05-22

    Anthocyanins and phenolic acids are major secondary metabolites in blueberry with important implications for human health maintenance. An improved protocol was developed for the accurate, efficient, and rapid comparative screening for large blueberry sample sets. Triplicates of six commercial cultivars and four breeding selections were analyzed using the new method. The compound recoveries ranged from 94.2 to 97.5 ± 5.3% when samples were spiked with commercial standards prior to extraction. Eighteen anthocyanins and 4 phenolic acids were quantified in frozen and freeze-dried fruits. Large variations for individual and total anthocyanins, ranging from 201.4 to 402.8 mg/100 g, were assayed in frozen fruits. The total phenolic acid content ranged from 23.6 to 61.7 mg/100 g in frozen fruits. Across all genotypes, freeze-drying resulted in minor reductions in anthocyanin concentration (3.9%) compared to anthocyanins in frozen fruits. However, phenolic acids increased by an average of 1.9-fold (±0.3) in the freeze-dried fruit. Different genotypes frequently had comparable overall levels of total anthocyanins and phenolic acids, but differed dramatically in individual profiles of compounds. Three of the genotypes contained markedly higher concentrations of delphinidin 3-O-glucoside, cyanidin 3-O-glucoside, and malvidin 3-O-glucoside, which have previously been implicated as bioactive principles in this fruit. The implications of these findings for human health benefits are discussed. PMID:23635035

  20. Dynamic of neurochemical alterations in striatum, hippocampus and cortex after the 6-OHDA mesostriatal lesion.

    PubMed

    Zhang, Sheng; Gui, Xue-Hong; Xue, Zhong-Feng; Huang, Li-Ping; Fang, Ruo-Ming; Ke, Xue-Hong; Li, Ling; Fang, Yong-Qi

    2014-08-01

    Immediate neurochemical alterations produced by 6-OHDA could explain the general toxic pattern in the central nervous system. However, no evidences describe the effects of 6-OHDA on early changes of neurotransmitters in rats' striatum, cortex and hippocampus. In our study, unilateral 6-OHDA injection into medial forebrain bundle (MFB) was used in rats, then five neurotransmitters were analyzed at 3, 6, 12, 24, 48 and 72 h, respectively. Results showed that 6-OHDA injection caused a sharp decline of striatal dopamine (DA) levels in the first 12h followed by a further reduction between 12 and 48 h. However, striatal levels of homovanillic acid (HVA) were stable in the first 12h and showed a marked reduction between 12 and 24h. Striatal levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) decreased linearly for 72 h, whereas levels of norepinephrine (NE) showed a slight reduction in the first 48 h, and returned back to normal afterwards. Striatal HVA/DA ratio increased significantly in the first 12h, but 5-HIAA/5-HT ratio showed a sharp increase between 12 and 72 h. Besides, neurochemical alterations were also found in hippocampus and cortex, and the correlations of neurotransmitters were analyzed. Our study indicated that NE system had little influence in the early phase of 6-OHDA injection, moreover, early neurochemical alterations were involved with striatum, hippocampus and cortex. PMID:24814667

  1. A Diamond-Based Electrode for Detection of Neurochemicals in the Human Brain

    PubMed Central

    Bennet, Kevin E.; Tomshine, Jonathan R.; Min, Hoon-Ki; Manciu, Felicia S.; Marsh, Michael P.; Paek, Seungleal B.; Settell, Megan L.; Nicolai, Evan N.; Blaha, Charles D.; Kouzani, Abbas Z.; Chang, Su-Youne; Lee, Kendall H.

    2016-01-01

    Deep brain stimulation (DBS), a surgical technique to treat certain neurologic and psychiatric conditions, relies on pre-determined stimulation parameters in an open-loop configuration. The major advancement in DBS devices is a closed-loop system that uses neurophysiologic feedback to dynamically adjust stimulation frequency and amplitude. Stimulation-driven neurochemical release can be measured by fast-scan cyclic voltammetry (FSCV), but existing FSCV electrodes rely on carbon fiber, which degrades quickly during use and is therefore unsuitable for chronic neurochemical recording. To address this issue, we developed durable, synthetic boron-doped diamond-based electrodes capable of measuring neurochemical release in humans. Compared to carbon fiber electrodes, they were more than two orders-of-magnitude more physically-robust and demonstrated longevity in vitro without deterioration. Applied for the first time in humans, diamond electrode recordings from thalamic targets in patients (n = 4) undergoing DBS for tremor produced signals consistent with adenosine release at a sensitivity comparable to carbon fiber electrodes. (Clinical trials # NCT01705301). PMID:27014033

  2. A Diamond-Based Electrode for Detection of Neurochemicals in the Human Brain.

    PubMed

    Bennet, Kevin E; Tomshine, Jonathan R; Min, Hoon-Ki; Manciu, Felicia S; Marsh, Michael P; Paek, Seungleal B; Settell, Megan L; Nicolai, Evan N; Blaha, Charles D; Kouzani, Abbas Z; Chang, Su-Youne; Lee, Kendall H

    2016-01-01

    Deep brain stimulation (DBS), a surgical technique to treat certain neurologic and psychiatric conditions, relies on pre-determined stimulation parameters in an open-loop configuration. The major advancement in DBS devices is a closed-loop system that uses neurophysiologic feedback to dynamically adjust stimulation frequency and amplitude. Stimulation-driven neurochemical release can be measured by fast-scan cyclic voltammetry (FSCV), but existing FSCV electrodes rely on carbon fiber, which degrades quickly during use and is therefore unsuitable for chronic neurochemical recording. To address this issue, we developed durable, synthetic boron-doped diamond-based electrodes capable of measuring neurochemical release in humans. Compared to carbon fiber electrodes, they were more than two orders-of-magnitude more physically-robust and demonstrated longevity in vitro without deterioration. Applied for the first time in humans, diamond electrode recordings from thalamic targets in patients (n = 4) undergoing DBS for tremor produced signals consistent with adenosine release at a sensitivity comparable to carbon fiber electrodes. (Clinical trials # NCT01705301). PMID:27014033

  3. Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids

    PubMed Central

    Kohli, Divyanshoo R.; Li, Yunfang; Khasabov, Sergey G.; Gupta, Pankaj; Kehl, Lois J.; Ericson, Marna E.; Nguyen, Julia; Gupta, Vinita; Hebbel, Robert P.; Simone, Donald A.

    2010-01-01

    Sickle cell disease causes severe pain. We examined pain-related behaviors, correlative neurochemical changes, and analgesic effects of morphine and cannabinoids in transgenic mice expressing human sickle hemoglobin (HbS). Paw withdrawal threshold and withdrawal latency (to mechanical and thermal stimuli, respectively) and grip force were lower in homozygous and hemizygous Berkley mice (BERK and hBERK1, respectively) compared with control mice expressing human hemoglobin A (HbA-BERK), indicating deep/musculoskeletal and cutaneous hyperalgesia. Peripheral nerves and blood vessels were structurally altered in BERK and hBERK1 skin, with decreased expression of μ opioid receptor and increased calcitonin gene-related peptide and substance P immunoreactivity. Activators of neuropathic and inflammatory pain (p38 mitogen-activated protein kinase, STAT3, and mitogen-activated protein kinase/extracellular signal-regulated kinase) showed increased phosphorylation, with accompanying increase in COX-2, interleukin-6, and Toll-like receptor 4 in the spinal cord of hBERK1 compared with HbA-BERK. These neurochemical changes in the periphery and spinal cord may contribute to hyperalgesia in mice expressing HbS. In BERK and hBERK1, hyperalgesia was markedly attenuated by morphine and cannabinoid receptor agonist CP 55940. We show that mice expressing HbS exhibit characteristics of pain observed in sickle cell disease patients, and neurochemical changes suggestive of nociceptor and glial activation. Importantly, cannabinoids attenuate pain in mice expressing HbS. PMID:20304807

  4. Soil organic carbon stocks quantification in Mediterranean natural areas, a trade-off between entire soil profiles and soil control sections

    NASA Astrophysics Data System (ADS)

    Parras-Alcántara, Luis; Lozano-García, Beatriz; Brevik, Eric. C.; Cerdá, Artemi

    2015-04-01

    Soil organic carbon (SOC) is extremely important in the global carbon (C) cycle; also, SOC is a soil property subject to changes, inasmuch as SOC is highly variable in space and time. The scientific community is researching the fate of the organic carbon in the ecosystems and this is why there is a blooming interest on this topic (Oliveira et al., 2014; Kukal et al., 2015). Soil organic matter play a key role in the Soil System (Fernández-Romero et al., 2014; Parras-Alcántara and Lozano García, 2014; Lozano-García and Parras-Alcántara; Parras-Alcántara et al., 2015).Globally it is known that soil C sequestration is a strategy to mitigate climate change. Over time, some researchers have analyzed entire soil profiles (ESP) by pedogenetic horizons and other researchers have analyzed soil control sections (SCS) (edaphic controls to different thickness), and in each case the benefits of the methodology established was justified. However, very few studies compare both methods (ESP versus SCS). This research sought to analyze the SOC stock (SOCS) variability using both methods (ESP and SCS) in The Despeñaperros Natural Park, a nature reserve that consists of a 76.8 km2 forested area in southern Spain. The park is in a Mediterranean environment and is a natural area (free of human disturbance). Thirty-four sampling points were selected in the study zone. Each sampling point was analyzed in two different ways, as ESP (by horizons) and as SCS with different depth increments (0-25, 25-50, 50-75 and 75-100 cm). The major goal of this research was to study the SOCS variability at regional scale. The studied soils were classified as Phaeozems, Cambisols, Regosols and Leptosols. The total SOCS in the Despeñaperros Natural Park was over 28.2% greater when SCS were used compared to ESP, ranging from 0.8144 Tg C to 0.6353 Tg C respectively (1 Tg = 10E12 g). However, when the top soil (surface horizon and superficial section control) was analyzed, this difference increased to

  5. Cocaine-induced endocannabinoid release modulates behavioral and neurochemical sensitization in mice.

    PubMed

    Mereu, Maddalena; Tronci, Valeria; Chun, Lauren E; Thomas, Alexandra M; Green, Jennifer L; Katz, Jonathan L; Tanda, Gianluigi

    2015-01-01

    The endocannabinoid system has been implicated in the development of synaptic plasticity induced by several drugs abused by humans, including cocaine. However, there remains some debate about the involvement of cannabinoid receptors/ligands in cocaine-induced plasticity and corresponding behavioral actions. Here, we show that a single cocaine injection in Swiss-Webster mice produces behavioral and neurochemical alterations that are under the control of the endocannabinoid system. This plasticity may be the initial basis for changes in brain processes leading from recreational use of cocaine to its abuse and ultimately to dependence. Locomotor activity was monitored with photobeam cell detectors, and accumbens shell/core microdialysate dopamine levels were monitored by high-performance liquid chromatography with electrochemical detection. Development of single-trial cocaine-induced behavioral sensitization, measured as increased distance traveled in sensitized mice compared to control mice, was paralleled by a larger stimulation of extracellular dopamine levels in the core but not the shell of the nucleus accumbens. Both the behavioral and neurochemical effects were reversed by CB1 receptor blockade produced by rimonabant pre-treatments. Further, both behavioral and neurochemical cocaine sensitization were facilitated by pharmacological blockade of endocannabinoid metabolism, achieved by inhibiting the fatty acid amide hydrolase enzyme. In conclusion, our results suggest that a single unconditioned exposure to cocaine produces sensitization through neuronal alterations that require regionally specific release of endocannabinoids. Further, the present results suggest that endocannabinoids play a primary role from the earliest stage of cocaine use, mediating the inception of long-term brain-adaptive responses, shaping central pathways and likely increasing vulnerability to stimulant abuse disorders. PMID:23910902

  6. Effect of chronic psychogenic stress on some behavioral and neurochemical characteristics of rats

    SciTech Connect

    Danchev, N.D.; Rozhanets, V.V.; Val'dman, A.V.

    1986-06-01

    This paper studies the behavioral, somatic, and certain neurochemical parameters in rats under conditions of unavoidable chronic stress, according to Hecht et al. in a situation of possible avoidance, with the same total number of aversive stimuli. Specific binding of tritium-flunitrazepam and tritium-dihydroalprenolol was studied. The dissociatin constant and the maximal concentration of ligand-receptor complexes were determined in Scatchard plots by means of an HP-33E computer. The protein concentration in the samples was determined by Peterson's method.

  7. Behavioral and neurochemical characterization of maternal care effects on juvenile Sprague-Dawley rats.

    PubMed

    Masís-Calvo, Marianela; Sequeira-Cordero, Andrey; Mora-Gallegos, Andrea; Fornaguera-Trías, Jaime

    2013-06-13

    Maternal care represents a major constituent of early life environment and has the potential to modulate critical neurobehavioral responses to stress. The aim of the present study was to determine the effects of naturally occurring variations in maternal care on behavioral and neurochemical responses of juvenile Sprague-Dawley rats. A group of dams were classified based on their licking behavior in high and low licking-grooming mothers. Afterwards, the male offspring was tested in a series of behavioral tests: open field test (OFT), elevated plus maze (EPM) and forced swimming test (FST). Additionally, monoamine concentrations were determined post-mortem in three brain regions: hippocampus, ventral striatum and prefrontal cortex. Our findings suggest that maternal care variations have an effect on several anxiety-related behaviors in OFT and EPM but not in depression-like behaviors in FST. Such behavioral differences could be related to an increased DOPAC concentration and 5-HT turnover in prefrontal cortex. These evidences suggest that natural variations in maternal care modified some behavioral and neurochemical parameters related with anxiety and stress in this strain. PMID:23711565

  8. [Neurochemical mechanisms of depression-like behavior in WAG/Rij rats].

    PubMed

    Sarkisova, K Iu; Kulikov, M A; Kudrin, V S; Narkevich, V B; Midzianovskaia, I S; Biriukova, L M; Folomkina, A A; Basian, A S

    2013-01-01

    Behavior in the light-dark choice, open-field, sucrose consumption/preference and forced swimming tests, monoamines and their metabolites level in 6 brain structures (prefrontal cortex, nucleus accumbens, striatum, hypothalamus, hippocampus, amygdala), and density of D2-like dopamine receptors in 21 brain regions were studied in WAG/Rij and Wistar rats. WAG/Rij rats exhibited symptoms of depression-like behavior such as increased immobility in the forced swim test and decreased sucrose consumption/preference (anhedonia). Substantial changes in behavior indicating increased anxiety in WAG/Rij rats were not revealed. Neurochemical abnormalities suggesting hypofunction of the mesolimbic dopaminergic brain system were found in "depressive" WAG/Rij rats compared with "normal" Wistar rats: decreased levels of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine in the nucleus accumbens, and increased density of D2-like dopamine receptors in the nucleus accumbens and ventral tegmental area. Reduced levels of dopamine were also observed in the prefrontal cortex and striatum. No substantial changes in the content of monoamines and their metabolites have been revealed in the hypothalamus, hippocampus and amygdala as well as in the content ofserotonin and its metabolite 5-hydroxyindolacetic acid in all studied brain structures with the exception of increased level ofserotonin in the amygdala. Results suggest that hypofunction of the mesolimbic dopaminergic brain system (nucleus accumbens) is a neurochemical mechanism of depression-like behavior in WAG/Rij rats. PMID:24450162

  9. Neurochemical correlates of cyanide-induced hypoxic neuronal damage in vitro.

    PubMed

    Sher, P K

    1988-02-01

    Neuronal cortical cell cultures obtained from fetal mice were subjected to an hypoxic insult produced by sodium cyanide (1 mM) for 24 h. Neurochemical assays were performed 13-14 days after plating on intact cells in situ to determine if there was a specific pattern of cellular dysfunction in addition to morphologic change. Ro5-4864-displaceable benzodiazepine (BDZ) binding and high-affinity [3H] beta-alanine uptake were not reduced when compared to control values. However, specific and clonazepam-displaceable BDZ binding (81 +/- 4% and 50 +/- 9% of control values, respectively), high-affinity [3H]GABA uptake (75 +/- 2%), and choline acetyltransferase activity (82 +/- 2%) were significantly lower. When the data were expressed in terms of protein content, high-affinity [3H] beta-alanine uptake was significantly increased in cyanide-exposed and magnesium-treated cultures (123 +/- 5% and 117 +/- 3%, respectively) as was R05-4864-displaceable BDZ binding (152 +/- 14%), consistent with stimulation of nonneuronal BDZ binding and increased glial neurotransmitter uptake. Moreover, pretreatment of the cultures with magnesium effectively prevented both the morphologic and neurochemical evidence of hypoxic injury. These data lend further support to the notion that the release of excitatory neurotransmitters may mediate neurotoxicity in developing brain. PMID:2834659

  10. The effect of spinal cord injury on the neurochemical properties of vagal sensory neurons

    PubMed Central

    Herrity, April N.; Petruska, Jeffrey C.; Stirling, David P.; Rau, Kristofer K.

    2015-01-01

    The vagus nerve is composed primarily of nonmyelinated sensory neurons whose cell bodies are located in the nodose ganglion (NG). The vagus has widespread projections that supply most visceral organs, including the bladder. Because of its nonspinal route, the vagus nerve itself is not directly damaged from spinal cord injury (SCI). Because most viscera, including bladder, are dually innervated by spinal and vagal sensory neurons, an impact of SCI on the sensory component of vagal circuitry may contribute to post-SCI visceral pathologies. To determine whether SCI, in male Wistar rats, might impact neurochemical characteristics of NG neurons, immunohistochemical assessments were performed for P2X3 receptor expression, isolectin B4 (IB4) binding, and substance P expression, three known injury-responsive markers in sensory neuronal subpopulations. In addition to examining the overall population of NG neurons, those innervating the urinary bladder also were assessed separately. All three of the molecular markers were represented in the NG from noninjured animals, with the majority of the neurons binding IB4. In the chronically injured rats, there was a significant increase in the number of NG neurons expressing P2X3 and a significant decrease in the number binding IB4 compared with noninjured animals, a finding that held true also for the bladder-innervating population. Overall, these results indicate that vagal afferents, including those innervating the bladder, display neurochemical plasticity post-SCI that may have implications for visceral homeostatic mechanisms and nociceptive signaling. PMID:25855310

  11. The effect of spinal cord injury on the neurochemical properties of vagal sensory neurons.

    PubMed

    Herrity, April N; Petruska, Jeffrey C; Stirling, David P; Rau, Kristofer K; Hubscher, Charles H

    2015-06-15

    The vagus nerve is composed primarily of nonmyelinated sensory neurons whose cell bodies are located in the nodose ganglion (NG). The vagus has widespread projections that supply most visceral organs, including the bladder. Because of its nonspinal route, the vagus nerve itself is not directly damaged from spinal cord injury (SCI). Because most viscera, including bladder, are dually innervated by spinal and vagal sensory neurons, an impact of SCI on the sensory component of vagal circuitry may contribute to post-SCI visceral pathologies. To determine whether SCI, in male Wistar rats, might impact neurochemical characteristics of NG neurons, immunohistochemical assessments were performed for P2X3 receptor expression, isolectin B4 (IB4) binding, and substance P expression, three known injury-responsive markers in sensory neuronal subpopulations. In addition to examining the overall population of NG neurons, those innervating the urinary bladder also were assessed separately. All three of the molecular markers were represented in the NG from noninjured animals, with the majority of the neurons binding IB4. In the chronically injured rats, there was a significant increase in the number of NG neurons expressing P2X3 and a significant decrease in the number binding IB4 compared with noninjured animals, a finding that held true also for the bladder-innervating population. Overall, these results indicate that vagal afferents, including those innervating the bladder, display neurochemical plasticity post-SCI that may have implications for visceral homeostatic mechanisms and nociceptive signaling. PMID:25855310

  12. Age-related changes in neurochemical components and retinal projections of rat intergeniculate leaflet.

    PubMed

    Fiuza, Felipe P; Silva, Kayo D A; Pessoa, Renata A; Pontes, André L B; Cavalcanti, Rodolfo L P; Pires, Raquel S; Soares, Joacil G; Nascimento Júnior, Expedito S; Costa, Miriam S M O; Engelberth, Rovena C G J; Cavalcante, Jeferson S

    2016-02-01

    Aging leads to several anatomical and functional deficits in circadian timing system. In previous works, we observed morphological alterations with age in hypothalamic suprachiasmatic nuclei, one central component of this system. However, there are few data regarding aging effects on other central components of this system, such as thalamic intergeniculate leaflet (IGL). In this context, we studied possible age-related alterations in neurochemical components and retinal projections of rat IGL. For this goal, young (3 months), adult (13 months), and aged (23 months) Wistar rats were submitted to an intraocular injection of neural tracer, cholera toxin subunit b (CTb), 5 days before a tissue fixation process by paraformaldehyde perfusion. Optical density measurements and cell count were performed at digital pictures of brain tissue slices processed by immunostaining for glutamic acid decarboxylase (GAD), enkephalin (ENK), neuropeptide Y (NPY) and CTb, characteristic markers of IGL and its retinal terminals. We found a significant age-related loss in NPY immunoreactive neurons, but not in immunoreactivity to GAD and ENK. We also found a decline of retinal projections to IGL with age. We conclude aging impairs both a photic environmental clue afferent to IGL and a neurochemical expression which has an important modulatory circadian function, providing strong anatomical correlates to functional deficits of the aged biological clock. PMID:26718202

  13. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake.

    PubMed

    Avena, Nicole M; Rada, Pedro; Hoebel, Bartley G

    2008-01-01

    [Avena, N.M., Rada, P., Hoebel B.G., 2007. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neuroscience and Biobehavioral Reviews XX(X), XXX-XXX]. The experimental question is whether or not sugar can be a substance of abuse and lead to a natural form of addiction. "Food addiction" seems plausible because brain pathways that evolved to respond to natural rewards are also activated by addictive drugs. Sugar is noteworthy as a substance that releases opioids and dopamine and thus might be expected to have addictive potential. This review summarizes evidence of sugar dependence in an animal model. Four components of addiction are analyzed. "Bingeing," "withdrawal," "craving" and "cross-sensitization" are each given operational definitions and demonstrated behaviorally with sugar bingeing as the reinforcer. These behaviors are then related to neurochemical changes in the brain that also occur with addictive drugs. Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin mRNA expression and dopamine and acetylcholine release in the nucleus accumbens. The evidence supports the hypothesis that under certain circumstances rats can become sugar dependent. This may translate to some human conditions as suggested by the literature on eating disorders and obesity. PMID:17617461

  14. Breathing Disorders in Rett Syndrome: Progressive Neurochemical Dysfunction in the Respiratory Network after Birth

    PubMed Central

    Katz, David M.; Dutschmann, Mathias; Ramirez, Jan-Marino; Hilaire, Gérard

    2009-01-01

    Disorders of respiratory control are a prominent feature of Rett syndrome (RTT), a severely debilitating condition caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2). RTT patients present with a complex respiratory phenotype that can include periods of hyperventilation, apnea, breath holds terminated by Valsalva maneuvers, forced and deep breathing and apneustic breathing, as well as abnormalities of heart rate control and cardiorespiratory integration. Recent studies of mouse models of RTT have begun to shed light on neurologic deficits that likely contribute to respiratory dysfunction including, in particular, defects in neurochemical signaling resulting from abnormal patterns of neurotransmitter and neuromodulator expression. The authors hypothesize that breathing dysregulation in RTT results from disturbances in mechanisms that modulate the respiratory rhythm, acting either alone or in combination with more subtle disturbances in rhythm and pattern generation. This article reviews the evidence underlying this hypothesis as well as recent efforts to translate our emerging understanding of neurochemical defects in mouse models of RTT into preclinical trials of potential treatments for respiratory dysfunction in this disease. PMID:19394452

  15. The trace amine-associated receptor 1 modulates methamphetamine's neurochemical and behavioral effects

    PubMed Central

    Cotter, Rachel; Pei, Yue; Mus, Liudmila; Harmeier, Anja; Gainetdinov, Raul R.; Hoener, Marius C.; Canales, Juan J.

    2015-01-01

    The newly discovered trace amine-associated receptor 1 (TAAR1) has the ability to regulate both dopamine function and psychostimulant action. Here, we tested in rats the ability of RO5203648, a selective TAAR1 partial agonist, to modulate the physiological and behavioral effects of methamphetamine (METH). In experiment 1, RO5203468 dose- and time-dependently altered METH-induced locomotor activity, manifested as an early attenuation followed by a late potentiation of METH's stimulating effects. In experiment 2, rats received a 14-day treatment regimen during which RO5203648 was co-administered with METH. RO5203648 dose-dependently attenuated METH-stimulated hyperactivity, with the effects becoming more apparent as the treatments progressed. After chronic exposure and 3-day withdrawal, rats were tested for locomotor sensitization. RO5203648 administration during the sensitizing phase prevented the development of METH sensitization. However, RO5203648, at the high dose, cross-sensitized with METH. In experiment 3, RO5203648 dose-dependently blocked METH self-administration without affecting operant responding maintained by sucrose, and exhibited lack of reinforcing efficacy when tested as a METH's substitute. Neurochemical data showed that RO5203648 did not affect METH-mediated DA efflux and uptake inhibition in striatal synaptosomes. In vivo, however, RO5203648 was able to transiently inhibit METH-induced accumulation of extracellular DA levels in the nucleus accumbens. Taken together, these data highlight the significant potential of TAAR1 to modulate METH's neurochemical and behavioral effects. PMID:25762894

  16. Assessing principal component regression prediction of neurochemicals detected with fast-scan cyclic voltammetry.

    PubMed

    Keithley, Richard B; Wightman, R Mark

    2011-06-01

    Principal component regression is a multivariate data analysis approach routinely used to predict neurochemical concentrations from in vivo fast-scan cyclic voltammetry measurements. This mathematical procedure can rapidly be employed with present day computer programming languages. Here, we evaluate several methods that can be used to evaluate and improve multivariate concentration determination. The cyclic voltammetric representation of the calculated regression vector is shown to be a valuable tool in determining whether the calculated multivariate model is chemically appropriate. The use of Cook's distance successfully identified outliers contained within in vivo fast-scan cyclic voltammetry training sets. This work also presents the first direct interpretation of a residual color plot and demonstrated the effect of peak shifts on predicted dopamine concentrations. Finally, separate analyses of smaller increments of a single continuous measurement could not be concatenated without substantial error in the predicted neurochemical concentrations due to electrode drift. Taken together, these tools allow for the construction of more robust multivariate calibration models and provide the first approach to assess the predictive ability of a procedure that is inherently impossible to validate because of the lack of in vivo standards. PMID:21966586

  17. [Neurochemical characteristics of the ventromedial hypothalamus and anti-aversive effects of anxiolytic agents in various anxiety models].

    PubMed

    Talalaenko, A N; Pankrat'ev, D V; Goncharenko, N V

    2001-09-01

    Neurochemical analysis using anxiosedative and anxioselective agents injected into the hypothalamus revealed that antiaversive action of camprione is only realised under conditions of domineering fear motivation whereas that of chlordiazepoxide, phenibut, indoter may also be realised under conditions of negative stressful zoo-social impacts mediated by serotonin. PMID:11763535

  18. Problematizing the neurochemical subject of anti-depressant treatment: the limits of biomedical responses to women's emotional distress.

    PubMed

    Fullagar, Simone; O'Brien, Wendy

    2013-01-01

    In this article we situate empirical research into women's problematic experiences of anti-depressant medication within broader debates about pharmaceuticalization and the rise of the neurochemical self. We explore how women interpreted and problematized anti-depressant medication as it impeded their recovery in a number of ways. Drawing upon Foucauldian and feminist work we conceptualize anti-depressants as biotechnologies of the self that shaped how women thought about and acted upon their embodied (and hence gendered) subjectivities. Through the interplay of biochemical, emotional and socio-cultural effects medication worked to shape women's self-in-recovery in ways that both reinscribed and undermined a neurochemical construction of depression. Our analysis outlines two key discursive constructions that focused on women's problematization of the neurochemical self in response to the side-effects of anti-depressant use. We identified how the failure of medication to alleviate depression contributed to women's reinterpretation of recovery as a process of 'working' on the emotional self. We argue that women's stories act as a form of subjugated knowledge about the material and discursive forces shaping depression and recovery. These findings offer a gendered critique of scientific and market orientated rationalities underpinning neurochemical recovery that obscure the embodied relations of affect and the social conditions that enable the self to change. PMID:22674747

  19. Software-assisted serum metabolite quantification using NMR.

    PubMed

    Jung, Young-Sang; Hyeon, Jin-Seong; Hwang, Geum-Sook

    2016-08-31

    The goal of metabolomics is to analyze a whole metabolome under a given set of conditions, and accurate and reliable quantitation of metabolites is crucial. Absolute concentration is more valuable than relative concentration; however, the most commonly used method in NMR-based serum metabolic profiling, bin-based and full data point peak quantification, provides relative concentration levels of metabolites and are not reliable when metabolite peaks overlap in a spectrum. In this study, we present the software-assisted serum metabolite quantification (SASMeQ) method, which allows us to identify and quantify metabolites in NMR spectra using Chenomx software. This software uses the ERETIC2 utility from TopSpin to add a digitally synthesized peak to a spectrum. The SASMeQ method will advance NMR-based serum metabolic profiling by providing an accurate and reliable method for absolute quantification that is superior to bin-based quantification. PMID:27506360

  20. Scoliosis quantification: an overview

    PubMed Central

    Kawchuk, Greg; McArthur, Ross

    1997-01-01

    Scoliotic curvatures have long been a focus of attention for clinicians and research scientists alike. The study, treatment and ultimately, the prevention of this prevalent health condition are impeded by the absence of an accurate, reliable, convenient and safe method of scoliosis quantification. The purpose of this paper is to provide an overview of the current methods of scoliosis quantification for clinicians who address this condition in their practices.

  1. Neurochemical characterization of the vestibular nerves in women with vulvar vestibulitis syndrome.

    PubMed

    Bohm-Starke, N; Hilliges, M; Falconer, C; Rylander, E

    1999-01-01

    Women with vulvar vestibulitis syndrome (VVS) have a distinct burning pain provoked by almost any stimuli in the area around the vaginal introitus. In a previous study we observed an increased number of intraepithelial free nerve endings in women with VVS. The aim of the present study was to neurochemically characterize the superficial nerves in the vulvar vestibular mucosa of women with VVS. Immunohistochemical methods were used to detect neuropeptides normally found in various types of nerve fibers. Calcitonin gene-related peptide, which is known to exist in nociceptive afferent nerves, was the only neuropeptide detected in the superficial nerves of the vestibular mucosa. These findings confirm our previous theory that the free nerve endings within the epithelium are nociceptors. PMID:10592432

  2. Modulation of the behavioral and neurochemical effects of psychostimulants by kappa-opioid receptor systems.

    PubMed

    Shippenberg, T S; Chefer, V I; Zapata, A; Heidbreder, C A

    2001-06-01

    The repeated, intermittent use of cocaine and other drugs of abuse produces profound and often long-lasting alterations in behavior and brain chemistry. It has been suggested that these consequences of drug use play a critical role in drug craving and relapse to addiction. This article reviews the effects of psychostimulant administration on dopaminergic and excitatory amino acid neurotransmission in brain regions comprising the brain's motive circuit and provides evidence that the activation of endogenous kappa-opioid receptor systems in these regions opposes the behavioral and neurochemical consequences of repeated drug use. The role of this opioid system in mediating alterations in mood and affect that occur during abstinence from repeated psychostimulant use are also discussed. PMID:11458540

  3. Features of adult neurogenesis and neurochemical signaling in the Cherry salmon Oncorhynchus masou brain☆

    PubMed Central

    Pushchina, Evgeniya V.; Obukhov, Dmitry K.; Varaksin, Anatoly A.

    2013-01-01

    We investigated the distribution of gamma aminobutyric acid, tyrosine hydroxylase and nitric oxide-producing elements in a cherry salmon Oncorhynchus masou brain at various stages of postnatal ontogenesis by immunohistochemical staining and histochemical staining. The periventricular region cells exhibited the morphology of neurons and glia including radial glia-like cells and contained several neurochemical substances. Heterogeneous populations of tyrosine hydroxylase-, gamma aminobutyric acid-immunoreactive, as well as nicotinamide adenine dinucleotide phosphate diaphorase-positive cells were observed in proliferating cell nuclear antigen-immunoreactive proliferative zones in periventricular area of diencephalon, central grey layer of dorsomedial tegmentum, medulla and spinal cord. Immunolocalization of Pax6 in the cherry salmon brain revealed a neuromeric construction of the brain at various stages of postnatal ontogenesis, and this was confirmed by tyrosine hydroxylase and gamma aminobutyric acid labeling. PMID:25206367

  4. Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice.

    PubMed

    Thelen, Connor; Sens, Jonathon; Mauch, Joseph; Pandit, Radhika; Pitychoutis, Pothitos M

    2016-10-01

    One of the most striking discoveries in the treatment of major depression was the finding that infusion of a single sub-anesthetic dose of ketamine induces rapid and sustained antidepressant effects in treatment-resistant depressed patients. However, ketamine's antidepressant-like actions are transient and can only be sustained by repeated drug treatment. Despite the fact that women experience major depression at roughly twice the rate of men, research regarding the neurobiological antidepressant-relevant effects of ketamine has focused almost exclusively on the male sex. Importantly, knowledge regarding the sex-differentiated effects, the frequency and the dose on which repeated ketamine administration stops being beneficial, is limited. In the current study, we investigated the behavioral, neurochemical and synaptic molecular effects of repeated ketamine treatment (10mg/kg; 21days) in male and female C57BL/6J mice. We report that ketamine induced beneficial antidepressant-like effects in male mice, but induced both anxiety-like (i.e., decreased time spent in the center of the open field arena) and depressive-like effects (i.e., enhanced immobility duration in the forced swim test; FST) in their female counterparts. Moreover, repeated ketamine treatment induced sustained sex-differentiated neurochemical and molecular effects, as it enhanced hippocampal synapsin protein levels and serotonin turnover in males, but attenuated glutamate and aspartate levels in female mice. Taken together, our findings indicate that repeated ketamine treatment induces opposite behavioral effects in male and female mice, and thus, present data have far-reaching implications for the sex-oriented use of ketamine in both experimental and clinical research settings. PMID:27343934

  5. REM sleep deprivation reverses neurochemical and other depressive-like alterations induced by olfactory bulbectomy.

    PubMed

    Maturana, Maira J; Pudell, Cláudia; Targa, Adriano D S; Rodrigues, Laís S; Noseda, Ana Carolina D; Fortes, Mariana H; Dos Santos, Patrícia; Da Cunha, Cláudio; Zanata, Sílvio M; Ferraz, Anete C; Lima, Marcelo M S

    2015-02-01

    There is compelling evidence that sleep deprivation (SD) is an effective strategy in promoting antidepressant effects in humans, whereas few studies were performed in relevant animal models of depression. Acute administration of antidepressants in humans and rats generates a quite similar effect, i.e., suppression of rapid eye movement (REM) sleep. Then, we decided to investigate the neurochemical alterations generated by a protocol of rapid eye movement sleep deprivation (REMSD) in the notably known animal model of depression induced by the bilateral olfactory bulbectomy (OBX). REMSD triggered antidepressant mechanisms such as the increment of brain-derived neurotrophic factor (BDNF) levels, within the substantia nigra pars compacta (SNpc), which were strongly correlated to the swimming time (r = 0.83; P < 0.0001) and hippocampal serotonin (5-HT) content (r = 0.66; P = 0.004). Moreover, there was a strong correlation between swimming time and hippocampal 5-HT levels (r = 0.70; P = 0.003), strengthen the notion of an antidepressant effect associated to REMSD in the OBX rats. In addition, REMSD robustly attenuated the hippocampal 5-HT deficiency produced by the OBX procedure. Regarding the rebound (REB) period, we observed the occurrence of a sustained antidepressant effect, indicated mainly by the swimming and climbing times which could be explained by the maintenance of the increased nigral BDNF expression. Hence, hippocampal 5-HT levels remained enhanced in the OBX group after this period. We suggested that the neurochemical complexity inflicted by the OBX model, counteracted by REMSD, is directly correlated to the nigral BDNF expression and hippocampal 5-HT levels. The present findings provide new information regarding the antidepressant mechanisms triggered by REMSD. PMID:24826915

  6. The gyri of the octopus vertical lobe have distinct neurochemical identities.

    PubMed

    Shigeno, Shuichi; Ragsdale, Clifton W

    2015-06-15

    The cephalopod vertical lobe is the largest learning and memory structure known in invertebrate nervous systems. It is part of the visual learning circuit of the central brain, which also includes the superior frontal and subvertical lobes. Despite the well-established functional importance of this system, little is known about neuropil organization of these structures and there is to date no evidence that the five longitudinal gyri of the vertical lobe, perhaps the most distinctive morphological feature of the octopus brain, differ in their connections or molecular identities. We studied the histochemical organization of these structures in hatchling and adult Octopus bimaculoides brains with immunostaining for serotonin, octopus gonadotropin-releasing hormone (oGNRH), and octopressin-neurophysin (OP-NP). Our major finding is that the five lobules forming the vertical lobe gyri have distinct neurochemical signatures. This is most prominent in the hatchling brain, where the median and mediolateral lobules are enriched in OP-NP fibers, the lateral lobule is marked by oGNRH innervation, and serotonin immunostaining heavily labels the median and lateral lobules. A major source of input to the vertical lobe is the superior frontal lobe, which is dominated by a neuropil of interweaving fiber bundles. We have found that this neuropil also has an intrinsic neurochemical organization: it is partitioned into territories alternately enriched or impoverished in oGNRH-containing fascicles. Our findings establish that the constituent lobes of the octopus superior frontal-vertical system have an intricate internal anatomy, one likely to reflect the presence of functional subsystems within cephalopod learning circuitry. PMID:25644267

  7. Individual differences in the forced swimming test and neurochemical kinetics in the rat brain.

    PubMed

    Sequeira-Cordero, Andrey; Mora-Gallegos, Andrea; Cuenca-Berger, Patricia; Fornaguera-Trías, Jaime

    2014-04-10

    Individual differences in the forced swimming test (FST) could be associated with differential temporal dynamics of gene expression and neurotransmitter activity. We tested juvenile male rats in the FST and classified the animals into those with low and high immobility according to the amount of immobility time recorded in FST. These groups and a control group which did not undergo the FST were sacrificed either 1, 6 or 24 h after the test. We analyzed the expression of the CRF, CRFR1, BDNF and TrkB in the prefrontal cortex, hippocampus and nucleus accumbens as well as norepinephrine, dopamine, serotonin, glutamate, GABA and glutamine in the hippocampus and nucleus accumbens. Animals with low immobility showed significant reductions of BDNF expression across time points in both the prefrontal cortex and the nucleus accumbens when compared with non-swim control. Moreover, rats with high immobility only showed a significant decrease of BDNF expression in the prefrontal cortex 6h after the FST. Regarding neurotransmitters, only accumbal dopamine turnover and hippocampal glutamate content showed an effect of individual differences (i.e. animals with low and high immobility), whereas nearly all parameters showed significant differences across time points. Correlational analyses suggest that immobility in the FST, probably reflecting despair, is related to prefrontal cortical BDNF and to the kinetics observed in several other neurochemical parameters. Taken together, our results suggest that individual differences observed in depression-like behavior can be associated not only with changes in the concentrations of key neurochemical factors but also with differential time courses of such factors. PMID:24518862

  8. Sensory receptors in the visceral pleura: neurochemical coding and live staining in whole mounts.

    PubMed

    Pintelon, Isabel; Brouns, Inge; De Proost, Ian; Van Meir, Frans; Timmermans, Jean-Pierre; Adriaensen, Dirk

    2007-05-01

    Today, diagnosis and treatment of chest pain related to pathologic changes in the visceral pleura are often difficult. Data in the literature on the sensory innervation of the visceral pleura are sparse. The present study aimed at identifying sensory end-organs in the visceral pleura, and at obtaining more information about neurochemical coding. The immunocytochemcial data are mainly based on whole mounts of the visceral pleura of control and vagally denervated rats. It was shown that innervation of the rat visceral pleura is characterized by nerve bundles that enter in the hilus region and gradually split into slender bundles with a few nerve fibers. Separate nerve fibers regularly give rise to characteristic laminar terminals. Because of their unique association with the elastic fibers of the visceral pleura, we decided to refer to them as "visceral pleura receptors" (VPRs). Cryostat sections of rat lungs confirmed a predominant location on mediastinal and interlobar lung surfaces. VPRs can specifically be visualized by protein gene product 9.5 immunostaining, and were shown to express vesicular glutamate transporters, calbindin D28K, Na+/K+-ATPase, and P2X3 ATP-receptors. The sensory nerve fibers giving rise to VPRs appeared to be myelinated and to have a spinal origin. Because several of the investigated proteins have been reported as markers for sensory terminals in other organs, the present study revealed that VPRs display the neurochemical characteristics of mechanosensory and/or nociceptive terminals. The development of a live staining method, using AM1-43, showed that VPRs can be visualized in living tissue, offering an interesting model for future physiologic studies. PMID:17170382

  9. Quantification of nonclassicality

    NASA Astrophysics Data System (ADS)

    Gehrke, C.; Sperling, J.; Vogel, W.

    2012-11-01

    To quantify single-mode nonclassicality, we start from an operational approach. A positive semidefinite observable is introduced to describe a measurement setup. The quantification is based on the negativity of the normally ordered version of this observable. Perfect operational quantumness corresponds to the quantum-noise-free measurement of the chosen observable. Surprisingly, even moderately squeezed states may exhibit perfect quantumness for a properly designed measurement. The quantification is also considered from an axiomatic viewpoint, based on the algebraic structure of the quantum states and the quantum superposition principle. Basic conclusions from both approaches are consistent with this fundamental principle of the quantum world.

  10. Vanillin Attenuated Behavioural Impairments, Neurochemical Deficts, Oxidative Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson's Disease.

    PubMed

    Dhanalakshmi, Chinnasamy; Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed; Kalandar, Ameer; Khan, Mohammed Abdul Sattar; Guillemin, Gilles J

    2016-08-01

    Vanillin (4-hydroxy-3-methoxybenzaldehyde), a pleasant smelling organic aromatic compound, is widely used as a flavoring additive in food, beverage, cosmetic and drug industries. It is reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. We previously reported the neuroprotective effect of vanillin against rotenone induced in in vitro model of PD. The present experiment was aimed to analyze the neuroprotective effect of vanillin on the motor and non-motor deficits, neurochemical variables, oxidative, anti-oxidative indices and the expression of apoptotic markers against rotenone induced rat model of Parkinson's disease (PD). Rotenone treatment exhibited motor and non-motor impairments, neurochemical deficits, oxidative stress and apoptosis, whereas oral administration of vanillin attenuated the above-said indices. However further studies are needed to explore the mitochondrial protective and anti-inflammatory properties of vanillin, as these processes play a vital role in the cause and progression of PD. PMID:27038927

  11. Sleep and neurochemical modulation by the nuclear peroxisome proliferator-activated receptor α (PPAR-α) in rat.

    PubMed

    Mijangos-Moreno, Stephanie; Poot-Aké, Alwin; Guzmán, Khalil; Arankowsky-Sandoval, Gloria; Arias-Carrión, Oscar; Zaldívar-Rae, Jaime; Sarro-Ramírez, Andrea; Murillo-Rodríguez, Eric

    2016-04-01

    The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear protein that plays an essential role in diverse neurobiological processes. However, the role of PPARα on the sleep modulation is unknown. Here, rats treated with an intrahypothalamic injection of Wy14643 (10μg/1μL; PPARα agonist) enhanced wakefulness and decreased slow wave sleep and rapid eye movement sleep whereas MK-886 (10μg/1μL; PPARα antagonist) promoted opposite effects. Moreover, Wy14643 increased dopamine, norepinephrine, serotonin, and adenosine contents collected from nucleus accumbens. The levels of these neurochemicals were diminished after MK-886 treatment. The current findings suggest that PPARα may participate in the sleep and neurochemical modulation. PMID:26450400

  12. Neurochemical features of endomorphin-2-containing neurons in the submucosal plexus of the rat colon

    PubMed Central

    Li, Jun-Ping; Zhang, Ting; Gao, Chang-Jun; Kou, Zhen-Zhen; Jiao, Xu-Wen; Zhang, Lian-Xiang; Wu, Zhen-Yu; He, Zhong-Yi; Li, Yun-Qing

    2015-01-01

    AIM: To investigate the distribution and neurochemical phenotype of endomorphin-2 (EM-2)-containing neurons in the submucosal plexus of the rat colon. METHODS: The mid-colons between the right and left flexures were removed from rats, and transferred into Kreb’s solution. For whole-mount preparations, the mucosal, outer longitudinal muscle and inner circular muscle layers of the tissues were separated from the submucosal layer attached to the submucosal plexus. The whole-mount preparations from each rat mid-colon were mounted onto seven gelatin-coated glass slides, and processed for immunofluorescence histochemical double-staining of EM-2 with calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT), nitric oxide synthetase (NOS), neuron-specific enolase (NSE), substance P (SP) and vasoactive intestinal peptide (VIP). After staining, all the fluorescence-labeled sections were observed with a confocal laser scanning microscope. To estimate the extent of the co-localization of EM-2 with CGRP, ChAT, NOS, NSE, SP and VIP, ganglia, which have a clear boundary and neuronal cell outline, were randomly selected from each specimen for this analysis. RESULTS: In the submucosal plexus of the mid-colon, many EM-2-immunoreactive (IR) and NSE-IR neuronal cell bodies were found in the submucosal plexus of the rat mid-colon. Approximately 6 ± 4.2 EM-2-IR neurons aggregated within each ganglion and a few EM-2-IR neurons were also found outside the ganglia. The EM-2-IR neurons were also immunopositive for ChAT, SP, VIP or NOS. EM-2-IR nerve fibers coursed near ChAT-IR neurons, and some of these fibers were even distributed around ChAT-IR neuronal cell bodies. Some EM-2-IR neuronal cell bodies were surrounded by SP-IR nerve fibers, but many long processes connecting adjacent ganglia were negative for EM-2 immunostaining. Long VIP-IR processes with many branches coursed through the ganglia and surrounded the EM-2-IR neurons. The percentages of the EM-2-IR neurons

  13. Piperine Augments the Protective Effect of Curcumin Against Lipopolysaccharide-Induced Neurobehavioral and Neurochemical Deficits in Mice.

    PubMed

    Jangra, Ashok; Kwatra, Mohit; Singh, Tavleen; Pant, Rajat; Kushwah, Pawan; Sharma, Yogita; Saroha, Babita; Datusalia, Ashok Kumar; Bezbaruah, Babul Kumar

    2016-06-01

    The aim of the present study was to investigate the protective effects of curcumin alone and in combination with piperine against lipopolysaccharide (LPS)-induced neurobehavioral and neurochemical deficits in the mice hippocampus. Mice were treated with curcumin (100, 200, and 400 mg/kg, p.o.) and piperine (20 mg/kg, p.o.) for 7 days followed by LPS (0.83 mg/kg, i.p.) administration. Animals exhibited anxiety and depressive-like phenotype after 3 and 24 h of LPS exposure, respectively. LPS administration increased the oxido-nitrosative stress as evident by elevated levels of malondialdehyde, nitrite, and depletion of glutathione level in the hippocampus. Furthermore, we found raised level of pro-inflammatory cytokines (IL-1β and TNF-α) in the hippocampus of LPS-treated mice. Pretreatment with curcumin alleviated LPS-induced neurobehavioral and neurochemical deficits. Furthermore, co-administration of curcumin with piperine significantly potentiated the neuroprotective effect of curcumin. These results demonstrate that piperine enhanced the neuroprotective effect of curcumin against LPS-induced neurobehavioral and neurochemical deficits. PMID:26970969

  14. The morphologic and neurochemical basis of dementia: aging, hierarchical patterns of lesion distribution and vulnerable neuronal phenotype.

    PubMed

    Hof, P R; Giannakopoulos, P; Vickers, J C; Bouras, C; Morrison, J H

    1995-01-01

    Alzheimer's disease is the most common form of dementia in elderly individuals. Approximately 11% of the population older than 65, and up to 50% of individuals over 85 qualify as having "probable Alzheimer's disease" on the basis of clinical evaluation. Since the early description of the clinical symptoms and neuropathologic features of Alzheimer's disease, there has been an extraordinary growth in the knowledge of the morphologic and molecular characteristics of Alzheimer's disease. Although the pathogenetic events that lead to dementia are not yet fully understood, several hypotheses regarding the formation of the hallmark pathologic structures of Alzheimer's disease have been proposed. In this context, the use of specific histochemical techniques in the primate brain has greatly expanded our understanding of neuron typology, connectivity and circuit distribution in relation to neurochemical identity. In this respect, very specific subsets of cortical neurons and cortical afferents can be identified by their particular content of certain neurotransmitters and structural proteins. In this article, we discuss the possible relationships between the distribution of pathologic changes in aging, Alzheimer's disease, and possibly related dementing conditions, in the context of the specific elements of the cortical circuitry that are affected by these alterations. Also, evidence for links between the neurochemical phenotype of a given neuron and its relative vulnerability or resistance to the degenerative process are presented in order to correlate the distribution of cellular pathologic changes, neurochemical characteristics related to vulnerability, and affected cortical circuits. PMID:8564027

  15. Transforming growth factor-alpha induces sex-specific neurochemical imbalance in the stress- and memory-associated brain structures.

    PubMed

    Koshibu, Kyoko; Levitt, Pat

    2006-06-01

    Transforming growth factor-alpha (TGFalpha) is a well-known regulator of many developmental processes. However, its role in adult nervous system is yet unclear. Studies have shown that TGFalpha can regulate stress and memory behavior in adult mice. When TGFalpha is reduced in Waved-1 (Wa-1) mutant mice, the stress response and memory are impaired predominantly in males and only after puberty. To determine the neurochemical changes resulting from the reduced TGFalpha levels that could explain the reported behavioral outcomes, biogenic amine and amino acid levels were determined in the brain regions associated with stress and memory. Interestingly, sex-specific alterations in neurochemical levels were detected, including elevated noradrenaline and reduced glutamate levels in striatum of Wa-1 males, increased noradrenaline and reduced serotonin metabolite levels in hippocampus of Wa-1 females, reduced serotonin metabolite levels in cortex and amygdala of Wa-1 females, and reduced noradrenaline, dopamine, serotonin, glutamate and glycine levels in hypothalamus of Wa-1 females compared to their respective controls. Increased dopamine turnover in cortex and reduced dopamine and serotonin turnover in amygdala were observed in both male and female Wa-1 mice. The data indicate sex-specific alterations of specific neurochemicals as a result of reduced TGFalpha expression, which may underlie sex-dependent stress response and memory impairment in Wa-1 mice. PMID:16442134

  16. Neurochemical and behavioral effects elicited by bupropion and diethylpropion in rats.

    PubMed

    Santamaría, Abel; Arias, Hugo R

    2010-07-29

    This study is an attempt to demonstrate whether bupropion (BP) and diethylpropion (DEP) exert their pharmacological actions by similar neurochemical mechanisms in the dorsal striatum. In this regard, the release of dopamine (DA), glutamate (Glu), and GABA, was determined in the rat dorsal striatum after acute (5 min) and chronic (15 consecutive days) treatments, and subsequently correlated with the locomotor activities produced by these drugs. The results from the acute experiments indicate that BP and DEP (40 mg/kg) increase locomotor activity, whereas chronic DEP treatment decreases locomotor activity by unspecific mechanisms. Acute BP treatment produces significant DA and Glu, but not GABA, releases. A lesser extent of DA release and tissue content of DA and its metabolites, and consequently less locomotor activity, was observed after chronic BP treatment. Acute DEP (5mg/kg) was only able to slightly increase DA release and to decrease the tissue levels of DA, but no other markers, with practically nil locomotor activity, whereas chronic DEP produced even less neurotransmitter release. The observed difference between BP and DEP might be based on that although both drugs inhibit the DA and norepinephrine transporters, the BP-induced nicotinic receptor inhibition has yet to be demonstrated for DEP. PMID:20307582

  17. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake

    PubMed Central

    Avena, Nicole M.; Rada, Pedro; Hoebel, Bartley G.

    2008-01-01

    The experimental question is whether or not sugar can be a substance of abuse and lead to a natural form of addiction. “Food addiction” seems plausible because brain pathways that evolved to respond to natural rewards are also activated by addictive drugs. Sugar is noteworthy as a substance that releases opioids and dopamine and thus might be expected to have addictive potential. This review summarizes evidence of sugar dependence in an animal model. Four components of addiction are analyzed. “Bingeing”, “withdrawal”, “craving” and cross-sensitization are each given operational definitions and demonstrated behaviorally with sugar bingeing as the reinforcer. These behaviors are then related to neurochemical changes in the brain that also occur with addictive drugs. Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin mRNA expression and dopamine and acetylcholine release in the nucleus accumbens. The evidence supports the hypothesis that under certain circumstances rats can become sugar dependent. This may translate to some human conditions as suggested by the literature on eating disorders and obesity. PMID:17617461

  18. Mercury exposure and neurochemical impacts in bald eagles across several Great Lakes states.

    PubMed

    Rutkiewicz, Jennifer; Nam, Dong-Ha; Cooley, Thomas; Neumann, Kay; Padilla, Irene Bueno; Route, William; Strom, Sean; Basu, Niladri

    2011-10-01

    In this study, we assessed mercury (Hg) exposure in several tissues (brain, liver, and breast and primary feathers) in bald eagles (Haliaeetus leucocephalus) collected from across five Great Lakes states (Iowa, Michigan, Minnesota, Ohio, and Wisconsin) between 2002-2010, and assessed relationships between brain Hg and neurochemical receptors (NMDA and GABA(A)) and enzymes (glutamine synthetase (GS) and glutamic acid decarboxylase (GAD)). Brain total Hg (THg) levels (dry weight basis) averaged 2.80 μg/g (range: 0.2-34.01), and levels were highest in Michigan birds. THg levels in liver (r(p) = 0.805) and breast feathers (r(p) = 0.611) significantly correlated with those in brain. Brain Hg was not associated with binding to the GABA(A) receptor. Brain THg and inorganic Hg (IHg) were significantly positively correlated with GS activity (THg r(p) = 0.190; IHg r(p) = 0.188) and negatively correlated with NMDA receptor levels (THg r(p) = -0245; IHg r(p) = -0.282), and IHg was negatively correlated with GAD activity (r(s) = -0.196). We also report upon Hg demethylation and relationships between Hg and Se in brain and liver. These results suggest that bald eagles in the Great Lakes region are exposed to Hg at levels capable of causing subclinical neurological damage, and that when tissue burdens are related to proposed avian thresholds approximately 14-27% of eagles studied here may be at risk. PMID:21735125

  19. [Organization and development of neurochemical research in the Dnepr area (the 60-80s)].

    PubMed

    Chernaia, V I; Nazarenko, V I

    1996-01-01

    The development of neurochemical investigations at the Institute of Biochemistry of the National Academy of Sciences of Ukraine initiated by Academician A. V. Palladin, has impelled specialists in some regions of the country to start research in this trend. The Department of Biophysics and Biochemistry of Dniepropetrovsk State University founded and headed by Professor O. D. Reva became one of such centres in the Dnieper area. The chief developments of scientific-research inventions were devoted to radiational neurochemistry, O. D. Reva should be accounted as a pioneer of the study of chemical composition and metabolism in functional and morphologically logically different sites of cats spinal cord lumbar enlargement. Thus, the significant statement, proposed by A. V. Palladin, was confirmed about the presence of biochemical differentiation in cerebrum besides the morphological and functional ones. While analysing the test data concerning the biochemical and biophysical indices of roentgen irradiation of cats in different terms and conditions an original scheme of radiation-biophysical and radiation-biochemical injury of spinal cord was proposed. Some tissue proteinases, as well as some neurospecific proteins in the norm and under the gamma-irradiation were selected and assayed. An immunoelectrophoretic technique for estimating glyolic fibrilar acid protein and cellular adhesion (N-CAM) in blood and surrounding fluid, as well as in human brain tumour was developed and a method of early prenatal diagnosis of embryo developmental disorders was proposed in order to prevent the birth of the underdeveloped infants. PMID:9229846

  20. Pre-hatching fluoxetine-induced neurochemical, neurodevelopmental, and immunological changes in newly hatched cuttlefish.

    PubMed

    Bidel, Flavie; Di Poi, Carole; Imarazene, Boudjema; Koueta, Noussithé; Budzinski, Hélène; Van Delft, Pierre; Bellanger, Cécile; Jozet-Alves, Christelle

    2016-03-01

    Embryonic and early postembryonic development of the cuttlefish Sepia officinalis (a cephalopod mollusk) occurs in coastal waters, an environment subject to considerable pressure from xenobiotic pollutants such as pharmaceutical residues. Given the role of serotonin in brain development and its interaction with neurodevelopmental functions, this study focused on fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI, antidepressant). The goal was to determine the effects of subchronic waterborne FLX exposure (1 and 10 μg L(-1)) during the last 15 days of embryonic development on neurochemical, neurodevelopmental, behavioral, and immunological endpoints at hatching. Our results showed for the first time that organic contaminants, such as FLX, could pass through the eggshell during embryonic development, leading to a substantial accumulation of this molecule in hatchlings. We also found that FLX embryonic exposure (1 and 10 μg L(-1)) (1) modulated dopaminergic but not serotonergic neurotransmission, (2) decreased cell proliferation in key brain structures for cognitive and visual processing, (3) did not induce a conspicuous change in camouflage quality, and (4) decreased lysozyme activity. In the long term, these alterations observed during a critical period of development may impair complex behaviors of the juvenile cuttlefish and thus lead to a decrease in their survival. Finally, we suggest a different mode of action by FLX between vertebrate and non-vertebrate species and raise questions regarding the vulnerability of early life stages of cuttlefish to the pharmaceutical contamination found in coastal waters. PMID:25966880

  1. Prospective neurochemical characterization of child offspring of parents with bipolar disorder.

    PubMed

    Singh, Manpreet K; Jo, Booil; Adleman, Nancy E; Howe, Meghan; Bararpour, Layla; Kelley, Ryan G; Spielman, Daniel; Chang, Kiki D

    2013-11-30

    We wished to determine whether decreases in N-acetyl aspartate (NAA) and increases in myoinositol (mI) concentrations as a ratio of creatine (Cr) occurred in the dorsolateral prefrontal cortex (DLPFC) of pediatric offspring of parents with bipolar disorder (BD) and a healthy comparison group (HC) over a 5-year period using proton magnetic resonance spectroscopy ((1)H-MRS). Paticipants comprised 64 offspring (9-18 years old) of parents with BD (36 with established BD, and 28 offspring with symptoms subsyndromal to mania) and 28 HCs, who were examined for group differences in NAA/Cr and mI/Cr in the DLPFC at baseline and follow-up at either 8, 10, 12, 52, 104, 156, 208, or 260 weeks. No significant group differences were found in metabolite concentrations at baseline or over time. At baseline, BD offspring had trends for higher mI/Cr concentrations in the right DLPFC than the HC group. mI/Cr concentrations increased with age, but no statistically significant group differences were found between groups on follow-up. It may be the case that with intervention youth at risk for BD are normalizing otherwise potentially aberrant neurochemical trajectories in the DLPFC. A longer period of follow-up may be required before observing any group differences. PMID:24028795

  2. Prospective neurochemical characterization of child offspring of parents with bipolar disorder

    PubMed Central

    Singh, Manpreet K.; Jo, Booil; Adleman, Nancy E.; Howe, Meghan; Bararpour, Layla; Kelley, Ryan G.; Spielman, Daniel; Chang, Kiki D.

    2013-01-01

    We wished to determine whether decreases in N-acetyl aspartate (NAA) and increases in myoinositol (mI) concentrations as a ratio of creatine (Cr) occurred in the dorsolateral prefrontal cortex (DLPFC) of pediatric offspring of parents with bipolar disorder (BD) and a healthy comparison group (HC) over a 5 year period using proton magnetic resonance spectroscopy (1H-MRS). Sixty-four youth (9–18 years old) of parents with BD (36 with established BD, and 28 offspring with symptoms subsyndromal to mania) and 28 HCs were examined for group differences in NAA/Cr and mI/Cr in the DLPFC at baseline and follow-up at either 8, 10, 12, 52, 104, 156, 208, or 260 weeks. No significant group differences were found in metabolite concentrations at baseline or over time. At baseline, BD offspring had trends for higher mI/Cr concentrations in the right DLPFC than the HC group. mI/Cr concentrations increased with age, but no statistically significant group differences were found between groups on follow up. It may be the case that with intervention, youth at risk for BD are normalizing otherwise potentially aberrant neurochemical trajectories in the dorsolateral prefrontal cortex. A longer period of follow up may be required before observing any group differences. PMID:24028795

  3. Genetic or pharmacological blockade of noradrenaline synthesis enhances the neurochemical, behavioural, and neurotoxic effects of methamphetamine

    PubMed Central

    Weinshenker, David; Ferrucci, Michela; Busceti, Carla L.; Biagioni, Francesca; Lazzeri, Gloria; Liles, L. Cameron; Lenzi, Paola; Murri, Luigi; Paparelli, Antonio; Fornai, Francesco

    2008-01-01

    N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions of the locus coeruleus (LC), the major brain noradrenergic nucleus, exacerbate the damage to nigrostriatal dopamine (DA) terminals caused by the psychostimulant methamphetamine (METH). However, because noradrenergic terminals contain other neuromodulators and the noradrenaline (NA) transporter, which may act as a neuroprotective buffer, it was unclear whether this enhancement of METH neurotoxicity was caused by the loss of noradrenergic innervation or the loss of NA itself. We addressed the specific role of NA by comparing the effects of METH in mice with noradrenergic lesions (DSP-4) and those with intact noradrenergic terminals but specifically lacking NA (genetic or acute pharmacological blockade of the NA biosynthetic enzyme dopamine β-hydroxylase; DBH). We found that genetic deletion of DBH (DBH −/− mice) and acute treatment of wild-type mice with a DBH inhibitor (fusaric acid) recapitulated the effects of DSP-4 lesions on METH responses. All three methods of NA depletion enhanced striatal DA release, extracellular oxidative stress (as measured by in vivo microdialysis of DA and 2,3-dihydroxybenzoic acid), and behavioural stereotypies following repeated METH administration. These effects accompanied a worsening of the striatal DA neuron terminal damage and ultrastructural changes to medium spiny neurons. We conclude that NA itself is neuroprotective and plays a fundamental role in the sensitivity of striatal DA terminals to the neurochemical, behavioural, and neurotoxic effects of METH. PMID:18042179

  4. Neurochemical and Neuropharmacological Aspects of Circadian Disruptions: An Introduction to Asynchronization

    PubMed Central

    Kohyama, Jun

    2011-01-01

    Circadian disruptions are common in modern society, and there is an urgent need for effective treatment strategies. According to standard diagnostic criteria, most adolescents showing both insomnia and daytime sleepiness are diagnosed as having behavioral-induced sleep efficiency syndrome resulting from insomnia due to inadequate sleep hygiene. However, a simple intervention of adequate sleep hygiene often fails to treat them. As a solution to this clinical problem, the present review first overviews the basic neurochemical and neuropharmachological aspects of sleep and circadian rhythm regulation, then explains several circadian disruptions from similar viewpoints, and finally introduces the clinical notion of asynchronization. Asynchronization is designated to explain the pathophysiology/pathogenesis of exhibition of both insomnia and hypersomnia in adolescents, which comprises disturbances in various aspects of biological rhythms. The major triggers for asynchronization are considered to be a combination of light exposure during the night, which disturbs the biological clock and decreases melatonin secretion, as well as a lack of light exposure in the morning, which prohibits normal synchronization of the biological clock to the 24-hour cycle of the earth and decreases the activity of serotonin. In the chronic phase of asynchronization, involvement of both wake- and sleep-promoting systems is suggested. Both conventional and alternative therapeutic approaches for potential treatment of asynchronization are suggested. PMID:22131941

  5. Negotiating the neurochemical self: anti-depressant consumption in women's recovery from depression.

    PubMed

    Fullagar, Simone

    2009-07-01

    Anti-depressant treatment can be viewed as an exercise of biopower that is articulated through policies and practices aimed at the reduction of depression, population healthcare costs and effects on labour force productivity. Drawing upon a feminist governmentality perspective, this article examines the discourses that shaped women's experiences of anti-depressant medication in an Australian qualitative study on recovery from depression. The majority of women had been prescribed anti-depressants to treat a chemical imbalance in the brain, manage symptoms and restore normal functioning. One-third of participants identified anti-depressants as helpful in their recovery, while two-thirds were either highly ambivalent about, or critical of, medication as a solution to depression. Thirty-one women who identified the ;positive' benefits of anti-depressants actively constituted themselves as biomedical consumers seeking to redress a chemical imbalance. The problem of depression, the emergence of molecular science and the push for pharmacological solutions are contributing to the discursive formation of new subject positions - such as the neurochemically deficient self. Three themes were identified in relation to medication use, namely restoring normality, signifying recovery success and control/uncertainty. Anti-depressant medication offered women a normalized pathway to successful recovery that stood in stark contrast to the biologically deficient and morally failing self. These women's stories importantly reveal the gender relations and paradoxes arising from biopolitical technologies that shape selfhood for women in advanced liberal societies. PMID:19491233

  6. Feeding conditions differentially affect the neurochemical and behavioral effects of dopaminergic drugs in male rats.

    PubMed

    Sevak, Rajkumar J; Koek, Wouter; Owens, William Anthony; Galli, Aurelio; Daws, Lynette C; France, Charles P

    2008-09-11

    The high co-morbidity of eating disorders and substance abuse suggests that nutritional status can impact vulnerability to drug abuse. These studies used rats to examine the effects of food restriction on dopamine clearance in striatum and on the behavioral effects of amphetamine (locomotion, conditioned place preference), the dopamine receptor agonist quinpirole (yawning), and the dopamine receptor antagonist raclopride (catalepsy). Amphetamine increased locomotion and produced conditioned place preference. Food restriction reduced dopamine clearance, which was restored by repeated treatment with amphetamine or by free feeding. Food restriction also decreased sensitivity to quinpirole-induced yawning and raclopride-induced catalepsy; normal sensitivity to both drugs was restored by free feeding. The same amphetamine treatment that normalized dopamine clearance, failed to restore normal sensitivity to quinpirole or raclopride, suggesting that in food-restricted rats the activity of dopamine transporters and dopamine receptors is differentially affected by pathways that are stimulated by amphetamine. These studies show that modest changes in nutritional status markedly alter dopamine neurotransmission and the behavioral effects of direct-acting dopamine receptor drugs (agonist and antagonist). These results underscore the potential importance of nutritional status (e.g., glucose and insulin) in modulating dopamine neurotransmission and in so doing they begin to establish a neurochemical link between the high co-morbidity of eating disorders and drug abuse. PMID:18652823

  7. Neurochemical and behavioral effects of Cinnamomi cassiae (Lauraceae) bark aqueous extract in obese rats.

    PubMed

    Bano, Farhat; Ikram, Huma; Akhtar, Naheed

    2014-05-01

    Obesity is a risk factor leading to a number of chronic and metabolic disorders. Obesity is the fifth leading cause of global deaths. At least 2.8 million adults are dying each year as being overweight or obese. Cinnamomi cassiae is widely used traditional medicinal plant, used indigenously, to decrease glucose and cholesterol. 5-Hydroxy tryptamine (5-HT; Serotonin) is an important neurotransmitter reported to be involved in the pathophysiology of anorexia. Present study was designed to investigate the neurochemical and behavioral effects of cinnamon bark aqueous extract (CBAE) in obese rats and to find the possible involvement of 5-HT in reducing the body weight in these experimental animals. CBAE was repeatedly administered orally in the test animals for 5 weeks. A decrease in the food intake along with a concomitant increase in brain 5-HT level was observed in rats administered with CBAE. Findings may help in extending therapeutics in the pathophysiology of obesity and related eating disorders. Decrease activities in behavioral models were also monitored in CBAE treated animals. PMID:24811817

  8. Placebo and nocebo effects: a complex interplay between psychological factors and neurochemical networks.

    PubMed

    Frisaldi, Elisa; Piedimonte, Alessandro; Benedetti, Fabrizio

    2015-01-01

    Placebo and nocebo effects have recently emerged as an interesting model to understand some of the intricate underpinnings of the mind-body interaction. A variety of psychological mechanisms, such as expectation, conditioning, anxiety modulation, and reward, have been identified, and a number of neurochemical networks have been characterized across different conditions, such as pain and motor disorders. What has emerged from the recent insights into the neurobiology of placebo and nocebo effects is that the psychosocial context around the patient and the therapy, which represents the ritual of the therapeutic act, may change the biochemistry and the neuronal circuitry of the patient's brain. Furthermore, the mechanisms activated by placebos and nocebos have been found to be the same as those activated by drugs, which suggests a cognitive/affective interference with drug action. Overall, these findings highlight the important role of therapeutic rituals in the overall therapeutic outcome, including hypnosis, which may have profound implications both in routine medical practice and in the clinical trials setting. PMID:25928679

  9. 18-Methoxycoronaridine acts in the medial habenula to attenuate behavioral and neurochemical sensitization to nicotine.

    PubMed

    Eggan, Branden L; McCallum, Sarah E

    2016-07-01

    Systemic 18-methoxycoronaridine, an alpha3beta4 nicotinic antagonist, slows the rate of induction of behavioral sensitization to nicotine (Glick et al., 1996; 2011). The primary mechanism of action of 18-MC is believed to be the inhibition of α3β4 nicotinic acetylcholine receptors which are densely expressed in the medial habenula and interpeduncular nucleus (Pace et al., 2004; Glick et al., 2012). Recently, these habenular nicotinic receptors and their multiple roles in nicotine aversion and withdrawal have been increasingly emphasized (Antolin-Fontes et al., 2015). Here, we investigated the effects of 18-MC on both behavioral and neurochemical sensitization to nicotine. Daily systemic administration of 18-MC slowed the rate of induction of behavioral sensitization to nicotine but failed to block the expression of a sensitized locomotor response when absent. In contrast, in nicotine sensitized animals, systemic 18-MC significantly reduced the expression of behavioral sensitization. Results from intra-habenular administration of 18-MC paralleled these findings in that the expression of behavioral sensitization was also reduced in sensitized animals. Consistent with its effects on behavioral sensitization, intra-MHb treatment with 18-MC completely abolished sensitized dopamine responses in the nucleus accumbens in nicotine sensitized animals. These results show that α3β4 nicotinic receptors in the MHb contribute to nicotine sensitization, a phenomenon associated with drug craving and relapse. PMID:27059333

  10. Behavioral, neurochemical and neuroendocrine effects of abnormal savda munziq in the chronic stress mice.

    PubMed

    Amat, Nurmuhammat; Hoxur, Parida; Ming, Dang; Matsidik, Aynur; Kijjoa, Anake; Upur, Halmurat

    2012-01-01

    Oral administration of Abnormal Savda Munsiq (ASMq), a herbal preparation used in Traditional Uighur Medicine, was found to exert a memory-enhancing effect in the chronic stressed mice, induced by electric foot-shock. The memory improvement of the stressed mice was shown by an increase of the latency time in the step-through test and the decrease of the latency time in the Y-maze test. Treatment with ASMq was found to significantly decrease the serum levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT) and β-endorphin (β-EP) as well as the brain and serum level of norepinephrine (NE). Furthermore, ASMq was able to significantly reverse the chronic stress by decreasing the brain and serum levels of the monoamine neurotransmitters dopamine (DA), 5-hydroxytryptamine (5-HT) and 3,4-dihydroxyphenylalanine (DOPAC). The results obtained from this study suggested that the memory-enhancing effect of ASMq was mediated through regulations of neurochemical and neuroendocrine systems. PMID:22919413

  11. [Motivation and Emotional States: Structural Systemic, Neurochemical, Molecular and Cellular Mechanisms].

    PubMed

    Bazyan, A S

    2016-01-01

    The structural, systemic, neurochemical, molecular and cellular mechanisms of organization and coding motivation and emotional states are describe. The GABA and glutamatergic synaptic systems of basal ganglia form a neural network and participate in the implementation of voluntary behavior. Neuropeptides, neurohormones and paracrine neuromodulators involved in the organization of motivation and emotional states, integrated with synaptic systems, controlled by neural networks and organizing goal-directed behavior. Structural centers for united and integrated of information in voluntary and goal-directed behavior are globus pallidus. Substantia nigra pars reticulata switches the information from corticobasal networks to thalamocortical networks, induces global dopaminergic (DA) signal and organize interaction of mesolimbic and nigostriatnoy DA systems controlled by prefrontal and motor cortex. Together with the motor cortex, substantia nigra displays information in the brainstem and spinal cord to implementation of behavior. Motivation states are formed in the interaction of neurohormonal and neuropeptide systems by monoaminergic systems of brain. Emotional states are formed by monoaminergic systems of the mid-brain, where the leading role belongs to the mesolimbic DA system. The emotional and motivation state of the encoded specific epigenetic molecular and chemical pattern of neuron. PMID:27149821

  12. ETIOLOGY, TRIGGERS AND NEUROCHEMICAL CIRCUITS ASSOCIATED WITH UNEXPECTED, EXPECTED, AND LABORATORY-INDUCED PANIC ATTACKS

    PubMed Central

    Johnson, Philip L.; Federici, Lauren M.; Shekhar, Anantha

    2014-01-01

    Panic disorder (PD) is a severe anxiety disorder that is characterized by recurrent panic attacks (PA), which can be unexpected (uPA, i.e., no clear identifiable trigger) or expected (ePA). Panic typically involves an abrupt feeling of catastrophic fear or distress accompanied by physiological symptoms such as palpitations, racing heart, thermal sensations, and sweating. Recurrent uPA and ePA can also lead to agoraphobia, where subjects with PD avoid situations that were associated with PA. Here we will review recent developments in our understanding of PD, which includes discussions on: symptoms and signs associated with uPA and ePAs; Diagnosis of PD and the new DSM-V; biological etiology such as heritability and gene x environment and gene x hormonal development interactions; comparisons between laboratory and naturally occurring uPAs and ePAs; neurochemical systems that are associated with clinical PAs (e.g. gene associations; targets for triggering or treating PAs), adaptive fear and panic response concepts in the context of new NIH RDoc approach; and finally strengths and weaknesses of translational animal models of adaptive and pathological panic states. PMID:25130976

  13. The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons.

    PubMed

    Helley, M P; Abate, W; Jackson, S K; Bennett, J H; Thompson, S W N

    2015-12-01

    The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naïve conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system. PMID:26434622

  14. Comparative neurochemical profile of 3,4-methylenedioxymethamphetamine and its metabolite alpha-methyldopamine on key targets of MDMA neurotoxicity.

    PubMed

    Escubedo, E; Abad, S; Torres, I; Camarasa, J; Pubill, D

    2011-01-01

    The neurotoxicity of MDMA or "Ecstasy" in rats is selectively serotonergic, while in mice it is both dopaminergic and serotonergic. MDMA metabolism may play a key role in this neurotoxicity. The function of serotonin and dopamine transporter and the effect of MDMA and its metabolites on them are essential to understand MDMA neurotoxicity. The aim of the present study was to investigate and compare the effects of MDMA and its metabolite alpha-methyldopamine (MeDA) on several molecular targets, mainly the dopamine and serotonin transporter functionality, to provide evidence for the role of this metabolite in the neurotoxicity of MDMA in rodents. MeDA had no affinity for the serotonin transporter but competed with serotonin for its uptake. It had no persistent effects on the functionalism of the serotonin transporter, in contrast to the effect of MDMA. Moreover, MeDA inhibited the uptake of dopamine into the serotonergic terminal and also MAO(B) activity. MeDA inhibited dopamine uptake with a lower IC(50) value than MDMA. After drug washout, the inhibition by MeDA persisted while that of MDMA was significantly reduced. The effect of MDMA on the dopamine transporter is related with dopamine release from vesicular stores, as this inhibition disappeared in reserpine-treated animals. However, the effect of MeDA seems to be a persistent conformational change of this transporter. Moreover, in contrast with MDMA, MeDA did not show affinity for nicotinic receptors, so no effects of MeDA derived from these interactions can be expected. The metabolite reduced cell viability at lower concentrations than MDMA. Apoptosis plays a key role in MDMA induced cellular toxicity but necrosis is the major process involved in MeDA cytotoxicity. We conclude that MeDA could protect against the serotonergic lesion induced by MDMA but potentiate the dopaminergic lesion as a result of the persistent blockade of the dopamine transporter induced this metabolite. PMID:21074589

  15. Quantificational logic of context

    SciTech Connect

    Buvac, Sasa

    1996-12-31

    In this paper we extend the Propositional Logic of Context, to the quantificational (predicate calculus) case. This extension is important in the declarative representation of knowledge for two reasons. Firstly, since contexts are objects in the semantics which can be denoted by terms in the language and which can be quantified over, the extension enables us to express arbitrary first-order properties of contexts. Secondly, since the extended language is no longer only propositional, we can express that an arbitrary predicate calculus formula is true in a context. The paper describes the syntax and the semantics of a quantificational language of context, gives a Hilbert style formal system, and outlines a proof of the system`s completeness.

  16. Antidepressant-like effect of trans-resveratrol in chronic stress model: behavioral and neurochemical evidences.

    PubMed

    Yu, Yingcong; Wang, Rui; Chen, Chunbai; Du, Xia; Ruan, Lina; Sun, Jiao; Li, Jianxin; Zhang, Lu; O'Donnell, James M; Pan, Jianchun; Xu, Ying

    2013-03-01

    Trans-resveratrol is a phenolic compound enriched in polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of trans-resveratrol. The present study investigated whether trans-resveratrol has antidepressant-like activity in rats exposed to chronic stress by using two behavioral tasks, shuttle box and sucrose preference tests. The monoamines (5-HT, noradrenaline and dopamine) and their metabolites as well as monoamine oxidase (MAO) enzyme activities in different brain regions were also measured. Compared to unstressed rats, those exposed to chronic stress paradigm showed performance deficits in the shuttle box, reduced sucrose preference, less weight gain and the increase in the ratio of adrenal gland to body weight, which were reversed by chronic treatment with trans-resveratrol (40 and 80 mg/kg, i.g.). The neurochemical assay showed that higher dose of trans-resveratrol (80 mg/kg) produced a marked increase of 5-HT levels in three brain regions, the frontal cortex, hippocampus and hypothalamus. Noradrenaline and dopamine levels were also increased both in the frontal cortex and striatum. Furthermore, chronic treatment with trans-resveratrol was found to inhibit monoamine oxidase-A (MAO-A) activity in all the four brain regions, particularly in the frontal cortex and hippocampus; while MAO-B activity was not affected. These findings indicate that the antidepressant-like effect of trans-resveratrol involves the regulation of the central serotonin and noradrenaline levels and the related MAO-A activities. PMID:23174668

  17. Brain Histamine Is Crucial for Selective Serotonin Reuptake Inhibitors‘ Behavioral and Neurochemical Effects

    PubMed Central

    Munari, Leonardo; Provensi, Gustavo; Passani, Maria Beatrice; Galeotti, Nicoletta; Cassano, Tommaso; Benetti, Fernando; Corradetti, Renato

    2015-01-01

    Backgound: The neurobiological changes underlying depression resistant to treatments remain poorly understood, and failure to respond to selective serotonin reuptake inhibitors may result from abnormalities of neurotransmitter systems that excite serotonergic neurons, such as histamine. Methods: Using behavioral (tail suspension test) and neurochemical (in vivo microdialysis, Western-blot analysis) approaches, here we report that antidepressant responses to selective serotonin reuptake inhibitors (citalopram or paroxetine) are abolished in mice unable to synthesize histamine due to either targeted disruption of histidine decarboxylase gene (HDC-/-) or injection of alpha-fluoromethylhistidine, a suicide inhibitor of this enzyme. Results: In the tail suspension test, all classes of antidepressants tested reduced the immobility time of controls. Systemic reboxetine or imipramine reduced the immobility time of histamine-deprived mice as well, whereas selective serotonin reuptake inhibitors did not even though their serotonergic system is functional. In in vivo microdialysis experiments, citalopram significantly increased histamine extraneuronal levels in the cortex of freely moving mice, and methysergide, a serotonin 5-HT1/5-HT2 receptor antagonist, abolished this effect, thus suggesting the involvement of endogenous serotonin. CREB phosphorylation, which is implicated in the molecular mechanisms of antidepressant treatment, was abolished in histamine-deficient mice treated with citalopram. The CREB pathway is not impaired in HDC-/- mice, as administration of 8-bromoadenosine 3’, 5’-cyclic monophosphate increased CREB phosphorylation, and in the tail suspension test it significantly reduced the time spent immobile by mice of both genotypes. Conclusions: Our results demonstrate that selective serotonin reuptake inhibitors selectively require the integrity of the brain histamine system to exert their preclinical responses. PMID:25899065

  18. Multimodal neuroimaging based classification of autism spectrum disorder using anatomical, neurochemical, and white matter correlates

    PubMed Central

    Libero, Lauren E.; DeRamus, Thomas P.; Lahti, Adrienne C.; Deshpande, Gopikrishna; Kana, Rajesh K.

    2016-01-01

    Neuroimaging techniques, such as fMRI, structural MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) have uncovered evidence for widespread functional and anatomical brain abnormalities in autism spectrum disorder (ASD) suggesting it to be a system-wide neural systems disorder. Nevertheless, most previous studies have focused on examining one index of neuropathology through a single neuroimaging modality, and seldom using multiple modalities to examine the same cohort of individuals. The current study aims to bring together multiple brain imaging modalities (structural MRI, DTI, and 1H-MRS) to investigate the neural architecture in the same set of individuals (19 high-functioning adults with ASD and 18 typically developing (TD) peers). Morphometry analysis revealed increased cortical thickness in ASD participants, relative to typical controls, across the left cingulate, left pars opercularis of the inferior frontal gyrus, left inferior temporal cortex, and right precuneus, and reduced cortical thickness in right cuneus and right precentral gyrus. ASD adults also had reduced fractional anisotropy (FA) and increased radial diffusivity (RD) for two clusters on the forceps minor of the corpus callosum, revealed by DTI analyses. 1H-MRS results showed a reduction in the N-acetylaspartate/Creatine ratio in dorsal anterior cingulate cortex (dACC) in ASD participants. A decision tree classification analysis across the three modalities resulted in classification accuracy of 91.9% with FA, RD, and cortical thickness as key predictors. Examining the same cohort of adults with ASD and their TD peers, this study found alterations in cortical thickness, white matter (WM) connectivity, and neurochemical concentration in ASD. These findings underscore the potential for multimodal imaging to better inform on the neural characteristics most relevant to the disorder. PMID:25797658

  19. Neurochemical impact of bisphenol A in the hippocampus and cortex of adult male albino rats.

    PubMed

    Khadrawy, Yasser A; Noor, Neveen A; Mourad, Iman M; Ezz, Heba S Aboul

    2016-09-01

    Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in the manufacture of polycarbonated plastics and epoxy resins and line metal beverage cans. Growing evidence suggests that BPA acts directly on neuronal functions as it is lipophilic and could accumulate in the brain. The present study aims to investigate the effect of two doses of BPA (10 mg/kg for 6 and 10 weeks and 25 mg/kg for 6 weeks) on excitatory (glutamate and aspartate) and inhibitory (γ-aminobutyric acid, glycine, and taurine) amino acid neurotransmitter levels in the cortex and hippocampus. This study extends to investigate the effect of BPA on acetylcholinesterase (AchE) activity and some oxidative stress parameters in the two regions. In the cortex, a significant increase in the excitatory and a significant decrease in the inhibitory amino acids occurred after BPA (10 mg/kg for 10 weeks and 25 mg/kg for 6 weeks). This was accompanied by a significant increase in lipid peroxidation, nitric oxide, and reduced glutathione after 6 weeks of BPA (25 mg/kg). In the hippocampus, a significant increase in the excitatory and inhibitory amino acid neurotransmitters occurred after 6 weeks of BPA. Hippocampal lipid peroxidation increased significantly after BPA exposure and hippocampal reduced glutathione increased significantly after 6 weeks of BPA exposure (10 mg/kg). BPA induced a significant increase in cortical and hippocampal AchE activity. The present neurochemical changes in the cortex and hippocampus suggest that BPA induced a state of excitotoxicity and oxidative stress. This may raise concerns about the exposure of humans to BPA due to its wide applications in industry. PMID:25903087

  20. Short term cadmium administration dose dependently elicits immediate biochemical, neurochemical and neurobehavioral dysfunction in male rats.

    PubMed

    Haider, Saida; Anis, Lubna; Batool, Zehra; Sajid, Irfan; Naqvi, Fizza; Khaliq, Saima; Ahmed, Shoaib

    2015-02-01

    Cadmium is a toxic environmental and industrial pollutant. Cadmium toxicity has been reported to produce biochemical and behavioral dysfunction that may cause adverse effects on several organs including the central nervous system. The present study was designed to investigate the neurotoxic effects of Cadmium Chloride (CdCl2) at three different doses by using different behavioral models. Lipid peroxidation (LPO), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities were also monitored following acute intraperitoneal injection of cadmium. Twenty four adult locally bred Albino Wistar rats were divided into control and 3 test groups (n = 6). Control rats were injected intraperitoneally with saline (0.9% NaCl) and test groups were injected with CdCl2 (1 mg/kg, 2 mg/kg and 3 mg/kg) dissolved in physiological solution. Behavioral activities of rats were monitored after 1 h of cadmium injection. Locomotor activity and depression-like symptoms were measured by Open Field Test (OFT) and Forced Swimming Test (FST) respectively. Anxiety like behavior was monitored using Light-dark Transition (LDT) test and memory functions of rats were assessed by Morris Water Maze test (MWM). In the present study acute cadmium administration dose dependently increased anxiety in rats as compared to control rats. A significant increase in depression-like symptoms was also exhibited by cadmium treated rats. These behavioral dysfunctions may be attributed to the decreased superoxide dismutase (SOD) activity and simultaneously increased brain lipid peroxidation (LPO). Moreover learning and memory assessed by MWM showed dose dependent impairment in memory function in cadmium treated rats as compared to control rats. Acetylcholinesterase (AChE) activity was also decreased in brains of cadmium administered rats. It is suggested in this study that behavioral, biochemical and neurochemical dysfunctions caused by acute cadmium administration occur in a dose dependent manner. PMID

  1. Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

    PubMed

    McClay, Joseph L; Vunck, Sarah A; Batman, Angela M; Crowley, James J; Vann, Robert E; Beardsley, Patrick M; van den Oord, Edwin J

    2015-09-01

    Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects. PMID:25850894

  2. Beneficial behavioral, neurochemical and molecular effects of 1-(R)-aminoindan in aged mice.

    PubMed

    Badinter, Felix; Amit, Tamar; Bar-Am, Orit; Youdim, Moussa B H; Weinreb, Orly

    2015-12-01

    Previous neuroprotective studies demonstrated that 1-(R)-aminoindan (AI), which is the major metabolite of the anti-Parkinsonian drug rasagiline, possesses beneficial pharmacological effects in various cell culture and animal models of neurodegeneration. The present study was aimed at investigating the possible neuroprotective effects of AI on cognitive impairments and neurochemical alterations in aged mice. Our findings provide evidence that following chronic systemic treatment with AI (5 mg/kg; daily; 3 months) of aged mice (24 months old), the compound exerted a significant positive impact on neuropsychiatric functions and cognitive behavior deficits, assessed in a variety of tasks (spatial learning and memory retention, working memory, learning abilities and nest building behavior) and produced an antidepressant-like effect. In addition, chronic AI treatment significantly enhanced expression levels of neurotrophins, including brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF), tyrosine kinase- B (Trk-B) receptor and synaptic plasticity markers, such as synapsin-1 and growth-associated protein-43 (GAP-43) in the striatum and hippocampus in aged mice. Our results also indicate that AI treatment up-regulated the expression levels of the pro-survival Bcl-2 mRNA, increased the anti-apoptotic index Bcl-2/Bax and enhanced the activity of the antioxidant enzyme catalase in the brain of aged mice. These effects of AI were also confirmed in aged rats (24 months old). Altogether, the present findings indicate that AI can induce neuroprotective effects on age-related alterations in neurobehavioral functions and exerts neurotrophic up-regulatory and anti-apoptotic properties in aged animals. PMID:26087462

  3. Gender and estrous cycle influences on behavioral and neurochemical alterations in adult rats neonatally administered ketamine.

    PubMed

    Célia Moreira Borella, Vládia; Seeman, Mary V; Carneiro Cordeiro, Rafaela; Vieira dos Santos, Júnia; Romário Matos de Souza, Marcos; Nunes de Sousa Fernandes, Ethel; Santos Monte, Aline; Maria Mendes Vasconcelos, Silvânia; Quinn, John P; de Lucena, David F; Carvalho, André F; Macêdo, Danielle

    2016-05-01

    Neonatal N-methyl-D-aspartate (NMDA) receptor blockade in rodents triggers schizophrenia (SCZ)-like alterations during adult life. SCZ is influenced by gender in age of onset, premorbid functioning, and course. Estrogen, the hormone potentially driving the gender differences in SCZ, is known to present neuroprotective effects such as regulate oxidative pathways and the expression of brain-derived neurotrophic factor (BDNF). Thus, the aim of this study was to verify if differences in gender and/or estrous cycle phase during adulthood would influence the development of behavioral and neurochemical alterations in animals neonatally administered ketamine. The results showed that ketamine-treated male (KT-male) and female-in-diestrus (KTF-diestrus, the low estrogen phase) presented significant deficits in prepulse inhibition of the startle reflex and spatial working memory, two behavioral SCZ endophenotypes. On the contrary, female ketamine-treated rats during proestrus (KTF-proestrus, the high estradiol phase) had no behavioral alterations. This correlated with an oxidative imbalance in the hippocampus (HC) of both male and KTF-diestrus female rats, that is, decreased levels of GSH and increased levels of lipid peroxidation and nitrite. Similarly, BDNF was decreased in the KTF-diestrus rats while no alterations were observed in KTF-proestrus and male animals. The changes in the HC were in contrast to those in the prefrontal cortex in which only increased levels of nitrite in all groups studied were observed. Thus, there is a gender difference in the adult rat HC in response to ketamine neonatal administration, which is based on the estrous cycle. This is discussed in relation to neuropsychiatric conditions and in particular SCZ. PMID:26215537

  4. Statistical Quantification of Methylation Levels by Next-Generation Sequencing

    PubMed Central

    Wu, Guodong; Yi, Nengjun; Absher, Devin; Zhi, Degui

    2011-01-01

    Background/Aims Recently, next-generation sequencing-based technologies have enabled DNA methylation profiling at high resolution and low cost. Methyl-Seq and Reduced Representation Bisulfite Sequencing (RRBS) are two such technologies that interrogate methylation levels at CpG sites throughout the entire human genome. With rapid reduction of sequencing costs, these technologies will enable epigenotyping of large cohorts for phenotypic association studies. Existing quantification methods for sequencing-based methylation profiling are simplistic and do not deal with the noise due to the random sampling nature of sequencing and various experimental artifacts. Therefore, there is a need to investigate the statistical issues related to the quantification of methylation levels for these emerging technologies, with the goal of developing an accurate quantification method. Methods In this paper, we propose two methods for Methyl-Seq quantification. The first method, the Maximum Likelihood estimate, is both conceptually intuitive and computationally simple. However, this estimate is biased at extreme methylation levels and does not provide variance estimation. The second method, based on Bayesian hierarchical model, allows variance estimation of methylation levels, and provides a flexible framework to adjust technical bias in the sequencing process. Results We compare the previously proposed binary method, the Maximum Likelihood (ML) method, and the Bayesian method. In both simulation and real data analysis of Methyl-Seq data, the Bayesian method offers the most accurate quantification. The ML method is slightly less accurate than the Bayesian method. But both our proposed methods outperform the original binary method in Methyl-Seq. In addition, we applied these quantification methods to simulation data and show that, with sequencing depth above 40–300 (which varies with different tissue samples) per cleavage site, Methyl-Seq offers a comparable quantification

  5. Relationships among mercury, selenium, and neurochemical parameters in common loons (Gavia immer) and bald eagles (Haliaeetus leucocephalus).

    PubMed

    Scheuhammer, A M; Basu, N; Burgess, N M; Elliott, J E; Campbell, G D; Wayland, M; Champoux, L; Rodrigue, J

    2008-02-01

    Fish-eating birds can be exposed to levels of dietary methylmercury (MeHg) known or suspected to adversely affect normal behavior and reproduction, but little is known regarding Hg's subtle effects on the avian brain. In the current study, we explored relationships among Hg, Se, and neurochemical receptors and enzymes in two fish-eating birds--common loons (Gavia immer) and bald eagles (Haliaeetus leucocephalus). In liver, both species demonstrated a wide range of total Hg (THg) concentrations, substantial demethylation of MeHg, and a co-accumulation of Hg and Se. In liver, there were molar excesses of Se over Hg up to about 50-60 microg/g THg, above which there was an approximate 1:1 molar ratio of Hg:Se in both species. However, in brain, bald eagles displayed a greater apparent ability to demethylate MeHg than common loons. There were molar excesses of Se over Hg in brains of bald eagles across the full range of THg concentrations, whereas common loons often had extreme molar excesses of Hg in their brains, with a higher proportion of THg remaining as MeHg compared with eagles. There were significant positive correlations between brain THg and muscarinic cholinergic receptor concentrations in both species studied; whereas significant negative correlations were observed between N-methyl-D-aspartic acid (NMDA) receptor levels and brain Hg concentration. There were no significant correlations between brain Se and neurochemical receptors or enzymes (cholinesterase and monoamine oxidase) in either species. Our findings suggest that there are significant differences between common loons and bald eagles with respect to cerebral metabolism and toxicodynamics of MeHg and Se. These interspecies differences may influence relative susceptibility to MeHg toxicity; however, neurochemical responses to Hg in both species were similar. PMID:17899374

  6. Neurochemical and cellular specializations in the mammalian neocortex reflect phylogenetic relationships: evidence from primates, cetaceans, and artiodactyls.

    PubMed

    Hof, P R; Glezer, I I; Nimchinsky, E A; Erwin, J M

    2000-06-01

    Most of the available data on the cytoarchitecture of the cerebral cortex in mammals rely on Nissl, Golgi, and myelin stains and few studies have explored the differential morphologic and neurochemical phenotypes of neuronal populations. In addition, the majority of studies addressing the distribution and morphology of identified neuronal subtypes have been performed in common laboratory animals such as the rat, mouse, cat, and macaque monkey, as well as in postmortem analyses in humans. Several neuronal markers, such as neurotransmitters or structural proteins, display a restricted cellular distribution in the mammalian brain, and recently, certain cytoskeletal proteins and calcium-binding proteins have emerged as reliable markers for morphologically distinct subpopulations of neurons in a large number of mammalian species. In this article, we review the morphologic characteristics and distribution of three calcium-binding proteins, parvalbumin, calbindin, and calretinin, and of the neurofilament protein triplet, a component of the neuronal cytoskeleton, to provide an overview of the presence and cellular typology of these proteins in the neocortex of various mammalian taxa. Considering the remarkable diversity in gross morphological patterns and neuronal organization that occurred during the evolution of mammalian neocortex, the distribution of these neurochemical markers may help define taxon-specific patterns. In turn, such patterns can be used as reliable phylogenetic traits to assess the degree to which neurochemical specialization of neurons, as well as their regional and laminar distribution in the neocortex, represent derived or ancestral features, and differ in certain taxa from the laboratory species that are most commonly studied. PMID:10971015

  7. Neurochemical changes correlated with behavior maintained under fixed-interval and fixed-ratio schedules of reinforcement.

    PubMed Central

    Barrett, J E; Hoffmann, S M

    1991-01-01

    Key pecking of 4 pigeons was maintained under a multiple 3-min fixed-interval, 30-response fixed-ratio schedule of food presentation. Only one schedule was in effect during an experimental session, and each was correlated with a different keylight stimulus and location (left vs. right). The different schedule components alternated across days or weeks. Cerebrospinal fluid was collected from chronically implanted intracerebroventricular cannulae following sessions with the different schedules, as well as following sessions in which reinforcement was withheld (extinction), when response-independent food was delivered, and when the experimental chamber was dark and there were no scheduled events. Metabolites of the neurotransmitters serotonin, norepinephrine, and dopamine were assayed in cerebrospinal fluid using high-performance liquid chromatography with electrochemical detection. Compared to the fixed-ratio condition, responding maintained under the fixed-interval schedule resulted in consistently higher levels of the serotonin metabolite 5-hydroxyindoleacetic acid and of the dopamine metabolite homovanillic acid in all pigeons. Levels of 3-methoxy-4-hydroxyphenylethylene glycol, a metabolite of norepinephrine, and dihydroxyphenylacetic acid, another dopamine metabolite, were also higher in 3 of the 4 pigeons following exposure to the fixed-interval schedules when compared to levels of these metabolites after exposure to the fixed-ratio schedule. Extinction of fixed-ratio responding resulted in large increases in 5-hydroxyindoleacetic acid compared to levels of this metabolite under the fixed-ratio schedule, whereas this serotonin metabolite decreased during extinction of responding under the fixed-interval schedule. Control procedures suggested that the neurochemical changes were not related to the rate of responding but were a function of the specific experimental conditions. Distinctive neurochemical changes that accompany schedule-controlled responding show the

  8. Expanding neurochemical investigations with multi-modal recording: simultaneous fast-scan cyclic voltammetry, iontophoresis, and patch clamp measurements.

    PubMed

    Kirkpatrick, D C; McKinney, C J; Manis, P B; Wightman, R M

    2016-08-01

    Multi-modal recording describes the simultaneous collection of information across distinct domains. Compared to isolated measurements, such studies can more easily determine relationships between varieties of phenomena. This is useful for neurochemical investigations which examine cellular activity in response to changes in the local chemical environment. In this study, we demonstrate a method to perform simultaneous patch clamp measurements with fast-scan cyclic voltammetry (FSCV) using optically isolated instrumentation. A model circuit simulating concurrent measurements was used to predict the electrical interference between instruments. No significant impact was anticipated between methods, and predictions were largely confirmed experimentally. One exception was due to capacitive coupling of the FSCV potential waveform into the patch clamp amplifier. However, capacitive transients measured in whole-cell current clamp recordings were well below the level of biological signals, which allowed the activity of cells to be easily determined. Next, the activity of medium spiny neurons (MSNs) was examined in the presence of an FSCV electrode to determine how the exogenous potential impacted nearby cells. The activities of both resting and active MSNs were unaffected by the FSCV waveform. Additionally, application of an iontophoretic current, used to locally deliver drugs and other neurochemicals, did not affect neighboring cells. Finally, MSN activity was monitored during iontophoretic delivery of glutamate, an excitatory neurotransmitter. Membrane depolarization and cell firing were observed concurrently with chemical changes around the cell resulting from delivery. In all, we show how combined electrophysiological and electrochemical measurements can relate information between domains and increase the power of neurochemical investigations. PMID:27314130

  9. [Neurochemical characteristics of rats during flight on the Kosmos-782 artificial satellite and after returning to earth].

    PubMed

    Gazenko, O G; Demin, N N; Panov, A N; Rashevskaia, D A; Rubinskaia, N L

    1979-01-01

    The brain of rats flown aboard the biosatellite Cosmos-782 was sampled immediately postflight and taken under neurochemical study. It was shown cytospectrophotometrically that the absolute content of RNA decreased by 20% in the cytoplasm of cerebellar Purkinje cells and remained unaltered in glial cells-satellites, and that the protein content did not change. In the frontal cortex (homogenates) the concentration of sulfhydryl groups decreased by 26%, activity of nonspecific cholinesterase by 33%. The activity of the latter in the cerebellum also diminished. PMID:502422

  10. Neurochemical Phenotype of Reelin Immunoreactive Cells in the Piriform Cortex Layer II

    PubMed Central

    Carceller, Hector; Rovira-Esteban, Laura; Nacher, Juan; Castrén, Eero; Guirado, Ramon

    2016-01-01

    Reelin, a glycoprotein expressed by Cajal-Retzius neurons throughout the marginal layer of developing neocortex, has been extensively shown to play an important role during brain development, guiding neuronal migration and detachment from radial glia. During the adult life, however, many studies have associated Reelin expression to enhanced neuronal plasticity. Although its mechanism of action in the adult brain remains mostly unknown, Reelin is expressed mainly by a subset of mature interneurons. Here, we confirm the described phenotype of this subpopulation in the adult neocortex. We show that these mature interneurons, although being in close proximity, lack polysialylated neural cell adhesion molecule (PSA-NCAM) expression, a molecule expressed by a subpopulation of mature interneurons, related to brain development and involved in neuronal plasticity of the adult brain as well. However, in the layer II of Piriform cortex there is a high density of cells expressing Reelin whose neurochemical phenotype and connectivity has not been described before. Interestingly, in close proximity to these Reelin expressing cells there is a numerous subpopulation of immature neurons expressing PSA-NCAM and doublecortin (DCX) in this layer of the Piriform cortex. Here, we show that Reelin cells express the neuronal marker Neuronal Nuclei (NeuN), but however the majority of neurons lack markers of mature excitatory or inhibitory neurons. A detail analysis of its morphology indicates these that some of these cells might correspond to semilunar neurons. Interestingly, we found that the majority of these cells express T-box brain 1 (TBR-1) a transcription factor found not only in post-mitotic neurons that differentiate to glutamatergic excitatory neurons but also in Cajal-Retzius cells. We suggest that the function of these Reelin expressing cells might be similar to that of the Cajal-Retzius cells during development, having a role in the maintenance of the immature phenotype of the

  11. Raphe serotonin neurons are not homogenous: Electrophysiological, morphological and neurochemical evidence

    PubMed Central

    Calizo, Lyngine H.; Ma, Xiaohang; Pan, Yuzhen; Lemos, Julia; Craige, Caryne; Heemstra, Lyndia; Beck, Sheryl G.

    2011-01-01

    The median (MR) and dorsal raphe (DR) nuclei contain the majority of the 5-hydroxytryptamine (5-HT, serotonin) neurons that project to limbic forebrain regions, are important in regulating homeostatic functions and are implicated in the etiology and treatment of mood disorders and schizophrenia. The primary synaptic inputs within and to the raphe are glutamatergic and GABAergic. The DR is divided into three subfields, i.e., ventromedial (vmDR), lateral wings (lwDR) and dorsomedial (dmDR). Our previous work shows that cell characteristics of 5-HT neurons and the magnitude of the 5-HT1A and 5-HT1B receptor-mediated responses in the vmDR and MR are not the same. We extend these observations to examine the electrophysiological properties across all four raphe subfields in both 5-HT and non-5-HT neurons. The neurochemical topography of glutamatergic and GABAergic cell bodies and nerve terminals were identified using immunohistochemistry and the morphology of the 5-HT neurons was measured. Although 5-HT neurons possessed similar physiological properties, important differences existed between subfields. Non-5-HT neurons were indistinguishable from 5-HT neurons. GABA neurons were distributed throughout the raphe, usually in areas devoid of 5-HT neurons. Although GABAergic synaptic innervation was dense throughout the raphe (immunohistochemical analysis of the GABA transporters GAT1 and GAT3), their distributions differed. Glutamate neurons, as defined by vGlut3 antibodies, were intermixed and co-localized with 5-HT neurons within all raphe subfields. Finally, the dendritic arbor of the 5-HT neurons was distinct between subfields. Previous studies regard 5-HT neurons as a homogenous population. Our data support a model of the raphe as an area composed of functionally distinct subpopulations of 5-HT and non-5-HT neurons, in part delineated by subfield. Understanding the interaction of the cell properties of the neurons in concert with their morphology, local distribution of

  12. Raphe serotonin neurons are not homogenous: electrophysiological, morphological and neurochemical evidence.

    PubMed

    Calizo, Lyngine H; Akanwa, Adaure; Ma, Xiaohang; Pan, Yu-Zhen; Lemos, Julia C; Craige, Caryne; Heemstra, Lydia A; Beck, Sheryl G

    2011-09-01

    The median (MR) and dorsal raphe (DR) nuclei contain the majority of the 5-hydroxytryptamine (5-HT, serotonin) neurons that project to limbic forebrain regions, are important in regulating homeostatic functions and are implicated in the etiology and treatment of mood disorders and schizophrenia. The primary synaptic inputs within and to the raphe are glutamatergic and GABAergic. The DR is divided into three subfields, i.e., ventromedial (vmDR), lateral wings (lwDR) and dorsomedial (dmDR). Our previous work shows that cell characteristics of 5-HT neurons and the magnitude of the 5-HT(1A) and 5-HT(1B) receptor-mediated responses in the vmDR and MR are not the same. We extend these observations to examine the electrophysiological properties across all four raphe subfields in both 5-HT and non-5-HT neurons. The neurochemical topography of glutamatergic and GABAergic cell bodies and nerve terminals were identified using immunohistochemistry and the morphology of the 5-HT neurons was measured. Although 5-HT neurons possessed similar physiological properties, important differences existed between subfields. Non-5-HT neurons were indistinguishable from 5-HT neurons. GABA neurons were distributed throughout the raphe, usually in areas devoid of 5-HT neurons. Although GABAergic synaptic innervation was dense throughout the raphe (immunohistochemical analysis of the GABA transporters GAT1 and GAT3), their distributions differed. Glutamate neurons, as defined by vGlut3 anti-bodies, were intermixed and co-localized with 5-HT neurons within all raphe subfields. Finally, the dendritic arbor of the 5-HT neurons was distinct between subfields. Previous studies regard 5-HT neurons as a homogenous population. Our data support a model of the raphe as an area composed of functionally distinct subpopulations of 5-HT and non-5-HT neurons, in part delineated by subfield. Understanding the interaction of the cell properties of the neurons in concert with their morphology, local

  13. Behavior in the forced swim test and neurochemical changes in the hippocampus in young rats after 2-week zinc deprivation.

    PubMed

    Tamano, Haruna; Kan, Fumika; Kawamura, Mika; Oku, Naoto; Takeda, Atsushi

    2009-12-01

    Abnormal behavior in zinc deficiency and its cause are poorly understood. In the present paper, behavior in the forced swim test and neurochemical changes in the brain associated with its behavior were studied focused on abnormal corticosterone secretion in zinc deficiency. The effect of chronic corticosterone treatment was also studied. Immobility time in the forced swim test was increased in young rats fed a zinc-deficient diet for 2 weeks, as well as corticosterone (40mg/kg/dayx14 days)-treated control rats. The basal Ca(2+) levels in the hippocampus, which were determined by fluo-4FF, AM, were increased in both brain slices from zinc-deficient and corticosterone-treated rats. Serum glucose level was decreased in zinc deficiency and hippocampal glucose metabolism, which is determined by [(14)C]2-deoxyglucose uptake, was elevated. Hippocampal ATP level was not decreased, whereas, the concentrations of glutamate, GABA and glutamine in the hippocampus, unlike the whole brain, were decreased in zinc deficiency. However, the decrease in these amino acids was restored by adrenalectomy prior to zinc deficiency. These results suggest that glucose is insufficient for the synthesis of amino acids in the hippocampus of zinc-deficient rats. It is likely that the neurochemical and metabolic changes in the hippocampus, which may be associated with abnormal corticosterone secretion, is the base of abnormal behavior associated with neuropsychological symptoms in zinc deficiency. PMID:19463882

  14. Neurochemical evidence for the presence of sympathetic nerve terminals in the rat mammary gland: Changes during the lactogenic cycle.

    PubMed

    Donoso, E A; Sapag-Hagar, M; Lara, H E

    1992-02-01

    Experiments were undertaken to obtain neurochemical evidence of the presence of sympathetic nerve terminals in the rat mammary gland and the changes occurring in them during the lactogenic cycle. The norepinephrine (NE) content of the gland changed during the lactogenic cycle. Higher levels of NE were found during virginity and involution, whereas a lower level was found at 14 days of lactation. Surgical and chemical (with 6-hydroxydopamine) denervation reduced the norepinephrine content of the gland by 61 and 90%, respectively. Uptake of [(3)H]norepinephrine by the mammary gland was saturable and specifically blocked by cocaine. No changes in the maximal capacity of incorporation during the lactogenic cycle were found, but the affinity of NE for the transmembrane carrier was low during lactation, as was the NE content, suggesting a decrease in the sympathetic nerve activity during this stage of the lactogenic cycle. In support of this, we found a decrease in total NE released after stimulation with 80 mM KCI. The neurochemical evidence obtained during this research strongly suggests that rat mammary gland is innervated by sympathetic nerves and that their activity changes during the lactogenic cycle. PMID:19912841

  15. Neurochemical substrates of the rewarding effects of MDMA: implications for the development of pharmacotherapies to MDMA dependence.

    PubMed

    Roger-Sánchez, Concepción; García-Pardo, María P; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, María A

    2016-04-01

    In recent years, studies with animal models of reward, such as the intracranial self-stimulation, self-administration, and conditioned place preference paradigms, have increased our knowledge on the neurochemical substrates of the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in rodents. However, pharmacological and neuroimaging studies with human participants are scarce. Serotonin [5-hydroxytryptamine (5-HT)], dopamine (DA), endocannabinoids, and endogenous opiates are the main neurotransmitter systems involved in the rewarding effects of MDMA in rodents, but other neurotransmitters such as glutamate, acetylcholine, adenosine, and neurotensin are also involved. The most important finding of recent research is the demonstration of differential involvement of specific neurotransmitter receptor subtypes (5-HT2, 5-HT3, DA D1, DA D2, CB1, μ and δ opioid, etc.) and extracellular proteins (DA and 5-HT transporters) in the acquisition, expression, extinction, and reinstatement of MDMA self-administration and conditioned place preference. It is important to extend the research on the effects of different compounds acting on these receptors/transporters in animal models of reward, especially in priming-induced, cue-induced, and stress-induced reinstatement. Increase in knowledge of the neurochemical substrates of the rewarding effects of MDMA may contribute to the design of new pharmacological treatments for individuals who develop MDMA dependence. PMID:26650254

  16. Treatment with Trehalose Prevents Behavioral and Neurochemical Deficits Produced in an AAV α-Synuclein Rat Model of Parkinson's Disease.

    PubMed

    He, Qing; Koprich, James B; Wang, Ying; Yu, Wen-Bo; Xiao, Bao-Guo; Brotchie, Jonathan M; Wang, Jian

    2016-05-01

    The accumulation of misfolded α-synuclein in dopamine (DA) neurons is believed to be of major importance in the pathogenesis of Parkinson's disease (PD). Animal models of PD, based on viral-vector-mediated over-expression of α-synuclein, have been developed and show evidence of dopaminergic toxicity, providing us a good tool to investigate potential therapies to interfere with α-synuclein-mediated pathology. An efficient disease-modifying therapeutic molecule should be able to interfere with the neurotoxicity of α-synuclein aggregation. Our study highlighted the ability of an autophagy enhancer, trehalose (at concentrations of 5 and 2 % in drinking water), to protect against A53T α-synuclein-mediated DA degeneration in an adeno-associated virus serotype 1/2 (AAV1/2)-based rat model of PD. Behavioral tests and neurochemical analysis demonstrated a significant attenuation in α-synuclein-mediated deficits in motor asymmetry and DA neurodegeneration including impaired DA neuronal survival and DA turnover, as well as α-synuclein accumulation and aggregation in the nigrostriatal system by commencing 5 and 2 % trehalose at the same time as delivery of AAV. Trehalose (0.5 %) was ineffective on the above behavioral and neurochemical deficits. Further investigation showed that trehalose enhanced autophagy in the striatum by increasing formation of LC3-II. This study supports the concept of using trehalose as a novel therapeutic strategy that might prevent/reverse α-synuclein aggregation for the treatment of PD. PMID:25972237

  17. Symmetry quantification and mapping using convergent beam electron diffraction.

    PubMed

    Kim, Kyou-Hyun; Zuo, Jian-Min

    2013-01-01

    We propose a new algorithm to quantify symmetry recorded in convergent beam electron diffraction (CBED) patterns and use it for symmetry mapping in materials applications. We evaluate the effectiveness of the profile R-factor (R(p)) and the normalized cross-correlation coefficient (γ) for quantifying the amount of symmetry in a CBED pattern. The symmetry quantification procedures are automated and the algorithm is implemented as a DM (Digital Micrograph(©)) script. Experimental and simulated CBED patterns recorded from a Si single crystal are used to calibrate the proposed algorithm for the symmetry quantification. The proposed algorithm is then applied to a Si sample with defects to test the sensitivity of symmetry quantification to defects. Using the mirror symmetry as an example, we demonstrate that the normalized cross-correlation coefficient provides an effective and robust measurement of the symmetry recorded in experimental CBED patterns. PMID:23142747

  18. Absolute and relative quantification of RNA modifications via biosynthetic isotopomers

    PubMed Central

    Kellner, Stefanie; Ochel, Antonia; Thüring, Kathrin; Spenkuch, Felix; Neumann, Jennifer; Sharma, Sunny; Entian, Karl-Dieter; Schneider, Dirk; Helm, Mark

    2014-01-01

    In the resurging field of RNA modifications, quantification is a bottleneck blocking many exciting avenues. With currently over 150 known nucleoside alterations, detection and quantification methods must encompass multiple modifications for a comprehensive profile. LC–MS/MS approaches offer a perspective for comprehensive parallel quantification of all the various modifications found in total RNA of a given organism. By feeding 13C-glucose as sole carbon source, we have generated a stable isotope-labeled internal standard (SIL-IS) for bacterial RNA, which facilitates relative comparison of all modifications. While conventional SIL-IS approaches require the chemical synthesis of single modifications in weighable quantities, this SIL-IS consists of a nucleoside mixture covering all detectable RNA modifications of Escherichia coli, yet in small and initially unknown quantities. For absolute in addition to relative quantification, those quantities were determined by a combination of external calibration and sample spiking of the biosynthetic SIL-IS. For each nucleoside, we thus obtained a very robust relative response factor, which permits direct conversion of the MS signal to absolute amounts of substance. The application of the validated SIL-IS allowed highly precise quantification with standard deviations <2% during a 12-week period, and a linear dynamic range that was extended by two orders of magnitude. PMID:25129236

  19. Ethanol, 3,4-methylenedioxymethamphetamine (ecstasy) and their combination: long-term behavioral, neurochemical and neuropharmacological effects in the rat.

    PubMed

    Cassel, Jean-Christophe; Riegert, Céline; Rutz, Susanne; Koenig, Julie; Rothmaier, Katharina; Cosquer, Brigitte; Lazarus, Christine; Birthelmer, Anja; Jeltsch, Hélène; Jones, Byron C; Jackisch, Rolf

    2005-10-01

    This study investigated long-term behavioral, neurochemical, and neuropharmacological effects of ethanol-(+/-)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) combinations. Over 4 consecutive days, male Long-Evans rats received 1.5 g/kg ethanol and/or 10 mg/kg MDMA, or saline. Rectal temperatures were taken in some rats. Starting 4 days after the last injection, we tested working memory, sensory-motor coordination, and anxiety. Subsequently, we measured cortical, striatal, septal, and hippocampal monoamines (last MDMA injection-euthanasia delay: 20 days), or electrically evoked release of serotonin (5-HT) in cortical and hippocampal slices, and its modulation in the presence of CP 93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrollo[3,2-b]pyrid-5-one) or methiotepin (last MDMA injection-euthanasia delays: 3-6 weeks). Ethanol attenuated the MDMA-induced hyperthermia, but only on the first day. In the long-term, MDMA reduced 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content in most brain regions. The behavioral and neurochemical effects of the ethanol-MDMA combination were comparable to those of MDMA alone; sensory-motor coordination was altered after ethanol and/or MDMA. In hippocampal slices from rats given ethanol and MDMA, the CP 93,129-induced inhibition and methiotepin-induced facilitation of 5-HT release were stronger and weaker, respectively, than in the other groups. This is the first study addressing long-term effects of repeated MDMA and EtOH combined treatments in experimental animals. Whereas the drug combination produced the same behavioral and neurochemical effects as MDMA alone, our neuropharmacological results suggest that MDMA-EtOH interactions may have specific long-term consequences on presynaptic modulation of hippocampal 5-HT release, but not necessarily related to MDMA-induced depletion of 5-HT. Thus, it is likely that the psycho(patho)logical problems reported by ecstasy users drinking alcohol are not solely due to the consumption of MDMA

  20. Wrappers, Aspects, Quantification and Events

    NASA Technical Reports Server (NTRS)

    Filman, Robert E.

    2005-01-01

    Talk overview: Object infrastructure framework (OIF). A system development to simplify building distributed applications by allowing independent implementation of multiple concern. Essence and state of AOP. Trinity. Quantification over events. Current work on a generalized AOP technology.

  1. Abuse-Related Neurochemical Effects of Para-Substituted Methcathinone Analogs in Rats: Microdialysis Studies of Nucleus Accumbens Dopamine and Serotonin.

    PubMed

    Suyama, Julie A; Sakloth, Farhana; Kolanos, Renata; Glennon, Richard A; Lazenka, Matthew F; Negus, S Stevens; Banks, Matthew L

    2016-01-01

    Methcathinone (MCAT) is a monoamine releaser and parent compound to a new class of designer drugs that includes the synthetic cathinones mephedrone and flephedrone. Using MCAT and a series of para-substituted (or 4-substituted) MCAT analogs, it has been previously shown that expression of abuse-related behavioral effects in rats correlates both with the volume of the para substituent and in vitro neurochemical selectivity to promote monoamine release via the dopamine (DA) versus serotonin (5-HT) transporters in rat brain synaptosomes. The present study used in vivo microdialysis to determine the relationship between these previous measures and the in vivo neurochemical selectivity of these compounds to alter nucleus accumbens (NAc) DA and 5-HT levels. Male Sprague-Dawley rats were implanted with bilateral guide cannulae targeting the NAc. MCAT and five para-substituted analogs (4-F, 4-Cl, 4-Br, 4-CH3, and 4-OCH3) produced dose- and time-dependent increases in NAc DA and/or 5-HT levels. Selectivity was determined as the dose required to increase peak 5-HT levels by 250% divided by the dose required to increase peak DA levels by 250%. This measure of in vivo neurochemical selectivity varied across compounds and correlated with 1) in vivo expression of abuse-related behavioral effects (r = 0.89, P = 0.02); 2) in vitro selectivity to promote monoamine release via DA and 5-HT transporters (r = 0.95, P < 0.01); and 3) molecular volume of the para substituent (r = -0.85, P = 0.03). These results support a relationship between these molecular, neurochemical, and behavioral measures and support a role for molecular structure as a determinant of abuse-related neurochemical and behavioral effects of MCAT analogs. PMID:26645638

  2. Nitrogen quantification with SNMS

    NASA Astrophysics Data System (ADS)

    Goschnick, J.; Natzeck, C.; Sommer, M.

    1999-04-01

    Plasma-based secondary neutral mass spectrometry (plasma SNMS) is a powerful analytical method for determining the elemental concentrations of almost any kind of material at low cost by using a cheap quadrupole mass filter. However, a quadrupole-based mass spectrometer is limited to nominal mass resolution. Atomic signals are sometimes superimposed by molecular signals (2 or 3 atomic clusters such as CH +, CH 2+ or metal oxide clusters) and/or intensities of double-charged species. Especially in the case of nitrogen several interferences can impede the quantification. This article reports on methods to recognize and deconvolute superpositions of N + with CH 2+, Li 2+, and Si 2+ at mass 14 D (Debye) occurring during analysis of organic and inorganic substances. The recognition is based on the signal pattern of N +, Li +, CH +, and Si +. The latter serve as indicators for a probable interference of molecular or double-charged species with N on mass 14 D. The subsequent deconvolution use different shapes of atomic and cluster kinetic energy distributions (kEDs) to determine the quantities of the intensity components by a linear fit of N + and non-atomic kEDs obtained from several organic and inorganic standards into the measured kED. The atomic intensity fraction yields a much better nitrogen concentration than the total intensity of mass 14 D after correction.

  3. Quantification of human responses

    NASA Technical Reports Server (NTRS)

    Steinlage, R. C.; Gantner, T. E.; Lim, P. Y. W.

    1992-01-01

    Human perception is a complex phenomenon which is difficult to quantify with instruments. For this reason, large panels of people are often used to elicit and aggregate subjective judgments. Print quality, taste, smell, sound quality of a stereo system, softness, and grading Olympic divers and skaters are some examples of situations where subjective measurements or judgments are paramount. We usually express what is in our mind through language as a medium but languages are limited in available choices of vocabularies, and as a result, our verbalizations are only approximate expressions of what we really have in mind. For lack of better methods to quantify subjective judgments, it is customary to set up a numerical scale such as 1, 2, 3, 4, 5 or 1, 2, 3, ..., 9, 10 for characterizing human responses and subjective judgments with no valid justification except that these scales are easy to understand and convenient to use. But these numerical scales are arbitrary simplifications of the complex human mind; the human mind is not restricted to such simple numerical variations. In fact, human responses and subjective judgments are psychophysical phenomena that are fuzzy entities and therefore difficult to handle by conventional mathematics and probability theory. The fuzzy mathematical approach provides a more realistic insight into understanding and quantifying human responses. This paper presents a method for quantifying human responses and subjective judgments without assuming a pattern of linear or numerical variation for human responses. In particular, quantification and evaluation of linguistic judgments was investigated.

  4. Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry

    PubMed Central

    Bledsoe, Jonathan M.; Kimble, Christopher J.; Covey, Daniel P.; Blaha, Charles D.; Agnesi, Filippo; Mohseni, Pedram; Whitlock, Sidney; Johnson, David M.; Horne, April; Bennet, Kevin E.; Lee, Kendall H.; Garris, Paul A.

    2009-01-01

    Object Emerging evidence supports the hypothesis that modulation of specific central neuronal systems contributes to the clinical efficacy of deep brain stimulation (DBS) and motor cortex stimulation (MCS). Real-time monitoring of the neurochemical output of targeted regions may therefore advance functional neurosurgery by, among other goals, providing a strategy for investigation of mechanisms, identification of new candidate neurotransmitters, and chemically guided placement of the stimulating electrode. The authors report the development of a device called the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for intraoperative neurochemical monitoring during functional neurosurgery. This device supports fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM) for real-time, spatially and chemically resolved neurotransmitter measurements in the brain. Methods The FSCV study consisted of a triangle wave scanned between −0.4 and 1 V at a rate of 300 V/second and applied at 10 Hz. All voltages were compared with an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single carbon fiber (r = 2.5 μm) into a glass capillary and pulling the capillary to a microscopic tip by using a pipette puller. The exposed carbon fiber (that is, the sensing region) extended beyond the glass insulation by ~ 100 μm. The neurotransmitter dopamine was selected as the analyte for most trials. Proof-of-principle tests included in vitro flow injection and noise analysis, and in vivo measurements in urethane-anesthetized rats by monitoring dopamine release in the striatum following high-frequency electrical stimulation of the medial forebrain bundle. Direct comparisons were made to a conventional hardwired system. Results The WINCS, designed in compliance with FDA-recognized consensus standards for medical electrical device safety, consisted of 4 modules: 1) front-end analog circuit for FSCV (that is, current-to-voltage transducer

  5. Visualization and Quantification of Rotor Tip Vortices in Helicopter Flows

    NASA Technical Reports Server (NTRS)

    Kao, David L.; Ahmad, Jasim U.; Holst, Terry L.

    2015-01-01

    This paper presents an automated approach for effective extraction, visualization, and quantification of vortex core radii from the Navier-Stokes simulations of a UH-60A rotor in forward flight. We adopt a scaled Q-criterion to determine vortex regions and then perform vortex core profiling in these regions to calculate vortex core radii. This method provides an efficient way of visualizing and quantifying the blade tip vortices. Moreover, the vortices radii are displayed graphically in a plane.

  6. Quantification noise in single cell experiments

    PubMed Central

    Reiter, M.; Kirchner, B.; Müller, H.; Holzhauer, C.; Mann, W.; Pfaffl, M. W.

    2011-01-01

    In quantitative single-cell studies, the critical part is the low amount of nucleic acids present and the resulting experimental variations. In addition biological data obtained from heterogeneous tissue are not reflecting the expression behaviour of every single-cell. These variations can be derived from natural biological variance or can be introduced externally. Both have negative effects on the quantification result. The aim of this study is to make quantitative single-cell studies more transparent and reliable in order to fulfil the MIQE guidelines at the single-cell level. The technical variability introduced by RT, pre-amplification, evaporation, biological material and qPCR itself was evaluated by using RNA or DNA standards. Secondly, the biological expression variances of GAPDH, TNFα, IL-1β, TLR4 were measured by mRNA profiling experiment in single lymphocytes. The used quantification setup was sensitive enough to detect single standard copies and transcripts out of one solitary cell. Most variability was introduced by RT, followed by evaporation, and pre-amplification. The qPCR analysis and the biological matrix introduced only minor variability. Both conducted studies impressively demonstrate the heterogeneity of expression patterns in individual cells and showed clearly today's limitation in quantitative single-cell expression analysis. PMID:21745823

  7. Neurochemical characterisation of lamina II inhibitory interneurons that express GFP in the PrP-GFP mouse

    PubMed Central

    2013-01-01

    Background Inhibitory interneurons in the superficial dorsal horn play important roles in modulating sensory transmission, and these roles are thought to be performed by distinct functional populations. We have identified 4 non-overlapping classes among the inhibitory interneurons in the rat, defined by the presence of galanin, neuropeptide Y, neuronal nitric oxide synthase (nNOS) and parvalbumin. The somatostatin receptor sst2A is expressed by ~50% of the inhibitory interneurons in this region, and is particularly associated with nNOS- and galanin-expressing cells. The main aim of the present study was to test whether a genetically-defined population of inhibitory interneurons, those expressing green fluorescent protein (GFP) in the PrP-GFP mouse, belonged to one or more of the neurochemical classes identified in the rat. Results The expression of sst2A and its relation to other neurochemical markers in the mouse was similar to that in the rat, except that a significant number of cells co-expressed nNOS and galanin. The PrP-GFP cells were entirely contained within the set of inhibitory interneurons that possessed sst2A receptors, and virtually all expressed nNOS and/or galanin. GFP was present in ~3-4% of neurons in the superficial dorsal horn, corresponding to ~16% of the inhibitory interneurons in this region. Consistent with their sst2A-immunoreactivity, all of the GFP cells were hyperpolarised by somatostatin, and this was prevented by administration of a selective sst2 receptor antagonist or a blocker of G-protein-coupled inwardly rectifying K+ channels. Conclusions These findings support the view that neurochemistry provides a valuable way of classifying inhibitory interneurons in the superficial laminae. Together with previous evidence that the PrP-GFP cells form a relatively homogeneous population in terms of their physiological properties, they suggest that these neurons have specific roles in processing sensory information in the dorsal horn. PMID

  8. Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers.

    PubMed

    García-Cabrerizo, Rubén; García-Fuster, M Julia

    2015-07-01

    While hippocampus is a brain region particularly susceptible to the effects of MDMA, the cellular and molecular changes induced by MDMA are still to be fully elucidated, being the dosage regimen, the species and the developmental stage under study great variables. This study compared the effects of one and four days of MDMA administration following a binge paradigm (3×5 mg/kg, i.p., every 2 h) on inducing hippocampal neurochemical changes in adolescent (PND 37) and young adult (PND 58) rats. The results showed that chronic MDMA caused hippocampal protein deficits in adolescent and young adult rats at different levels: (1) impaired serotonergic (5-HT2A and 5-HT2C post-synaptic receptors) and GABAergic (GAD2 enzyme) signaling, and (2) decreased structural cytoskeletal neurofilament proteins (NF-H, NF-M and NF-L). Interestingly, these effects were not accompanied by an increase in apoptotic markers. In fact, chronic MDMA inhibited proteins of the apoptotic pathway (i.e., pro-apoptotic FADD, Bax and cytochrome c) leading to an inhibition of cell death markers (i.e., p-JNK1/2, cleavage of PARP-1) and suggesting regulatory mechanisms in response to the neurochemical changes caused by the drug. The data, together with the observed lack of GFAP activation, support the view that chronic MDMA effects, regardless of the rat developmental age, extends beyond neurotransmitter systems to impair other hippocampal structural cell markers. Interestingly, inhibitory changes in proteins from the apoptotic pathway might be taking place to overcome the protein deficits caused by MDMA. PMID:26068050

  9. Distinct neurochemical and functional properties of GAD67-containing 5-HT neurons in the rat dorsal raphe nucleus.

    PubMed

    Shikanai, Hiroki; Yoshida, Takayuki; Konno, Kohtarou; Yamasaki, Miwako; Izumi, Takeshi; Ohmura, Yu; Watanabe, Masahiko; Yoshioka, Mitsuhiro

    2012-10-10

    The serotonergic (5-HTergic) system arising from the dorsal raphe nucleus (DRN) is implicated in various physiological and behavioral processes, including stress responses. The DRN is comprised of several subnuclei, serving specific functions with distinct afferent and efferent connections. Furthermore, subsets of 5-HTergic neurons are known to coexpress other transmitters, including GABA, glutamate, or neuropeptides, thereby generating further heterogeneity. However, despite the growing evidence for functional variations among DRN subnuclei, relatively little is known about how they map onto neurochemical diversity of 5-HTergic neurons. In the present study, we characterized functional properties of GAD67-expressing 5-HTergic neurons (5-HT/GAD67 neurons) in the rat DRN, and compared with those of neurons expressing 5-HTergic molecules (5-HT neurons) or GAD67 alone. While 5-HT/GAD67 neurons were absent in the dorsomedial (DRD) or ventromedial (DRV) parts of the DRN, they were selectively distributed in the lateral wing of the DRN (DRL), constituting 12% of the total DRL neurons. They expressed plasmalemmal GABA transporter 1, but lacked vesicular inhibitory amino acid transporter. By using whole-cell patch-clamp recording, we found that 5-HT/GAD67 neurons had lower input resistance and firing frequency than 5-HT neurons. As revealed by c-Fos immunohistochemistry, neurons in the DRL, particularly 5-HT/GAD67 neurons, showed higher responsiveness to exposure to an open field arena than those in the DRD and DRV. By contrast, exposure to contextual fear conditioning stress showed no such regional differences. These findings indicate that 5-HT/GAD67 neurons constitute a unique neuronal population with distinctive neurochemical and electrophysiological properties and high responsiveness to innocuous stressor. PMID:23055511

  10. An investigation of whether there are sex differences in certain behavioural and neurochemical parameters in the rat.

    PubMed

    Simpson, Joy; Kelly, John P

    2012-04-01

    In clinical populations, sex differences in disease prevalence, symptoms and outcome have been established. Despite this, female rats are frequently omitted from preclinical research; growing preclinical evidence, however, illustrates meaningful sex differences in behavioural, neurochemical and neuroanatomical endpoints. This review outlines the effects of sex on tests of depression- and anxiety-like symptoms, learning and memory, and responses to stress in rats. In addition, sexual dimorphisms in monoamine neurotransmitter and neurotrophic factor levels, neurogenesis and plasticity, and responsiveness to drugs of abuse are reviewed. Female rats display greater baseline activity levels compared to males, test-specific sex differences also exist in learning and memory protocols as females respond more actively in conditioning paradigms and are somewhat impaired in tests of spatial memory compared to males. Differential baseline and stress-induced hypothalamic-pituitary-adrenal axis responses between male and female rats depend on the nature of the stressor. Females are more responsive to the effects of psychomotor stimulant drugs; sexual dimorphisms in response to psychotropic drugs are likely mediated by neurochemical differences between male and female rats. Differences exist in neurotransmitter activity, transporter and receptor expression between the sexes. Studies of ovariectomised and intact female rats demonstrate a potent impact of elevated estrogen during the estrous cycle on behaviour, neurochemistry, dendritic growth and drug response. Sex differences in baseline behaviours and the methodological procedures employed can influence behavioural pharmacology result interpretation. In addition, the inclusion of both male and female rats in studies investigating neurochemistry and neuromorphology may enhance the validity of drug or rehabilitative treatments. PMID:22230114

  11. Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 Tesla.

    PubMed

    Bednařík, Petr; Tkáč, Ivan; Giove, Federico; DiNuzzo, Mauro; Deelchand, Dinesh K; Emir, Uzay E; Eberly, Lynn E; Mangia, Silvia

    2015-04-01

    Several laboratories have consistently reported small concentration changes in lactate, glutamate, aspartate, and glucose in the human cortex during prolonged stimuli. However, whether such changes correlate with blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been determined. The present study aimed at characterizing the relationship between metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI data were acquired from 12 volunteers. A short echo-time semi-LASER localization sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS data. The group analysis confirmed that during stimulation lactate and glutamate increased by 0.26 ± 0.06 μmol/g (~30%) and 0.28 ± 0.03 μmol/g (~3%), respectively, while aspartate and glucose decreased by 0.20 ± 0.04 μmol/g (~5%) and 0.19 ± 0.03 μmol/g (~16%), respectively. The single-subject analysis revealed that BOLD-fMRI signals were positively correlated with glutamate and lactate concentration changes. The results show a linear relationship between metabolic and BOLD responses in the presence of strong excitatory sensory inputs, and support the notion that increased functional energy demands are sustained by oxidative metabolism. In addition, BOLD signals were inversely correlated with baseline γ-aminobutyric acid concentration. Finally, we discussed the critical importance of taking into account linewidth effects on metabolite quantification in fMRS paradigms. PMID:25564236

  12. Conessine, an H3 receptor antagonist, alters behavioral and neurochemical effects of ethanol in mice.

    PubMed

    Morais-Silva, Gessynger; Ferreira-Santos, Mariane; Marin, Marcelo T

    2016-05-15

    Ethanol abuse potential is mainly due to its reinforcing properties, crucial in the transition from the recreational to pathological use. These properties are mediated by mesocorticolimbic and nigrostriatal dopaminergic pathways and neuroadaptations in these pathways seem to be responsible for addiction. Both pathways are modulated by other neurotransmitters systems, including neuronal histaminergic system. Among the histamine receptors, H3 receptor stands out due to its role in modulation of histamine and other neurotransmitters release. Thus, histaminergic system, through H3 receptors, may have an important role in ethanol addiction development. Aiming to understand these interactions, conessine, an H3 receptor antagonist, was given to mice subjected to the evaluation of ethanol-induced psychostimulation, ethanol CPP and quantification of norepinephrine, dopamine, serotonin and their metabolites in mesocorticolimbic and nigrostriatal pathways following acute ethanol treatment. Systemic conessine administration exacerbated ethanol effects on locomotor activity. Despite of conessine reinforcing effect on CPP, this drug did not alter acquisition of ethanol CPP. Ethanol treatment affects the serotoninergic neurotransmission in the ventral tegmental area, the dopaminergic neurotransmission in the pre-frontal cortex (PFC) and caudate-putamen nucleus (CPu) and the noradrenergic neurotransmission in the CPu. In the PFC, conessine blocked ethanol effects on dopaminergic and noradrenergic neurotransmission. The blockade of H3 receptors and ethanol seem to interact in the modulation of dopaminergic neurotransmission of nigrostriatal pathway, decreasing dopamine metabolites in substantia nigra. In conclusion, conessine was able to change psychostimulant effect of ethanol, without altering its reinforcing properties. This exacerbation of ethanol-induced psychostimulation would be related to alterations in dopaminergic neurotransmission in the nigrostriatal pathway. PMID

  13. MAMA Software Features: Quantification Verification Documentation-1

    SciTech Connect

    Ruggiero, Christy E.; Porter, Reid B.

    2014-05-21

    This document reviews the verification of the basic shape quantification attributes in the MAMA software against hand calculations in order to show that the calculations are implemented mathematically correctly and give the expected quantification results.

  14. Early Postnatal Exposure to Ultrafine Particulate Matter Air Pollution: Persistent Ventriculomegaly, Neurochemical Disruption, and Glial Activation Preferentially in Male Mice

    PubMed Central

    Allen, Joshua L.; Liu, Xiufang; Pelkowski, Sean; Palmer, Brian; Conrad, Katherine; Oberdörster, Günter; Weston, Douglas; Mayer-Pröschel, Margot

    2014-01-01

    Background: Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression. Objectives: We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development. Methods: We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4–7 and 10–13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified. Results: We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males. Conclusions: We observed brain region– and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be

  15. Mercury, selenium and neurochemical biomarkers in different brain regions of migrating common loons from Lake Erie, Canada.

    PubMed

    Hamilton, Melanie; Scheuhammer, Anton; Basu, Niladri

    2011-10-01

    Common loons (Gavia immer) can be exposed to relatively high levels of dietary methylmercury (MeHg) through fish consumption, and several studies have documented MeHg-associated health effects in this species. To further study the neurological risks of MeHg accumulation, migrating loons dying of Type E botulism were collected opportunistically from the Lake Erie shore at Long Point (Ontario, Canada) and relationships between total mercury (THg), selenium (Se), and selected neurochemical receptors and brain enzymes were investigated. THg concentrations were 1-78 μg/g in liver; and 0.3-4 μg/g in the brain (all concentrations reported on a dry weight basis). A significant (p < 0.05) positive correlation was found between THg in liver and THg in 3 subregions of the brain (cerebral cortex: r = 0.433; cerebellum: r = 0.293; brain stem: r = 0.405). THg varied significantly among different brain regions, with the cortex having the highest concentrations. Se levels in the cortex and cerebellum were 1-29 and 1-10 μg/g, respectively, with no significant differences between regions. Se was not measured in brain stem due to insufficient tissue mass. There were molar excesses of Se over mercury (Hg) in both cortex and cerebellum at all Hg concentrations, and a significant positive relationship between THg and the Hg:Se molar ratio (cortex: r = 0.63; cerebellum: r = 0.47). No significant associations were observed between brain THg and the N-methyl-D-aspartic acid (NMDA) receptor concentration, nor between THg and muscarinic cholinergic (mACh) receptor concentration; however, brain THg levels were lower than in previous studies that reported significant Hg-associated changes in neuroreceptor densities. Together with previous studies, the current findings add to our understanding of Hg distribution in the brain of common loons, and the associations between Hg and sub-lethal neurochemical changes in fish-eating wildlife. PMID:21847660

  16. Transplacental exposure to AZT induces adverse neurochemical and behavioral effects in a mouse model: protection by L-acetylcarnitine.

    PubMed

    Zuena, Anna Rita; Giuli, Chiara; Venerosi Pesciolini, Aldina; Tramutola, Antonella; Ajmone-Cat, Maria Antonietta; Cinque, Carlo; Alemà, Giovanni Sebastiano; Giovine, Angela; Peluso, Gianfranco; Minghetti, Luisa; Nicolai, Raffaella; Calamandrei, Gemma; Casolini, Paola

    2013-01-01

    Maternal-fetal HIV-1 transmission can be prevented by administration of AZT, alone or in combination with other antiretroviral drugs to pregnant HIV-1-infected women and their newborns. In spite of the benefits deriving from this life-saving prophylactic therapy, there is still considerable uncertainty on the potential long-term adverse effects of antiretroviral drugs on exposed children. Clinical and experimental studies have consistently shown the occurrence of mitochondrial dysfunction and increased oxidative stress following prenatal treatment with antiretroviral drugs, and clinical evidence suggests that the developing brain is one of the targets of the toxic action of these compounds possibly resulting in behavioral problems. We intended to verify the effects on brain and behavior of mice exposed during gestation to AZT, the backbone of antiretroviral therapy during human pregnancy. We hypothesized that glutamate, a neurotransmitter involved in excitotoxicity and behavioral plasticity, could be one of the major actors in AZT-induced neurochemical and behavioral alterations. We also assessed the antioxidant and neuroprotective effect of L-acetylcarnitine, a compound that improves mitochondrial function and is successfully used to treat antiretroviral-induced polyneuropathy in HIV-1 patients. We found that transplacental exposure to AZT given per os to pregnant mice from day 10 of pregnancy to delivery impaired in the adult offspring spatial learning and memory, enhanced corticosterone release in response to acute stress, increased brain oxidative stress also at birth and markedly reduced expression of mGluR1 and mGluR5 subtypes and GluR1 subunit of AMPA receptors in the hippocampus. Notably, administration during the entire pregnancy of L-acetylcarnitine was effective in preventing/ameliorating the neurochemical, neuroendocrine and behavioral adverse effects induced by AZT in the offspring. The present preclinical findings provide a mechanistic hypothesis for

  17. Absolute protein quantification of the yeast chaperome under conditions of heat shock

    PubMed Central

    Mackenzie, Rebecca J.; Lawless, Craig; Holman, Stephen W.; Lanthaler, Karin; Beynon, Robert J.; Grant, Chris M.; Hubbard, Simon J.

    2016-01-01

    Chaperones are fundamental to regulating the heat shock response, mediating protein recovery from thermal‐induced misfolding and aggregation. Using the QconCAT strategy and selected reaction monitoring (SRM) for absolute protein quantification, we have determined copy per cell values for 49 key chaperones in Saccharomyces cerevisiae under conditions of normal growth and heat shock. This work extends a previous chemostat quantification study by including up to five Q‐peptides per protein to improve confidence in protein quantification. In contrast to the global proteome profile of S. cerevisiae in response to heat shock, which remains largely unchanged as determined by label‐free quantification, many of the chaperones are upregulated with an average two‐fold increase in protein abundance. Interestingly, eight of the significantly upregulated chaperones are direct gene targets of heat shock transcription factor‐1. By performing absolute quantification of chaperones under heat stress for the first time, we were able to evaluate the individual protein‐level response. Furthermore, this SRM data was used to calibrate label‐free quantification values for the proteome in absolute terms, thus improving relative quantification between the two conditions. This study significantly enhances the largely transcriptomic data available in the field and illustrates a more nuanced response at the protein level. PMID:27252046

  18. Absolute protein quantification of the yeast chaperome under conditions of heat shock.

    PubMed

    Mackenzie, Rebecca J; Lawless, Craig; Holman, Stephen W; Lanthaler, Karin; Beynon, Robert J; Grant, Chris M; Hubbard, Simon J; Eyers, Claire E

    2016-08-01

    Chaperones are fundamental to regulating the heat shock response, mediating protein recovery from thermal-induced misfolding and aggregation. Using the QconCAT strategy and selected reaction monitoring (SRM) for absolute protein quantification, we have determined copy per cell values for 49 key chaperones in Saccharomyces cerevisiae under conditions of normal growth and heat shock. This work extends a previous chemostat quantification study by including up to five Q-peptides per protein to improve confidence in protein quantification. In contrast to the global proteome profile of S. cerevisiae in response to heat shock, which remains largely unchanged as determined by label-free quantification, many of the chaperones are upregulated with an average two-fold increase in protein abundance. Interestingly, eight of the significantly upregulated chaperones are direct gene targets of heat shock transcription factor-1. By performing absolute quantification of chaperones under heat stress for the first time, we were able to evaluate the individual protein-level response. Furthermore, this SRM data was used to calibrate label-free quantification values for the proteome in absolute terms, thus improving relative quantification between the two conditions. This study significantly enhances the largely transcriptomic data available in the field and illustrates a more nuanced response at the protein level. PMID:27252046

  19. Best practices for metabolite quantification in drug development: updated recommendation from the European Bioanalysis Forum.

    PubMed

    Timmerman, Philip; Blech, Stefan; White, Stephen; Green, Martha; Delatour, Claude; McDougall, Stuart; Mannens, Geert; Smeraglia, John; Williams, Stephen; Young, Graeme

    2016-06-01

    Metabolite quantification and profiling continues to grow in importance in today's drug development. The guidance provided by the 2008 FDA Metabolites in Safety Testing Guidance and the subsequent ICH M3(R2) Guidance (2009) has led to a more streamlined process to assess metabolite exposures in preclinical and clinical studies in industry. In addition, the European Bioanalysis Forum (EBF) identified an opportunity to refine the strategies on metabolite quantification considering the experience to date with their recommendation paper on the subject dating from 2010 and integrating the recent discussions on the tiered approach to bioanalytical method validation with focus on metabolite quantification. The current manuscript summarizes the discussion and recommendations from a recent EBF Focus Workshop into an updated recommendation for metabolite quantification in drug development. PMID:27217058

  20. Luminometric Label Array for Quantification and Identification of Metal Ions.

    PubMed

    Pihlasalo, Sari; Montoya Perez, Ileana; Hollo, Niklas; Hokkanen, Elina; Pahikkala, Tapio; Härmä, Harri

    2016-05-17

    Quantification and identification of metal ions has gained interest in drinking water and environmental analyses. We have developed a novel label array method for the quantification and identification of metal ions in drinking water. This simple ready-to-go method is based on the nonspecific interactions of multiple unstable lanthanide chelates and nonantenna ligands with sample leading to a luminescence signal profile, unique to the sample components. The limit of detection at ppb concentration level and average coefficient of variation of 10% were achieved with the developed label array. The identification of 15 different metal ions including different oxidation states Cr(3+)/Cr(6+), Cu(+)/Cu(2+), Fe(2+)/Fe(3+), and Pb(2+)/Pb(4+) was demonstrated. Moreover, a binary mixture of Cu(2+) and Fe(3+) and ternary mixture of Cd(2+), Ni(2+), and Pb(2+) were measured and individual ions were distinguished. PMID:27086705

  1. Lack of Specific Involvement of (+)-Naloxone and (+)-Naltrexone on the Reinforcing and Neurochemical Effects of Cocaine and Opioids.

    PubMed

    Tanda, Gianluigi; Mereu, Maddalena; Hiranita, Takato; Quarterman, Juliana C; Coggiano, Mark; Katz, Jonathan L

    2016-10-01

    Effective medications for drug abuse remain a largely unmet goal in biomedical science. Recently, the (+)-enantiomers of naloxone and naltrexone, TLR4 antagonists, have been reported to attenuate preclinical indicators of both opioid and stimulant abuse. To further examine the potential of these compounds as drug-abuse treatments, we extended the previous assessments to include a wider range of doses and procedures. We report the assessment of (+)-naloxone and (+)-naltrexone on the acute dopaminergic effects of cocaine and heroin determined by in vivo microdialysis, on the reinforcing effects of cocaine and the opioid agonist, remifentanil, tested under intravenous self-administration procedures, as well as the subjective effects of cocaine determined by discriminative-stimulus effects in rats. Pretreatments with (+)-naloxone or (+)-naltrexone did not attenuate, and under certain conditions enhanced the stimulation of dopamine levels produced by cocaine or heroin in the nucleus accumbens shell. Furthermore, although an attenuation of either cocaine or remifentanil self-administration was obtained at the highest doses of (+)-naloxone and (+)-naltrexone, those doses also attenuated rates of food-maintained behaviors, indicating a lack of selectivity of TLR4 antagonist effects for behaviors reinforced with drug injections. Drug-discrimination studies failed to demonstrate a significant interaction of (+)-naloxone with subjective effects of cocaine. The present studies demonstrate that under a wide range of doses and experimental conditions, the TLR4 antagonists, (+)-naloxone and (+)-naltrexone, did not specifically block neurochemical or behavioral abuse-related effects of cocaine or opioid agonists. PMID:27296151

  2. Distinct synaptic and neurochemical changes to the granule cell-CA3 projection in Bassoon mutant mice

    PubMed Central

    Dieni, Sandra; Nestel, Sigrun; Sibbe, Mirjam; Frotscher, Michael; Hellwig, Sabine

    2015-01-01

    Proper synaptic function depends on a finely-tuned balance between events such as protein synthesis and structural organization. In particular, the functional loss of just one synaptic-related protein can have a profound impact on overall neuronal network function. To this end, we used a mutant mouse model harboring a mutated form of the presynaptic scaffolding protein Bassoon (Bsn), which is phenotypically characterized by: (i) spontaneous generalized epileptic seizure activity, representing a chronically-imbalanced neuronal network; and (ii) a dramatic increase in hippocampal brain-derived neurotrophic factor (BDNF) protein concentration, a key player in synaptic plasticity. Detailed morphological and neurochemical analyses revealed that the increased BDNF levels are associated with: (i) modified neuropeptide distribution; (ii) perturbed expression of selected markers of synaptic activation or plasticity; (iii) subtle changes to microglial structure; and (iv) morphological alterations to the mossy fiber (MF) synapse. These findings emphasize the important contribution of Bassoon protein to normal hippocampal function, and further characterize the Bsn-mutant as a useful model for studying the effects of chronic changes to network activity. PMID:26557085

  3. Senescence-accelerated mouse (SAM) as an animal model of senile dementia: pharmacological, neurochemical and molecular biological approach.

    PubMed

    Okuma, Y; Nomura, Y

    1998-12-01

    To elucidate the fundamental mechanism of age-related deficiencies of learning and to develop effective drugs for intervention in age-related diseases such as learning dysfunctions, pertinent animal models that have characteristics closely similar to human dysfunctions should be established. SAM (senescence-accelerated mouse) has been established as a murine model of the SAM strains, groups of related inbred strains including nine strains of accelerated senescence-prone, short-lived mice (SAMP) and three strains of accelerated senescence-resistant, long-lived mice (SAMR). SAMP-strain mice show relatively strain-specific age-associated phenotypic pathologies such as shortened life span and early manifestation of senescence. Among the SAMP-strain mice, SAMP8 mice show an age-related deterioration in learning ability. Here, the neuropathological, neurochemical and pharmacological features of SAM are reported, especially for SAMP8. Moreover, the effects of several drugs on the biochemical and behavioral alterations in SAMP8 and the etiologic manifestation of accelerated senescence are also discussed. PMID:9920195

  4. A history of caloric restriction induces neurochemical and behavioral changes in rats consistent with models of depression

    PubMed Central

    Chandler-Laney, P.C.; Castaneda, E.; Pritchett, C.E.; Smith, M.L.; Giddings, M.; Artiga, A.I.; Boggiano, M.M.

    2007-01-01

    A history of dieting is common in individuals suffering from eating disorders for which depression and mood disturbances are also comorbid. We investigated the effect of a history of caloric restriction (HCR) in rats that involved cyclic food restriction and refeeding with varying levels of access to palatable food (PF) on: 1) responses to the SSRI, fluoxetine; 2) monoamine levels in brain regions central to the control of feeding, reward, and mood regulation; and 3) behavioral tests of anxiety and depression. HCR coupled with intermittent but not daily access to PF exaggerated rats’ anorectic response to fluoxetine (p<0.05); was associated with a significant 71% and 58% reduction of 5-HT and dopamine, respectively, in the medial prefrontal cortex; and induced behaviors consistent with models of depression. HCR, irrespective of access to PF, abolished the strong association between 5-HT and dopamine turnover in the nucleus accumbens in control rats (r =0.71 vs. -0.06, p<0.01). Access to PF, irrespective of HCR, reduced hypothalamic dopamine. Together, these findings suggest that a history of frequent food restriction-induced weight fluctuation imposes neurochemical changes that negatively impact feeding and mood regulation. PMID:17490740

  5. Benzoyl chloride derivatization with liquid chromatography-mass spectrometry for targeted metabolomics of neurochemicals in biological samples.

    PubMed

    Wong, Jenny-Marie T; Malec, Paige A; Mabrouk, Omar S; Ro, Jennifer; Dus, Monica; Kennedy, Robert T

    2016-05-13

    Widely targeted metabolomic assays are useful because they provide quantitative data on large groups of related compounds. We report a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method that utilizes benzoyl chloride labeling for 70 neurologically relevant compounds, including catecholamines, indoleamines, amino acids, polyamines, trace amines, antioxidants, energy compounds, and their metabolites. The method includes neurotransmitters and metabolites found in both vertebrates and insects. This method was applied to analyze microdialysate from rats, human cerebrospinal fluid, human serum, fly tissue homogenate, and fly hemolymph, demonstrating its broad versatility for multiple physiological contexts and model systems. Limits of detection for most assayed compounds were below 10nM, relative standard deviations were below 10%, and carryover was less than 5% for 70 compounds separated in 20min, with a total analysis time of 33min. This broadly applicable method provides robust monitoring of multiple analytes, utilizes small sample sizes, and can be applied to diverse matrices. The assay will be of value for evaluating normal physiological changes in metabolism in neurochemical systems. The results demonstrate the utility of benzoyl chloride labeling with HPLC-MS/MS for widely targeted metabolomics assays. PMID:27083258

  6. Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: an in vivo localized (1)H MRS study.

    PubMed

    Iltis, Isabelle; Koski, Dee M; Eberly, Lynn E; Nelson, Christopher D; Deelchand, Dinesh K; Valette, Julien; Ugurbil, Kamil; Lim, Kelvin O; Henry, Pierre-Gilles

    2009-08-01

    Acute phencyclidine (PCP) administration mimics some aspects of schizophrenia in rats, such as behavioral alterations, increased dopaminergic activity and prefrontal cortex dysfunction. In this study, we used single-voxel (1)H-MRS to investigate neurochemical changes in rat prefrontal cortex in vivo before and after an acute injection of PCP. A short-echo time sequence (STEAM) was used to acquire spectra in a 32-microL voxel positioned in the prefrontal cortex area of 12 rats anesthetized with isoflurane. Data were acquired for 30 min before and for 140 min after a bolus of PCP (10 mg/kg, n = 6) or saline (n = 6). Metabolites were quantified with the LCModel. Time courses for 14 metabolites were obtained with a temporal resolution of 10 min. The glutamine/glutamate ratio was significantly increased after PCP injection (p < 0.0001, pre- vs. post-injection), while the total concentration of these two metabolites remained constant. Glucose was transiently increased (+70%) while lactate decreased after the injection (both p < 0.0001). Lactate, but not glucose and glutamine, returned to baseline levels after 140 min. These results show that an acute injection of PCP leads to changes in glutamate and glutamine concentrations, similar to what has been observed in schizophrenic patients, and after ketamine administration in humans. MRS studies of this pharmacological rat model may be useful for assessing the effects of potential anti-psychotic drugs in vivo. PMID:19338025

  7. Distinct synaptic and neurochemical changes to the granule cell-CA3 projection in Bassoon mutant mice.

    PubMed

    Dieni, Sandra; Nestel, Sigrun; Sibbe, Mirjam; Frotscher, Michael; Hellwig, Sabine

    2015-01-01

    Proper synaptic function depends on a finely-tuned balance between events such as protein synthesis and structural organization. In particular, the functional loss of just one synaptic-related protein can have a profound impact on overall neuronal network function. To this end, we used a mutant mouse model harboring a mutated form of the presynaptic scaffolding protein Bassoon (Bsn), which is phenotypically characterized by: (i) spontaneous generalized epileptic seizure activity, representing a chronically-imbalanced neuronal network; and (ii) a dramatic increase in hippocampal brain-derived neurotrophic factor (BDNF) protein concentration, a key player in synaptic plasticity. Detailed morphological and neurochemical analyses revealed that the increased BDNF levels are associated with: (i) modified neuropeptide distribution; (ii) perturbed expression of selected markers of synaptic activation or plasticity; (iii) subtle changes to microglial structure; and (iv) morphological alterations to the mossy fiber (MF) synapse. These findings emphasize the important contribution of Bassoon protein to normal hippocampal function, and further characterize the Bsn-mutant as a useful model for studying the effects of chronic changes to network activity. PMID:26557085

  8. In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain.

    PubMed

    Schmidt, C J; Levin, J A; Lovenberg, W

    1987-03-01

    A single high dose of methylenedioxymethamphetamine, a psychedelic agent, produced a rapid and persistent depletion of striatal indoles similar to that observed following administration of the serotonergic neurotoxin p-chloroamphetamine. The drug had little effect on dopaminergic variables. Like p-chloroamphetamine, methylenedioxymethamphetamine was found to be a relatively selective agent for inducing [3H]serotonin release in vitro. The serotonin uptake inhibitor, citalopram, blocked both [3H]serotonin release in vitro and striatal serotonin depletion in vivo, indicating that both processes were carrier dependent. In vivo comparisons of the stereoisomers of methylenedioxymethamphetamine indicated two phases of serotonin depletion similar to those reported for p-chloroamphetamine. Although both the (+)- and (-)-stereoisomers produced an acute (3 hr) decrease in striatal indoles, the long-term effects of the drug showed stereoselectivity in that the (+)-enantiomer produced the most dramatic serotonin depletion. Comparison of the effects of the stereoisomers of methylenedioxymethamphetamine and its n-desmethyl analog, methylenedioxyamphetamine, on [3H]serotonin and [3H]dopamine release in vitro showed the (+)-enantiomer of both drugs to be the more potent releasing agent. In spite of its reported lack of hallucinogenic activity, (+)methylenedioxyamphetamine was found to be of a potency similar to that of (+)methylenedioxymethamphetamine in inducing [3H]serotonin release in vitro. The results are discussed in terms of the neurochemical similarities between methylenedioxymethamphetamine and p-chloroamphetamine as well as the proposed role of serotonin release in the behavioral effects of methylenedioxymethamphetamine. PMID:2881549

  9. Neurochemical abnormalities in anterior cingulate cortex on betel quid dependence: a 2D 1H MRS investigation

    PubMed Central

    Liu, Tao; Li, Jianjun; Huang, Shixiong; Zhao, Zhongyan; Yang, Guoshuai; Pan, Mengjie; Li, Changqing; Chen, Feng; Pan, Suyue

    2015-01-01

    The effects of betel quid dependence (BQD) on biochemical changes remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered neurochemicals in Magnetic Resonance Spectroscopy Imaging (MRSI) and those changes are usually earlier than structural alteration. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an 2D 1H-MRS study to observe brain biochemical alterations in the anterior cingulated cortex (ACC) associated with the severity of BQD and duration of BQD. In the bilateral ACC, our study found NAA/Cr were lower in BQD individuals compared to the healthy controls, Cho/Cr and Glx/Cr were higher in individuals with BQD compared to the healthy group, but increase was noted for mI/Cr in BQD individuals only in the left ACC. NAA/Cr ratios of the right ACC negatively correlated with BQDS and duration, NAA/Cr ratios of the left ACC negatively correlated with duration, Glx/Cr ratios of the right ACC positively correlated with BQDS. The findings of the study support previous analyses of a role for ACC area in the mediation of BQ addiction and mechanistically explain past observations of reduced ACC grey matter in BQD patients. These data jointly point to state related abnormalities of BQ effect and provide a novel strategy of therapeutic intervention designed to normalize Glu transmission and function during treating BQ addiction. PMID:26885276

  10. Mass spectrometry based proteomics for absolute quantification of proteins from tumor cells

    PubMed Central

    Wang, Hong; Hanash, Sam

    2015-01-01

    In-depth quantitative profiling of the proteome and sub-proteomes of tumor cells has relevance to tumor classification, the development of novel therapeutics, and of prognostic and predictive markers and to disease monitoring. In particular the tumor cell surface represents a highly relevant compartment for the development of targeted therapeutics and immunotherapy. We have developed a proteomic platform to profile tumor cells that encompasses enrichment of surface membrane proteins, intact protein fractionation and label-free mass spectrometry based absolute quantification. Here we describe the methodology for capture, identification and quantification of cell surface proteins using biotinylation for labeling of the cell surface, avidin for capture of biotinylated proteins and ion mobility mass spectrometry for protein identification and quantification. PMID:25794949

  11. An HPLC-ECD method for monoamines and metabolites quantification in cuttlefish (cephalopod) brain tissue.

    PubMed

    Bidel, Flavie; Corvaisier, Sophie; Jozet-Alves, Christelle; Pottier, Ivannah; Dauphin, François; Naud, Nadège; Bellanger, Cécile

    2016-08-01

    The cuttlefish belongs to the mollusk class Cephalopoda, considered as the most advanced marine invertebrates and thus widely used as models to study the biology of complex behaviors and cognition, as well as their related neurochemical mechanisms. Surprisingly, methods to quantify the biogenic monoamines and their metabolites in cuttlefish brain remain sparse and measure a limited number of analytes. This work aims to validate an HPLC-ECD method for the simultaneous quantification of dopamine, serotonin, norepinephrine and their main metabolites in cuttlefish brain. In comparison and in order to develop a method suitable to answer both ecological and biomedical questions, the validation was also carried out on a phylogenetically remote species: mouse (mammals). The method was shown to be accurate, precise, selective, repeatable and sensitive over a wide range of concentrations for 5-hydroxyindole-3-acetic acid, serotonin, dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine in the both extracts of cuttlefish and mouse brain, though with low precision and recovery for 4-hydroxy-3-methoxyphenylethylene glycol. Homovanillic acid, accurately studied in rodents, was not detectable in the brain of cuttlefish. Overall, we described here the first fully validated HPLC method for the routine measurement of both monoamines and metabolites in cuttlefish brain. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26613377

  12. Neuregulin-1β Regulates the migration of Different Neurochemical Phenotypic Neurons from Organotypically Cultured Dorsal Root Ganglion Explants.

    PubMed

    Li, Yunfeng; Liu, Guixiang; Li, Hao; Bi, Yanwen

    2016-01-01

    Neuregulin-1β (NRG-1β) has multiple roles in the development and function in the nervous system and exhibits potent neuroprotective properties. In the present study, organotypically cultured dorsal root ganglion (DRG) explants were used to evaluate the effects of NRG-1β on migration of two major phenotypic classes of DRG neurons. The signaling pathways involved in these effects were also determined. Organotypically cultured DRG explants were exposed to NRG-1β (20 nmol/L), the phosphatidylinositol 3-kinase inhibitor LY294002 (10 μmol/L) plus NRG-1β (20 nmol/L), the extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 (10 μmol/L) plus NRG-1β (20 nmol/L), and LY294002 (10 μmol/L) plus PD98059 (10 μmol/L) plus NRG-1β (20 nmol/L), respectively, for 3 days. The DRG explants were continuously exposed to culture media as a control. After that, all above cultures were processed for detecting the mRNA levels of calcitonin gene-related peptide (CGRP) and neurofilament-200 (NF-200) by real-time PCR analysis. CGRP and NF-200 expression in situ was determined by fluorescent labeling technique. The results showed that NRG-1β elevated the mRNA and protein levels of CGRP and NF-200. NRG-1β also increased the number and the percentage of CGRP-immunoreactive (IR) migrating neurons and NF-200-IR migrating neurons. Inhibitors (LY294002, PD98059) either alone or in combination blocked the effects of NRG-1β. The contribution of NRG-1β on modulating distinct neurochemical phenotypic plasticity of DRG neurons suggested that NRG-1β signaling system might play an important role on the biological effects of primary sensory neurons. PMID:26093851

  13. In vivo and In vitro neurochemical-based assessments of wastewater effluents from the Maumee River area of concern.

    PubMed

    Arini, Adeline; Cavallin, Jenna E; Berninger, Jason P; Marfil-Vega, Ruth; Mills, Marc; Villeneuve, Daniel L; Basu, Niladri

    2016-04-01

    Wastewater treatment plant (WWTP) effluents contain potentially neuroactive chemicals though few methods are available to screen for the presence of such agents. Here, two parallel approaches (in vivo and in vitro) were used to assess WWTP exposure-related changes to neurochemistry. First, fathead minnows (FHM, Pimephales promelas) were caged for four days along a WWTP discharge zone into the Maumee River (Ohio, USA). Grab water samples were collected and extracts obtained for the detection of alkylphenols, bisphenol A (BPA) and steroid hormones. Second, the extracts were then used as a source of in vitro exposure to brain tissues from FHM and four additional species relevant to the Great Lakes ecosystem (rainbow trout (RT), river otter (RO), bald eagle (BE) and human (HU)). The ability of the wastewater (in vivo) or extracts (in vitro) to interact with enzymes (monoamine oxidase (MAO) and glutamine synthetase (GS)) and receptors (dopamine (D2) and N-methyl-D-aspartate receptor (NMDA)) involved in dopamine and glutamate-dependent neurotransmission were examined on brain homogenates. In vivo exposure of FHM led to significant decreases of NMDA receptor binding in females (24-42%), and increases of MAO activity in males (2.8- to 3.2-fold). In vitro, alkylphenol-targeted extracts significantly inhibited D2 (66% in FHM) and NMDA (24-54% in HU and RT) receptor binding, and induced MAO activity in RT, RO, and BE brains. Steroid hormone-targeted extracts inhibited GS activity in all species except FHM. BPA-targeted extracts caused a MAO inhibition in FHM, RT and BE brains. Using both in vivo and in vitro approaches, this study shows that WWTP effluents contain agents that can interact with neurochemicals important in reproduction and other neurological functions. Additional work is needed to better resolve in vitro to in vivo extrapolations (IVIVE) as well as cross-species differences. PMID:26736051

  14. ELEVATED LEVELS OF KYNURENIC ACID DURING GESTATION PRODUCE NEUROCHEMICAL, MORPHOLOGICAL, AND COGNITIVE DEFICITS IN ADULTHOOD: IMPLICATIONS FOR SCHIZOPHRENIA

    PubMed Central

    Pershing, Michelle L.; Bortz, David M.; Pocivavsek, Ana; Fredericks, Peter J.; Jørgensen, Christinna V.; Vunck, Sarah A.; Leuner, Benedetta; Schwarcz, Robert; Bruno, John P.

    2016-01-01

    The levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha 7 nicotinic acetylcholine receptors (α7nAChRs), are elevated in the brains of patients with schizophrenia (SZ). We reported that increases of brain KYNA in rats, through dietary exposure to its precursor kynurenine from embryonic day (ED)15 to postnatal day (PD) 21, result in neurochemical and cognitive deficits in adulthood. The present experiments focused on the effects of prenatal exposure to elevated kynurenine on measures of prefrontal excitability known to be impaired in SZ. Pregnant dams were fed a mash containing kynurenine (100 mg/day; progeny = EKYNs) from ED15 until ED22. Controls were fed an unadulterated mash (progeny = ECONs). The dietary loading procedure elevated maternal and fetal plasma kynurenine (2223% and 693% above controls, respectively) and increased fetal KYNA (forebrain; 500% above controls) on ED21. Elevations in forebrain KYNA disappeared after termination of the loading (PD2), but KYNA levels in the prefrontal cortex (PFC) were unexpectedly increased again when measured in adults (PD56-80; 75% above controls). We also observed changes in several markers of prefrontal excitability, including expression of the α7nAChR (22% and 17% reductions at PD2 and PD56-80), expression of mGluR2 (31% and 24% reductions at ED21 and PD56-80), dendritic spine density (11–14% decrease at PD56-80), subsensitive mesolimbic stimulation of glutamate release in PFC, and reversal/extra-dimensional shift deficits in the prefrontally-mediated set-shifting task. These results highlight the deleterious impact of elevated KYNA levels during sensitive periods of early development, which model the pathophysiological and cognitive deficits seen in SZ. PMID:25446576

  15. Behavioral and neurochemical characterization of TrkB-dependent mechanisms of agomelatine in glucocorticoid receptor-impaired mice.

    PubMed

    Boulle, F; Velthuis, H; Koedam, K; Steinbusch, H W; van den Hove, D L A; Kenis, G; Gabriel, C; Mocaer, E; Franc, B; Rognan, D; Mongeau, R; Lanfumey, L

    2016-01-01

    Growing evidence indicates that impairment of the stress response, in particular the negative feedback regulation mechanism exerted by the hypothalamo-pituitary-adrenal (HPA) axis, might be responsible for the hippocampal atrophy observed in depressed patients. Antidepressants, possibly through the activation of BDNF signaling, may enhance neuroplasticity and restore normal hippocampal functions. In this context, glucocorticoid receptor-impaired (GR-i) mice-a transgenic mouse model of reduced GR-induced negative feedback regulation of the HPA axis-were used to investigate the role of BDNF/TrkB signaling in the behavioral and neurochemical effects of the new generation antidepressant drug, agomelatine. GR-i mice exhibited marked alterations in depressive-like and anxiety-like behaviors, together with a decreased cell proliferation and altered levels of neuroplastic and epigenetic markers in the hippocampus. GR-i mice and their wild-type littermates were treated for 21 days with vehicle, agomelatine (50mg/kg/day; i.p) or the TrkB inhibitor Ana-12 (0.5mg/kg/day, i.p) alone, or in combination with agomelatine. Chronic treatment with agomelatine resulted in antidepressant-like effects in GR-i mice and reversed the deficit in hippocampal cell proliferation and some of the alterations of mRNA plasticity markers in GR-i mice. Ana-12 blocked the effect of agomelatine on motor activity as well as its ability to restore a normal hippocampal cell proliferation and expression of neurotrophic factors. Altogether, our findings indicate that agomelatine requires TrkB signaling to reverse some of the molecular and behavioral alterations caused by HPA axis impairment. PMID:26653128

  16. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder. PMID:26498253

  17. The P-glycoprotein inhibitor cyclosporin A differentially influences behavioural and neurochemical responses to the antidepressant escitalopram.

    PubMed

    O'Brien, Fionn E; O'Connor, Richard M; Clarke, Gerard; Donovan, Maria D; Dinan, Timothy G; Griffin, Brendan T; Cryan, John F

    2014-03-15

    Recent studies have raised the possibility that P-glycoprotein (P-gp) inhibition may represent a putative augmentation strategy for treatment with certain antidepressants. Indeed, we have previously shown that administration of the P-gp inhibitor verapamil increased the brain distribution and behavioural effects of the antidepressant escitalopram. The aim of the current study was to investigate if similar effects occur with another P-gp inhibitor, cyclosporin A (CsA). CsA pre-treatment exacerbated the severity of behaviours in an escitalopram-induced mouse model of serotonin syndrome, a potentially life-threatening adverse drug reaction associated with serotonergic drugs. P-gp inhibition by CsA enhanced the brain distribution of escitalopram by 70-80%. Serotonin (5-HT) turnover in the prefrontal cortex was reduced by escitalopram, and this effect was augmented by CsA. However, CsA pre-treatment did not augment the effect of escitalopram in the tail suspension test (TST) of antidepressant-like activity. Microdialysis experiments revealed that pre-treatment with CsA failed to augment, but blunted, the increase in extracellular 5-HT in response to escitalopram administration. This blunting effect may contribute to the lack of augmentation in the TST. Taken together, the present studies demonstrate that co-administration of CsA and escitalopram produces differential effects depending on the behavioural and neurochemical assays employed. Thus, the results highlight the need for further studies involving more selective pharmacological tools to specifically evaluate the impact of P-gp inhibition on behavioural responses to antidepressants which are subject to efflux by P-gp. PMID:24280122

  18. Non-parametric analysis of neurochemical effects and Arc expression in amphetamine-induced 50-kHz ultrasonic vocalization.

    PubMed

    Hamed, Adam; Daszczuk, Patrycja; Kursa, Miron Bartosz; Turzyńska, Danuta; Sobolewska, Alicja; Lehner, Małgorzata; Boguszewski, Paweł M; Szyndler, Janusz

    2016-10-01

    A number of studies have identified the importance of dopaminergic, opioid, serotonergic, noradrenergic and glutamatergic neurotransmission in amphetamine-induced "50-kHz" ultrasonic vocalizations (USVs). Amphetamine became a topic of interest for many researchers interested in USVs due to its ability to induce 50-kHz USVs. To date, it has been difficult to identify the neurotransmitters responsible for this phenomenon. The aim of this study was to determine the following: (i) concentrations of neurotransmitters in selected structures of the rat brain after re-exposure of the rats to amphetamine administration; (ii) changes in Arc in the medial prefrontal cortex, striatum, nucleus accumbens core and shell, hippocampus, amygdala and ventral tegmental area; and (iii) a biological basis for differences in 50-kHz USV emissions in response to amphetamine administration. Re-exposure to amphetamine increased 50-kHz USVs. This parameter do not correlate with distance covered by the investigated animals. An increased concentration of noradrenaline in the nucleus accumbens (NAcc) strongly correlated with the number of 50-kHz USVs. We found that NAcc noradrenaline concentrations negatively correlated with the concentration of dopamine and dopamine metabolites and positively correlated with the concentration of GABA and 5-HIAA (serotonin metabolite) in this structure. We have also identified a positive correlation between striatal 3-MT (dopamine metabolite) concentrations and Arc expression in the hippocampal DG as well as a negative correlation between the concentration of GABA in the amygdala and Arc expression in the central amygdala. Thus, the relationship between the emission of 50-kHz USVs and the neurochemical changes that occur after re-exposure to amphetamine indicates cross-talk between NA, DA, 5-HT and GABA neurotransmission in the NAcc. PMID:27288591

  19. Behavioral and Neurochemical Deficits in Aging Rats with Increased Neonatal Iron Intake: Silibinin’s Neuroprotection by Maintaining Redox Balance

    PubMed Central

    Chen, Hanqing; Wang, Xijin; Wang, Meihua; Yang, Liu; Yan, Zhiqiang; Zhang, Yuhong; Liu, Zhenguo

    2015-01-01

    Aging is a critical risk factor for Parkinson’s disease. Silibinin, a major flavonoid in Silybum marianum, has been suggested to display neuroprotective properties against various neurodegenerative diseases. In the present study, we observed that neonatal iron (120 μg/g body weight) supplementation resulted in significant abnormality of behavior and depletion of striatal dopamine (DA) in the aging male and female rats while it did not do so in the young male and female rats. No significant change in striatal serotonin content was observed in the aging male and female rats with neonatal supplementation of the same dose of iron. Furthermore, we found that the neonatal iron supplementation resulted in significant increase in malondialdehyde (MDA) and decrease in glutathione (GSH) in the substantia nigra (SN) of the aging male and female rats. No significant change in content of MDA and GSH was observed in the cerebellum of the aging male and female rats with the neonatal iron supplementation. Interestingly, silibinin (25 and 50 mg/kg body weight) treatment significantly and dose-dependently attenuated depletion of striatal DA and improved abnormality of behavior in the aging male and female rats with the neonatal iron supplementation. Moreover, silibinin significantly reduced MDA content and increased GSH content in the SN of the aging male and female rats. Taken together, our results indicate that elevated neonatal iron supplementation may result in neurochemical and behavioral deficits in the male and female rats with aging and silibinin may exert dopaminergic neuroprotection by maintaining redox balance. PMID:26578951

  20. Microfluidic Platform with In-Chip Electrophoresis Coupled to Mass Spectrometry for Monitoring Neurochemical Release from Nerve Cells.

    PubMed

    Li, Xiangtang; Hu, Hankun; Zhao, Shulin; Liu, Yi-Ming

    2016-05-17

    Chemical stimulus-induced neurotransmitter release from neuronal cells is well-documented. However, the dynamic changes in neurochemical release remain to be fully explored. In this work, a three-layered microfluidic chip was fabricated and evaluated for studying the dynamics of neurotransmitter release from PC-12 cells. The chip features integration of a nanoliter sized chamber for cell perfusion, pneumatic pressure valves for fluidic control, a microfluidic channel for electrophoretic separation, and a nanoelectrospray emitter for ionization in MS detection. Deploying this platform, a microchip electrophoresis-mass spectrometric method (MCE-MS) was developed to simultaneously quantify important neurotransmitters, including dopamine (DA), serotonin (5-HT), aspartic acid (Asp), and glutamic acid (Glu) without need for labeling or enrichment. Monitoring neurotransmitter release from PC-12 cells exposed to KCl (or alcohol) revealed that all four neurotransmitters investigated were released. Two release patterns were observed, one for the two monoamine neurotransmitters (i.e., DA and 5-HT) and another for the two amino acid neurotransmitters. Release dynamics for the two monoamine neurotransmitters was significantly different. The cells released DA most quickly and heavily in response to the stimulation. After exposure to the chemical stimulus for 4 min, the DA level in the perfusate from the cells was 86% lower than that at the beginning. Very interestingly, the cells started to release 5-HT in large quantities when they stopped releasing DA. These results suggest that DA and 5-HT are packaged into different vesicle pools and they are mobilized differently in response to chemical stimuli. The microfluidic platform proposed is proven useful for monitoring cellular release in biological studies. PMID:27111409

  1. The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains.

    PubMed

    Eicher, J D; Stein, C M; Deng, F; Ciesla, A A; Powers, N R; Boada, R; Smith, S D; Pennington, B F; Iyengar, S K; Lewis, B A; Gruen, J R

    2015-04-01

    A major milestone of child development is the acquisition and use of speech and language. Communication disorders, including speech sound disorder (SSD), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to SSD remain largely unknown. To identify associated genes, we assessed the association of the DYX2 dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with SSD and related endophenotypes. We first performed separate primary associations in two independent samples - Cleveland SSD (210 affected and 257 unaffected individuals in 127 families) and Denver SSD (113 affected individuals and 106 unaffected individuals in 85 families) - and then combined results by meta-analysis. DYX2 markers, specifically those in the 3' untranslated region of DCDC2 (P = 1.43 × 10(-4) ), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic-related genes ANKK1 (P = 1.02 × 10(-2) ) and DRD2 (P = 9.22 × 10(-3) ) and nicotinic-related genes CHRNA3 (P = 2.51 × 10(-3) ) and BDNF (P = 8.14 × 10(-3) ) with case-control status and articulation. Our results further implicate variation in putative regulatory regions in the DYX2 locus, particularly in DCDC2, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., DYX2) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and SSD). How these factors interactively yield different neurocognitive and language-related outcomes remains to be elucidated. PMID:25778907

  2. Behavioral and neurochemical effects of chronic L-DOPA treatment on non-motor sequelae in the hemiparkinsonian rat

    PubMed Central

    Eskow Jaunarajs, Karen L.; Dupre, Kristin B.; Ostock, Corinne Y.; Button, Thomas; Deak, Terrence; Bishop, Christopher

    2010-01-01

    Depression and anxiety are prevalent non-motor symptoms that worsen quality of life for Parkinson’s disease (PD) patients. While dopamine (DA) cell loss is a commonly proposed mechanism, the reported efficacy of DA replacement therapy with L-DOPA on affective symptoms is inconsistent. In order to delineate the effects of DA denervation and chronic L-DOPA treatment on affective behaviors, male Sprague-Dawley rats received unilateral 6-OHDA or sham lesions and were treated daily with L-DOPA (12 mg/kg + benserazide, 15 mg/kg, sc) or vehicle (0.9% NaCl, 0.1% ascorbic acid) for 28 days before commencing investigations into anxiety (locomotor chambers, social interaction) and depression-like behaviors (forced swim test) during the OFF phase of L-DOPA. One h after final treatments, rats were killed and striatum, prefrontal cortex, hippocampus, and amygdala were analyzed via high performance liquid chromatography for monoamine levels. In locomotor chambers and social interaction, DA lesions exerted mild anxiogenic effects. Surprisingly, chronic L-DOPA treatment did not improve these effects. While DA lesion reduced climbing behaviors on day 2 of exposure to the forced swim test, chronic L-DOPA treatment did not reverse these effects. Neurochemically, L-DOPA treatment in hemiparkinsonian rats reduced NE levels in the prefrontal cortex, striatum, and hippocampus. Collectively, the present data suggest that chronic L-DOPA therapy in severely DA-lesioned rats does not improve non-motor symptoms and may impair non-dopaminergic processes, indicating that long-term L-DOPA therapy does not exert necessary cause neuroplastic changes for improving affect. PMID:20838211

  3. Neurochemical effects of a 20 kHz magnetic field on the central nervous system in prenatally exposed mice

    SciTech Connect

    Dimberg, Y.

    1995-09-01

    C57/B1 mice were exposed during pregnancy (gestation days 0--19) to a 20 kHz magnetic field (MF). The asymmetric sawtooth-waveform magnetic field in the exposed racks had a flux density of 15 {micro}T (peak to peak). After 19 days, the exposure was terminated, and the mice were housed individually under normal laboratory conditions. On postnatal day (PD) 1, PD21, and PD308, various neurochemical markers in the brains of the offspring were investigated and the brains weighed. No significant difference was found in the whole brain weight at PD1 or PD21 between exposed offspring and control animals. However, on PD308, a significant decrease in weight of the whole brain was detected in exposed animals. No significant differences were found in the weight of cortex, hippocampus, septum, or cerebellum on nay of the sampling occasions, nor were any significant differences detected in protein-, DNA-level, nerve growth factor (NGF), acetylcholine esterase- (AChE), or 2{prime},3{prime}-cyclic nucleotide 3{prime}-phosphodiesterase- (CNP; marker for oligodendrocytes) activities on PD21 in cerebellum. Cortex showed a more complex pattern of response to MF: MF treatment resulted in a decrease in DNA level and increases in the activities of CNP, AChE, and NGF protein. On PD308, the amount of DNA was significantly reduced in MF-treated cerebellum and CNP activity was still enhanced in MF-treated cortex compared to controls. Most of the effect of MF treatment during the embryonic period were similar to those induced by ionizing radiation but much weaker. However, the duration of the exposure required to elucidate the response of different markers to MF seems to be greater and effects appear later during development compared to responses to ionizing radiation.

  4. The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains

    PubMed Central

    Eicher, J. D.; Stein, C. M.; Deng, F.; Ciesla, A. A.; Powers, N. R.; Boada, R.; Smith, S. D.; Pennington, B. F.; Iyengar, S. K.; Lewis, B. A.; Gruen, J. R.

    2015-01-01

    A major milestone of child development is the acquisition and use of speech and language. Communication disorders, including speech sound disorder (SSD), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to SSD remain largely unknown. To identify associated genes, we assessed the association of the DYX2 dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with SSD and related endophenotypes. We first performed separate primary associations in two independent samples – Cleveland SSD (210 affected and 257 unaffected individuals in 127 families) and Denver SSD (113 affected individuals and 106 unaffected individuals in 85 families) – and then combined results by meta-analysis. DYX2 markers, specifically those in the 3′ untranslated region of DCDC2 (P = 1.43 × 10–4), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic-related genes ANKK1 (P = 1.02 × 10–2) and DRD2 (P = 9.22 × 10–3) and nicotinic-related genes CHRNA3 (P = 2.51 × 10–3) and BDNF (P = 8.14 × 10–3) with case–control status and articulation. Our results further implicate variation in putative regulatory regions in the DYX2 locus, particularly in DCDC2, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., DYX2) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and SSD). How these factors interactively yield different neurocognitive and language-related outcomes remains to be elucidated. PMID:25778907

  5. Effect of JWH-250, JWH-073 and their interaction on "tetrad", sensorimotor, neurological and neurochemical responses in mice.

    PubMed

    Ossato, Andrea; Canazza, Isabella; Trapella, Claudio; Vincenzi, Fabrizio; De Luca, Maria Antonietta; Rimondo, Claudia; Varani, Katia; Borea, Pier Andrea; Serpelloni, Giovanni; Marti, Matteo

    2016-06-01

    JWH-250 and JWH-073 are two synthetic cannabinoid agonists with nanomolar affinity at CB1 and CB2 receptors. They are illegally marketed within "herbal blend" for theirs psychoactive effects greater than those produced by Cannabis. Recently, we analyzed an "herbal" preparation containing a mixture of both JWH-250 and JWH-073. The present study was aimed at investigating the in vitro and in vivo pharmacological activity of JWH-250 and JWH-073 in male CD-1 mice. In vitro competition binding experiments performed on mouse and human CB1 and CB2 receptors revealed a nanomolar affinity and potency of the JWH-250 and JWH-073. In vivo studies showed that JWH-250 and JWH-073, administered separately, induced a marked hypothermia, increased pain threshold to both noxious mechanical and thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic and tactile), caused seizures, myoclonia, hyperreflexia and promote aggressiveness in mice. Moreover, microdialysis study in freely moving mice showed that systemic administration of JWH-250 and JWH-073 stimulated dopamine release in the nucleus accumbens in a dose-dependent manner. Behavioral, neurological and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251. Co-administration of ineffective doses of JWH-250 and JWH-073 impaired visual sensorimotor responses, improved mechanical pain threshold and stimulated mesolimbic DA transmission in mice, living unchanged all other behavioral and physiological parameters. For the first time the present study demonstrates the overall pharmacological effects induced by the administration of JWH-250 and JWH-073 in mice and it reveals their potentially synergistic action suggesting that co-administration of different synthetic cannabinoids may potentiate the detrimental effects of individual compounds increasing their dangerousness and abuse potential. PMID:26780169

  6. Effects of polychlorinated biphenyl (PCB) on regulation of thyroid-, growth-, and neurochemically related developmental processes in young rats

    SciTech Connect

    Juarez de Ku, L.M.

    1992-01-01

    Neonatal exposure to the toxic chemical polychlorinated biphenyl (PCB) induces hypothyroidism and retarded growth. Neonatal rats made hypothyroid by chemical or surgical means experience retarded growth and subnormal activity of choline acetyltransferase (ChAT) This study compared thyroid-, growth-, and neurochemically-related processes altered by hypothyroidism induced by other means, with PCB-induced hypothyroidism: (1) titers of thyroid stimulating hormone (TSH); (2) titers of hormones that regulate growth [growth hormone (GH), insulin-growth like factor-I (IGF-1), growth hormone releasing hormone (GHRH) and somatostatin (SS)]; or (3) brain ChAT activity. Whether PCB-induced growth retardation and other alterations are secondary to accompanying hypothyroidism rather than or in addition to a direct effect of PCB was also examined. Pregnant rats were fed chow containing 0 (controls), 62.5, 125, or 250 ppm PCB (entering offspring through placenta and milk) throughout pregnancy and lactation. Neonates exposed to PCB displayed many alterations similar to those made hypothyroid by other means: depression of overall and skeletal growth, circulating by other means: depression of overall and skeletal growth, circulating T[sub 4] levels and ChAT activity, and no change in hypothalamic GHRH and SS concentrations. Differences included a paradoxical increase in circulating GH levels, and no significant alteration of circulation IGF-1 and TSH levels and pituitary GH and TSH levels (although trends were in the expected direction). Thus, PCB-induced hypothyroidism may partially cause altered skeletal growth, circulating GH and TSH concentrations, and ChAT activity. Both T[sub 4] and T[sub 3] injections returned circulating TSH and GH levels and pituitary TSH content toward control levels; T[sub 3] restored skeletal, but not overall growth; and T[sub 4] elevated ChAT activity.

  7. Gas plume quantification in downlooking hyperspectral longwave infrared images

    NASA Astrophysics Data System (ADS)

    Turcotte, Caroline S.; Davenport, Michael R.

    2010-10-01

    Algorithms have been developed to support quantitative analysis of a gas plume using down-looking airborne hyperspectral long-wave infrared (LWIR) imagery. The resulting gas quantification "GQ" tool estimates the quantity of one or more gases at each pixel, and estimates uncertainty based on factors such as atmospheric transmittance, background clutter, and plume temperature contrast. GQ uses gas-insensitive segmentation algorithms to classify the background very precisely so that it can infer gas quantities from the differences between plume-bearing pixels and similar non-plume pixels. It also includes MODTRAN-based algorithms to iteratively assess various profiles of air temperature, water vapour, and ozone, and select the one that implies smooth emissivity curves for the (unknown) materials on the ground. GQ then uses a generalized least-squares (GLS) algorithm to simultaneously estimate the most likely mixture of background (terrain) material and foreground plume gases. Cross-linking of plume temperature to the estimated gas quantity is very non-linear, so the GLS solution was iteratively assessed over a range of plume temperatures to find the best fit to the observed spectrum. Quantification errors due to local variations in the camera-topixel distance were suppressed using a subspace projection operator. Lacking detailed depth-maps for real plumes, the GQ algorithm was tested on synthetic scenes generated by the Digital Imaging and Remote Sensing Image Generation (DIRSIG) software. Initial results showed pixel-by-pixel gas quantification errors of less than 15% for a Freon 134a plume.

  8. Benchmarking RNA-Seq quantification tools

    PubMed Central

    Chandramohan, R.; Wu, Po-Yen; Phan, J.H.; Wang, M.D.

    2016-01-01

    RNA-Seq, a deep sequencing technique, promises to be a potential successor to microarraysfor studying the transcriptome. One of many aspects of transcriptomics that are of interest to researchers is gene expression estimation. With rapid development in RNA-Seq, there are numerous tools available to estimate gene expression, each producing different results. However, we do not know which of these tools produces the most accurate gene expression estimates. In this study we have addressed this issue using Cufflinks, IsoEM, HTSeq, and RSEM to quantify RNA-Seq expression profiles. Comparing results of these quantification tools, we observe that RNA-Seq relative expression estimates correlate with RT-qPCR measurements in the range of 0.85 to 0.89, with HTSeq exhibiting the highest correlation. But, in terms of root-mean-square deviation of RNA-Seq relative expression estimates from RT-qPCR measurements, we find HTSeq to produce the greatest deviation. Therefore, we conclude that, though Cufflinks, RSEM, and IsoEM might not correlate as well as HTSeq with RT-qPCR measurements, they may produce expression values with higher accuracy. PMID:24109770

  9. Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices

    NASA Technical Reports Server (NTRS)

    Hof, P. R.; Nimchinsky, E. A.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    The neurochemical characteristics of the neuronal subsets that furnish different types of corticocortical connections have been only partially determined. In recent years, several cytoskeletal proteins have emerged as reliable markers to distinguish subsets of pyramidal neurons in the cerebral cortex of primates. In particular, previous studies using an antibody to nonphosphorylated neurofilament protein (SMI-32) have revealed a consistent degree of regional and laminar specificity in the distribution of a subpopulation of pyramidal cells in the primate cerebral cortex. The density of neurofilament protein-immunoreactive neurons was shown to vary across corticocortical pathways in macaque monkeys. In the present study, we have used the antibody SMI-32 to examine further and to quantify the distribution of a subset of corticocortically projecting neurons in a series of long ipsilateral corticocortical pathways in comparison to short corticocortical, commissural, and limbic connections. The results demonstrate that the long association pathways interconnecting the frontal, parietal, and temporal neocortex have a high representation of neurofilament protein-enriched pyramidal neurons (45-90%), whereas short corticocortical, callosal, and limbic pathways are characterized by much lower numbers of such neurons (4-35%). These data suggest that different types of corticocortical connections have differential representation of highly specific neuronal subsets that share common neurochemical characteristics, thereby determining regional and laminar cortical patterns of morphological and molecular heterogeneity. These differences in neuronal neurochemical phenotype among corticocortical circuits may have considerable influence on cortical processing and may be directly related to the type of integrative function subserved by each cortical pathway. Finally, it is worth noting that neurofilament protein-immunoreactive neurons are dramatically affected in the course of

  10. Comparative behavioral and neurochemical analysis of phenytoin and valproate treatment on epilepsy induced learning and memory deficit: Search for add on therapy.

    PubMed

    Mishra, Awanish; Goel, Rajesh Kumar

    2015-08-01

    Our previous work demonstrated, chronic epilepsy affects learning and memory of rodents along with peculiar neurochemical changes in discrete brain parts. Most commonly used antiepileptic drugs (phenytoin and sodium valproate) also worsen learning and memory in the patients with epilepsy. Therefore this study was designed to carry out comparison of behavioral and neurochemical changes with phenytoin and sodium valproate treatment in pentylenetetrazole-kindling induced learning and memory deficit to devise add on therapy for this menace. For the experimental epilepsy, animals were kindled using PTZ (35 mg/kg; i.p., at 48 ± 2 h intervals) and successful kindled animals were involved in the study. These kindled animals were treated with saline, phenytoin (30 mg/kg/day, i.p.) and sodium valproate (300 mg/kg/day, i.p.) for 20 days. These animals were challenged with PTZ challenging dose (35 mg/kg) on day 5, 10, 15 and 20 to evaluate the effect on seizure severity score on different days. Effect on learning and memory was evaluated using elevated plus maze and passive shock avoidance paradigm. On day 20, after behavioral evaluations, animals were sacrificed to analyze glutamate, GABA, norepinephrine, dopamine, serotonin, total nitrite level and acetylcholinesterase level in cortex and hippocampus. Behavioral evaluations suggested that phenytoin and sodium valproate treatment significantly reduced seizure severity in the kindled animals, while sodium valproate treatment controls seizures with least memory deficit in comparison to phenytoin. Neurochemical findings revealed that elevated cortical acetylcholinesterase level could be one of the responsible factors leading to memory deficit in phenytoin treated animals. However sodium valproate treatment reduced cortical acetylcholinesterase level and had least debilitating consequences on memory deficit. Therefore, attenuation of elevated AChE activity can be one of add-on approach for management of memory deficit

  11. The Qiagen Investigator® Quantiplex HYres as an alternative kit for DNA quantification.

    PubMed

    Frégeau, Chantal J; Laurin, Nancy

    2015-05-01

    The Investigator® Quantiplex HYres kit was evaluated as a potential replacement for dual DNA quantification of casework samples. This kit was determined to be highly sensitive with a limit of quantification and limit of detection of 0.0049ng/μL and 0.0003ng/μL, respectively, for both human and male DNA, using full or half reaction volumes. It was also accurate in assessing the amount of male DNA present in 96 mock and actual casework male:female mixtures (various ratios) processed in this exercise. The close correlation between the male/human DNA ratios expressed in percentages derived from the Investigator® Quantiplex HYres quantification results and the male DNA proportion calculated in mixed AmpFlSTR® Profiler® Plus or AmpFlSTR® Identifiler® Plus profiles, using the Amelogenin Y peak and STR loci, allowed guidelines to be developed to facilitate decisions regarding when to submit samples to Y-STR rather than autosomal STR profiling. The internal control (IC) target was shown to be more sensitive to inhibitors compared to the human and male DNA targets included in the Investigator® Quantiplex HYres kit serving as a good quality assessor of DNA extracts. The new kit met our criteria of enhanced sensitivity, accuracy, consistency, reliability and robustness for casework DNA quantification. PMID:25603128

  12. Statistical Approach to Protein Quantification*

    PubMed Central

    Gerster, Sarah; Kwon, Taejoon; Ludwig, Christina; Matondo, Mariette; Vogel, Christine; Marcotte, Edward M.; Aebersold, Ruedi; Bühlmann, Peter

    2014-01-01

    A major goal in proteomics is the comprehensive and accurate description of a proteome. This task includes not only the identification of proteins in a sample, but also the accurate quantification of their abundance. Although mass spectrometry typically provides information on peptide identity and abundance in a sample, it does not directly measure the concentration of the corresponding proteins. Specifically, most mass-spectrometry-based approaches (e.g. shotgun proteomics or selected reaction monitoring) allow one to quantify peptides using chromatographic peak intensities or spectral counting information. Ultimately, based on these measurements, one wants to infer the concentrations of the corresponding proteins. Inferring properties of the proteins based on experimental peptide evidence is often a complex problem because of the ambiguity of peptide assignments and different chemical properties of the peptides that affect the observed concentrations. We present SCAMPI, a novel generic and statistically sound framework for computing protein abundance scores based on quantified peptides. In contrast to most previous approaches, our model explicitly includes information from shared peptides to improve protein quantitation, especially in eukaryotes with many homologous sequences. The model accounts for uncertainty in the input data, leading to statistical prediction intervals for the protein scores. Furthermore, peptides with extreme abundances can be reassessed and classified as either regular data points or actual outliers. We used the proposed model with several datasets and compared its performance to that of other, previously used approaches for protein quantification in bottom-up mass spectrometry. PMID:24255132

  13. Quantification of wastewater sludge dewatering.

    PubMed

    Skinner, Samuel J; Studer, Lindsay J; Dixon, David R; Hillis, Peter; Rees, Catherine A; Wall, Rachael C; Cavalida, Raul G; Usher, Shane P; Stickland, Anthony D; Scales, Peter J

    2015-10-01

    Quantification and comparison of the dewatering characteristics of fifteen sewage sludges from a range of digestion scenarios are described. The method proposed uses laboratory dewatering measurements and integrity analysis of the extracted material properties. These properties were used as inputs into a model of filtration, the output of which provides the dewatering comparison. This method is shown to be necessary for quantification and comparison of dewaterability as the permeability and compressibility of the sludges varies by up to ten orders of magnitude in the range of solids concentration of interest to industry. This causes a high sensitivity of the dewaterability comparison to the starting concentration of laboratory tests, thus simple dewaterability comparison based on parameters such as the specific resistance to filtration is difficult. The new approach is demonstrated to be robust relative to traditional methods such as specific resistance to filtration analysis and has an in-built integrity check. Comparison of the quantified dewaterability of the fifteen sludges to the relative volatile solids content showed a very strong correlation in the volatile solids range from 40 to 80%. The data indicate that the volatile solids parameter is a strong indicator of the dewatering behaviour of sewage sludges. PMID:26003332

  14. A quantitative study of neurochemically defined excitatory interneuron populations in laminae I–III of the mouse spinal cord

    PubMed Central

    Gutierrez-Mecinas, Maria; Furuta, Takahiro; Watanabe, Masahiko

    2016-01-01

    Background Excitatory interneurons account for the majority of neurons in laminae I–III, but their functions are poorly understood. Several neurochemical markers are largely restricted to excitatory interneuron populations, but we have limited knowledge about the size of these populations or their overlap. The present study was designed to investigate this issue by quantifying the neuronal populations that express somatostatin (SST), neurokinin B (NKB), neurotensin, gastrin-releasing peptide (GRP) and the γ isoform of protein kinase C (PKCγ), and assessing the extent to which they overlapped. Since it has been reported that calretinin- and SST-expressing cells have different functions, we also looked for co-localisation of calretinin and SST. Results SST, preprotachykinin B (PPTB, the precursor of NKB), neurotensin, PKCγ or calretinin were detected with antibodies, while cells expressing GRP were identified in a mouse line (GRP-EGFP) in which enhanced green fluorescent protein (EGFP) was expressed under control of the GRP promoter. We found that SST-, neurotensin-, PPTB- and PKCγ-expressing cells accounted for 44%, 7%, 12% and 21% of the neurons in laminae I–II, and 16%, 8%, 4% and 14% of those in lamina III, respectively. GRP-EGFP cells made up 11% of the neuronal population in laminae I–II. The neurotensin, PPTB and GRP-EGFP populations showed very limited overlap, and we estimate that between them they account for ∼40% of the excitatory interneurons in laminae I–II. SST which is expressed by ∼60% of excitatory interneurons in this region, was found in each of these populations, as well as in cells that did not express any of the other peptides. Neurotensin and PPTB were often found in cells with PKCγ, and between them, constituted around 60% of the PKCγ cells. Surprisingly, we found extensive co-localisation of SST and calretinin. Conclusions These results suggest that cells expressing neurotensin, NKB or GRP form largely non-overlapping sets

  15. Wireless Instantaneous Neurotransmitter Concentration System–based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring

    PubMed Central

    Agnesi, Filippo; Tye, Susannah J.; Bledsoe, Jonathan M.; Griessenauer, Christoph J.; Kimble, Christopher J.; Sieck, Gary C.; Bennet, Kevin E.; Garris, Paul A.; Blaha, Charles D.; Lee, Kendall H.

    2009-01-01

    model, the pig. Results The WINCS, which is designed in compliance with FDA-recognized consensus standards for medical electrical device safety, successfully measured dopamine, glutamate, and adenosine, both in vitro and in vivo. The WINCS detected striatal dopamine release at the implanted CFM during DBS of the MFB. The DBS-evoked adenosine release in the rat thalamus and MCS-evoked glutamate release in the pig cortex were also successfully measured. Overall, in vitro and in vivo testing demonstrated signals comparable to a commercial hardwired electrochemical system for FPA. Conclusions By incorporating FPA, the chemical repertoire of WINCS-measurable neurotransmitters is expanded to include glutamate and other nonelectroactive species for which the evolving field of enzyme-linked biosensors exists. Because many neurotransmitters are not electrochemically active, FPA in combination with enzyme-linked microelectrodes represents a powerful intraoperative tool for rapid and selective neurochemical sampling in important anatomical targets during functional neurosurgery. PMID:19425899

  16. In ovo exposure to organophosphorous flame retardants: survival, development, neurochemical, and behavioral changes in white leghorn chickens.

    PubMed

    Bradley, Mark; Rutkiewicz, Jennifer; Mittal, Krittika; Fernie, Kimberly; Basu, Niladri

    2015-01-01

    Organophosphorous flame retardants (OPFRs) are contaminants of emerging concern. There is growing evidence of environmental contamination and exposures to both humans and wildlife. Here, the objective was to increase understanding of the potential neurodevelopmental effects of two relevant OPFRs, TMPP (tri (methylphenyl) phosphate; a non-halogen-containing OPFR) and TDCIPP (tris (1,3-dichloro-isopropyl) phosphate; a halogen-containing OPFR) in an avian embryo/chick model. We injected white leghorn chicken eggs with a range of TMPP (0, 10, 100, and 1000 ng/g) or TDCIPP (0, 10, 100, 1000, 50,000 ng/g) concentrations at incubation day 0 exposing embryos throughout the ~21-day in ovo period. Hatching success was unaffected by TMPP, but TDCIPP-exposed chicks had higher early-incubation mortality in 100 and 50,000 ng/g groups. On 7-9-day-old chicks, we assessed behavior via tests concerning righting reflex, angled balance beams, gait patterns, wing flap reflex, and open field movements. Chicks exposed to 100 ng/g TDCIPP achieved 40% lower maximum velocity in the open field test than vehicle-exposed controls, while those exposed to 1000 ng/g TDCIPP achieved 20% higher maximum velocity than vehicle-exposed controls. Chicks exposed to 50,000 ng/g TDCIPP showed reduced righting response success. There were no dose- or treatment-related differences in angled beam, gait analysis, or wing flap reflex tests. Cerebrum hemispheres from 10-day-old chicks were examined for neurochemistry (acetylcholinesterase [AChE] activity and both nicotinic [nACh] and muscarinic [mACh] acetylcholine receptor levels) and cerebellums were examined for histopathology. TDCIPP-exposed chicks had reduced number of degenerate Purkinje cells (TDCIPP, 1000 ng/g), possibly indicating disruption of neurodevelopment. No neurochemical effects were found in TMPP- or TDCIPP-exposed chicks. In general this study shows some possible neurodevelopmental effects in chicks exposed to TDCIPP when levels greatly

  17. Detection and Quantification of Neurotransmitters in Dialysates

    PubMed Central

    Zapata, Agustin; Chefer, Vladimir I.; Shippenberg, Toni S.; Denoroy, Luc

    2010-01-01

    Sensitive analytical methods are needed for the separation and quantification of neurotransmitters obtained in microdialysate studies. This unit describes methods that permit quantification of nanomolar concentrations of monoamines and their metabolites (high-pressure liquid chromatography electrochemical detection), acetylcholine (HPLC-coupled to an enzyme reactor), and amino acids (HPLC-fluorescence detection; capillary electrophoresis with laser-induced fluorescence detection). PMID:19575473

  18. Species, Sex and Individual Differences in the Vasotocin/Vasopressin System: Relationship to Neurochemical Signaling in the Social Behavior Neural Network

    PubMed Central

    Albers, H. Elliott

    2014-01-01

    Arginine-vasotocin(AVT)/arginine vasopressin (AVP) are members of the AVP/oxytocin (OT) superfamily of peptides that are involved in the regulation of social behavior, social cognition and emotion. Comparative studies have revealed that AVT/AVP and their receptors are found throughout the “Social Behavior Neural Network” and display the properties expected from a signaling system that controls social behavior (i.e., species, sex and individual differences and modulation by gonadal hormones and social factors). Neurochemical signaling within the SBNN likely involves a complex combination of synaptic mechanisms that co-release multiple chemical signals (e.g., classical neurotransmitters and AVT/AVP as well as other peptides) and non-synaptic mechanisms (i.e., volume transmission). Crosstalk between AVP/OT peptides and receptors within the SBNN is likely. A better understanding of the functional properties of neurochemical signaling in the SBNN will allow for a more refined examination of the relationships between this peptide system and species, sex and individual differences in sociality. PMID:25102443

  19. Dysregulation of Brain Reward Systems in Eating Disorders: Neurochemical Information from Animal Models of Binge Eating, Bulimia Nervosa, and Anorexia Nervosa

    PubMed Central

    Avena, Nicole M.; Bocarsly, Miriam E.

    2012-01-01

    Food intake is mediated, in part, through brain pathways for motivation and reinforcement. Dysregulation of these pathways may underlay some of the behaviors exhibited by patients with eating disorders. Research using animal models of eating disorders has greatly contributed to the detailed study of potential brain mechanisms that many underlie the causes or consequences of aberrant eating behaviors. This review focuses on neurochemical evidence of reward-related brain dysfunctions obtained through animal models of binge eating, bulimia nervosa, or anorexia nervosa. The findings suggest that alterations in dopamine (DA), acetylcholine (ACh) and opioid systems in reward-related brain areas occur in response to binge eating of palatable foods. Moreover, animal models of bulimia nervosa suggest that while bingeing on palatable food releases DA, purging attenuates the release of ACh that might otherwise signal satiety. Animal models of anorexia nervosa suggest that restricted access to food enhances the reinforcing effects of DA when the animal does eat. The activity-based anorexia model suggests alterations in mesolimbic DA and serotonin occur as a result of starvation coupled with excessive wheel running. These findings with animal models complement data obtained through neuroimaging and pharmacotherapy studies of clinical populations. Finally, information on the neurochemical consequences of the behaviors associated with these eating disorders will be useful in understanding these complex disorders and may inform future therapeutic approaches, as discussed here. PMID:22138162

  20. Dysregulation of brain reward systems in eating disorders: neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa.

    PubMed

    Avena, Nicole M; Bocarsly, Miriam E

    2012-07-01

    Food intake is mediated, in part, through brain pathways for motivation and reinforcement. Dysregulation of these pathways may underlay some of the behaviors exhibited by patients with eating disorders. Research using animal models of eating disorders has greatly contributed to the detailed study of potential brain mechanisms that many underlie the causes or consequences of aberrant eating behaviors. This review focuses on neurochemical evidence of reward-related brain dysfunctions obtained through animal models of binge eating, bulimia nervosa, or anorexia nervosa. The findings suggest that alterations in dopamine (DA), acetylcholine (ACh) and opioid systems in reward-related brain areas occur in response to binge eating of palatable foods. Moreover, animal models of bulimia nervosa suggest that while bingeing on palatable food releases DA, purging attenuates the release of ACh that might otherwise signal satiety. Animal models of anorexia nervosa suggest that restricted access to food enhances the reinforcing effects of DA when the animal does eat. The activity-based anorexia model suggests alterations in mesolimbic DA and serotonin occur as a result of restricted eating coupled with excessive wheel running. These findings with animal models complement data obtained through neuroimaging and pharmacotherapy studies of clinical populations. Information on the neurochemical consequences of the behaviors associated with these eating disorders will be useful in understanding these complex disorders and may inform future therapeutic approaches, as discussed here. This article is part of a Special Issue entitled 'Central Control of Food Intake'. PMID:22138162

  1. Neurochemical Plasticity of the Coeliac-Superior Mesenteric Ganglion Complex Neurons Projecting to the Prepyloric Area of the Porcine Stomach following Hyperacidity.

    PubMed

    Palus, Katarzyna; Całka, Jarosław

    2016-01-01

    This study was designed to determine neurochemical properties of the coeliac-superior mesenteric ganglion (CSMG) neurons supplying the prepyloric area of the porcine stomach in physiological state and following experimentally induced hyperacidity. To localize sympathetic neurons innervating the studied area of stomach, the neuronal retrograde tracer Fast Blue (FB) was applied to control animals and hydrochloric acid infusion (HCl) groups. After 23 days, animals of the HCl group were reintroduced into a state of general anesthesia and intragastrically given 5 mL/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were sacrificed. The CSMG complexes were then collected and processed for double-labeling immunofluorescence. In the control animals, FB-positive perikarya displayed immunoreactivity to tyrosine hydroxylase (TH), dopamine β-hydroxylase (DβH), neuropeptide Y (NPY), and galanin (GAL). Experimentally induced gastric hyperacidity changed the neurochemical phenotype of the studied neurons. An upregulated expression of GAL and NPY and the de novo synthesis of neuronal nitric oxide synthase (nNOS) and leu5-enkephalin (LENK) as well as downregulated expression of TH and DβH in the stomach-projecting neurons were observed. These findings enrich existing knowledge about the participation of these active substances in adaptive mechanism(s) of the sympathetic neurons during pathological processes within the gastrointestinal tract. PMID:27293908

  2. Short- and long-lasting behavioral and neurochemical adaptations: relationship with patterns of cocaine administration and expectation of drug effects in rats.

    PubMed

    Puig, S; Noble, F; Benturquia, N

    2012-01-01

    Cocaine dependence is a significant public health problem, characterized by periods of abstinence. Chronic exposure to drugs of abuse induces important modifications on neuronal systems, including the dopaminergic system. The pattern of administration is an important factor that should be taken into consideration to study the neuroadaptations. We compared the effects of intermittent (once daily) and binge (three times a day) cocaine treatments for 1 (WD1) and 14 (WD14) days after the last cocaine injection on spontaneous locomotor activity and dopamine (DA) levels in the nucleus accumbens (Nac). The intermittent treatment led to a spontaneous increase in DA (WD1/WD14), and in locomotor activity (WD1) at the exact hour which rats were habituated to receive a cocaine injection. These results underline that taking into consideration the hours of the day at which the experiments are performed is crucial. We also investigated these behavioral and neurochemical adaptations in response to an acute cocaine challenge on WD1 and WD14. We observed that only the binge treatment led to sensitization of locomotor effects of cocaine, associated to a DA release sensitization in the Nac, whereas the intermittent treatment did not. We demonstrate that two different patterns of administration induced distinct behavioral and neurochemical consequences. We unambiguously demonstrated that the intermittent treatment induced drug expectation associated with higher basal DA level in the Nac when measured at the time of chronic cocaine injection and that the binge treatment led to behavioral and sensitization effects of cocaine. PMID:23092979

  3. Neurochemical Plasticity of the Coeliac-Superior Mesenteric Ganglion Complex Neurons Projecting to the Prepyloric Area of the Porcine Stomach following Hyperacidity

    PubMed Central

    Całka, Jarosław

    2016-01-01

    This study was designed to determine neurochemical properties of the coeliac-superior mesenteric ganglion (CSMG) neurons supplying the prepyloric area of the porcine stomach in physiological state and following experimentally induced hyperacidity. To localize sympathetic neurons innervating the studied area of stomach, the neuronal retrograde tracer Fast Blue (FB) was applied to control animals and hydrochloric acid infusion (HCl) groups. After 23 days, animals of the HCl group were reintroduced into a state of general anesthesia and intragastrically given 5 mL/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were sacrificed. The CSMG complexes were then collected and processed for double-labeling immunofluorescence. In the control animals, FB-positive perikarya displayed immunoreactivity to tyrosine hydroxylase (TH), dopamine β-hydroxylase (DβH), neuropeptide Y (NPY), and galanin (GAL). Experimentally induced gastric hyperacidity changed the neurochemical phenotype of the studied neurons. An upregulated expression of GAL and NPY and the de novo synthesis of neuronal nitric oxide synthase (nNOS) and leu5-enkephalin (LENK) as well as downregulated expression of TH and DβH in the stomach-projecting neurons were observed. These findings enrich existing knowledge about the participation of these active substances in adaptive mechanism(s) of the sympathetic neurons during pathological processes within the gastrointestinal tract. PMID:27293908

  4. Neuroblastoma: A neurochemical approach

    SciTech Connect

    Schor, N.F. )

    1991-07-01

    Neuroblastoma is among the most common malignancies of childhood. Despite greatly improved therapy for some pediatric tumors, the prognosis for children with metastatic neuroblastoma has not changed significantly in the past 10 years. With conventional chemotherapy, radiation therapy, and surgery, children with metastatic neuroblastoma have a 20% long-term survival rate. The authors describe here approaches to neuroblastoma that target its neuronal characteristics. On the one hand, the neurotransmitter receptors on the surface of the neuroblastoma cells and, on the other hand, specific isozymes that distinguish neuroblastoma cells from their normal counterparts are the focus of these experimental therapies. In the former case, specificity for tumor cells is effected by (1) selective protection of normal neuronal elements from toxicity, or (2) selective potentiation of toxicity for neural tumor cells. It is hoped that these strategies will be generalizable to other neural crest-derived tumors. 32 references.

  5. Progressive damage state evolution and quantification in composites

    NASA Astrophysics Data System (ADS)

    Patra, Subir; Banerjee, Sourav

    2016-04-01

    Precursor damage state quantification can be helpful for safety and operation of aircraft and defense equipment's. Damage develops in the composite material in the form of matrix cracking, fiber breakages and deboning, etc. However, detection and quantification of the damage modes at their very early stage is not possible unless modifications of the existing indispensable techniques are conceived, particularly for the quantification of multiscale damages at their early stage. Here, we present a novel nonlocal mechanics based damage detection technique for precursor damage state quantification. Micro-continuum physics is used by modifying the Christoffel equation. American society of testing and materials (ASTM) standard woven carbon fiber (CFRP) specimens were tested under Tension-Tension fatigue loading at the interval of 25,000 cycles until 500,000 cycles. Scanning Acoustic Microcopy (SAM) and Optical Microscopy (OM) were used to examine the damage development at the same interval. Surface Acoustic Wave (SAW) velocity profile on a representative volume element (RVE) of the specimen were calculated at the regular interval of 50,000 cycles. Nonlocal parameters were calculated form the micromorphic wave dispersion curve at a particular frequency of 50 MHz. We used a previously formulated parameter called "Damage entropy" which is a measure of the damage growth in the material calculated with the loading cycle. Damage entropy (DE) was calculated at every pixel on the RVE and the mean of DE was plotted at the loading interval of 25,000 cycle. Growth of DE with fatigue loading cycles was observed. Optical Imaging also performed at the interval of 25,000 cycles to investigate the development of damage inside the materials. We also calculated the mean value of the Surface Acoustic Wave (SAW) velocity and plotted with fatigue cycle which is correlated further with Damage Entropy (DE). Statistical analysis of the Surface Acoustic Wave profile (SAW) obtained at different

  6. Advancing agricultural greenhouse gas quantification*

    NASA Astrophysics Data System (ADS)

    Olander, Lydia; Wollenberg, Eva; Tubiello, Francesco; Herold, Martin

    2013-03-01

    1. Introduction Better information on greenhouse gas (GHG) emissions and mitigation potential in the agricultural sector is necessary to manage these emissions and identify responses that are consistent with the food security and economic development priorities of countries. Critical activity data (what crops or livestock are managed in what way) are poor or lacking for many agricultural systems, especially in developing countries. In addition, the currently available methods for quantifying emissions and mitigation are often too expensive or complex or not sufficiently user friendly for widespread use. The purpose of this focus issue is to capture the state of the art in quantifying greenhouse gases from agricultural systems, with the goal of better understanding our current capabilities and near-term potential for improvement, with particular attention to quantification issues relevant to smallholders in developing countries. This work is timely in light of international discussions and negotiations around how agriculture should be included in efforts to reduce and adapt to climate change impacts, and considering that significant climate financing to developing countries in post-2012 agreements may be linked to their increased ability to identify and report GHG emissions (Murphy et al 2010, CCAFS 2011, FAO 2011). 2. Agriculture and climate change mitigation The main agricultural GHGs—methane and nitrous oxide—account for 10%-12% of anthropogenic emissions globally (Smith et al 2008), or around 50% and 60% of total anthropogenic methane and nitrous oxide emissions, respectively, in 2005. Net carbon dioxide fluxes between agricultural land and the atmosphere linked to food production are relatively small, although significant carbon emissions are associated with degradation of organic soils for plantations in tropical regions (Smith et al 2007, FAO 2012). Population growth and shifts in dietary patterns toward more meat and dairy consumption will lead to

  7. Protein inference: A protein quantification perspective.

    PubMed

    He, Zengyou; Huang, Ting; Liu, Xiaoqing; Zhu, Peijun; Teng, Ben; Deng, Shengchun

    2016-08-01

    In mass spectrometry-based shotgun proteomics, protein quantification and protein identification are two major computational problems. To quantify the protein abundance, a list of proteins must be firstly inferred from the raw data. Then the relative or absolute protein abundance is estimated with quantification methods, such as spectral counting. Until now, most researchers have been dealing with these two processes separately. In fact, the protein inference problem can be regarded as a special protein quantification problem in the sense that truly present proteins are those proteins whose abundance values are not zero. Some recent published papers have conceptually discussed this possibility. However, there is still a lack of rigorous experimental studies to test this hypothesis. In this paper, we investigate the feasibility of using protein quantification methods to solve the protein inference problem. Protein inference methods aim to determine whether each candidate protein is present in the sample or not. Protein quantification methods estimate the abundance value of each inferred protein. Naturally, the abundance value of an absent protein should be zero. Thus, we argue that the protein inference problem can be viewed as a special protein quantification problem in which one protein is considered to be present if its abundance is not zero. Based on this idea, our paper tries to use three simple protein quantification methods to solve the protein inference problem effectively. The experimental results on six data sets show that these three methods are competitive with previous protein inference algorithms. This demonstrates that it is plausible to model the protein inference problem as a special protein quantification task, which opens the door of devising more effective protein inference algorithms from a quantification perspective. The source codes of our methods are available at: http://code.google.com/p/protein-inference/. PMID:26935399

  8. Mass Spectrometric Quantification of N-Linked Glycans by Reference to Exogenous Standards.

    PubMed

    Mehta, Nickita; Porterfield, Mindy; Struwe, Weston B; Heiss, Christian; Azadi, Parastoo; Rudd, Pauline M; Tiemeyer, Michael; Aoki, Kazuhiro

    2016-09-01

    Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following release from glycoprotein and subsequent HPLC or capillary electrophoretic separation. Such labeling-based approaches provide a robust means of quantifying glycan amount based on fluorescence yield. Mass spectrometry, on the other hand, has generally been limited to relative quantification in which the contribution of the signal intensity for an individual glycan is expressed as a percent of the signal intensity summed over the total profile. Relative quantification has been valuable for highlighting changes in glycan expression between samples; sensitivity is high, and structural information can be derived by fragmentation. We have investigated whether MS-based glycomics is amenable to absolute quantification by referencing signal intensities to well-characterized oligosaccharide standards. We report the qualification of a set of N-linked oligosaccharide standards by NMR, HPLC, and MS. We also demonstrate the dynamic range, sensitivity, and recovery from complex biological matrices for these standards in their permethylated form. Our results indicate that absolute quantification for MS-based glycomic analysis is reproducible and robust utilizing currently available glycan standards. PMID:27432553

  9. Discrimination between neurochemical and macromolecular signals in human frontal lobes using short echo time proton magnetic resonance spectroscopy.

    PubMed

    McLean, Mary A; Simister, Robert J; Barker, Gareth J; Duncan, John S

    2004-01-01

    Magnetic resonance spectra from large (35 cm3) frontal lobe voxels in vivo were analyzed using LCModel, with and without subtraction of a "metabolite nulled" spectrum with an inversion time of 650 ms to characterize the macromolecule baseline. Baseline subtraction decreased the signal to noise ratio (SNR), but improved the reliability of LCModel quantification of most metabolites, as reflected in the Cramer-Rao lower bounds, in particular for glutamate and glutamine. The reported concentrations increased for glutamine, creatine, and lactate, and decreased for glutamate, myo-inositol and NAAG, but the sum of all metabolites remained constant, as did the standard deviation of the concentrations in the control group. Macromolecule subtraction is worthwhile when SNR is high, as in the characterization of normal-appearing tissue in the brain. PMID:14992401

  10. The NASA Langley Multidisciplinary Uncertainty Quantification Challenge

    NASA Technical Reports Server (NTRS)

    Crespo, Luis G.; Kenny, Sean P.; Giesy, Daniel P.

    2014-01-01

    This paper presents the formulation of an uncertainty quantification challenge problem consisting of five subproblems. These problems focus on key aspects of uncertainty characterization, sensitivity analysis, uncertainty propagation, extreme-case analysis, and robust design.