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Sample records for administration protect hippocampus

  1. Pre-training administration of tianeptine, but not propranolol, protects hippocampus-dependent memory from being impaired by predator stress.

    PubMed

    Campbell, Adam M; Park, Collin R; Zoladz, Phillip R; Muñoz, Carmen; Fleshner, Monika; Diamond, David M

    2008-02-01

    Extensive research has shown that the antidepressant tianeptine blocks the adverse effects of chronic stress on hippocampal functioning. The current series of experiments extended this area of investigation by examining the influence of tianeptine on acute stress-induced impairments of spatial (hippocampus-dependent) memory. Tianeptine (10 mg/kg, ip) administered to adult male rats before, but not after, water maze training blocked the amnestic effects of predator stress (occurring between training and retrieval) on memory. The protective effects of tianeptine on memory occurred in rats which had extensive pre-stress training, as well as in rats which had only a single day of training. Tianeptine blocked stress effects on memory without altering the stress-induced increase in corticosterone levels. Propranolol, a beta-adrenergic receptor antagonist (5 and 10 mg/kg, ip), in contrast, did not block stress-induced amnesia. These findings indicate that treatment with tianeptine, unlike propanolol, provides an effective means with which to block the adverse effects of stress on cognitive functions of the hippocampus.

  2. Protective effect of systemic L-kynurenine and probenecid administration on behavioural and morphological alterations induced by toxic soluble amyloid beta (25-35) in rat hippocampus.

    PubMed

    Carrillo-Mora, Paul; Méndez-Cuesta, Luis A; Pérez-De La Cruz, Verónica; Fortoul-van Der Goes, Teresa I; Santamaría, Abel

    2010-07-11

    Amyloid beta (Abeta) peptide exerts different toxic effects at a cellular level, including over-activation of N-methyl-D-aspartate receptor (NMDAr) and excitotoxicity, synaptic dysfunction and neuronal death. Kynurenic acid (KYNA) is an endogenous antagonist of NMDAr and alpha7 nicotinic receptors. Systemic administrations of both the immediate metabolic precursor of KYNA, L-kynurenine (L-KYN), and a proved inhibitor of KYNA's brain transport, probenecid (PROB), have shown to produce neuroprotective effects in a considerable number of experimental toxic conditions; however, this strategy has not been tested in the toxic model Abeta peptide so far. In this study we evaluated the effects of systemic administration of PROB (50 mg/kg/day for 7 days), L-KYN (75 mg/kg/day for 7 days) and their combination, on behavioural (locomotor activity and spatial memory) and morphological alterations induced by an intrahippocampal infusion of Abeta 25-35 to rats. An additional group was administered with the potent NMDAr antagonist dizocilpine (MK-801, 0.8 mg/kg/day for 7 days) for comparative purposes. A significant improvement of spatial memory was evident in Abeta-lesioned rats since post-lesion day 21 with all treatments tested and this effect was correlated with a reduction of cell damage and a decrease in reactive gliosis in hippocampal CA1 area. Neither L-KYN, nor PROB, or their combination, produced major alterations in motor function when given alone to rats. These results suggest that modulation of NMDAr activity by mean of therapeutic strategies designed to enhance KYNA in the brain may help to counteract neurodegenerative events coursing with Abeta toxicity and excitotoxic patterns.

  3. Administrator Protections in Negotiated Contracts.

    ERIC Educational Resources Information Center

    Pisapia, John Ralph; Sells, Jack D.

    1978-01-01

    Presents specific examples of provisions currently found in administrator-board collective bargaining agreements that protect administrators from the adverse effects of both bilateral decisions made by boards with teachers, and unilateral decisions made by boards concerning principals. (Author)

  4. Imipramine protects mouse hippocampus against tunicamycin-induced cell death.

    PubMed

    Ono, Yoko; Shimazawa, Masamitsu; Ishisaka, Mitsue; Oyagi, Atsushi; Tsuruma, Kazuhiro; Hara, Hideaki

    2012-12-05

    Endoplasmic reticulum (ER) stress is implicated in various diseases. Recently, some reports have suggested that the sigma-1 receptor may play a role in ER stress, and many antidepressants have a high affinity for the sigma-1 receptor. In the present study, we focused on imipramine, a widely used antidepressant, and investigated whether it might protect against the neuronal cell death induced by tunicamycin, an ER stress inducer. In mouse cultured hippocampal HT22 cells, imipramine inhibited cell death and caspase-3 activation induced by tunicamycin, although it did not alter the elevated expressions of 78 kDa glucose-regulated protein (GRP78) and C/EBP-homologous protein (CHOP). Interestingly, in such cells application of imipramine normalized the expression of the sigma-1 receptor, which was decreased by treatment with tunicamycin alone. Additionally, NE-100, a selective sigma-1 receptor antagonist, abolished the protective effect of imipramine against such tunicamycin-induced cell death. Imipramine inhibited the reduction of mitochondrial membrane potential induced by tunicamycin, and NE-100 blocked this modulating effect of imipramine. Furthermore, in anesthetized mice intracerebroventricular administration of tunicamycin decreased the number of neuronal cells in the hippocampus, particularly in the CA1 and dentate gyrus (DG) areas, and 7 days' imipramine treatment (10mg/kg/day; i.p.) significantly suppressed these reductions in CA1 and DG. These findings suggest that imipramine protects against ER stress-induced hippocampal neuronal cell death both in vitro and in vivo. Such protection may be partly due to the sigma-1 receptor.

  5. The Effect of Ascorbic Acid and Garlic Administration on Lead-Induced Neural Damage in Rat Offspring’s Hippocampus

    PubMed Central

    Sadeghi, Akram; Ebrahimzadeh Bideskan, Alireza; Alipour, Fatemeh; Fazel, Alireza; Haghir, Hossein

    2013-01-01

    Objective(s): The aim of this study was to investigate ascorbic acid and garlic protective effects on lead-induced neurotoxicity during rat hippocampus development. Materials and Methods: 90 pregnant wistar rats were divided randomly into nine groups: 1- Animals received leaded water (L). 2- Rats received leaded water and ascorbic acid (L+AA). 3- Animals received leaded water and garlic juice (L+G). 4-Animals received leaded water, ascorbic acid and garlic juice (L+G+AA). 5- Rats treated with ascorbic acid (AA). 6- Rats treated with garlic juice (G). 7- Rats treated with ascorbic acid and garlic juice (AA+G). 8- Rats treated with tap water plus 0.4 ml/l normal hydrogen chloride (HCl) and 0.5 mg/l Glucose (Sham). 9- Normal group (N). Leaded water (1500 ppm), garlic juice (1 ml/100g/day, gavage) and ascorbic acid (500 mg/kg/day, IP) were used. Finally, blood lead levels (BLL) were measured in both rats and their offspring. The rat offspring brain sections were stained using Toluidine Blue and photographed. Dark neurons (DNs) were counted to compare all groups. Results: BLL significantly increased in L group compared to control and sham groups and decreased in L+G and L+AA groups in comparison to the L group (P<0.05). the number of DNs in the CA1, CA3, and DG of rat offspring hippocampus significantly increased in L group in comparison to control and sham groups (P<0.05) and decreased in L+G and L+AA groups compared to L group (P<0.05). Conclusion: Garlic juice and ascorbic acid administration during pregnancy and lactation may protect lead-induced neural damage in rat offspring hippocampus. PMID:24298384

  6. Alterations of the oxidative status in rat hippocampus and prodepressant effect of chronic testosterone enanthate administration.

    PubMed

    Joksimović, Jovana; Selaković, Dragica; Jakovljević, Vladimir; Mihailović, Vladimir; Katanić, Jelena; Boroja, Tatjana; Rosić, Gvozden

    2017-03-24

    In a last few decades, anabolic-androgenic steroids (AASs) abuse has become serious health concern especially among adolescents. AASs abuse has been reported to be involved in pathogenesis of various mood disorders, including depression. In order to evaluate the effects of chronic (6 weeks) testosterone enanthate (TE) treatment in supraphysiological dose and exercise on depression-like behavior in rats, 32 male rats were divided into four groups: control (C), testosterone enanthate (T, 20 mg/kg/w, s.c.), exercise (E, swimming for 1 h/day), and combined group-testosterone enanthate plus exercise (T + E). TE produced prodepressant effect in tail suspension test (TST) parameters compared to the control and exercise groups, while exercise induced the opposite effect. Simultaneous TE administration along with exercise attenuated the antidepressant effect of exercise reversing the parameters of TST to the control values. Oxidative stress markers in rat hippocampus were significantly altered following applied protocols. TE administration increased index of lipid peroxidation (TBARS) and decreased superoxide dismutase activity (SOD), while exercise induced the opposite effect, with no change in glutathione (GSH) levels. Our results indicate that TE chronic treatment resulted in clear depressive-like behavior, even abolishing beneficial antidepressant effects of exercise in TST that was accompanied with increased oxidative damage in rat hippocampus. The antidepressant effect of exercise correlated with the improvement of redox status in hippocampal tissue. Behavioral parameters obtained in TST significantly correlated with the levels of oxidative stress markers.

  7. Melatonin administration reverses the alteration of amyloid precursor protein-cleaving secretases expression in aged mouse hippocampus.

    PubMed

    Mukda, Sujira; Panmanee, Jiraporn; Boontem, Parichart; Govitrapong, Piyarat

    2016-05-16

    Beta-amyloid (Aβ) peptide is the pathological hallmark of Alzheimer's disease (AD). Interestingly, Aβ is normally synthesized in the brain of healthy people; however, during advanced aging, the level of Aβ peptides increases. As a result, the aggregation of Aβ peptides leads to trafficking problems, synaptic loss, inflammation, and cell death. Melatonin, the hormone primarily synthesized and secreted from the pineal gland, is decreased with progressing age, particularly in Alzheimer's disease patients. The loss of melatonin levels and the abnormal accumulation of some proteins, such as Aβ peptides in the brains of AD patients are considered important factors in the initiation of the cognitive symptoms of dementia. A previous study in mice reported that increased brain melatonin levels remarkably diminished the potentially toxic Aβ peptide levels. The present study showed that aged mice significantly impaired spatial memory in the Morris Water Maze task. We also showed that α-, β-, and γ-secretases, which are type-I membrane protein proteases responsible for Aβ production, showed alterations in both mRNA and protein expression in the hippocampus of aged mice. The long-term administration of melatonin, mice had shorter escape latencies and remained in the target quadrant longer compared to the aged group. Melatonin attenuated the reduction of α-secretase and inhibited the increase of β- and γ-secretases. Moreover, melatonin attenuated the upregulation of pNFkB and the reduction of sirtuin1 in the hippocampus of aged mice. These results suggested that melatonin protected against Aβ peptide production in aged mice. Hence, melatonin loss in aging could be recompensed through dietary supplementation as a beneficial therapeutic strategy for AD prevention and progression.

  8. The effects of nano-silver and garlic administration during pregnancy on neuron apoptosis in rat offspring hippocampus

    PubMed Central

    Ataei, Maryam Lale; Ebrahimzadeh-bideskan, Ali Reza

    2014-01-01

    Objective(s): The aim of this study was to investigate the effects of nano-silver and garlic administration during pregnancy on neuron apoptosis in rat offspring hippocampus. Materials and Methods: Fifty pregnant wistar rats were randomly divided into five groups: 1- nano-silver (N.S) group; 30 mg/kg of N.S treated via gavage. 2- Control (C) group, administrated with distilled water via gavage. 3- N.S and garlic (N.S+G) group; N.S (30 mg/kg) and garlic juice (1 ml/100 g) treated via gavage simultaneously. 4- Garlic group (G); garlic juice (1 ml/100 g) administrated via gavage, 5- normal (N) without any intervention. All the interventions were done during pregnancy (21 days). Finally, the brains of rat offspring were removed to use for nano-silver level measurement and TUNEL staining. The mean of TUNEL positive cell numbers per unit area (NA) in different regions of hippocampus were compared in all animal groups. Results: The results revealed a significant increase of hippocampus nano-silver level in N.S and N.S+G groups comparing to N group (P<0.05) and a significant decrease in nano-silver level in N.S+G group comparing to N.S group (P<0.01). The number of TUNEL positive cells in the CA1, CA3, and DG fields of rat offspring hippocampus increased in N.S and N.S+G groups comparing to other ones, and also reduced significantly in N.S+G group comparing to N.S group (¥ P< 0.01). Conclusion: Our results showed that co-administration of nano-silver and garlic during pregnancy may lead to reduce nano-silver induced apoptotic cells in their offspring hippocampus. PMID:25140202

  9. Self administration of oxycodone alters synaptic plasticity gene expression in the hippocampus differentially in male adolescent and adult mice.

    PubMed

    Zhang, Y; Brownstein, A J; Buonora, M; Niikura, K; Ho, A; Correa da Rosa, J; Kreek, M J; Ott, J

    2015-01-29

    Abuse and addiction to prescription opioids such as oxycodone (a short-acting Mu opioid receptor (MOP-r) agonist) in adolescence is a pressing public health issue. We have previously shown differences in oxycodone self-administration behaviors between adolescent and adult C57BL/6J mice and expression of striatal neurotransmitter receptor genes, in areas involved in reward. In this study, we aimed to determine whether oxycodone self-administration differentially affects genes regulating synaptic plasticity in the hippocampus of adolescent compared to adult mice, since the hippocampus may be involved in learning aspects associated with chronic drug self administration. Hippocampus was isolated for mRNA analysis from mice that had self administered oxycodone (0.25 mg/kg/infusion) 2h/day for 14 consecutive days or from yoked saline controls. Gene expression was analyzed with real-time polymerase chain reaction (PCR) using a commercially available "synaptic plasticity" PCR array containing 84 genes. We found that adolescent and adult control mice significantly differed in the expression of several genes in the absence of oxycodone exposure, including those coding for mitogen-activated protein kinase, calcium/calmodulin-dependent protein kinase II gamma subunit, glutamate receptor, ionotropic AMPA2 and metabotropic 5. Chronic oxycodone self administration increased proviral integration site 1 (Pim1) and thymoma viral proto-oncogene 1 mRNA levels compared to controls in both age groups. Both Pim1 and cadherin 2 mRNAs showed a significant combined effect of Drug Condition and Age × Drug Condition. Furthermore, the mRNA levels of both cadherin 2 and cAMP response element modulators showed an experiment-wise significant difference between oxycodone and saline control in adult but not in adolescent mice. Overall, this study demonstrates for the first time that chronic oxycodone self-administration differentially alters synaptic plasticity gene expression in the hippocampus

  10. Chronic morphine administration induces over-expression of aldolase C with reduction of CREB phosphorylation in the mouse hippocampus.

    PubMed

    Yang, Hai-Yu; Pu, Xiao-Ping

    2009-05-01

    In recent studies, alterations in the activity and expression of metabolic enzymes, such as those involved in glycolysis, have been detected in morphine-dependent patients and animals. Increasing evidence demonstrates that the hippocampus is an important brain region associated with morphine dependence, but the molecular events occurring in the hippocampus following chronic exposure to morphine are poorly understood. Aldolase C is the brain-specific isoform of fructose-1, 6-bisphosphate aldolase which is a glycolytic enzyme catalyzing reactions in the glycolytic, gluconeogenic, and fructose metabolic pathways. Using Western blot and immunofluorescence assays, we found the expression of aldolase C was markedly increased in the mouse hippocampus following chronic morphine treatment. Naloxone pretreatment before morphine administration suppressed withdrawal jumping, weight loss, and overexpression of aldolase C. CREB is a transcription factor regulated through phosphorylation on Ser133, which is known to play a key role in the mechanism of morphine dependence. When detecting the expression of phosphorylated CREB (p-CREB) in the mouse hippocampus using Western blot and immunohistochemistry, we found CREB phosphorylation was clearly decreased following chronic morphine treatment. Interestingly, laser-confocal microscopy showed that overexpression of aldolase C in mouse hippocampal neurons was concomitant with the decreased immunoreactivity of p-CREB. The results suggest potential links between the morphine-induced alteration of aldolase C and the regulation of CREB phosphorylation, a possible mechanism of morphine dependence.

  11. Repeated administration of dopaminergic agents in the dorsal hippocampus and morphine-induced place preference.

    PubMed

    Zarrindast, M-R; Nasehi, M; Rostami, P; Rezayof, A; Fazli-Tabaei, S

    2005-03-01

    The aim of the present experiments was to investigate whether repeated intra-hippocampal CA1 (intra-CA1) administration of dopaminergic agents can affect morphine-induced conditioned place preference (CPP). Effects of repeated intra-CA1 injections of dopamine (DA) receptor agonists and antagonists on morphine-induced CPP in rats were investigated using an unbiased 3-day schedule of place conditioning. Animals receiving once-daily subcutaneous (s.c.) injections of morphine (1-9 mg/kg) or saline (1.0 ml/kg, s.c.) showed a significant place preference in a dose-dependent manner: the maximum response was observed with 3 mg/kg morphine. Three days' intra-CA1 injections of apomorphine (0.25-1 microg/rat) followed by 5 days free of the drug, significantly decreased morphine CPP (1 and 3 mg/kg, s.c.). Moreover, pre-treatment with the highest dose of apomorphine (1 microg/rat) altered the effect of morphine to an aversive response. The morphine (1 and 3 mg/kg) CPP was also significantly decreased in animals that previously received three intra-CA1 injections of SKF 38393 (2-9 microg/rat), quinpirole (1-3 microg/rat) or sulpiride (1-3 microg/rat), and significantly increased in animals that had previously received three intra-CA1 injections of SCH 23390 (0.02 microg/rat). The 3-day pre-treatment with apomorphine, SKF 38393 or quinpirole reduced locomotor activity in the test session, while SCH 23390 and sulpiride did not have any influence on locomotor activity. It is concluded that repeated injections of DA receptor agents in the dorsal hippocampus, followed by 5 days free of the drugs, can affect morphine reward.

  12. Poppy seed oil protection of the hippocampus after cerebral ischemia and re-perfusion in rats.

    PubMed

    Cevik-Demirkan, A; Oztaşan, N; Oguzhan, E O; Cil, N; Coskun, S

    2012-11-01

    The brain is highly sensitive to hypoxia; this is true particularly of parts that are crucial for cognitive function. The effects of hypoxia are especially dramatic in the hippocampus. We evaluated the potential protective effects of poppy seed oil on the number of hippocampus cells and the serum antioxidant/oxidant status after cerebral ischemia and re-perfusion (CIR). Eighteen rats were divided into three equal groups. Group 1 served as the control group without CIR. Group 2 received poppy seed oil daily by oral gavage at a dose of 0.4 ml/kg, while group 3 was given 0.4 ml/kg saline solution by oral gavage per day; these treatments were continued for one month. Groups 2 and 3 were subjected to CIR induced by clamps on two points of both of the carotid arteries for 45 min followed by 45 min re-perfusion. There were significant decreases in the number of hippocampus cells between groups 1 and 2, and between groups 1 and 3. The mean cell number in group 2 was not significantly different from that of group 3. The serum nitric oxide levels in CIR groups were elevated significantly compared to controls, and were significantly higher in group 2 than in group 3. The glutathione levels were increased significantly in the poppy seed oil treated group compared to the saline CIR groups. The malondialdehyde levels were markedly increased in group 3 compared to both groups 1 and 2. Our study suggests that poppy seed oil can improve antioxidant defense capacity after CIR, although this treatment did not alter significantly the frequency of cell death.

  13. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.

    PubMed

    Nibuya, M; Nestler, E J; Duman, R S

    1996-04-01

    The present study demonstrates that chronic, but not acute, adminstration of several different classes of antidepressants, including serotonin- and norepinephrine-selective reuptake inhibitors, increases the expression of cAMP response element binding protein (CREB) mRNA in rat hippocampus. In contrast, chronic administration of several nonantidepressant psychotropic drugs did not influence expression of CREB mRNA, demonstrating the pharmacological specificity of this effect. In situ hybridization analysis demonstrates that antidepressant administration increases expression of CREB mRNA in CA1 and CA3 pyramidal and dentate gyrus granule cell layers of the hippocampus. In addition, levels of CRE immunoreactivity and of CRE binding activity were increased by chronic antidepressant administration, which indicates that expression and function of CREB protein are increased along with its mRNA. Chronic administration of the phosphodiesterase (PDE) inhibitors rolipram or papaverine also increased expression of CREB mRNA in hippocampus, demonstrating a role for the cAMP cascade. Moreover, coadministration of rolipram with imipramine resulted in a more rapid induction of CREB than with either treatment alone. Increased expression and function of CREB suggest that specific target genes may be regulated by these treatments. We have found that levels of brain-derived neurotrophic factor (BDNF) and trkB mRNA are also increased by administration of antidepressants or PDE inhibitors. These findings indicate that upregulation of CREB is a common action of chronic antidepressant treatments that may lead to regulation of specific target genes, such as BDNF and trkB, and to the long-term effects of these treatments on brain function.

  14. Modulation of axonal sprouting along rostro-caudal axis of dorsal hippocampus and no neuronal survival in parahippocampal cortices by long-term post-lesion melatonin administration in lithium-pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Ganjkhani, Mahin; Ali, Rostami; Iraj, Jafari Anarkooli

    2016-01-01

    Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in melatonin treated lithium-pilocarpine epileptic rats during early and chronic phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction, 5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals were killed 60 days post SE induction and the histological features of the rosrto-caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining. Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. The number of counted granular cells by melatonin (20 mg/kg) treatment increased along the rostro-caudal axis of the dorsal hippocampus in comparison to the untreated epileptic group. The density of Timm granules in the inner molecular layer of the dentate gyrus decreased significantly in all melatonin treated groups in comparison to the untreated epileptic animals. The increased density of synapsin I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated epileptic rats showed a profound decrease following melatonin treatment. There was no neuronal protection in the piriform and entorhinal cortices whatever the melatonin treatment. Long-term melatonin administration as a co-adjuvant probably could reduce the post-lesion histological consequences of TLE in a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. PMID:27051565

  15. Early induction of secretoneurin expression following kainic acid administration at convulsant doses in the rat and gerbil hippocampus.

    PubMed

    Marti, E; Blasi, J; Ferrer, I

    2002-01-01

    The expression of secretogranin-II and its major proteolytic product secretoneurin (SN) is under the control of neuronal excitation, as demonstrated by treating rats with the excitotoxic kainic acid (KA). Differences in the structure and function of the hippocampus in rats and gerbils have been described; these suggest possible differential reactive responses to KA. In the present study, the SN immunostaining pattern in relation with cell damage is analyzed from 6 h to 4 days following KA administration in rats and gerbils. Dramatic differences in the expression of SN were found in the hippocampal complex following KA administration in gerbils and rats. A robust increase in SN immunoreactivity was detected in the pyramidal cell layer of the rat hippocampus, especially in the CA1 area. In the gerbil, however, a strong increase in SN immunostaining was detected in interneurons of the hippocampal formation, as shown by double-labeling immunohistochemistry to SN and the calcium-binding proteins parvalbumin, calbindin, and calretinin. In addition, no damage (in the hippocampal formation) or moderate damage (in the entorhinal cortex) was observed in the gerbil, in contrast to the rat. The administration of KA and the GABA-B receptor inhibitors (CGP56999A or CGP36742) to the gerbil resulted in a strong rise in SN immunoreactitivty in the CA1 pyramidal cell layer of the hippocampus, as in the rat. However, no increased cell damage was observed under these conditions. The present data provide evidence of a species-differential reactive response to KA that might be based, in part, on distinct inhibitory intrahippocampal circuitry.

  16. Neonatal bilateral lidocaine administration into the ventral hippocampus caused postpubertal behavioral changes: An animal model of neurodevelopmental psychopathological disorders.

    PubMed

    Blas-Valdivia, Vanessa; Cano-Europa, Edgar; Hernández-García, Adelaida; Ortiz-Butrón, Rocio

    2009-01-01

    Our aim was to investigate if neonatal bilateral administration of lidocaine into the ventral hippocampus would cause behavioral changes related to schizophrenia. A neonatal ventral-hippocampal lesion (nVH lesion) was made with lidocaine in Wistar male pups. Two groups were formed, the first received lidocaine (4 mug/0.3 muL) and the second an equal volume of vehicle. At day 35 and 56, both groups were tested for social contact, immobility caused by clamping the neck and dorsal immobility, locomotor activity in an open field, and tail flick (TF) latency after a painful heat stimulus. All animals were then killed. Coronal cuts (7 mum) of the brain were obtained and each brain section was stained with cresyl violet-eosin. The animals which received the nVH lesion with lidocaine had decreased social interaction at both ages. The rats with lesions, only at day 58 postnatal, increased their distance traveled and ambulatory time, with a decrease in their nonambulatory and reset time. The rats with lesions had a longer duration of immobility caused by clamping the neck and a longer dorsal immobility at both days 34 and 57 compared to control rats. The lidocaine-treated group spent less time to deflect the tail compared to the control group at postpubertal age. The neonatal bilateral administration of lidocaine into the ventral hippocampus caused some alterations, such as chromatin condensation, nucleolus loss, and cell shrinkage, but glial proliferation was not seen. Neonatal bilateral lidocaine administration into the ventral hippocampus caused postpubertal behavioral changes.

  17. Changes in ensemble activity of hippocampus CA1 neurons induced by chronic morphine administration in freely behaving mice.

    PubMed

    Liu, F; Jiang, H; Zhong, W; Wu, X; Luo, J

    2010-12-15

    The hippocampus plays an important role in the formation of new memories and spatial navigation. Recently, growing evidence supports the view that it is also involved in addiction to opiates and other drugs. Theoretical and experimental studies suggest that hippocampal neural-network oscillations at specific frequencies and unit firing patterns reflect information of learning and memory encoding. Here, using multichannel recordings from the hippocampal CA1 area in behaving mice, we investigated the phase correlations between the theta (4-10 Hz) and gamma (40-100 Hz) oscillations, and the timing of spikes modulated by these oscillations. Local field potentials and single unit recordings in the CA1 area of mice receiving chronic morphine treatment revealed that the power of the theta rhythm was strongly increased; at the same time, the theta frequency during different behavioral states shifted markedly, and the characteristic coupling of theta and gamma oscillations was altered. Surprisingly, though the gamma oscillation frequency changed, the power of gamma lacking theta did not. Moreover, the timing of pyramidal cell spikes relative to the theta rhythm and the timing of interneuron spikes relative to the gamma rhythm changed during chronic morphine administration. Furthermore, these responses were impaired by a selective D1/D5 receptor antagonist intra-hippocampus injection. These results indicate that chronic morphine administration induced the changes of ensemble activity in the CA1 area, and these changes were dependent on local dopamine receptor activation.

  18. Differential regulation of catalytic and non-catalytic trkB messenger RNAs in the rat hippocampus following seizures induced by systemic administration of kainate.

    PubMed

    Dugich-Djordjevic, M M; Ohsawa, F; Okazaki, T; Mori, N; Day, J R; Beck, K D; Hefti, F

    1995-06-01

    Ribonuclease protection analysis and quantitative in situ hybridization histochemistry were used to investigate the coordination and regional expression of catalytic and non-catalytic trkB messenger RNAs in the adult rat hippocampus following systemic kainate-induced seizures. Changes in trkB expression were compared with the messenger RNA expression of its neurotrophic ligands, brain-derived neurotrophic factor and neurotrophin-3. TrkB messenger RNA expression was increased in the dentate granule cells at 1-4 h following the onset of seizures, and returned to control levels 16-24 h thereafter. In addition, seizures also induced expression of trkB messenger RNA in putative non-neuronal cells at four to seven days in the molecular layer of the dentate gyrus and the stratum lacunosum moleculare of the CA1 region. Hybridization with probes specific for the non-catalytic trkB receptor and the catalytic trkB receptor revealed that the increases at four and seven days in the molecular layers of the hippocampus reflected an up-regulation of only the non-catalytic form of the receptor. Furthermore, the neuronal increases observed 1-4 h were due to an up-regulation of both trkB TK- and trkB TK+ messenger RNAs. It was established that systemic administration of kainate increased brain-derived neurotrophic factor messenger RNA levels in the pyramidal and granule cell regions of the hippocampus 1-4 h following the onset of behaviorally manifested seizure activity. Early changes in neuronal expression of trkB TK- and trkB TK+ messenger RNA paralleled changes in brain-derived neurotrophic factor messenger RNA in the dentate granule cell and CA1 pyramidal cell layers, but not in the CA3 subregion. These data suggest that concomitant regulation of brain-derived neurotrophic factor and its cognate receptor may play a role in the selective vulnerability of hippocampal subregions to kainate-induced neuropathology. Furthermore, these data suggest a dual function for trkB receptor

  19. Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats.

    PubMed

    Monserrat Hernández-Hernández, Elizabeth; Serrano-García, Carolina; Antonio Vázquez-Roque, Rubén; Díaz, Alfonso; Monroy, Elibeth; Rodríguez-Moreno, Antonio; Florán, Benjamin; Flores, Gonzalo

    2016-05-01

    Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease.

  20. Chronic administration of troxerutin protects mouse brain against D-galactose-induced impairment of cholinergic system.

    PubMed

    Lu, Jun; Wu, Dong-Mei; Hu, Bin; Cheng, Wei; Zheng, Yuan-Lin; Zhang, Zi-Feng; Ye, Qin; Fan, Shao-Hua; Shan, Qun; Wang, Yong-Jian

    2010-02-01

    Previous evidence showed that administration of d-galactose (d-gal) increased ROS production and resulted in impairment of cholinergic system. Troxerutin, a natural bioflavonoid, has been reported to have many benefits and medicinal properties. In this study, we evaluated the protective effect of troxerutin against d-gal-induced impairment of cholinergic system, and explored the potential mechanism of its action. Our results displayed that troxerutin administration significantly improved behavioral performance of d-gal-treated mice in step-through test and morris water maze task. One of the potential mechanisms of this action was decreased AGEs, ROS and protein carbonyl levels in the basal forebrain, hippocampus and front cortex of d-gal-treated mice. Furthermore, our results also showed that troxerutin significantly inhibited cholinesterase (AchE) activity, increased the expression of nicotinic acetylcholine receptor alpha 7 (nAchRalpha7) and enhanced interactions between nAchRalpha7 and either postsynaptic density protein 95 (PSD95) or N-methyl-d-aspartate receptors subunit 1 (NMDAR1) in the basal forebrain, hippocampus and front cortex of d-gal-treated mice, which could help restore impairment of brain function.

  1. Administrator Tenure Statutes and Other Legislative Protection of Position.

    ERIC Educational Resources Information Center

    Gluckman, Ivan

    1983-01-01

    A pamphlet reviewing the employment rights of school administrators in each state, this report distinguishes between substantive and procedural rights for administrators threatened with demotion or dismissal. The author argues that principals should be aware of the kind and degree of statutory employment protection in their states, which differ in…

  2. 37 CFR 404.12 - Protection and administration of inventions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of inventions. 404.12 Section 404.12 Patents, Trademarks, and Copyrights ASSISTANT SECRETARY FOR TECHNOLOGY POLICY, DEPARTMENT OF COMMERCE LICENSING OF GOVERNMENT OWNED INVENTIONS § 404.12 Protection and administration of inventions. A Federal agency may take any suitable and necessary steps to protect...

  3. Protection of Human Subjects: A Primer for the New Administrator.

    ERIC Educational Resources Information Center

    Steinert, Bruce W.

    2002-01-01

    Discusses clinical trials in general, protecting human research subjects, and the role the research administrator can play in facilitating the process. The discussion is not intended to be a thorough treatise on clinical trials, but is an overview of new and lesser known human protection issues that are better handled prospectively. (EV)

  4. Upregulation of nucleoside triphosphate diphosphohydrolase-1 and ecto-5'-nucleotidase in rat hippocampus after repeated low-dose dexamethasone administration.

    PubMed

    Drakulić, Dunja; Stanojlović, Miloš; Nedeljković, Nadežda; Grković, Ivana; Veličković, Nataša; Guševac, Ivana; Mitrović, Nataša; Buzadžić, Ivana; Horvat, Anica

    2015-04-01

    Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5'-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under the influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.

  5. Acute ethanol administration affects memory reactivation: a look at the neuronal density and apoptosis in the rat hippocampus.

    PubMed

    Alijan-pour, J; Abrari, K; Bluki, T Lashkar; Ghorbanian, M T; Goudarzi, I; Salmani, M Elahdadi; Mirshekar, M

    2012-08-01

    This study is an attempt to examine whether administration of ethanol after memory reactivation will modulate expression of memory in rats or not. We further examined whether this administration alters the number of tunnel positive cells in hippocampus. Adult male Wistar rats were trained in a fear conditioning system using two 1s , 0.6 mA shock with an interval of 180 s. 24 h later the rats were returned to the chamber for reactivation, and then they were injected with ethanol (0.5, 1, 1.5 mg/kg) or saline, ip. Again, one, seven and fourteen days after reactivation, the rats were returned to the context for 5 min. The freezing time (absence of all movements except respiration) was scored in seconds. In the second experiment, after test 1, the animals were anesthetized and a transcardial perfuse with phosphate buffer and paraformaldehyde 4% was conducted. After post-fixation of brains 5-μm sections were stained with cresyl violet. Finally, paraffin-embedded sections of 10 μm were cut out throughout the tissue and each sample was processed with TUNEL. The number of apoptotic cells in a 130 μm-long segment of the hippocampal CA1 and CA3 fields and dentate gyrus was counted. The data demonstrate that ethanol exposure impairs post retrieval processes. Rats receiving ethanol (1.5 mg/kg) showed lower freezing levels during the first test. Moreover, ethanol decreases the density of CA1, CA3 and DG cells and increases the density of apoptotic cells in all regions of hippocampus. Therefore, ethanol exposure impairs reconsolidation of contextual fear conditioning probably via decreasing the density of CA1, CA3 and DG cells.

  6. The effects of cocaine self-administration on dendritic spine density in the rat hippocampus are dependent on genetic background.

    PubMed

    Miguéns, Miguel; Kastanauskaite, Asta; Coria, Santiago M; Selvas, Abraham; Ballesteros-Yañez, Inmaculada; DeFelipe, Javier; Ambrosio, Emilio

    2015-01-01

    Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds.

  7. Intracerebroventricular kainic acid administration to neonatal rats alters interneuron development in the hippocampus.

    PubMed

    Dong, Hongxin; Csernansky, Cynthia A; Chu, Yunxiang; Csernansky, John G

    2003-10-10

    The effects of neonatal exposure to excitotoxins on the development of interneurons have not been well characterized, but may be relevant to the pathogenesis of neuropsychiatric disorders. In this study, the excitotoxin, kainic acid (KA) was administered to rats at postnatal day 7 (P7) by intracerebroventricular (i.c.v.) infusion. At P14, P25, P40 and P60, Nissl staining and immunohistochemical studies with the interneuron markers, glutamic acid decarboxylase (GAD-67), calbindin-D28k (CB) and parvalbumin (PV) were performed in the hippocampus. In control animals, the total number of interneurons, as well as the number of interneurons stained with GAD-67, CB and PV, was nearly constant from P14 through P60. In KA-treated rats, Nissl staining, GAD-67 staining, and CB staining revealed a progressive decline in the overall number of interneurons in the CA1 and CA3 subfields from P14 to P60. In contrast, PV staining in KA-treated rats showed initial decreases in the number of interneurons in the CA1 and CA3 subfields at P14 followed by increases that approached control levels by P60. These results suggest that, in general, early exposure to the excitotoxin KA decreases the number of hippocampal interneurons, but has a more variable effect on the specific population of interneurons labeled by PV. The functional impact of these changes may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia.

  8. Estrogen administration modulates hippocampal GABAergic subpopulations in the hippocampus of trimethyltin-treated rats

    PubMed Central

    Corvino, Valentina; Di Maria, Valentina; Marchese, Elisa; Lattanzi, Wanda; Biamonte, Filippo; Michetti, Fabrizio; Geloso, Maria Concetta

    2015-01-01

    Given the well-documented involvement of estrogens in the modulation of hippocampal functions in both physiological and pathological conditions, the present study investigates the effects of 17-beta estradiol (E2) administration in the rat model of hippocampal neurodegeneration induced by trimethyltin (TMT) administration (8 mg/kg), characterized by loss of pyramidal neurons in CA1, CA3/hilus hippocampal subfields, associated with astroglial and microglial activation, seizures and cognitive impairment. After TMT/saline treatment, ovariectomized animals received two doses of E2 (0.2 mg/kg intra-peritoneal) or vehicle, and were sacrificed 48 h or 7 days after TMT-treatment. Our results indicate that in TMT-treated animals E2 administration induces the early (48 h) upregulation of genes involved in neuroprotection and synaptogenesis, namely Bcl2, trkB, cadherin 2 and cyclin-dependent-kinase-5. Increased expression levels of glutamic acid decarboxylase (gad) 67, neuropeptide Y (Npy), parvalbumin, Pgc-1α and Sirtuin 1 genes, the latter involved in parvalbumin (PV) synthesis, were also evident. Unbiased stereology performed on rats sacrificed 7 days after TMT treatment showed that although E2 does not significantly influence the extent of TMT-induced neuronal death, significantly enhances the TMT-induced modulation of GABAergic interneuron population size in selected hippocampal subfields. In particular, E2 administration causes, in TMT-treated rats, a significant increase in the number of GAD67-expressing interneurons in CA1 stratum oriens, CA3 pyramidal layer, hilus and dentate gyrus, accompanied by a parallel increase in NPY-expressing cells, essentially in the same regions, and of PV-positive cells in CA1 pyramidal layer. The present results add information concerning the role of in vivo E2 administration on mechanisms involved in cellular plasticity in the adult brain. PMID:26594149

  9. Exercise increases insulin signaling in the hippocampus: physiological effects and pharmacological impact of intracerebroventricular insulin administration in mice.

    PubMed

    Muller, Alexandre P; Gnoatto, Jussânia; Moreira, Julia D; Zimmer, Eduardo R; Haas, Clarissa B; Lulhier, Francisco; Perry, Marcos L S; Souza, Diogo O; Torres-Aleman, Ignácio; Portela, Luis V

    2011-10-01

    Increasing evidence indicates that physical exercise induces adaptations at the cellular, molecular, and systemic levels that positively affect the brain. Insulin plays important functional roles within the brain that are mediated by insulin-receptor (IR) signaling. In the hippocampus, insulin improves synaptic plasticity, memory formation, and learning via direct modulation of GABAergic and glutamatergic receptors. Separately, physical exercise and central insulin administration exert relevant roles in cognitive function. We here use CF1 mice to investigate (i) the effects of voluntary exercise on hippocampal insulin signaling and memory performance and (ii) whether central insulin administration alters the effects of exercise on hippocampal insulin signaling and memory performance. Adult mice performed 30 days of voluntary exercise on running wheel and afterward both, sedentary and exercised groups, received intracerebroventricular (icv) injection of saline or insulin (0.5-5 mU). Memory performance was assessed using the inhibitory avoidance and water maze tasks. Hippocampal tissue was measured for [U-(14)C] glucose oxidation and the immunocontent of insulin receptor/signaling (IR, pTyr, pAktser473). Additionally, the phosphorylation of the glutamate NMDA receptor NR2B subunit and the capacity of glutamate uptake were measured, and immunohistochemistry was used to determine glial reactivity. Exercise significantly increased insulin peripheral sensitivity, spatial learning, and hippocampal IR/pTyrIR/pAktser473 immunocontent. Glucose oxidation, glutamate uptake, and astrocyte number also increased relative to the sedentary group. In both memory tasks, 5 mU icv insulin produced amnesia but only in exercised animals. This amnesia was associated a rapid (15 min) and persistent (24 h) increase in hippocampal pNR2B immunocontent that paralleled the increase in glial reactivity. In conclusion, physical exercise thus increased hippocampal insulin signaling and improved

  10. Enhanced dendritic spine number of neurons of the prefrontal cortex, hippocampus and nucleus accumbens in old rats after chronic donepezil administration

    PubMed Central

    Alcantara-Gonzalez, Faviola; Juarez, Ismael; Solis, Oscar; Martinez-Tellez, Isaura; Camacho-Abrego, Israel; Masliah, Eliezer; Mena, Raul; Flores, Gonzalo

    2010-01-01

    In Alzheimer's disease brains morphological changes in the dendrites of pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been observed. These changes are particularly reflected in the decrement of both the dendritic tree and spine number. Donepezil is a potent and selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease. We have studied the effect of oral administration of this drug on the morphology of neuronal cells from the brain of aged rats. We examined dendrites of pyramidal neurons of the PFC, dorsal or ventral hippocampus and medium spiny neurons of the nucleus accumbens (NAcc). Donepezil (1 mg/Kg, vo) was administrated every day for 60 days to rats aged 10 and 18 months. Dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at 12 and 20 months ages, respectively. In all Donepezil treated-rats a significant increment of the dendritic spines number in pyramidal neurons of the PFC, dorsal hippocampus was observed. However, pyramidal neurons of the ventral hippocampus and medium spiny cells of the NAcc only showed an increase in the number of their spines in 12 months old-rats. Our results suggest that Donepezil prevents the alterations of the neuronal dendrite morphology caused by aging. PMID:20336627

  11. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression.

    PubMed

    Chen, Hao-Hao; Zhang, Ning; Li, Wei-Yun; Fang, Ma-Rong; Zhang, Hui; Fang, Yuan-Shu; Ding, Ming-Xing; Fu, Xiao-Yan

    2015-09-01

    Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippocampus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

  12. Layered virus protection for the operations and administrative messaging system

    NASA Technical Reports Server (NTRS)

    Cortez, R. H.

    2002-01-01

    NASA's Deep Space Network (DSN) is critical in supporting the wide variety of operating and plannedunmanned flight projects. For day-to-day operations it relies on email communication between the three Deep Space Communication Complexes (Canberra, Goldstone, Madrid) and NASA's Jet Propulsion Laboratory. The Operations & Administrative Messaging system, based on the Microsoft Windows NTand Exchange platform, provides the infrastructure that is required for reliable, mission-critical messaging. The reliability of this system, however, is threatened by the proliferation of email viruses that continue to spread at alarming rates. A layered approach to email security has been implemented across the DSN to protect against this threat.

  13. Transgenic Overexpression of 14-3-3 Zeta Protects Hippocampus against Endoplasmic Reticulum Stress and Status Epilepticus In Vivo

    PubMed Central

    Brennan, Gary P.; Jimenez-Mateos, Eva M.; McKiernan, Ross C.; Engel, Tobias; Tzivion, Guri; Henshall, David C.

    2013-01-01

    14-3-3 proteins are ubiquitous molecular chaperones that are abundantly expressed in the brain where they regulate cell functions including metabolism, the cell cycle and apoptosis. Brain levels of several 14-3-3 isoforms are altered in diseases of the nervous system, including epilepsy. The 14-3-3 zeta (ζ) isoform has been linked to endoplasmic reticulum (ER) function in neurons, with reduced levels provoking ER stress and increasing vulnerability to excitotoxic injury. Here we report that transgenic overexpression of 14-3-3ζ in mice results in selective changes to the unfolded protein response pathway in the hippocampus, including down-regulation of glucose-regulated proteins 78 and 94, activating transcription factors 4 and 6, and Xbp1 splicing. No differences were found between wild-type mice and transgenic mice for levels of other 14-3-3 isoforms or various other 14-3-3 binding proteins. 14-3-3ζ overexpressing mice were potently protected against cell death caused by intracerebroventricular injection of the ER stressor tunicamycin. 14-3-3ζ overexpressing mice were also potently protected against neuronal death caused by prolonged seizures. These studies demonstrate that increased 14-3-3ζ levels protect against ER stress and seizure-damage despite down-regulation of the unfolded protein response. Delivery of 14-3-3ζ may protect against pathologic changes resulting from prolonged or repeated seizures or where injuries provoke ER stress. PMID:23359526

  14. Protective effects of C-phycocyanin against kainic acid-induced neuronal damage in rat hippocampus.

    PubMed

    Rimbau, V; Camins, A; Romay, C; González, R; Pallàs, M

    1999-12-03

    The neuroprotective role of C-phycocyanin was examined in kainate-injured brains of rats. The effect of three different treatments with C-phycocyanin was studied. The incidence of neurobehavioral changes was significantly lower in animals receiving C-phycocyanin. These animals also gained significantly more weight than the animals only receiving kainic acid, whereas their weight gain did not differed significantly from controls. Equivalent results were found when the neuronal damage in the hippocampus was evaluated through changes in peripheral benzodiazepine receptors (microglial marker) and heat shock protein 27 kD expression (astroglial marker). Our results are consistent with the oxygen radical scavenging properties of C-phycocyanin described elsewhere. Our findings and the virtual lack of toxicity of C-phycocyanin suggest this drug could be used to treat oxidative stress-induced neuronal injury in neurodegenerative diseases, such as Alzheimer's and Parkinson's.

  15. 19 CFR 206.66 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... business information under administrative protective order. 206.66 Section 206.66 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION NONADJUDICATIVE INVESTIGATIONS INVESTIGATIONS RELATING TO GLOBAL... certain confidential business information under administrative protective order. In an investigation...

  16. 3'-5' cyclic-guanosine monophosphate increase in rat brain hippocampus after gamma-hydroxybutyrate administration. Prevention by valproate and naloxone

    SciTech Connect

    Vayer, P.; Gobaille, S.; Mandel, P.; Maitre, M.

    1987-08-03

    An increase (123%) of cyclic GMP (cGMP) was observed in the hippocampus of the rat killed by microwave irradiation 45 min after administration of 500 mg/kg el-hydroxybutyrate (GHB) IP. This increase is time and dose dependent. No modification in cyclic nucleotide content was observed in striatum and in cerebellum. As the role of GHB has been implicated in neurotransmission, the fact that this compound increases cyclic GMP accumulation in hippocampus in vivo may represent a mechanism by which the actions of GHB are mediated at the cellular level. Valproate (400 mg/kg) or naloxone (10 mg/kg) pretreatment completely abolish the cGMP increase due to GHB. A GABAergic and/or opiate phenomenon may be involved in the mechanism of GHB induced increase of cGMP. 34 references, 4 figures.

  17. Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus.

    PubMed

    Wang, Qun; Tompkins, Kenneth D; Simonyi, Agnes; Korthuis, Ronald J; Sun, Albert Y; Sun, Grace Y

    2006-05-23

    Increased production of reactive oxygen species (ROS) following cerebral ischemia-reperfusion (I/R) is an important underlying cause for neuronal injury leading to delayed neuronal death (DND). In this study, apocynin, a specific inhibitor for NADPH oxidase, was used to test whether suppression of ROS by the NADPH oxidase inhibitor can protect against ischemia-induced ROS generation and decrease DND. Global cerebral ischemia was induced in gerbils by a 5-min occlusion of bilateral common carotid arteries (CCA). Using measurement of 4-hydroxy-2-nonenal (HNE) as a marker for lipid peroxidation, apocynin (5 mg/kg body weight) injected i.p. 30 min prior to ischemia significantly attenuated the early increase in HNE in hippocampus measured at 3 h after I/R. Apocynin also protected against I/R-induced neuronal degeneration and DND, oxidative DNA damage, and glial cell activation. Taken together, the neuroprotective effects of apocynin against ROS production during early phase of I/R and subsequent I/R-induced neuronal damage provide strong evidence that inhibition of NADPH oxidase could be a promising therapeutic mechanism to protect against stroke damage in the brain.

  18. Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

    PubMed

    Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

    2015-02-01

    Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus.

  19. 19 CFR 207.7 - Limited disclosure of certain business proprietary information under administrative protective...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... information under administrative protective order. 207.7 Section 207.7 Customs Duties UNITED STATES... administrative protective order. (a)(1) Disclosure. Upon receipt of a timely application filed by an authorized... authorized applicant under an administrative protective order described in paragraph (b) of this section....

  20. 19 CFR 207.7 - Limited disclosure of certain business proprietary information under administrative protective...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... information under administrative protective order. 207.7 Section 207.7 Customs Duties UNITED STATES... administrative protective order. (a)(1) Disclosure. Upon receipt of a timely application filed by an authorized... authorized applicant under an administrative protective order described in paragraph (b) of this section....

  1. 19 CFR 207.7 - Limited disclosure of certain business proprietary information under administrative protective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... information under administrative protective order. 207.7 Section 207.7 Customs Duties UNITED STATES... administrative protective order. (a)(1) Disclosure. Upon receipt of a timely application filed by an authorized... authorized applicant under an administrative protective order described in paragraph (b) of this section....

  2. Repeated citalopram administration counteracts kainic acid-induced spreading of PSA-NCAM-immunoreactive cells and loss of reelin in the adult mouse hippocampus.

    PubMed

    Jaako, Külli; Aonurm-Helm, Anu; Kalda, Anti; Anier, Kaili; Zharkovsky, Tamara; Shastin, Dmitri; Zharkovsky, Alexander

    2011-09-01

    Systemic or intracerebral administration of kainic acid in rodents induces neuronal death followed by a cascade of neuroplastic changes in the hippocampus. Kainic acid-induced neuroplasticity is evidenced by alterations in hippocampal neurogenesis, dispersion of the granule cell layer and re-organisation of mossy fibres. Similar abnormalities are observed in patients with temporal lobe epilepsy and, therefore, kainic acid-induced hippocampal neuroplasticity might mimic pathological mechanisms leading to the formation of 'epileptic brain' in patients with temporal lobe epilepsy. Previous studies have demonstrated that selective serotonin re-uptake inhibitor antidepressants might reduce the severity of seizures in epileptic patients and reduce neuronal death in laboratory animal models of kainic acid-induced neurotoxicity. In the present study, we investigated whether kainic acid-induced neuroplasticity in mice is modulated by the repeated administration of citalopram, a selective serotonin reuptake inhibitor. We found that at the histopathological level, repeated citalopram treatment counteracted the kainic acid-induced neuronal loss and dispersion of young granule neurons expressing the polysialylated neural cell adhesion molecule within the granule cell layer of the hippocampus. Citalopram also counteracted the downregulation of reelin on both mRNA and protein levels induced by kainic acid administration. Our findings indicate that repeated administration of citalopram is able to prevent kainic acid-induced abnormal brain plasticity and thereby prevent the formation of an epileptic phenotype.

  3. Resveratrol decreases the insoluble Aβ1-42 level in hippocampus and protects the integrity of the blood-brain barrier in AD rats.

    PubMed

    Zhao, H F; Li, N; Wang, Q; Cheng, X J; Li, X M; Liu, T T

    2015-12-03

    Our previous studies demonstrated resveratrol (Res) administration protected Alzheimer's disease (AD) rats from developing memory decline by anti-oxidation. Beta-amyloid peptide 1-42 (Aβ1-42) is not only the primary protein component of senile plaques in AD but also is believed to play an important part in its pathology. Increasing evidence has shown neuroinflammation and the integrity of the blood-brain barrier (BBB) is closely related to the pathogenesis of AD. The aim of the present study is to further elucidate whether Res prevents AD rats from inflammation induced by Aβ1-42 and protects the integrity of BBB. Rats were divided into six groups: (1) ovariectomized (OVX)+D-galactose (D-gal) 100mg/kg group (OVX+D-gal); (2-4) OVX, D-gal and Res 20, 40 and 80 mg/kg treated groups; and (5) OVX, D-gal and estradiol valerate 0.8 mg/kg treated group (ET); (6) Sham control group. 12 weeks later, Res 40 and 80 mg/kg treatment exhibited a significant decrease of Aβ1-42 compared with the OVX+D-gal rats of hippocampus, which was accompanied by decreased expression of advanced glycation endproducts (RAGE), matrix metalloprotein-9 (MMP-9), nuclear factor kappaB (NF-κB) and the increase of Claudin-5. These results suggest that Res is useful not only in protecting OVX+D-gal rats from neuroinflammation mediated by Aβ1-42 by decreasing the expression of NF-κB but also the integrity of BBB by increasing Claudin-5 and decreasing RAGE, MMP-9.

  4. Effects of Ketamine on Levels of Inflammatory Cytokines IL-6, IL-1β, and TNF-α in the Hippocampus of Mice Following Acute or Chronic Administration.

    PubMed

    Li, Yanning; Shen, Ruipeng; Wen, Gehua; Ding, Runtao; Du, Ao; Zhou, Jichuan; Dong, Zhibin; Ren, Xinghua; Yao, Hui; Zhao, Rui; Zhang, Guohua; Lu, Yan; Wu, Xu

    2017-01-01

    Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Our results showed that ketamine at the dose of 60 mg/kg induced spatial recognition memory deficit and reduced anxiety-like behaviors in mice after chronic administration. Moreover, we found that ketamine increased the hippocampal levels of IL-6 and IL-1β after single, multiple and long-term administration in a dose-dependent manner. However, the expression level of TNF-α differed in the mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α, whereas multiple and long-term administration decreased it significantly. We considered that TNF-α expression could be controlled by a bi-directional regulatory pathway, which was associated with the dose and duration of ketamine administration. Our results suggest that the alterations in the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α may be involved in the neurotoxicity of ketamine.

  5. Effects of Ketamine on Levels of Inflammatory Cytokines IL-6, IL-1β, and TNF-α in the Hippocampus of Mice Following Acute or Chronic Administration

    PubMed Central

    Li, Yanning; Shen, Ruipeng; Wen, Gehua; Ding, Runtao; Du, Ao; Zhou, Jichuan; Dong, Zhibin; Ren, Xinghua; Yao, Hui; Zhao, Rui; Zhang, Guohua; Lu, Yan; Wu, Xu

    2017-01-01

    Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Our results showed that ketamine at the dose of 60 mg/kg induced spatial recognition memory deficit and reduced anxiety-like behaviors in mice after chronic administration. Moreover, we found that ketamine increased the hippocampal levels of IL-6 and IL-1β after single, multiple and long-term administration in a dose-dependent manner. However, the expression level of TNF-α differed in the mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α, whereas multiple and long-term administration decreased it significantly. We considered that TNF-α expression could be controlled by a bi-directional regulatory pathway, which was associated with the dose and duration of ketamine administration. Our results suggest that the alterations in the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α may be involved in the neurotoxicity of ketamine. PMID:28373844

  6. Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection

    PubMed Central

    Onody, Peter; Aranyi, Peter; Turoczi, Zsolt; Stangl, Rita; Fulop, Andras; Dudas, Emese; Lotz, Gabor; Szijarto, Attila

    2016-01-01

    Aims and Objectives Acute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction. Methods Male Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2μg/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected. Results Systemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-α levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion. Conclusion The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications. PMID:27684548

  7. Protective effects of bupivacaine against kainic acid-induced seizure and neuronal cell death in the rat hippocampus.

    PubMed

    Chiu, Kuan Ming; Wu, Chia Chan; Wang, Ming Jiuh; Lee, Ming Yi; Wang, Su Jane

    2015-01-01

    The excessive release of glutamate is a critical element in the neuropathology of epilepsy, and bupivacaine, a local anesthetic agent, has been shown to inhibit the release of glutamate in rat cerebrocortical nerve terminals. This study investigated whether bupivacaine produces antiseizure and antiexcitotoxic effects using a kainic acid (KA) rat model, an animal model used for temporal lobe epilepsy, and excitotoxic neurodegeneration experiments. The results showed that administering bupivacaine (0.4 mg/kg or 2 mg/kg) intraperitoneally to rats 30 min before intraperitoneal injection of KA (15 mg/kg) increased seizure latency and reduced the seizure score. In addition, bupivacaine attenuated KA-induced hippocampal neuronal cell death, and this protective effect was accompanied by the inhibition of microglial activation and production of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the hippocampus. Moreover, bupivacaine shortened the latency of escaping onto the platform in the Morris water maze learning performance test. Collectively, these data suggest that bupivacaine has therapeutic potential for treating epilepsy.

  8. 6 CFR 29.4 - Protected Critical Infrastructure Information Program administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Protected Critical Infrastructure Information Management System (PCIIMS). The PCII Program Manager shall... be known as the “Protected Critical Infrastructure Information Management System” (PCIIMS), to record... Program administration. (a) Preparedness Directorate Program Management. The Secretary of...

  9. Effect of chronic administration of morphine on the gene expression level of sodium-dependent vitamin C transporters in rat hippocampus and lumbar spinal cord.

    PubMed

    Zarebkohan, Amir; Javan, Mohammad; Satarian, Leila; Ahmadiani, Abolhasan

    2009-07-01

    Chronic morphine leads to dependence, tolerance, and neural apoptosis. Vitamin C inhibits the withdrawal syndrome in morphine-dependent subjects and prevents apoptosis in experimental models. Sodium-dependent vitamin C transporter (SVCT) type-2 is the main transporter for carrying vitamin C into the brain and neural cells. The mechanism(s) by which vitamin C inhibits morphine dependence in not understood. SVCT activity determines the vitamin C availably within the nervous system. We have examined the alterations in the expression of SVCT1, SVCT2, and its splice variants in morphine-tolerant rats. Morphine (20 mg/kg) was injected twice/day to male rats for either 7 or 14 days. The development of analgesic tolerance was assessed using tail-flick test. Lumbar spinal cord and the hippocampus were isolated for RNA extraction. Semiquantitative reverse transcriptase-polymerase chain reaction method was used to assess the levels of gene expression. Administration of morphine for 7 or 14 days reduced the expression level of SVCT2 in both hippocampus and dorsal lumbar spinal cord of rats. SVCT2 expression was reduced in vitamin C-, and vitamin C combined with morphine-treated animals. Results did not show SVCT2 splice variation. SVCT1 did not express in control or morphine-treated rats. It seems that reduced expression level of SVCT2 might be involved in the development of morphine side effects such as tolerance and dependency.

  10. Changes in Gene Expression in the Hippocampus Following Exposure to 56Fe Particles and Protection by Berry Diets

    NASA Astrophysics Data System (ADS)

    Shukitt-Hale, Barbara; Lau, Francis; Carey, Amanda; Carrihill-Knoll, Kirsty; Rabin, Bernard; Joseph, James

    Exposing young rats to particles of high energy and charge (HZE particles), such as 56 Fe, enhances indices of oxidative stress and inflammation and disrupts the functioning of the dopaminergic system and behaviors mediated by this system in a manner similar to that seen in aged animals. Behaviors affected by radiation include deficits in motor performance, spatial learning and memory behavior, amphetamine-induced conditioned taste aversion learning, conditioned place preference, and operant conditioning. Berry fruit diets are high in antioxidant and antiinflammatory activity, and prevent the occurrence of the neurochemical and behavioral changes that occur in aging and by exposure to 56 Fe particles. In the present study, we examined whether gene expression in the hippocampus, an area of the brain important in memory, is affected by exposure to 56 Fe particles 36 hours post-irradiation. We also evaluated whether the blueberry (BB) and strawberry (SB) diets could ameliorate irradiation-induced deficits in gene expression by maintaining rats on these diets or a control diet for 8 weeks prior to being exposed to radiation. Therefore, to measure gene expression, 4 rats/group were euthanized 36 hours post whole-body irradiation with 1.5 Gy or 2.5 Gy of 1 GeV/n high-energy 56 Fe particles. Alterations in gene expression profile induced by radiation were analyzed by pathway-focused microarrays on the inflammatory cytokines and genes involved in NF-κB signal transduction pathways. For the diet studies, 3 rats/group were irradiated with 2.5 Gy of 56 Fe following 8 weeks supplementation with either the 2% BB or the 2% SB diet. We found that genes that directly or indirectly interact in the regulation of growth and differentiation of neurons were changed following irradiation. Genes that regulate apoptosis were up-regulated whereas genes that modulate cellular proliferation were down-regulated, possibly to eliminate damaged cells and to stop cell proliferation to prevent

  11. Protection of Radial Glial-Like Cells in the Hippocampus of APP/PS1 Mice: a Novel Mechanism of Memantine in the Treatment of Alzheimer's Disease.

    PubMed

    Sun, Dayu; Chen, Junhua; Bao, Xiaohang; Cai, Yulong; Zhao, Jinghui; Huang, Jing; Huang, Wei; Fan, Xiaotang; Xu, Haiwei

    2015-08-01

    The failure of adult neurogenesis in the hippocampal dentate gyrus (DG) is closely correlated with memory decline in Alzheimer's disease (AD). Radial glial-like cells (RGLs) localized to the adult DG generate intermediate progenitor cells and immature neurons and thus contribute to adult hippocampus neurogenesis. Memantine (MEM) has been indicated to dramatically increase hippocampal neurogenesis by promoting the proliferation of RGLs. In this study, we examined the effect of MEM on the capacity for hippocampal cell proliferation and the amount of RGLs in APPswe/PS1∆E9 transgenic (APP/PS1) mice between 9 and 13 months of age. MEM could enhance hippocampal neurogenesis and increase the number of RGLs in the DG subgranular zone (DG-SGZ) of APP/PS1 mice of both ages. Moreover, MEM decreased amyloidogenesis in 13-month-old APP/PS1 mice and protected cultured radial glia cells (RGCs, L2.3 cells) from apoptosis induced by the β amyloid peptide (Aβ). Additionally, MEM inhibited microglial activation in a vertical process in DG-SGZ of APP/PS1 mice and decreased interacting with RGL processes. Reelin is involved in the proliferation of RGLs in the hippocampus, which was typically upregulated in the hippocampus of APP/PS1 mice by MEM and thought to be an active signaling pathway associated with the MEM-induced increase in RGLs. Our data suggest a previously uncharacterized role for MEM in treating AD.

  12. Changes in gene expression in the rat hippocampus following exposure to 56 fe particles and protection by berry diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposing young rats to particles of high energy and charge (HZE particles), such as 56Fe, enhances indices of oxidative stress and inflammation and disrupts behavior, including spatial learning and memory. In the present study, we examined whether gene expression in the hippocampus, an area of the b...

  13. Pharmacological Administration of the Isoflavone Daidzein Enhances Cell Proliferation and Reduces High Fat Diet-Induced Apoptosis and Gliosis in the Rat Hippocampus

    PubMed Central

    Rivera, Patricia; Pérez-Martín, Margarita; Pavón, Francisco J.; Serrano, Antonia; Crespillo, Ana; Cifuentes, Manuel; López-Ávalos, María-Dolores; Grondona, Jesús M.; Vida, Margarita; Fernández-Llebrez, Pedro; de Fonseca, Fernando Rodríguez; Suárez, Juan

    2013-01-01

    Soy extracts have been claimed to be neuroprotective against brain insults, an effect related to the estrogenic properties of isoflavones. However, the effects of individual isoflavones on obesity-induced disruption of adult neurogenesis have not yet been analyzed. In the present study we explore the effects of pharmacological administration of daidzein, a main soy isoflavone, in cell proliferation, cell apoptosis and gliosis in the adult hippocampus of animals exposed to a very high-fat diet. Rats made obese after 12-week exposure to a standard or high-fat (HFD, 60%) diets were treated with daidzein (50 mg kg−1) for 13 days. Then, plasma levels of metabolites and metabolic hormones, cell proliferation in the subgranular zone of the dentate gyrus (SGZ), and immunohistochemical markers of hippocampal cell apoptosis (caspase-3), gliosis (GFAP and Iba-1), food reward factor FosB and estrogen receptor alpha (ERα) were analyzed. Treatment with daidzein reduced food/caloric intake and body weight gain in obese rats. This was associated with glucose tolerance, low levels of HDL-cholesterol, insulin, adiponectin and testosterone, and high levels of leptin and 17β-estradiol. Daidzein increased the number of phospho-histone H3 and 5-bromo-2-deoxyuridine (BrdU)-ir cells detected in the SGZ of standard diet and HFD-fed rats. Daidzein reversed the HFD-associated enhanced immunohistochemical expression of caspase-3, FosB, GFAP, Iba-1 and ERα in the hippocampus, being more prominent in the dentate gyrus. These results suggest that pharmacological treatment with isoflavones regulates metabolic alterations associated with enhancement of cell proliferation and reduction of apoptosis and gliosis in response to high-fat diet. PMID:23741384

  14. Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus.

    PubMed

    Rivera, Patricia; Pérez-Martín, Margarita; Pavón, Francisco J; Serrano, Antonia; Crespillo, Ana; Cifuentes, Manuel; López-Ávalos, María-Dolores; Grondona, Jesús M; Vida, Margarita; Fernández-Llebrez, Pedro; de Fonseca, Fernando Rodríguez; Suárez, Juan

    2013-01-01

    Soy extracts have been claimed to be neuroprotective against brain insults, an effect related to the estrogenic properties of isoflavones. However, the effects of individual isoflavones on obesity-induced disruption of adult neurogenesis have not yet been analyzed. In the present study we explore the effects of pharmacological administration of daidzein, a main soy isoflavone, in cell proliferation, cell apoptosis and gliosis in the adult hippocampus of animals exposed to a very high-fat diet. Rats made obese after 12-week exposure to a standard or high-fat (HFD, 60%) diets were treated with daidzein (50 mg kg(-1)) for 13 days. Then, plasma levels of metabolites and metabolic hormones, cell proliferation in the subgranular zone of the dentate gyrus (SGZ), and immunohistochemical markers of hippocampal cell apoptosis (caspase-3), gliosis (GFAP and Iba-1), food reward factor FosB and estrogen receptor alpha (ERα) were analyzed. Treatment with daidzein reduced food/caloric intake and body weight gain in obese rats. This was associated with glucose tolerance, low levels of HDL-cholesterol, insulin, adiponectin and testosterone, and high levels of leptin and 17β-estradiol. Daidzein increased the number of phospho-histone H3 and 5-bromo-2-deoxyuridine (BrdU)-ir cells detected in the SGZ of standard diet and HFD-fed rats. Daidzein reversed the HFD-associated enhanced immunohistochemical expression of caspase-3, FosB, GFAP, Iba-1 and ERα in the hippocampus, being more prominent in the dentate gyrus. These results suggest that pharmacological treatment with isoflavones regulates metabolic alterations associated with enhancement of cell proliferation and reduction of apoptosis and gliosis in response to high-fat diet.

  15. Rat-strain dependent changes of dendritic and spine morphology in the hippocampus after cocaine self-administration.

    PubMed

    Selvas, Abraham; Coria, Santiago M; Kastanauskaite, Asta; Fernaud-Espinosa, Isabel; DeFelipe, Javier; Ambrosio, Emilio; Miguéns, Miguel

    2017-01-01

    We previously showed that cocaine self-administration increases spine density in CA1 hippocampal neurons in Lewis (LEW) but not in Fischer 344 (F344) rats. Dendritic spine morphology is intimately related to its function. Thus, we conducted a 3D morphological analysis of CA1 dendrites and dendritic spines in these two strains of rats. Strain-specific differences were observed prior to cocaine self-administration: LEW rats had significantly larger dendritic diameters but lower spine density than the F344 strain. After cocaine self-administration, proximal dendritic volume, dendritic surface area and spine density were increased in LEW rats, where a higher percentage of larger spines were also observed. In addition, we found a strong positive correlation between dendritic volume and spine morphology, and a moderate correlation between dendritic volume and spine density in cocaine self-administered LEW rats, an effect that was not evident in any other condition. By contrast, after cocaine self-administration, F334 rats showed decreased spine head volumes. Our findings suggest that genetic differences could play a key role in the structural plasticity induced by cocaine in CA1 pyramidal neurons. These cocaine-induced alterations could be related to differences in the memory processing of drug reward cues that could potentially explain differential individual vulnerability to cocaine addiction.

  16. Effects of neuregulin-1 administration on neurogenesis in the adult mouse hippocampus, and characterization of immature neurons along the septotemporal axis

    PubMed Central

    Mahar, Ian; MacIsaac, Angus; Kim, John Junghan; Qiang, Calvin; Davoli, Maria Antonietta; Turecki, Gustavo; Mechawar, Naguib

    2016-01-01

    Adult hippocampal neurogenesis is associated with learning and affective behavioural regulation. Its diverse functionality is segregated along the septotemporal axis from the dorsal to ventral hippocampus. However, features distinguishing immature neurons in these regions have yet to be characterized. Additionally, although we have shown that administration of the neurotrophic factor neuregulin-1 (NRG1) selectively increases proliferation and overall neurogenesis in the mouse ventral dentate gyrus (DG), likely through ErbB3, NRG1’s effects on intermediate neurogenic stages in immature neurons are unknown. We examined whether NRG1 administration increases DG ErbB3 phosphorylation. We labeled adultborn cells using BrdU, then administered NRG1 to examine in vivo neurogenic effects on immature neurons with respect to cell survival, morphology, and synaptogenesis. We also characterized features of immature neurons along the septotemporal axis. We found that neurogenic effects of NRG1 are temporally and subregionally specific to proliferation in the ventral DG. Particular morphological features differentiate immature neurons in the dorsal and ventral DG, and cytogenesis differed between these regions. Finally, we identified synaptic heterogeneity surrounding the granule cell layer. These results indicate neurogenic involvement of NRG1-induced antidepressant-like behaviour is particularly associated with increased ventral DG cell proliferation, and identify novel distinctions between dorsal and ventral hippocampal neurogenic development. PMID:27469430

  17. Effects of chronic ethanol administration on expression of BDNF and trkB mRNAs in rat hippocampus after experimental brain injury.

    PubMed

    Zhang, L; Dhillon, H S; Barron, S; Hicks1, R R; Prasad, R M; Seroogy, K B

    2000-06-23

    Previous evidence indicates that both chronic alcohol treatment and traumatic brain injury modulate expression of certain neurotrophins and neurotrophin receptors in cortical tissue. However, the combined effects of chronic alcohol and brain trauma on expression of neurotrophins and their receptors have not been investigated. In the present study, we examined the effects of 6 weeks of chronic ethanol administration on lateral fluid percussion (FP) brain injury-induced alterations in expression of mRNAs for the neurotrophin brain-derived neurotrophic factor (BDNF) and its high affinity receptor, trkB, in rat hippocampus. In both the control- (pair-fed isocaloric sucrose) diet and the chronic ethanol-diet groups, unilateral FP brain injury induced a bilateral increase in levels of both BDNF and trkB mRNAs in the dentate gyrus granule cell layer, and of BDNF mRNA in hippocampal region CA3. However, no significant differences in expression were found between the control-diet and ethanol-diet groups, in either the sham-injured or FP-injured animals. These findings suggest that 6 weeks of chronic ethanol administration does not alter the plasticity of hippocampal BDNF/trkB expression in response to experimental brain injury.

  18. Both prolactin (PRL) and a molecular mimic of phosphorylated PRL, S179D-PRL, protect the hippocampus of female rats against excitotoxicity.

    PubMed

    Morales, T; Lorenson, M; Walker, A M; Ramos, E

    2014-01-31

    Prolactin (PRL) has many functions in the CNS, including neuroprotection. During lactation, the dorsal hippocampus is protected from excitotoxic kainic acid (KA)-induced cellular damage. We have previously reported that systemic pre-treatment with ovine PRL had similar protective effects in female rats. Here, we asked (1) whether intracerebral human PRL (hPRL) would have the same action, (2) because phosphorylated PRL is high in lactation, whether a mimic of phosphorylated hPRL, human prolactin in which the normally phosphorylated serine at position 179 is replaced with an aspartate (S179D-PRL), had similar activity, and (3) what signaling pathways mediated the protective effect. Female ovariectomized (OVX, 1 month) rats were implanted with micro-osmotic pumps connected to unilateral icv cannulae directed at the right lateral ventricle. The pumps delivered 0.10 ng/h of hPRL, S179D-PRL, a combination of hPRL+S179D-PRL, or saline vehicle for 7 days prior to a systemic dose of 7.5mg/kg of KA. Rats were sacrificed 48 h after KA injection. Immunostaining for neuronal nuclei (Neu-N) revealed a significant KA-induced decrease in cell number in the CA1, CA3, and CA4 hippocampal areas of rats (∼55% of control). Treatment with either hPRL or S179D-PRL or the combination prevented the damaging effect of KA in these hippocampal regions (∼95% of corresponding control), but was not completely effective at preventing early seizure-related behaviors such as staring and wet dog shakes. Analysis of signals generated by hPRL and S179D-PRL showed no activation of signal transducer and activation of transcription 5 (Stat5) or other signaling molecules in the hippocampus, but activation of extracellular-regulated kinase (ERK)1/2 in the amygdala. These results support a central protective effect of both PRL forms and suggest that PRL could be exerting its protective action by indirectly modulating input signals to the hippocampus and thus regulating excitability.

  19. 36 CFR 213.3 - Protection, occupancy, use, administration, and exercise of reservations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., administration, and exercise of reservations. 213.3 Section 213.3 Parks, Forests, and Public Property FOREST... TENANT ACT BY THE FOREST SERVICE § 213.3 Protection, occupancy, use, administration, and exercise of... the rules and regulations to govern the exercise of reservations in conveyances to the United...

  20. 36 CFR 213.3 - Protection, occupancy, use, administration, and exercise of reservations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., administration, and exercise of reservations. 213.3 Section 213.3 Parks, Forests, and Public Property FOREST... TENANT ACT BY THE FOREST SERVICE § 213.3 Protection, occupancy, use, administration, and exercise of... the rules and regulations to govern the exercise of reservations in conveyances to the United...

  1. 36 CFR 213.3 - Protection, occupancy, use, administration, and exercise of reservations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., administration, and exercise of reservations. 213.3 Section 213.3 Parks, Forests, and Public Property FOREST... TENANT ACT BY THE FOREST SERVICE § 213.3 Protection, occupancy, use, administration, and exercise of... the rules and regulations to govern the exercise of reservations in conveyances to the United...

  2. 36 CFR 213.3 - Protection, occupancy, use, administration, and exercise of reservations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., administration, and exercise of reservations. 213.3 Section 213.3 Parks, Forests, and Public Property FOREST... TENANT ACT BY THE FOREST SERVICE § 213.3 Protection, occupancy, use, administration, and exercise of... the rules and regulations to govern the exercise of reservations in conveyances to the United...

  3. 36 CFR 213.3 - Protection, occupancy, use, administration, and exercise of reservations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., administration, and exercise of reservations. 213.3 Section 213.3 Parks, Forests, and Public Property FOREST... TENANT ACT BY THE FOREST SERVICE § 213.3 Protection, occupancy, use, administration, and exercise of... the rules and regulations to govern the exercise of reservations in conveyances to the United...

  4. Estradiol and Progesterone Administration After pMCAO Stimulates the Neurological Recovery and Reduces the Detrimental Effect of Ischemia Mainly in Hippocampus.

    PubMed

    Perez-Alvarez, Maria Jose; Mateos, Laura; Alonso, Alvaro; Wandosell, Francisco

    2015-12-01

    Epidemiological studies have suggested a differential response, males versus female, in stroke incidence and prognosis. These divergences in brain response after damage are based mostly on hormonal differences. To date, estradiol and progesterone administered independently have demonstrated neuroprotection after ischemia in animal models. Nonetheless, contradictory results were revealed using a combined administration. In order to evaluate the effects of combinatorial treatment administered after ischemia induction, we used two different approaches: in vivo and in vitro models. Male rats which underwent permanent middle cerebral artery occlusion were treated with a combination of estradiol/progesterone at 6, 24 and 48 h after injury and sacrificed at 54 h post-ischemia. The rat brains were evaluated for reactive gliosis, NeuN-positive neurons, levels of synapse-associated proteins and activity levels of PI3K/Akt/GSK3/β-catenin survival pathway. Also, primary cortical neurons were subjected to oxygen and glucose deprivation for 17 h and returned to a normal environment in the presence of estradiol or estradiol/progesterone. Cell viability was evaluated, and activity levels of the PI3K/Akt/GSK3/β-catenin pathway. Our results indicate that some beneficial effects of estradiol were abolished in the presence of progesterone, particularly in the cerebral cortex (core). However, the combinatorial treatment showed positive effects in the hippocampus.

  5. Effects of systemic administration of the essential oil of bergamot (BEO) on gross behaviour and EEG power spectra recorded from the rat hippocampus and cerebral cortex.

    PubMed

    Rombolà, Laura; Corasaniti, Maria Tiziana; Rotiroti, Domenicantonio; Tassorelli, Cristina; Sakurada, Shinobu; Bagetta, G; Morrone, Luigi Antonio

    2009-01-01

    Bergamot (Citrus bergamia Risso et Poiteau) is a citrus fruit growing almost exclusively in the South of Italy. Its essential oil is obtained by cold pressing of the epicarp and, partly, of the mesocarp of the fresh fruit. Although this phytocomplex has been used for centuries, reputedly effectively, as a traditional medicine, there is very little verified scientific evidence to support this use. This paper reports original data on the systemic effects of the essential oil of bergamot (BEO) on gross behaviour and EEG activity recorded from the hippocampus and cerebral cortex of the rat. The Fast Fourier Transformation (FFT) was used to analyse and quantify the energy in single frequency bands of the EEG spectrum. The results obtained indicate that systemic administration of increasing volumes of BEO produces dose-dependent increases in locomotor and exploratory activity that correlate with a predominant increase in the energy in the faster frequency bands of the EEG spectrum. These data contribute to our understanding of the neurobiological profile of BEO.

  6. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus.

    PubMed

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-08-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

  7. Levels of neural progenitors in the hippocampus predict memory impairment and relapse to drug seeking as a function of excessive methamphetamine self-administration.

    PubMed

    Recinto, Patrick; Samant, Anjali Rose H; Chavez, Gustavo; Kim, Airee; Yuan, Clara J; Soleiman, Matthew; Grant, Yanabel; Edwards, Scott; Wee, Sunmee; Koob, George F; George, Olivier; Mandyam, Chitra D

    2012-04-01

    Methamphetamine affects the hippocampus, a brain region crucial for learning and memory, as well as relapse to drug seeking. Rats self-administered methamphetamine for 1 h twice weekly (intermittent-short-I-ShA), 1 h daily (limited-short-ShA), or 6 h daily (extended-long-LgA) for 22 sessions. After 22 sessions, rats from each access group were withdrawn from self-administration and underwent spatial memory (Y-maze) and working memory (T-maze) tests followed by extinction and reinstatement to methamphetamine seeking or received one intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) to label progenitors in the hippocampal subgranular zone (SGZ) during the synthesis phase. Two-hour-old and 28-day-old surviving BrdU-immunoreactive cells were quantified. I-ShA rats performed better on the Y-maze and had a greater number of 2-h-old SGZ BrdU cells than nondrug controls. LgA rats, but not ShA rats, performed worse on the Y- and T-maze and had a fewer number of 2-h-old SGZ BrdU cells than nondrug and I-ShA rats, suggesting that new hippocampal progenitors, decreased by methamphetamine, were correlated with impairment in the acquisition of new spatial cues. Analyses of addiction-related behaviors after withdrawal and extinction training revealed methamphetamine-primed reinstatement of methamphetamine-seeking behavior in all three groups (I-ShA, ShA, and LgA), and this effect was enhanced in LgA rats compared with I-ShA and ShA rats. Protracted withdrawal from self-administration enhanced the survival of SGZ BrdU cells, and methamphetamine seeking during protracted withdrawal enhanced Fos expression in the dentate gyrus and medial prefrontal cortex in LgA rats to a greater extent than in ShA and I-ShA rats. These results indicate that changes in the levels of the proliferation and survival of hippocampal neural progenitors and neuronal activation of hippocampal granule cells predict the effects of methamphetamine self-administration (limited vs extended access) on

  8. A free-radical scavenger protects the neural progenitor cells in the dentate subgranular zone of the hippocampus from cell death after X-irradiation.

    PubMed

    Motomura, Kazuya; Ogura, Masatoshi; Natsume, Atsushi; Yokoyama, Hidenori; Wakabayashi, Toshihiko

    2010-11-12

    It has been elucidated that cognitive dysfunction following cranial radiotherapy might be linked to the oxidative stress-induced impairment of hippocampal neurogenesis that is mediated by proliferating neural stem or progenitor cells. The novel free-radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been clinically used to reduce neuronal damage following ischemic stroke. Previously, we reported that the free-radical scavenger, edaravone, which is currently used to treat patients with brain ischemia, protected cultured human neural stem cells (NSCs) from radiation-induced cell death; the protective effect was observed more significantly in NSCs than in brain tumor cells. Here, in animal models, we demonstrate that edaravone protects neurons in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus from cell death after irradiation. Moreover, edaravone protected spatial memory retention deficits as determined by Morris water maze tests. Our study may shed some light on the beneficial effects of free-radical scavengers in impaired neurogenesis following cranial radiation therapy.

  9. Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: In vivo proton magnetic resonance spectroscopy findings.

    PubMed

    Han, Fang; Xiao, Bing; Wen, Lili; Shi, Yuxiu

    2015-05-30

    Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus. SPS increased the N-acetylaspartate (NAA)/creatine (Cr) and choline moieties (Cho)/Cr ratios in the bilateral amygdala on day 4, decreased the NAA/Cr ratio in the left hippocampus on day 1, and increased both ratios in the right hippocampus on day 14. But no significant change was found in the thalamus. Fluoxetine treatment corrected the SPS increases in the NAA/Cr and Cho/Cr levels in the amygdala on day 4 and in the hippocampus on day 14, but it failed to normalise SPS-associated decreases in NAA/Cr levels in the left hippocampus on day 1. These results suggested that metabolic abnormalities in the amygdala and the hippocampus were involved in SPS, and different effects of fluoxetine in correcting SPS-induced neurometabolite changes among the three areas. These findings have implications for fluoxetine treatment in PTSD.

  10. Manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic administration of MnCl₂: hippocampal signal enhancement without disruption of hippocampus-dependent behavior.

    PubMed

    Jackson, Stewart J; Hussey, Rosalind; Jansen, Maurits A; Merrifield, Gavin D; Marshall, Ian; MacLullich, Alasdair; Yau, Joyce L W; Bast, Tobias

    2011-01-01

    Manganese (Mn(2+))-enhanced magnetic resonance (MR) imaging (MEMRI) in rodents offers unique opportunities for the longitudinal study of hippocampal structure and function in parallel with cognitive testing. However, Mn(2+) is a potent toxin and there is evidence that it can interfere with neuronal function. Thus, apart from causing adverse peripheral side effects, Mn(2+) may disrupt the function of brain areas where it accumulates to produce signal enhancement and, thereby, Mn(2+) administration may confound cognitive testing. Here, we examined in male adult Lister hooded rats if a moderate systemic dose of MnCl₂ (200 μmol/kg; two intraperitoneal injections of 100 μmol/kg separated by 1 h) that produces hippocampal MR signal enhancement would disrupt hippocampal function. To this end, we used a delayed-matching-to-place (DMP) watermaze task, which requires rapid allocentric place learning and is highly sensitive to interference with hippocampal function. Tested on the DMP task 1 h and 24 h after MnCl₂ injection, rats did not show any impairment in indices of memory performance (latencies, search preference) or any sensorimotor effects. However, MnCl₂ injection caused acute peripheral effects (severe ataxia and erythema, i.e. redness of paws, ears, and nose) which subsided over 30 min. Additionally, rats injected with MnCl₂ showed reduced weight 1 day after injection and failed to reach the normal weight-growth curve of control rats within the 16 days monitored. Our results indicate that 200 μmol/kg MnCl₂ produces hippocampal MR signal enhancement without disrupting hippocampus-dependent behavior on a rapid place learning task, even though attention must be paid to peripheral side effects.

  11. TOMORROW: EPA Administrator to Focus on Protecting Clean Water in Travel to Minnesota, Texas and Illinois

    EPA Pesticide Factsheets

    WASHINGTON - Tomorrow, EPA Administrator Gina McCarthy is hitting the road to focus on the important need to protect the critical streams and wetlands that provide 1 in 3 Americans their drinking water and that are currently vulnerable to pollution

  12. Intranasal administration of live Lactobacillus species facilitates protection against influenza virus infection in mice.

    PubMed

    Youn, Ha-Na; Lee, Dong-Hun; Lee, Yu-Na; Park, Jae-Keun; Yuk, Seong-Su; Yang, Si-Yong; Lee, Hyun-Jeong; Woo, Seo-Hyung; Kim, Hyoung-Moon; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2012-01-01

    Influenza virus infections continue to be a significant public health problem. For improved therapies and preventive measures against influenza, there has been an increased tendency in modern medicine involving the use of probiotics. In this study, we compared the protective efficacy of various live and dead Lactobacillus species against challenge with influenza virus in mice according to the administration route and dose. In addition, to understand the underlying mechanism behind this clinical protective effect, we performed immunologic assays including examination of IgA levels and cytokine profiles in the lung. The survival rate of mice receiving intranasal administration of Lactobacillus was higher than after oral administration, and administration of live bacteria was more protective than of dead bacteria. The lung levels of interleukin (IL)-12 and IgA were significantly increased (P<0.05). Conversely, the levels of the pro-inflammatory cytokines tumor necrosis factor-alpha and IL-6 were decreased. Interestingly, there were huge differences in protective effects of various Lactobacillus strains on influenza virus infection. Therefore, for clinical applications, selection of effective strains could be critical and individually optimized application regimens of the selected strains are required.

  13. Gonadal status-dependent effects of in vivo β-estradiol administration to female rats on in vitro epileptiform activity induced by low [Mg2+]₀ in combined hippocampus-entorhinal cortex slices.

    PubMed

    Velíšková, Jana; Velíšek, Libor

    2013-12-01

    There are controversial data regarding estrogen effects on neuronal excitability. We investigated whether β-estradiol (EB) administration to ovariectomized (OVX) or gonadally intact female rats alters epileptiform activity within the dentate gyrus network induced in vitro by removing [Mg2+]o in combined hippocampus-entorhinal cortex slices. In vivo EB administration significantly influenced the epileptiform activity in gonadal status-dependent manner. The onset of epileptiform discharges was modestly delayed in slices from OVX rats replaced with physiologically relevant doses of EB but the number of discharges was not affected. In contrast, EB administration to gonadally intact rats had robust effects such that: EB delayed the onset of discharges but significantly increased their number within the dentate gyrus network. Our data suggest that EB in physiologically relevant concentrations does not seem to negatively affect hippocampal neuronal excitability, nevertheless supraphysiological EB levels may enhance seizure severity.

  14. Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain - histopathological, and biochemical approach.

    PubMed

    Sumathi, Thangarajan; Shobana, Chandrasekar; Thangarajeswari, Mohan; Usha, Ramakrishnan

    2015-01-01

    L-Theanine is an amino acid derivative primarily found in tea. It has been reported to promote relaxation and have neuroprotective effects. The present study was designed to investigate the role of oxidative stress and the status of antioxidant system in the management of aluminum chloride (AlCl3) induced brain toxicity in various rat brain regions and further to elucidate the potential role of L-Theanine in alleviating such negative effects. Aluminium administration significantly decreased the level of reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Na(+)/K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase and increased the level of lipid peroxidation and the activities of alkaline phosphatase, acid phosphatase, alanine transaminase and aspartate transaminase in all the brain regions when compared with control rats. Pre-treatment with L-Theanine at a dose of 200 mg/kg b.w. significantly increased the antioxidant status and activities of membrane bound enzymes and also decreased the level of LPO and the activities of marker enzymes, when compared with aluminium induced rats. Aluminium induction also caused histopathological changes in the cerebral cortex, cerebellum and hippocampus of rat brain which was reverted by pretreatment with L-Theanine. The present study clearly indicates the potential of L-Theanine in counteracting the damage inflicted by aluminium on rat brain regions.

  15. Prolonged Oral Administration of Oleuropein Might Protect Heart against Aconitine-induced Arrhythmia

    PubMed Central

    Esmailidehaj, Mansour; Mirhosseini, Seyed-Jalil; Rezvani, Mohammad Ebrahim; Rasoulian, Bahram; Mosaddeghmehrjardi, Mohammad Hossein; Haghshenas, Damoon

    2012-01-01

    In this study, it was surveyed to know whether an oral single dose of oleuropein could mimic the cardiac preconditioning in rats’ hearts or whether its prolonged oral administration could protect the heart against the aconitine-induced arrhythmia in rats. Eighty male Wistar rats were divided into two series (n = 8 in each group). In the first series, all groups (except the control (Con) group) were given a single oral dose of oleuropein (20 mg/Kg) 1, 3, 24 and 48 h before the infusion of aconitine. In the second series, except the Con group, the other four groups were given oral oleuropein (20 mg/Kg/day) for 3, 7, 14 and 28 days, before the infusion of aconitine. Electrocardiogram was recorded to monitor arrhythmia. Data of the first series showed that the initiation time of arrhythmia, the initiation of ventricular tachycardia (VT), the numbers of reversible ventricular fibrillation (VF) and the death time had no significant difference compared with Con group. In the second series, a significant protection was occurred only in the 28 days group that was evident with increased initiation time of arrhythmia, increased initiation time of VT, and increased the number of reversible VF and death time in compared to the Con group. The findings of this study show that the oral administration of a single dose of oleuropein could not mimic the preconditioning effects in rat hearts, but the prolonged administration of oleuropein for about four weeks could protect the heart against aconitine-induced arrhythmia. PMID:24250560

  16. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-01-01

    Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice. PMID:26950150

  17. Dexamethasone loaded nanoparticles exert protective effects against Cisplatin-induced hearing loss by systemic administration.

    PubMed

    Sun, Changling; Wang, Xueling; Chen, Dongye; Lin, Xin; Yu, Dehong; Wu, Hao

    2016-04-21

    Ototoxicity is one of the most important adverse effects of cisplatin chemotherapy. As a common treatment of acute sensorineural hearing loss, systemic administration of steroids was demonstrated ineffective against cisplatin-induced hearing loss (CIHL) in published studies. The current study aimed to evaluate the potential protective effect of dexamethasone (DEX) encapsulated in polyethyleneglycol-coated polylactic acid (PEG-PLA) nanoparticles (DEX-NPs) against cisplatin-induced hearing loss following systemic administration. DEX was fabricated into PEG-PLA nanoparticles using emulsion and evaporation technique as previously reported. DEX or DEX-NPs was administered intraperitoneally to guinea pigs 1h before cisplatin administration. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (4, 8, 16, and 24kHz) 1 day before and three days after cisplatin injection. Cochlear morphology was examined to evaluate inner ear injury induced by cisplatin exposure. A single dose of DEX-NPs 1h before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea, which was equivalent to the effect of multidose (3 days) DEX injection. In contrast, no significant protective effect was observed by single dose injection of DEX. The results of histological examination of the cochleae were consistent with the functional measurements. In conclusion, a single dose DEX-NPs significantly attenuated cisplatin ototoxicity in guinea pigs after systemic administration at both histological and functional levels indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of DEX in acute sensorineural hearing loss.

  18. Neurodegeneration and inflammation in hippocampus in experimental autoimmune encephalomyelitis induced in rats by one--time administration of encephalitogenic T cells.

    PubMed

    Kurkowska-Jastrzębska, I; Swiątkiewicz, M; Zaremba, M; Cudna, A; Piechal, A; Pyrzanowska, J; Widy-Tyszkiewicz, E; Członkowska, A

    2013-09-17

    Cognitive dysfunction is relatively frequent in multiple sclerosis (MS) and it happens from the early stages of the disease. There is increasing evidence that the grey matter may be involved in autoimmune inflammation during relapses of MS. The purpose of this study was to evaluate if a single transfer of encephalitogenic T cells, mimicking a relapse of MS, may cause hippocampal damage and memory disturbances in rats. Lewis rats were injected with anti-MBP CD4+ T cells, that induced one-phase autoimmune encephalomyelitis (EAE) with full recovery from motor impairments at 10-15 days. The spatial learning and memory were tested by the Morris water maze test in control and EAE animals, 30 and 90 days post-induction (dpi). The neural injury and inflammation was investigated in the hippocampus by immunohistochemistry and quantitative analyses. There was a marked decrease in the number of CA1 and CA4 pyramidal neurons 5 dpi. The loss of neurons then aggravated till the 90 dpi. An increase in microglial and astroglial activation and in pro-inflammatory cytokines mRNA expression in the hippocampus, were present 30 and 90 dpi. Nerve growth factor and brain-derived neurotrophic factor mRNA levels were also significantly elevated. The water maze test, however, did not reveal memory deficits. The present data indicate that a single transfer of autoimmune T cells results in preserved inflammation and probable on-going neuronal injury in the hippocampus, long after recovery from motor disturbances. These findings suggest that any relapse of the MS may start the neurodegenerative process in the hippocampus, which is not necessarily connected with memory deficits.

  19. NAP (davunetide) protects primary hippocampus culture by modulating expression profile of antioxidant genes during limiting oxygen conditions.

    PubMed

    Arya, A; Meena, R; Sethy, N K; Das, M; Sharma, M; Bhargava, K

    2015-04-01

    Hypoxia is a well-known threat to neuronal cells and triggers the pathophysiological syndromes in extreme environments such as high altitudes and traumatic conditions such as stroke. Among several prophylactic molecules proven suitable for ameliorating free radical damage, NAP (an octapeptide with initial amino acids: asparagine/N, alanine/A, and proline/P) can be considered superlative, primarily due to its high permeability into brain through blood-brain barrier and observed activity at femtomolar concentrations. Several mechanisms of action of NAP have been hypothesized for its protective role during hypoxia, yet any distinct mechanism is unknown. Oxidative stress is advocated as the leading event in hypoxia; we, therefore, investigated the regulation of key antioxidant genes to understand the regulatory role of NAP in providing neuroprotection. Primary neuronal culture of rat was subjected to cellular hypoxia by limiting the oxygen concentration to 0.5% for 72 h and observing the prophylactic efficacies of 15fM NAP by conventional cell death assays using flow cytometry. We performed real-time quantitative polymerase chain reaction to comprehend the regulatory mechanism. Further, we validated the significantly regulated candidates by enzyme assays and immunoblotting. In the present study, we report that NAP regulates a major clad of cellular antioxidants and there is an involvement of more than one route of action in neuroprotection during hypoxia.

  20. Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier

    PubMed Central

    Zhai, Qixiao; Tian, Fengwei; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan

    2016-01-01

    ABSTRACT The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of Lactobacillus plantarum CCFM8610 alleviated Cd-induced cytotoxicity in the human intestinal cell line HT-29 and protected the disruption of tight junctions in the cell monolayers. In a mouse model, probiotics with either good Cd-binding or antioxidative ability increased fecal Cd levels and decreased Cd accumulation in the tissue of Cd-exposed mice. Compared with the Cd-only group, cotreatment with probiotics also reversed the disruption of tight junctions, alleviated inflammation, and decreased the intestinal permeability of mice. L. plantarum CCFM8610, a strain with both good Cd binding and antioxidative abilities, exhibited significantly better protection than the other two strains. These results suggest that along with initial intestinal Cd sequestration, probiotics can inhibit Cd absorption by protecting the intestinal barrier, and the protection is related to the alleviation of Cd-induced oxidative stress. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure. IMPORTANCE The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain; therefore, the intestinal tract is the first organ that is susceptible to Cd

  1. Augmentation of protective immune responses against viral infection by oral administration of schizophyllan

    PubMed Central

    Itoh, Wataru

    1997-01-01

    An oral administration of fungal polysaccharide schizophyllan has augmented protective immune responses to Sendai virus infection in mice and the rodshaped DNA virus of Penaeus japonicus (RV-PJ) infection in Kuruma shrimps. When schizophyllan was administered orally at a dose of 50 or 100 mg/kg body weight per day, the survival rates after virus challenge were significantly higher than those of the control groups. High phagocytic activities were observed in the haemocytes of the schizophyllan-fed shrimps.These results suggest that schizophyllan confers effective protection against viral infection by increasing antiviral immune responses, and that it could be used to boost immunity to virus infection in animals or in invertebrates. PMID:18472856

  2. The HMG-CoA reductase inhibitor, atorvastatin, attenuates the effects of acute administration of amyloid-beta1-42 in the rat hippocampus in vivo.

    PubMed

    Clarke, Rachael M; O'Connell, Florence; Lyons, Anthony; Lynch, Marina A

    2007-01-01

    One response of the brain to stressors is to increase microglial activation with the consequent production of proinflammatory cytokines like interleukin-1beta (IL-1beta), which has been shown to exert an inhibitory effect on long-term potentiation (LTP) in the hippocampus. It has been consistently shown, particularly in vitro, that amyloid-beta (Abeta) peptides increase activation of microglia, while its inhibitory effect on LTP is well documented, and associated with the Abeta-induced increase in IL-1beta. Here we set out to establish whether the Abeta-induced inhibition of LTP in perforant path-granule cell synapses, was coupled with evidence of microglial activation and to assess whether atorvastatin, which is used primarily in the treatment of hyperlipidaemia but which possesses anti-inflammatory properties, might modulate the effect of Abeta on LTP. We report that intracerebroventricular injection of Abeta increased expression of several markers of microglial activation, and in parallel, inhibited LTP in dentate gyrus. The data show that atorvastatin abrogated the Abeta-induced microglial activation and the associated deficit in LTP. On the basis of the evidence presented, we propose that the action of atorvastatin is mediated by its ability to increase production of the anti-inflammatory cytokine, interleukin-4, which we report mimics several of the actions of atorvastatin in the rat hippocampus.

  3. Protective effect of co-administration of curcumin and sildenafil in alcohol induced neuropathy in rats.

    PubMed

    Kaur, Maninder; Singh, Amarjeet; Kumar, Bimlesh; Singh, Sachin Kumar; Bhatia, Amit; Gulati, Monica; Prakash, T; Bawa, Palak; Malik, Adil Hussain

    2017-03-16

    Neuropathic pain associated with chronic alcohol consumption is a medico-socioeconomical problem that affects both central and peripheral nervous system and has no satisfactory treatment till date. The present study was designed to investigate the protective effect of co-administration of curcumin and sildenafil on alcohol induced neuropathic pain in rats. In order to carry out this, ethanol (35% v/v, 10g/kg, p.o.) was administered for 10 weeks to induce neuropathic pain. Curcumin (30 and 60mg/kg, i.p.) and sildenafil (5 and 10mg/kg, i.p.) were given alone and in combination at their lower doses (30mg/kg curcumin and 5mg/kg, sildenafil, i.p.) to investigate the changes in thermal and mechanical hyperalgesia, allodynia and histopathological parameters. Biochemical estimations of thiobarbituric acid reactive species, glutathione and protein was also carried out to evaluate oxidative stress. The results revealed that chronic alcohol consumption for 10 weeks caused significant thermal and mechanical hyperalgesia, allodynia and increased oxidative stress. Individual administration of both the drugs at their low as well as high doses were able to improve the symptoms of alcohol induced neuropathic pain. Whereas co-administration of curcumin and sildenafil at their lower doses itself were found to significantly improve nerve functions, biochemical and histopathological parameters as compared to their individual administration. It is therefore proposed that co-administration of curcumin and sildenafil may bring new dimension towards attenuation of alcohol induced neuropathic pain affecting central as well as peripheral nervous system.

  4. Systemic Administration of Proteoglycan Protects BALB/c Retired Breeder Mice from Experimental Arthritis.

    PubMed

    Ishikawa, Larissa Lumi Watanabe; Colavite, Priscila Maria; Fraga-Silva, Thais Fernanda de Campos; Mimura, Luiza Ayumi Nishiyama; França, Thais Graziela Donegá; Zorzella-Pezavento, Sofia Fernanda Gonçalves; Chiuso-Minicucci, Fernanda; Marcolino, Larissa Doddi; Marques, Camila; Ikoma, Maura Rosane Valerio; Sartori, Alexandrina

    2016-01-01

    This study was undertaken to evaluate the prophylactic potential of proteoglycan (PG) administration in experimental arthritis. Female BALB/c retired breeder mice received two (2xPG50 and 2xPG100 groups) or three (3xPG50 group) intraperitoneal doses of bovine PG (50 μg or 100 μg) every three days. A week later the animals were submitted to arthritis induction by immunization with three i.p. doses of bovine PG associated with dimethyldioctadecylammonium bromide adjuvant at intervals of 21 days. Disease severity was daily assessed after the third dose by score evaluation. The 3xPG50 group showed significant reduction in prevalence and clinical scores. This protective effect was associated with lower production of IFN-γ and IL-17 and increased production of IL-5 and IL-10 by spleen cells restimulated in vitro with PG. Even though previous PG administration restrained dendritic cells maturation this procedure did not alter the frequency of regulatory Foxp3(+) T cells. Lower TNF-α and IL-6 levels and higher expression of ROR-γ and GATA-3 were detected in the paws of protected animals. A delayed-type hypersensitivity reaction confirmed specific tolerance induction. Taken together, these results indicate that previous PG inoculation determines a specific tolerogenic effect that is able to decrease severity of subsequently induced arthritis.

  5. Systemic Administration of Proteoglycan Protects BALB/c Retired Breeder Mice from Experimental Arthritis

    PubMed Central

    Ishikawa, Larissa Lumi Watanabe; Colavite, Priscila Maria; Fraga-Silva, Thais Fernanda de Campos; Mimura, Luiza Ayumi Nishiyama; França, Thais Graziela Donegá; Zorzella-Pezavento, Sofia Fernanda Gonçalves; Chiuso-Minicucci, Fernanda; Marcolino, Larissa Doddi; Marques, Camila; Ikoma, Maura Rosane Valerio; Sartori, Alexandrina

    2016-01-01

    This study was undertaken to evaluate the prophylactic potential of proteoglycan (PG) administration in experimental arthritis. Female BALB/c retired breeder mice received two (2xPG50 and 2xPG100 groups) or three (3xPG50 group) intraperitoneal doses of bovine PG (50 μg or 100 μg) every three days. A week later the animals were submitted to arthritis induction by immunization with three i.p. doses of bovine PG associated with dimethyldioctadecylammonium bromide adjuvant at intervals of 21 days. Disease severity was daily assessed after the third dose by score evaluation. The 3xPG50 group showed significant reduction in prevalence and clinical scores. This protective effect was associated with lower production of IFN-γ and IL-17 and increased production of IL-5 and IL-10 by spleen cells restimulated in vitro with PG. Even though previous PG administration restrained dendritic cells maturation this procedure did not alter the frequency of regulatory Foxp3+ T cells. Lower TNF-α and IL-6 levels and higher expression of ROR-γ and GATA-3 were detected in the paws of protected animals. A delayed-type hypersensitivity reaction confirmed specific tolerance induction. Taken together, these results indicate that previous PG inoculation determines a specific tolerogenic effect that is able to decrease severity of subsequently induced arthritis. PMID:27294161

  6. In vivo protective role against water contamination with cerium via chronic administration of omega 3.

    PubMed

    Beltifa, Asma; Borgi, Mohamed Ali; Ferieni, Anouar; Elfekih, Abdelfettah; Mansour, Hedi Ben; Allagui, Mohamed Sallah

    2017-01-01

    In the present study, adult, healthy male Wistar rats (120 ± 10 g) were pre-treated by intragastric administration of cerium chloride (CeCl3) 10 mg/kg (BW) each day during 60 days. Control animal were treated with omega 3, a polyunsaturated fatty acid (ω-3), by an intragastric administration at 10 mg/kg of BW for 60 days. Our results showed that CeCl3-induced alterations in all tested oxidative stress markers. In fact, CeCl3-induced the increase the level of both the creatinine concentration and the expression of lactate dehydrogenase, alkaline phosphatase, and transaminase activities in serum. On the other hand, CeCl3 significantly increased the levels of lipid peroxidation in the renal and hepatic tissues. The capacity of CeCl3 to generate reactive oxygen species (ROS) could explain his ability to induce morphological alterations, such as centrilobular hemorrhage, hepatic necrosis, and vacuolization of the cytoplasm in hepatic tissues, and the atrophy of the glomerulus and dilatation of urinary space in renal tissues. However, omega 3, after gastric administration, reduced significantly the toxic effect caused by CeCl3 according to his high ability to scavenge ROS. The present study indicates that omega 3 is a significant compound with protective activity against intoxication with heavy metal, the cerium, and thus may be useful for chemoprevention.

  7. Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats.

    PubMed

    Díaz, Alfonso; Treviño, Samuel; Guevara, Jorge; Muñoz-Arenas, Guadalupe; Brambila, Eduardo; Espinosa, Blanca; Moreno-Rodríguez, Albino; Lopez-Lopez, Gustavo; Peña-Rosas, Ulises; Venegas, Berenice; Handal-Silva, Anabella; Morán-Perales, José Luis; Flores, Gonzalo; Aguilar-Alonso, Patricia

    2016-01-01

    Energy drinks (EDs) are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis) at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx) and hippocampus (Hp) of adult rats (90 days old). Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats.

  8. Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats

    PubMed Central

    Díaz, Alfonso; Treviño, Samuel; Guevara, Jorge; Muñoz-Arenas, Guadalupe; Brambila, Eduardo; Espinosa, Blanca; Moreno-Rodríguez, Albino; Lopez-Lopez, Gustavo; Peña-Rosas, Ulises; Venegas, Berenice; Handal-Silva, Anabella; Morán-Perales, José Luis; Flores, Gonzalo; Aguilar-Alonso, Patricia

    2016-01-01

    Energy drinks (EDs) are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis) at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx) and hippocampus (Hp) of adult rats (90 days old). Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats. PMID:27069534

  9. Lithium chloride administration prevents spatial learning and memory impairment in repeated cerebral ischemia-reperfusion mice by depressing apoptosis and increasing BDNF expression in hippocampus.

    PubMed

    Fan, Mingyue; Jin, Wei; Zhao, Haifeng; Xiao, Yining; Jia, Yanqiu; Yin, Yu; Jiang, Xin; Xu, Jing; Meng, Nan; Lv, Peiyuan

    2015-09-15

    Lithium has been reported to have neuroprotective effects, but the preventive and treated role on cognition impairment and the underlying mechanisms have not been determined. In the present study, C57Bl/6 mice were subjected to repeated bilateral common carotid artery occlusion to induce the learning and memory deficits. 2 mmol/kg or 5 mmol/kg of lithium chloride (LiCl) was injected intraperitoneally per day before (for 7 days) or post (for 28 days) the operation. This repeated cerebral ischemia-reperfusion (IR) induced dynamic overexpression of ratio of Bcl-2/Bax and BDNF in hippocampus of mice. LiCl pretreatment and treatment significantly decreased the escape latency and increased the percentage of time that the mice spent in the target quadrant in Morris water maze. 2 mmol/kg LiCl evidently reversed the morphologic changes, up-regulated the survival neuron count and increased the BDNF gene and protein expression. 5 mmol/kg pre-LiCl significantly increased IR-stimulated reduce of Bcl-2/Bax and p-CREB/CREB. These results described suggest that pre-Li and Li treatment may induce a pronounced prevention on cognitive impairment. These effects may relay on the inhibition of apoptosis and increasing BDNF and p-CREB expression.

  10. Oral Administration of Fermented Soymilk Products Protects the Skin of Hairless Mice against Ultraviolet Damage

    PubMed Central

    Kano, Mitsuyoshi; Kubota, Norihiro; Masuoka, Norie; Hori, Tetsuji; Miyazaki, Kouji; Ishikawa, Fumiyasu

    2016-01-01

    The protective effect of isoflavones on skin damage from ultraviolet (UV) radiation and their bioavailability were investigated in ovariectomized hairless mice fed diets composed of fermented soymilk containing aglycone forms of isoflavones or control soymilk containing glucose-conjugated forms of isoflavones. The erythema intensity of dorsal skin was significantly higher in ovariectomized mice than in sham-operated mice (p < 0.05). The erythema intensity and epidermal thickness of dorsal skin were significantly lower in the fermented soymilk diet group than in the control diet group (each p < 0.05). Levels of cyclobutane pyrimidine dimers in dorsal skin were significantly lower in the fermented soymilk diet group than in the control group (p < 0.05). Serum and dorsal skin isoflavone concentrations were significantly higher in the fermented soymilk diet group than in the soymilk diet group (p < 0.05). These results indicate that oral administration of a fermented soymilk diet increases isoflavone concentrations in the blood and skin, effectively scavenging the reactive oxygen species generated by UV irradiation and exerting an estrogen-like activity, with a consequent protective effect on skin photodamage in hairless mice. PMID:27556484

  11. Parenteral administration of attenuated Salmonella Typhimurium ΔznuABC is protective against salmonellosis in piglets.

    PubMed

    Ruggeri, J; Pesciaroli, M; Gaetarelli, B; Scaglione, F E; Pregel, P; Ammendola, S; Battistoni, A; Bollo, E; Alborali, G L; Pasquali, P

    2014-07-07

    A major cause of salmonellosis in humans is the contamination of pork products. Infection in pigs can be controlled using bio-security programs, but they are not sufficient in countries where a high level of infection is recorded. In this context, the use of vaccines can represent a valid supplementary method of control. Recently, we have demonstrated that an attenuated strain of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium ΔznuABC) is protective against systemic and enteric salmonellosis in mouse and pig infection models, candidating this strain as an oral attenuated vaccine. In this study, we compared the efficacy of this attenuated Salmonella Typhimurium strain when administered orally or parenterally. Furthermore, in order to reproduce a pseudo-natural infection model, vaccinated pigs were allocated in the same pen with animals shedding virulent Salmonella Typhimurium. Animals were monitored weekly after vaccination and contact with infected piglets. Diarrhea and ataxia were recorded and Salmonella shedding was tested individually through bacterial culture. After four weeks of cohousing, piglets were euthanized, after which lymph nodes reactivity and gross lesions of the gut sections were scored at necropsy. Organs were submitted to microbiological and histological analyses. The data reported herein show that parenterally vaccinated animals do not shed the attenuated strain, and at the same time the absence of symptoms and decrease in virulent strain shedding in feces from day 6 after challenge demonstrated protection against infection induced by virulent Salmonella Typhimurium. In conclusion, our findings suggest that this is an alternative route of Salmonella Typhimurium ΔznuABC administration, without ignoring the advantages associated with oral vaccination.

  12. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis.

    PubMed

    Lin, Yan-Ren; Li, Chao-Jui; Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Wu, Han-Ping; Hsu Chen, Cheng; Lu, Huai-En; Chen, Wen-Liang

    2016-01-01

    Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.

  13. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis

    PubMed Central

    Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Hsu Chen, Cheng

    2016-01-01

    Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level. PMID:28058255

  14. 6 CFR 29.4 - Protected Critical Infrastructure Information Program administration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Protected Critical Infrastructure Information... SECRETARY PROTECTED CRITICAL INFRASTRUCTURE INFORMATION § 29.4 Protected Critical Infrastructure Information...) Protected Critical Infrastructure Information Management System (PCIIMS). The PCII Program Manager...

  15. Oral Administration of a Salmonella enterica-Based Vaccine Expressing Bacillus anthracis Protective Antigen Confers Protection against Aerosolized B. anthracis▿

    PubMed Central

    Stokes, Margaret G. M.; Titball, Richard W.; Neeson, Brendan N.; Galen, James E.; Walker, Nicola J.; Stagg, Anthony J.; Jenner, Dominic C.; Thwaite, Joanne E.; Nataro, James P.; Baillie, Leslie W. J.; Atkins, Helen S.

    2007-01-01

    Bacillus anthracis is the causative agent of anthrax, a disease that affects wildlife, livestock, and humans. Protection against anthrax is primarily afforded by immunity to the B. anthracis protective antigen (PA), particularly PA domains 4 and 1. To further the development of an orally delivered human vaccine for mass vaccination against anthrax, we produced Salmonella enterica serovar Typhimurium expressing full-length PA, PA domains 1 and 4, or PA domain 4 using codon-optimized PA DNA fused to the S. enterica serovar Typhi ClyA and under the control of the ompC promoter. Oral immunization of A/J mice with Salmonella expressing full-length PA protected five of six mice against a challenge with 105 CFU of aerosolized B. anthracis STI spores, whereas Salmonella expressing PA domains 1 and 4 provided only 25% protection (two of eight mice), and Salmonella expressing PA domain 4 or a Salmonella-only control afforded no measurable protection. However, a purified recombinant fusion protein of domains 1 and 4 provided 100% protection, and purified recombinant 4 provided protection in three of eight immunized mice. Thus, we demonstrate for the first time the efficacy of an oral S. enterica-based vaccine against aerosolized B. anthracis spores. PMID:17145938

  16. TUESDAY: EPA Administrator to Discuss Historic Clean Power Plan to Cut U.S. Carbon Pollution and Protect Public Health

    EPA Pesticide Factsheets

    WASHINGTON - On Tuesday, August 11, EPA Administrator Gina McCarthy will be discussing the Clean Power Plan at the Resources for the Future (RFF) Leadership Forum. The Clean Power Plan will protect public health, spur clean energy investments and st

  17. Heat shock protein 70 protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus via inhibition of nuclear factor-κB activation-induced nitric oxide synthase II expression.

    PubMed

    Chang, Chiung-Chih; Chen, Shang-Der; Lin, Tsu-Kung; Chang, Wen-Neng; Liou, Chia-Wei; Chang, Alice Y W; Chan, Samuel H H; Chuang, Yao-Chung

    2014-02-01

    Status epilepticus induces subcellular changes that may eventually lead to neuronal cell death in the hippocampus. Based on an animal model of status epilepticus, our laboratory showed previously that sustained hippocampal seizure activity activates nuclear factor-κB (NF-κB) and upregulates nitric oxide synthase (NOS) II gene expression, leading to apoptotic neuronal cell death in the hippocampus. The present study examined the potential modulatory role of heat shock protein 70 (HSP70) on NF-κB signaling in the hippocampus following experimental status epilepticus. In Sprague-Dawley rats, kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 subfield to induce prolonged bilateral seizure activity. Expression of HSP70 was elevated as early as 1h after the elicitation of sustained seizure activity, followed by a progressive elevation that peaked at 24h. Pretreatment with an antisense oligonucleotide against hsp70 decreased the HSP70 expression, and significantly augmented IκB kinase (IKK) activity and phosphorylation of IκBα, alongside enhanced nuclear translocation and DNA binding activity of NF-κB in the hippocampal CA3 neurons and glial cells. These cellular events were followed by enhanced upregulation of NOS II and peroxynitrite expression 3h after sustained seizure activity that led to an increase of caspase-3 and DNA fragmentation in the hippocampal CA3 neurons 7days after experimental status epilepticus. We concluded that HSP70 protects against apoptotic cell death induced by NF-κB activation and NOS II-peroxynitrite signaling cascade in the hippocampal CA3 and glial cells following experimental status epilepticus via suppression of IKK activity and deactivation of IκBα.

  18. Activation of γ-aminobutyric Acid (A) Receptor Protects Hippocampus from Intense Exercise-induced Synapses Damage and Apoptosis in Rats

    PubMed Central

    Ding, Yi; Xie, Lan; Chang, Cun-Qing; Chen, Zhi-Min; Ai, Hua

    2015-01-01

    Background: Our previous study has confirmed that one bout of exhaustion (Ex) can cause hippocampus neurocyte damage, excessive apoptosis, and dysfunction. Its initial reason is intracellular calcium overload in hippocampus triggered by N-methyl-D-aspartic acid receptor (NMDAR) over-activation. NMDAR activation can be suppressed by γ-aminobutyric acid (A) receptor (GABAAR). Whether GABAAR can prevent intense exercise-induced hippocampus apoptosis, damage, or dysfunction will be studied in this study. Methods: According to dose test, rats were randomly divided into control (Con), Ex, muscimol (MUS, 0.1 mg/kg) and bicuculline (BIC, 0.5 mg/kg) groups, then all rats underwent once swimming Ex except ones in Con group only underwent training. Intracellular free calcium concentration ([Ca2+]i) was measured by Fura-2-acetoxymethyl ester; glial fibrillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were also performed; apoptosis were displayed by dUTP nick end labeling (TUNEL) stain; endoplasmic reticulum stress-induced apoptosis pathway was detected by Western blotting analysis; Morris water maze was used to detect learning ability and spatial memory. Results: The appropriate dose was 0.1 mg/kg for MUS and 0.5 mg/kg for BIC. Ex group showed significantly increased [Ca2+]i and astrogliosis; TUNEL positive cells and levels of GFAP, B cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase-3, caspase-12 cleavage, CCAAT/enhancer binding protein homologous protein (CHOP), and p-Jun amino-terminal kinase (p-JNK) in Ex group also raised significantly compared to Con group, while SYP, synapse plasticity, and Bcl-2 levels in Ex group were significantly lower than those in Con group. These indexes were back to normal in MUS group. BIC group had the highest levels of [Ca2+]i, astrogliosis, TUNEL positive cell, GFAP, Bax, caspase-3, caspase-12 cleavage, CHOP, and p-JNK, it also gained the lowest SYP, synapse plasticity, and Bcl-2 levels among all groups

  19. Antidepressant-like cognitive and behavioral effects of acute ketamine administration associated with plasticity in the ventral hippocampus to medial prefrontal cortex pathway

    PubMed Central

    Jett, Julianne D.; Boley, Angela M.; Girotti, Milena; Shah, Amiksha; Lodge, Daniel J.; Morilak, David A.

    2015-01-01

    Rationale Acute low-dose administration of the NMDA receptor antagonist, ketamine, produces rapid and sustained antidepressant-like effects in humans and rodents. Recently, we found that the long-lasting effect of ketamine on the forced swim test requires ventral hippocampal (vHipp) activity at the time of drug administration. The medial prefrontal cortex (mPFC), a target of the vHipp dysregulated in depression, is important for cognitive flexibility and response strategy selection. Deficits in cognitive flexibility, the ability to modify thoughts and behaviors in response to changes in the environment, are associated with depression. We have shown that chronic stress impairs cognitive flexibility on the attentional set-shifting test (AST), and induces a shift from active to passive response strategies on the shock-probe defensive burying test (SPDB). Objective In this study, we tested the effects of ketamine on chronic stress-induced changes in cognitive flexibility and coping behavior on the AST and SPDB, respectively. Subsequently, we investigated vHipp-mPFC plasticity as a potential mechanism of ketamine’s therapeutic action. Results Ketamine reversed deficits in cognitive flexibility and restored active coping behavior in chronically stressed rats. Further, high frequency stimulation in the vHipp replicated ketamine’s antidepressant-like effects on the forced swim test and AST, but not on the SPDB. Conclusion These results show that ketamine restores cognitive flexibility and coping response strategy compromised by stress. Activity in the vHipp-mPFC pathway may represent a neural substrate for some of the antidepressant-like behavioral effects of ketamine, including cognitive flexibility, but other circuits may mediate the effects of ketamine on coping response strategy. PMID:25986748

  20. 6 CFR 29.4 - Protected Critical Infrastructure Information Program administration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 6 Domestic Security 1 2012-01-01 2012-01-01 false Protected Critical Infrastructure Information... SECRETARY PROTECTED CRITICAL INFRASTRUCTURE INFORMATION § 29.4 Protected Critical Infrastructure Information... as a PCII Officer in order to carry out the responsibilities stated in paragraph (d) of this...

  1. 6 CFR 29.4 - Protected Critical Infrastructure Information Program administration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Protected Critical Infrastructure Information Management System (PCIIMS). The PCII Program Manager shall... be known as the “Protected Critical Infrastructure Information Management System” (PCIIMS), to record... 6 Domestic Security 1 2013-01-01 2013-01-01 false Protected Critical Infrastructure...

  2. 6 CFR 29.4 - Protected Critical Infrastructure Information Program administration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Protected Critical Infrastructure Information Management System (PCIIMS). The PCII Program Manager shall... be known as the “Protected Critical Infrastructure Information Management System” (PCIIMS), to record... 6 Domestic Security 1 2014-01-01 2014-01-01 false Protected Critical Infrastructure...

  3. [Protective action figurations for superoxide dismutase - chondroitin sulfate - catalase bienzyme conjugate after its medicative administration in endotoxin shock].

    PubMed

    Maksimenko, A V; Vavaeva, A V; Zvyagintseva, M A; Abramov, A A; Timoshin, A A; Vavaev, A V; Lakomkin, V L

    2016-03-01

    Previously it found that the bienzymatic conjugate superoxide dismutase-chondroitin sulfate, catalase (SOD-CHS-CAT) increased the survival rate of rats with endotoxic shock caused by the administration of lipopolysaccharide (LPS). This effect was observed both in preventive (before LPS) and therapeutic conjugate administration (after the administration of LPS). This study shows that the development of endotoxic shock is accompanied by increased levels of NO in the liver, lungs, kidneys, heart; administration of the SOD-CHS-CAT conjugate insignificantly influenced this parameter. At the same time, the changes in blood urea and creatinine suggest the protective effect of the conjugate on renal function, while diverse changes in biochemical parameters studied complicate the formation of the agreed conclusions on the state of other organs.

  4. Administration of kefir-fermented milk protects mice against Giardia intestinalis infection.

    PubMed

    Franco, Mariana Correa; Golowczyc, Marina A; De Antoni, Graciela L; Pérez, Pablo F; Humen, Martín; Serradell, María de los Angeles

    2013-12-01

    Giardiasis, caused by the protozoan Giardia intestinalis, is one of the most common intestinal diseases worldwide and constitutes an important problem for the public health systems of various countries. Kefir is a probiotic drink obtained by fermenting milk with 'kefir grains', which consist mainly of bacteria and yeasts that coexist in a complex symbiotic association. In this work, we studied the ability of kefir to protect mice from G. intestinalis infection, and characterized the host immune response to this probiotic in the context of the intestinal infection. Six- to 8-week-old C75BL/6 mice were separated into four groups: controls, kefir mice (receiving 1 : 100 dilution of kefir in drinking water for 14 days), Giardia mice (infected orally with 4×10(7) trophozoites of G. intestinalis at day 7) and Giardia-kefir mice (kefir-treated G. intestinalis-infected mice), and killed at 2 or 7 days post-infection. Kefir administration was able to significantly reduce the intensity of Giardia infection at 7 days post-infection. An increase in the percentage of CD4(+) T cells at 2 days post-infection was observed in the Peyer's patches (PP) of mice belonging to the Giardia group compared with the control and kefir groups, while the percentage of CD4(+) T cells in PP in the Giardia-kefir group was similar to that of controls. At 2 days post-infection, a reduction in the percentage of B220-positive major histocompatibility complex class II medium cells in PP was observed in infected mice compared with the other groups. At 7 days post-infection, Giardia-infected mice showed a reduction in RcFcε-positive cells compared with the control group, suggesting a downregulation of the inflammatory response. However, the percentages of RcFcε-positive cells did not differ from controls in the kefir and Giardia-kefir groups. An increase in IgA-positive cells was observed in the lamina propria of the kefir group compared with controls at 2 days post-infection. Interestingly, the

  5. Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques

    PubMed Central

    Rosenberg, Yvonne J.; Montefiori, David C.; LaBranche, Celia C.; Lewis, Mark G.; Sack, Markus; Lees, Jonathan P.; Jiang, Xiaoming

    2016-01-01

    Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown promise for prevention and treatment of HIV infection. However, multiple IV administrations in geographic locations with poor accessibility to medical care have practical limitations. We have assessed the efficacy of plant-derived PGT121 delivered subcutaneously (SC) against pre-and post-intravaginal challenge using a rigorous SHIV-SF162P3 macaque protection model. SC administered PGT121 exhibited a longer serum half-life than IV administration and was more consistent than intramuscular delivery. A dose of 3.5mg/kg PGT121 prevented infection at a minimum ID50 neutralization titer of 1:295 while 5mg/kg protected five of six macaques when delivered immediately post-challenge. These results suggest the utility of plant-derived bnAbs delivered SC for HIV prevention. PMID:27031108

  6. Influence of Route of Administration on Immediate and Extended Protection in Rats Immunized with Escherichia coli Heat-Labile Enterotoxin

    PubMed Central

    Klipstein, Frederick A.; Engert, Richard F.

    1980-01-01

    The effect of route of administration, dosage, and number of boosts employed during immunization with the polymyxin-release form of Escherichia coli heat-labile (LT) enterotoxin on the degree and duration of protection afforded was evaluated in rats which were challenged by the ligated loop technique. Increasing the boosting dosage by fivefold from 50 to 250 μg resulted in a marked increase in protection against challenge with toxin in rats immunized either just by the parenteral route (i.p./i.p.) or by a parenteral prime, followed by peroral boosts (i.p./p.o.) in rats pretreated with cimetidine to ablate gastric secretions; such was not the case, however, even with a 50-fold increase in dosage in rats immunized just by the peroral route (p.o./p.o.). Four weekly peroral boosts were required to achieve the strongest degree of protection. Increasing the boosting dosage also increased the degree of protection against challenge with viable LT+/ST− and LT+/ST+ strains (ST indicates heat-stable enterotoxin) in rats immunized by the i.p./p.o., but not by the i.p./i.p., route; no protection was evident against an LT−/ST+ strain. Protection was lost within 3 weeks after immunization in rats immunized by the i.p./i.p. route. In contrast, protection was extended over the 3-month observation period in those immunized by the i.p./p.o. route; the degree of protection was enhanced in rats which received an additional boost at 2 months. These observations establish the fact that immunization with LT is similar to that with cholera toxin in that arousal of the local immune intestinal response by means of peroral immunization provides maximal extended protection. PMID:6987180

  7. In vivo administration of extracellular cGMP normalizes TNF-α and membrane expression of AMPA receptors in hippocampus and spatial reference memory but not IL-1β, NMDA receptors in membrane and working memory in hyperammonemic rats.

    PubMed

    Cabrera-Pastor, Andrea; Hernandez-Rabaza, Vicente; Taoro-Gonzalez, Lucas; Balzano, Tiziano; Llansola, Marta; Felipo, Vicente

    2016-10-01

    Patients with hepatic encephalopathy (HE) show working memory and visuo-spatial orientation deficits. Hyperammonemia is a main contributor to cognitive impairment in HE. Hyperammonemic rats show impaired spatial learning and learning ability in the Y maze. Intracerebral administration of extracellular cGMP restores learning in the Y-maze. The underlying mechanisms remain unknown. It also remains unknown whether extracellular cGMP improves neuroinflammation or restores spatial learning in hyperammonemic rats and if it affects differently reference and working memory. The aims of this work were: Spatial working and reference memory were assessed using the radial and Morris water mazes and neuroinflammation by immunohistochemistry and Western blot. Membrane expression of NMDA and AMPA receptor subunits was analyzed using the BS3 crosslinker. Extracellular cGMP was administered intracerebrally using osmotic minipumps. Chronic hyperammonemia induces neuroinflammation in hippocampus, with astrocytes activation and increased IL-1β, which are associated with increased NMDA receptors membrane expression and impaired working memory. This process is not affected by extracellular cGMP. Hyperammonemia also activates microglia and increases TNF-α, alters membrane expression of AMPA receptor subunits (increased GluA1 and reduced GluA2) and impairs reference memory. All these changes are reversed by extracellular cGMP. These results show that extracellular cGMP modulates spatial reference memory but not working memory. This would be mediated by modulation of TNF-α levels and of membrane expression of GluA1 and GluA2 subunits of AMPA receptors.

  8. Protective effect of selenium on certain hepatotoxic and pancreotoxic manifestations of subacute cadmium administration.

    PubMed

    Merali, Z; Singhal, R L

    1975-10-01

    Administration of cadmium chloride (1.0 mg/kg s.c.) to rats, twice a day for 7 days, significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase, markedly increased the concentration of hepatic cyclic adenosine monophosphate and circulating blood glucose and significantly reduced serum insulin levels. Furthermore, subacute exposure to cadmium induced glucose intolerance that was associated with a decreased pancreatic secretory activity as evidenced by lowered insulinogenic indices and marked inhibition of phentolamine-stimulated insulin release. In contrast to cadmium, administration of selenium dioxide (2 X 1.0 mg/kg/day s.c., 7 days) failed to alter significantly the activities of gluconeogenic enzymes, hepatic cyclic adenosine monophosphate, blood glucose or serum insulin levels, glucose tolerance or the pancreatic secretory activity. However, administration of selenium concurrently with cadmium completely prevented the cadmium-induced increases of hepatic gluconeogenic enzymes. Treatment with selenium ameliorated the cadmium-induced hyperglycemia, hypoinsulinemia, glucose intolerance and the suppression of pancreatic secretory activity, whereas it failed to alter significantly the cadmium-induced elevation of hepatic cyclic AMP levels. Data provide evidence suggesting that subacute exposure to cadmium alters several parameters of carbohydrate metabolism and suppresses pancreatic secretory activity and that administration of selenium alone is without any appreciable effect on the above parameters. However, administration of selenium concurrently with cadmium prevents, to varying degrees, several of the cadmium-induced metabolic and functional changes.

  9. Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

    NASA Astrophysics Data System (ADS)

    Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

    2004-03-01

    Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

  10. Protection against Amorimia septentrionalis poisoning in goats by the continuous administration of sodium monofluoroacetate-degrading bacteria.

    PubMed

    da Silva, Layze C A; Pessoa, Danielle A N; Lopes, Jose R G; de Albuquerque, Laio G; da Silva, Leomyr S A; Garino Junior, Felicio; Riet-Correa, Franklin

    2016-03-01

    The intraruminal inoculation of sodium monofluoroacetate (MFA)-degrading bacteria has been proposed as a method to prevent poisoning by MFA-containing plants. In previous experiments, MFA-degrading bacteria were inoculated intraruminally before or concurrent with plant challenge, with both strategies conferring partial protection to poisoning. To evaluate the protection to Amorimia septentrionalis poisoning provided by the continuous inoculation of MFA-degrading bacteria isolated from plants and soils, 18 goats were divided into three experimental groups of six animals each: Group 1 goats received daily doses of a mixture of Paenibacillus sp. and Cupriavidus sp., and Group 2 goats received a mixture of Ralstonia sp. and Burkholderia sp., for 40 days, while Group 3 goats were not inoculated. Ten days after initiation of bacterial inoculation in Groups 1 and 2, all goats were challenged daily with 5 g/kg body weight of green leaves from A. septentrionalis. Four goats from Group 1 consumed the leaves throughout the 30-day consumption period and showed clinical signs such as transient tachycardia and engorgement of the jugular. The two remaining animals from Group 1 showed obvious signs of intoxication, and plant administration was suspended on days 17 and 19. The goats in Group 2 consumed the leaves throughout the 30-day study without showing signs of poisoning. The goats from Group 3 (control) manifested severe clinical signs of poisoning between the 3rd and 10th days following the start of the A. septentrionalis challenge. Under the conditions of this experiment continuous intraruminal administration of Ralstonia sp. and Burkholderia sp. provided complete protection to poisoning by A. septentrionalis in goats, while continuous intraruminal administration of Paenibacillus sp. and Cupriavidus sp. provided partial protection.

  11. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK

    SciTech Connect

    Li, Ying; Li, Jia; Li, Shanshan; Li, Yi; Wang, Xiangxiang; Liu, Baolin; Fu, Qiang; Ma, Shiping

    2015-07-01

    Curcumin is a natural polyphenolic compound in Curcuma longa with beneficial effects on neuronal protection. This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essential for the suppression of ER stress. As a result, curcumin reduced TXNIP expression and inhibited NLRP3 inflammasome activation by downregulation of NLRP3 and cleaved caspase-1 induction, and thus reduced IL-1β secretion. Specific fluorescent probe and flow cytometry analysis showed that curcumin prevented mitochondrial malfunction and protected cell survival from glutamate neurotoxicity. Moreover, oral administration of curcumin reduced brain infarct volume and attenuated neuronal damage in rats subjected to middle cerebral artery occlusion. Immunohistochemistry showed that curcumin inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region. Together, these results showed that curcumin attenuated glutamate neurotoxicity by inhibiting ER stress-associated TXNIP/NLRP3 inflammasome activation via the regulation of AMPK, and thereby protected the hippocampus from ischemic insult. - Highlights: • Curcumin attenuates glutamate neurotoxicity in the hippocampus. • Curcumin suppresses ER stress in glutamate-induced hippocampus slices. • Curcumin inhibits TXNIP/NLRP3 inflammasome activation. • Regulation of AMPK by curcumin contributes to suppressing ER stress.

  12. 19 CFR 351.103 - Central Records Unit and Administrative Protective Order and Dockets Unit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... and 5 p.m. on business days. Among other things, the Central Records Unit is responsible for... the APO/Dockets Unit are between 8:30 a.m. and 5 p.m. on business days. Among other things, the APO... 19 Customs Duties 3 2011-04-01 2011-04-01 false Central Records Unit and Administrative...

  13. Exogenous NAD+ administration significantly protects against myocardial ischemia/reperfusion injury in rat model

    PubMed Central

    Zhang, Youjun; Wang, Ban; Fu, Xingli; Guan, Shaofeng; Han, Wenzheng; Zhang, Jie; Gan, Qian; Fang, Weiyi; Ying, Weihai; Qu, Xinkai

    2016-01-01

    Acute myocardial infarction is one of the leading causes for death around the world. Although essential for successful interventional therapy, it is inevitably complicated by reperfusion injury. Thus effective approaches to reduce ischemia/reperfusion (I/R) injury are still critically needed. To test our hypothesis that intravenous administration of NAD+ can attenuate I/R injury by reducing apoptotic damage and enhancing antioxidant capacity, we used a rat mode of myocardial I/R. Our study found that administration of 10-20 mg/kg NAD+ can dose dependently reduce myocardial infarct induced by I/R, with an approximately 85% reduction of the infarct at the dosage of 20 mg/kg NAD+. We further found that the injection of NAD+ can significantly decrease I/R-induced apoptotic damage in the heart: NAD+ administration can both decrease the TUNEL signals, Bax, cleaved caspase-3 levels and increase the Bcl-XL levels in the rats that are subjected to myocardial I/R injury. NAD+ administration can also significantly attenuate I/R-induced decreases in SOD activity and SOD-2 protein levels in the hearts. NAD+ can profoundly decrease myocardial I/R injury at least partially by attenuating apoptotic damage and enhancing the antioxidant capacity, thus suggesting that NAD+ may become a promising therapeutic agent for myocardial I/R injury. PMID:27648125

  14. Hippocampus and consciousness.

    PubMed

    Behrendt, Ralf-Peter

    2013-01-01

    An important assumption concerning the physiology of consciousness is that all varieties of conscious experience are closely related to each other and, hence, are subserved by the same neural mechanism. There are several considerations that lead us to implicate the hippocampus in the generation of conscious perception and, ultimately, of conscious experiences of all kinds. Firstly, conscious perception of external events is intricately linked with the formation of episodic (declarative) memories, a key function attributed to the hippocampus. Secondly, conscious experience is allocentric and contextualized. Consciousness creates or simulates an image of the world that appears to surround us and to be independent of our observation of it. What is characteristic of wakeful consciousness and dreaming alike is that objects or events are experienced as being embedded in an external, that is, allocentric, frame of space and time. The hippocampus has been implicated in the rapid formation and memorization of allocentric representations that embed objects or events in a world context. Thirdly, the hippocampus is ideally positioned to bind information processed in different sensory association cortices. It is argued that rapidly forming patterns of neuronal ensemble firing in the hippocampus, particularly in region CA3, which encode arbitrary associations between objects and their spatiotemporal and emotional context, that is, associations between information derived from different neocortical processing streams, define the informational content of consciousness. Evidence suggestive of an important contribution of the hippocampus to conscious observation, mental imagery, dreaming, conscious anticipation of outcomes, and hallucinations will be reviewed.

  15. 97 Savvy Secrets for Protecting Self and School: A Practical Guide for Today's Teachers and Administrators.

    ERIC Educational Resources Information Center

    Sesno, Alice Healy

    A teacher's professional integrity faces numerous challenges in the classroom. To help educators safeguard against potentially career-ending incidents, numerous "survival rules" are provided in this text. It argues that teachers must safeguard themselves with self-protecting knowledge and, in some instances, must reprogram themselves…

  16. 19 CFR 206.17 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... industry engaged in the manufacture, production, or wholesale of a like or directly competitive article in the United States; (E) A trade or business association a majority of whose members manufacture... materials sought to be protected from public disclosure by a person do not constitute confidential...

  17. 19 CFR 206.17 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... industry engaged in the manufacture, production, or wholesale of a like or directly competitive article in the United States; (E) A trade or business association a majority of whose members manufacture... materials sought to be protected from public disclosure by a person do not constitute confidential...

  18. 19 CFR 206.17 - Limited disclosure of certain confidential business information under administrative protective...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... industry engaged in the manufacture, production, or wholesale of a like or directly competitive article in the United States; (E) A trade or business association a majority of whose members manufacture... materials sought to be protected from public disclosure by a person do not constitute confidential...

  19. Sublingual administration of Lactobacillus rhamnosus affects respiratory immune responses and facilitates protection against influenza virus infection in mice.

    PubMed

    Lee, Yu-Na; Youn, Ha-Na; Kwon, Jung-Hoon; Lee, Dong-Hun; Park, Jae-Keun; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Kim, Ki-Taek; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2013-05-01

    The extensive morbidity and mortality caused by influenza A viruses worldwide prompts the need for a deeper understanding of the host immune response and novel therapeutic and/or prophylactic interventions. In this study, we assessed the sublingual route as an effective means of delivering probiotics against influenza virus in mice. In addition, IgA levels, NK cell activity, T cell activation, and cytokine profiles in the lungs were examined to understand the mechanism underlying this protective effect. Sublingual administration of Lactobacillus rhamnosus provided enhanced protection against influenza virus infection by enhancing mucosal secretory IgA production, and T and NK cell activity. Moreover, interleukin (IL)-12 levels in the lungs increased significantly. Conversely, IL-6 and tumor necrosis factor alpha levels in the lungs decreased significantly. On the basis of these promising findings, we propose that the sublingual mucosal route is an attractive alternative to mucosal routes for administering probiotics against influenza virus.

  20. Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease.

    PubMed

    Olcese, James M; Cao, Chuanhai; Mori, Takashi; Mamcarz, Malgorzata B; Maxwell, Anne; Runfeldt, Melissa J; Wang, Li; Zhang, Chi; Lin, Xiaoyang; Zhang, Guixin; Arendash, Gary W

    2009-08-01

    The neurohormone melatonin has been reported to exert anti-beta-amyloid aggregation, antioxidant, and anti-inflammatory actions in various in vitro and animal models. To comprehensively determine the potential for long-term melatonin treatment to protect Alzheimer's transgenic mice against cognitive impairment and development of beta-amyloid (Abeta) neuropathology, we administered melatonin (100 mg/L drinking water) to APP + PS1 double transgenic (Tg) mice from 2-2.5 months of age to their killing at age 7.5 months. A comprehensive behavioral battery administered during the final 6 weeks of treatment revealed that Tg mice given melatonin were protected from cognitive impairment in a variety of tasks of working memory, spatial reference learning/memory, and basic mnemonic function; Tg control mice remained impaired in all of these cognitive tasks/domains. Immunoreactive Abeta deposition was significantly reduced in hippocampus (43%) and entorhinal cortex (37%) of melatonin-treated Tg mice. Although soluble and oligomeric forms of Abeta1-40 and 1-42 were unchanged in the hippocampus and cortex of the same melatonin-treated Tg mice, their plasma Abeta levels were elevated. These Abeta results, together with our concurrent demonstration that melatonin suppresses Abeta aggregation in brain homogenates, are consistent with a melatonin-facilitated removal of Abeta from the brain. Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha were decreased in hippocampus (but not plasma) of Tg+ melatonin mice. Finally, the cortical mRNA expression of three antioxidant enzymes (SOD-1, glutathione peroxidase, and catalase) was significantly reduced to non-Tg levels by long-term melatonin treatment in Tg mice. Thus, melatonin's cognitive benefits could involve its anti-Abeta aggregation, anti-inflammatory, and/or antioxidant properties. Our findings provide support for long-term melatonin therapy as a primary or complementary strategy for abating the progression of

  1. Protective effect of oral L-arginine administration on gentamicin-induced renal failure in rats.

    PubMed

    Can, C; Sen, S; Boztok, N; Tuglular, I

    2000-03-03

    We investigated the effects of orally supplemented L-arginine, the substrate of nitric oxide (NO) and N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide-synthase inhibitor in gentamicin-induced renal failure. Rats were given gentamicin (100 mg/kg/day s.c.), gentamicin and L-arginine (2 g/l, drinking water), gentamicin and L-NAME (100 mg/l, drinking water) or gentamicin plus L-arginine and L-NAME. After 8 days, the gentamicin group developed marked renal failure, characterized by a significantly decreased creatinine clearance and increased blood creatinine, fractional excretion of sodium, fractional excretion of lithium, urine gamma glutamyl transferase, systolic blood pressure and daily urine volume when compared to controls. Renal histological analysis confirmed tubular necrosis. L-arginine administration caused normalization of these parameters, whereas L-NAME led to aggravation of the failure. Concomitant administration of L-NAME and L-arginine to gentamicin-treated rats caused no significant changes when compared to the rats receiving gentamicin alone. We conclude that L-arginine supplementation has beneficial effects in gentamicin-induced renal failure in rats and that these effects are reversed by the NO-synthase inhibitor, L-NAME.

  2. Cognition Enhancing and Neuromodulatory Propensity of Bacopa monniera Extract Against Scopolamine Induced Cognitive Impairments in Rat Hippocampus.

    PubMed

    Pandareesh, M D; Anand, T; Khanum, Farhath

    2016-05-01

    Cognition-enhancing activity of Bacopa monniera extract (BME) was evaluated against scopolamine-induced amnesic rats by novel object recognition test (NOR), elevated plus maze (EPM) and Morris water maze (MWM) tests. Scopolamine (2 mg/kg body wt, i.p.) was used to induce amnesia in rats. Piracetam (200 mg/kg body wt, i.p.) was used as positive control. BME at three different dosages (i.e., 10, 20 and 40 mg/kg body wt.) improved the impairment induced by scopolamine by increasing the discrimination index of NOR and by decreasing the transfer latency of EPM and escape latency of MWM tests. Our results further elucidate that BME administration has normalized the neurotransmitters (acetylcholine, glutamate, 5-hydroxytryptamine, dopamine, 3,4 dihydroxyphenylacetic acid, norepinephrine) levels that were altered by scopolamine administration in hippocampus of rat brain. BME administration also ameliorated scopolamine effect by down-regulating AChE and up-regulating BDNF, muscarinic M1 receptor and CREB expression in brain hippocampus confirms the potent neuroprotective role and these results are in corroboration with the earlier in vitro studies. BME administration showed significant protection against scopolamine-induced toxicity by restoring the levels of antioxidant and lipid peroxidation. These results indicate that, cognition-enhancing and neuromodulatory propensity of BME is through modulating the expression of AChE, BDNF, MUS-1, CREB and also by altering the levels of neurotransmitters in hippocampus of rat brain.

  3. Myocardial protection by intracoronary nicardipine administration during percutaneous transluminal coronary angioplasty.

    PubMed

    Hanet, C; Rousseau, M F; Vincent, M F; Lavenne-Pardonge, E; Pouleur, H

    1987-05-01

    To determine if the calcium antagonist nicardipine protects the myocardium against ischemia, myocardial lactate, hypoxanthine and prostanoid function was studied in 12 patients during percutaneous transluminal coronary angioplasty (PTCA). Values were obtained before balloon inflation and during 4 minutes after deflation. Intracoronary injection of 0.2 mg of nicardipine distal to the stenosis was done randomly before the first or second inflation; the other inflation served as a control. One minute after deflation, coronary sinus flow levels were similar during the nicardipine and control procedure (161 +/- 61 vs 159 +/- 72 ml/min); lactate (-9 +/- 21% vs -17 +/- 21%, p less than 0.025) and hypoxanthine production (-107 +/- 85% vs -218 +/- 153%, p less than 0.05) were less severe after nicardipine pretreatment than after control. All patients reverted to lactate extraction 4 minutes after inflation plus nicardipine infusion, whereas lactate was still produced 4 minutes after control inflation. No significant changes in thromboxane B2 or prostacyclin levels were observed in the coronary sinus 1 minute after inflation, but higher arterial thromboxane B2 values were observed after control inflation than after inflation with nicardipine infusion (median values 169 vs 78 pg/ml, p less than 0.05). In conclusion, intracoronary infusion of nicardipine reduced signs of ischemia and alterations in prostanoid handling after coronary occlusion. The mechanisms of myocardial protection appeared unrelated to coronary sinus blood flow changes or to a systemic effect of nicardipine.

  4. Administration of defined microbiota is protective in a murine Salmonella infection model.

    PubMed

    Martz, Sarah-Lynn E; McDonald, Julie A K; Sun, Jun; Zhang, Yong-Guo; Gloor, Gregory B; Noordhof, Curtis; He, Shu-Mei; Gerbaba, Teklu K; Blennerhassett, Michael; Hurlbut, David J; Allen-Vercoe, Emma; Claud, Erika C; Petrof, Elaine O

    2015-11-04

    Salmonella typhimurium is a major cause of diarrhea and causes significant morbidity and mortality worldwide, and perturbations of the gut microbiota are known to increase susceptibility to enteric infections. The purpose of this study was to investigate whether a Microbial Ecosystem Therapeutic (MET-1) consisting of 33 bacterial strains, isolated from human stool and previously used to cure patients with recurrent Clostridium difficile infection, could also protect against S. typhimurium disease. C57BL/6 mice were pretreated with streptomycin prior to receiving MET-1 or control, then gavaged with S. typhimurium. Weight loss, serum cytokine levels, and S. typhimurium splenic translocation were measured. NF-κB nuclear staining, neutrophil accumulation, and localization of tight junction proteins (claudin-1, ZO-1) were visualized by immunofluorescence. Infected mice receiving MET-1 lost less weight, had reduced serum cytokines, reduced NF-κB nuclear staining, and decreased neutrophil infiltration in the cecum. MET-1 also preserved cecum tight junction protein expression, and reduced S. typhimurium translocation to the spleen. Notably, MET-1 did not decrease CFUs of Salmonella in the intestine. MET-1 may attenuate systemic infection by preserving tight junctions, thereby inhibiting S. typhimurium from gaining access to the systemic circulation. We conclude that MET-1 may be protective against enteric infections besides C. difficile infection.

  5. Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure.

    PubMed

    Johnson, D W; Pat, B; Vesey, D A; Guan, Z; Endre, Z; Gobe, G C

    2006-05-01

    Administration of human recombinant erythropoietin (EPO) at time of acute ischemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa (DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats (N = 4 per group), followed by reperfusion for 1-7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation (T0), or post-treated (6 h after the onset of reperfusion, T6) with EPO (5000 IU/kg), DPO (25 mug/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.08 +/- 0.03 mmol/l vs EPO-IRI 0.04 +/- 0.01 mmol/l, P = 0.01). Delayed administration of DPO or EPO (T6) also significantly abrogated subsequent renal dysfunction (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.06 +/- 0.01 mmol/l vs EPO-IRI 0.03 +/- 0.03 mmol/l, P = 0.01). There was also significantly decreased tissue injury (apoptosis, P < 0.05), decreased proapoptotic Bax, and increased regenerative capacity, especially in the outer stripe of the outer medulla, with DPO or EPO at T0 or T6. These results reaffirm the potential clinical application of DPO and EPO as novel renoprotective agents for patients at risk of ischemic acute renal failure or after having sustained an ischemic renal insult.

  6. Stress, memory, and the hippocampus.

    PubMed

    Wingenfeld, Katja; Wolf, Oliver T

    2014-01-01

    Stress hormones, i.e. cortisol in human and cortisone in rodents, influence a wide range of cognitive functions, including hippocampus-based declarative memory performance. Cortisol enhances memory consolidation, but impairs memory retrieval. In this context glucocorticoid receptor sensitivity and hippocampal integrity play an important role. This review integrates findings on the relationships between the hypothalamus-pituitary-adrenal (HPA) axis, one of the main coordinators of the stress response, hippocampus, and memory. Findings obtained in healthy participants will be compared with selected mental disorders, including major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). These disorders are characterized by alterations of the HPA axis and hippocampal dysfunctions. Interestingly, the acute effects of stress hormones on memory in psychiatric patients are different from those found in healthy humans. While cortisol administration has failed to affect memory retrieval in patients with MDD, patients with PTSD and BPD have been found to show enhanced rather than impaired memory retrieval after hydrocortisone. This indicates an altered sensitivity to stress hormones in these mental disorders.

  7. Unsolved mysteries: the hippocampus.

    PubMed

    Isaacson, Robert L

    2002-06-01

    The continuing explosion of scientific interest in the hippocampus began in the 1950s, initiated in large part by the recognition of the importance of the observations of hippocampectomized monkeys made by Klüver and Bucy and the remarkable memory loss of patient H. M. following temporal lobe surgery. Subsequent to these studies, research and theories about the hippocampus grew exponentially in number and diversity. As yet, no theory of hippocampal function explains all of the phenomena discovered in the clinic or laboratory. In this article, experimental results that have been forgotten or ignored in most theories are presented. Adequate theories of hippocampal function must account for known, reliable postsurgical behavioral observations and consider the conditions under which anomalies are noted. Comprehensive theories will require new approaches in which the interactions of the hippocampus with the central nervous system are understood.

  8. Therapeutic Administration of a Monoclonal Anti-Il-1β Antibody Protects Against Experimental Melioidosis

    PubMed Central

    Weehuizen, Tassili A. F.; Lankelma, Jacqueline M.; De Jong, Hanna K.; De Boer, Onno J.; Roelofs, Joris J. T. H.; Day, Nicholas P.; Gram, Hermann; De Vos, Alex F.; Wiersinga, W. Joost

    2016-01-01

    ABSTRACT Background: Melioidosis, caused by the gram-negative bacterium Burkholderia pseudomallei, is a common cause of community-acquired sepsis in Southeast Asia and Northern Australia. The NLRP3 inflammasome and its downstream product interleukin-1 beta (IL-1β) have been proposed to play crucial roles in melioidosis. In this study, we characterized the role of IL-1β more closely and we assessed its therapeutic potential. Methods: mRNA expression of inflammasome components was determined in isolated leukocytes of 32 healthy controls and 34 patients with sepsis caused by B pseudomallei. Wild-type (WT), NLRP3-deficient (Nlrp3−/−), and Asc−/− mice were infected with B pseudomallei. In additional experiments, infected WT mice were treated with an anti-IL-1β antibody. After 24, 48, and 72 hours (h) mice were sacrificed and organs were harvested. Furthermore, survival studies were performed. Results: Patients with melioidosis exhibited lower mRNA levels of caspase-1, NLRP3, and ASC. Bacterial dissemination and organ damage were increased in B pseudomallei-infected Nlrp3−/− and Asc−/− mice, together with a reduced pulmonary cell influx. Anti-IL-1β treatment of B pseudomallei challenged mice resulted in strongly reduced bacterial counts, organ damage, and pulmonary granulocyte influx together with reduced mortality. Postponement of anti-IL-1β treatment for 24 h postinfection still protected mice during melioidosis. Conclusion: Expression of caspase-1, NLRP3, and ASC is altered in melioidosis patients. In mice, both NLRP3 and ASC contribute to the host defense against melioidosis. Anti-IL-1β treatment protects mice against B pseudomallei infection and might be a novel treatment strategy in melioidosis. PMID:27219859

  9. Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague.

    PubMed

    Sun, Wei; Sanapala, Shilpa; Rahav, Hannah; Curtiss, Roy

    2015-11-27

    A Yersinia pseudotuberculosis PB1+ (Yptb PB1+) mutant strain combined with chromosome insertion of the caf1R-caf1A-caf1M-caf1 operon and deletions of yopJ and yopK, χ10068 [pYV-ω2 (ΔyopJ315 ΔyopK108) ΔlacZ044::caf1R-caf1M-caf1A-caf1] was constructed. Results indicated that gene insertion and deletion did not affect the growth rate of χ10068 compared to wild-type Yptb cultured at 26 °C. In addition, the F1 antigen in χ10068 was synthesized and secreted on the surface of bacteria at 37 °C (mammalian body temperature), not at ambient culture temperature (26 °C). Immunization with χ10068 primed antibody responses and specific T-cell responses to F1 and YpL (Y. pestis whole cell lysate). Oral immunization with a single dose of χ10068 provided 70% protection against a subcutaneous (s.c.) challenge with ∼ 2.6 × 10(5) LD50 of Y. pestis KIM6+ (pCD1Ap) (KIM6+Ap) and 90% protection against an intranasal (i.n.) challenge with ∼ 500 LD50 of KIM6+Ap in mice. Our results suggest that χ10068 can be used as an effective precursor to make a safe vaccine to prevent plague in humans and to eliminate plague circulation among humans and animals.

  10. Serotonin Receptors in Hippocampus

    PubMed Central

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  11. Oral administration of Lactobacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging.

    PubMed

    Kim, Hyun Mee; Lee, Dong Eun; Park, Soo Dong; Kim, Yong-Tae; Kim, Yu Jin; Jeong, Ji Woong; Jang, Sung Sik; Ahn, Young-Tae; Sim, Jae-Hun; Huh, Chul-Sung; Chung, Dae Kyun; Lee, Jung-Hee

    2014-11-28

    Ultraviolet (UV) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage, including photoaging. In recent years, probiotics have gained interest due to their beneficial effects on skin health, such as inhibiting atopic dermatitis and improving skin immunity or inflammation. However, little is known about the effects of probiotics on UVBinduced photoaging. In this study, we evaluated the effect of Lactobacillus plantarum HY7714 against UVB-induced photoaging in human dermal fibroblasts and hairless mice. The results showed that L. plantarum HY7714 treatment effectively rescued UVB-reduced procollagen expression through the inhibition of UVB-induced matrix metalloproteinase (MMP)-1 expression in human dermal fibroblasts. Data from a western blot showed that L. plantarum HY7714 inhibited the phosphorylation of Jun N-terminal kinase, thereby suppressing the UVB-induced phosphorylation and expression of c-Jun. Oral administration of L. plantarum HY7714 clearly inhibited the number, depth, and area of wrinkles in hairless mouse skin. Histological data showed that L. plantarum HY7714 significantly inhibited UVB-induced epidermal thickness in mice. Western blot and zymography data also revealed that L. plantarum HY7714 effectively inhibited MMP-13 expression as well as MMP-2 and -9 activities in dermal tissue. Collectively, these results provide further insight regarding the skin biological actions of L. plantarum HY7714, a potential skin anti-photoaging agent.

  12. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    PubMed

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent.

  13. Protective effects of sildenafil citrate administration on cisplatin-induced ovarian damage in rats.

    PubMed

    Taskin, Mine Islimye; Yay, Arzu; Adali, Ertan; Balcioglu, Esra; Inceboz, Umit

    2015-04-01

    The aim of this study is to evaluate the effects of sildenafil citrate on cisplatin-induced ovarian toxicity. Thirty-two female rats were divided into four groups. Group 1: saline control; group 2: cisplatin; group 3: sildenafil citrate; and group 4: cisplatin plus sildenafil citrate group. In groups 2 and 4, the rats were injected with 5 mg/kg cisplatin intraperitoneally (i.p.). In groups 3 and 4, the rats were injected with 1.4 mg/kg sildenafil citrate i.p. The ovaries were removed two weeks later in all groups. Histopathologic examination, follicle counting and classification were performed. The expression of anti-Müllerian hormone (AMH) was detected immunohistochemically in the ovarian tissues. Sildenafil alleviated cisplatin-induced histopathological changes in the ovarian tissue. Primordial, secondary and tertiary follicles were diminished in group 2 compared with group 1 (p < 0.05). Pretreatment with sildenafil citrate preserved primordial follicle count in group 4 compared with group 2, and the difference was statistically significant (p < 0.05). According to our results, immunoreactivity intensity of AMH was lower in group 2 compared with group 1 (92.4 ± 3.97 versus 88.8 ± 1.77) but not significantly, whereas immunoreactivity intensity of AMH was higher in group 4 compared with group 2 (88.8 ± 1.77 versus 94.1 ± 2.36; p < 0.05). Our results demonstrated that pretreatment with sildenafil citrate is beneficial for protecting the ovaries from cisplatin-induced damage. Sildenafil citrate can be a choice for fertility preservation.

  14. Systemic Administration of Oleoylethanolamide Protects from Neuroinflammation and Anhedonia Induced by LPS in Rats

    PubMed Central

    Sayd, Aline; Antón, María; Alén, Francisco; Caso, Javier Rubén; Pavón, Javier; Leza, Juan Carlos; Rodríguez de Fonseca, Fernando

    2015-01-01

    Background: The acylethanolamides oleoylethanolamide and palmitoylethanolamide are endogenous lipid mediators with proposed neuroprotectant properties in central nervous system (CNS) pathologies. The precise mechanisms remain partly unknown, but growing evidence suggests an antiinflammatory/antioxidant profile. Methods: We tested whether oleoylethanolamide/palmitoylethanolamide (10mg/kg, i.p.) attenuate neuroinflammation and acute phase responses (hypothalamus-pituitary-adrenal (HPA) stress axis stress axis activation, thermoregulation, and anhedonia) induced by lipopolysaccharide (0.5mg/kg, i.p.) in rats. Results: Lipopolysaccharide increased mRNA levels of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6, nuclear transcription factor-κB activity, and the expression of its inhibitory protein IκBα in cytoplasm, the inducible isoforms of nitric oxide synthase and cyclooxygenase-2, microsomal prostaglandin E2 synthase mRNA, and proinflammatory prostaglandin E2 content in frontal cortex 150 minutes after administration. As a result, the markers of nitrosative/oxidative stress nitrites (NO2 -) and malondialdehyde were increased. Pretreatment with oleoylethanolamide/ palmitoylethanolamide reduced plasma tumor necrosis factor-α levels after lipopolysaccharide, but only oleoylethanolamide significantly reduced brain tumor necrosis factor-α mRNA. Oleoylethanolamide and palmitoylethanolamide prevented lipopolysaccharide-induced nuclear transcription factor-κB (NF-κB)/IκBα upregulation in nuclear and cytosolic extracts, respectively, the expression of inducible isoforms of nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E2 synthase and the levels of prostaglandin E2. Additionally, both acylethanolamides reduced lipopolysaccharide-induced oxidative/nitrosative stress. Neither oleoylethanolamide nor palmitoylethanolamide modified plasma corticosterone levels after lipopolysaccharide, but both

  15. CBLB502 administration protects gut mucosal tissue in ulcerative colitis by inhibiting inflammation

    PubMed Central

    Xu, Yang; Dong, Hongxia; Ge, Changhui; Gao, Yan; Liu, Haifeng

    2016-01-01

    Background Ulcerative colitis (UC) is a nonspecific inflammatory disease for which medications and therapeutic strategies have only been moderately successful. CBLB502, a toll-like receptor 5 (TLR5) agonist derived from Salmonella flagellin, exhibits anticancer and radioprotective activities via modulation of TLRs and the nuclear factor kappa B (NF-κB) signaling pathway and can protect against acute renal ischemic failure. In this study, we intend to examine the effects of CBLB502 on both TLR responses and the interleukin (IL) and NF-κB signaling pathways in UC treatment. Methods The UC mouse model was prepared in BALB/c mice by administering 2,4,6-trinitrobenzene sulfonic acid (TNBS). CBLB502 was used as the therapeutic drug. After CBLB502 therapy, the IL and tumor necrosis factor-α (TNF-α) levels were measured by ELISA. Total RNA and protein of colon samples was extracted. Results We found that CBLB502 had a distinctive therapeutic effect in the UC model. In control group animals, IL-10 expression in serum was 91.48±24.38 ng/mL; this was higher than in the model group (59.36±14.46 ng/mL, P<0.05) or the treatment group (54.29±5.83 ng/mL, P<0.05). In model group animals, the concentration of TNF-α in serum was 140.11±12.70 ng/mL, which was lower than protein levels in the control group (173.86±29.26 ng/mL, P<0.05). The mRNA levels of TLR1, 2, 3, 4, 6, 7, 8, and 9 in the CBLB502 treatment group were significantly lower than in the model group (P<0.05). Western blot revealed that CBLB502 also reduced NF-κB expression in the mouse colon, but that NF-κB expression was not significantly lower than the model group. Conclusions CBLB502 can reduce mucosal damage induced by TNBS and inhibit inflammation and TLR expression. The inhibition of UC by CBLB502 is strictly TLR-IL-dependent and is dose-dependent within the efficacious dose range. Therefore, our results suggested that CBLB502 might be a candidate drug for the treatment of UC. PMID:27668221

  16. Gene expression analysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agouti rats

    PubMed Central

    2013-01-01

    Background 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions, impairments frequently described in heavy MDMA users. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the effects of a single dose of MDMA (15 mg/kg) 3 weeks earlier. Results The number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of 'memory’ and 'cognition’, 'dendrite development’ and 'regulation of synaptic plasticity’ gene sets in the hippocampus, parallel to the upregulation of the CB1 cannabinoid- and Epha4, Epha5, Epha6 ephrin receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while 'dendrite development’, 'regulation of synaptic plasticity’ and 'positive regulation of synapse assembly’ gene sets were upregulated. Changes in the dorsal raphe region were mild and in most cases not significant. Conclusion The present data raise the possibility of new synapse formation/synaptic reorganization in the frontal cortex three weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is suggested by the data, which underlines the particular vulnerability of this brain region after the drug treatment. Finally, our results also suggest the substantial contribution of CB1 receptor and

  17. Protection of the infant thyroid from radioactive contamination by the administration of stable iodide. An experimental evaluation in chimpanzees.

    PubMed

    Noteboom, J L; Hummel, W A; Broerse, J J; de Vijlder, J J; Vulsma, T; van Bekkum, D W

    1997-06-01

    Protection of the thyroid from radioactive contamination by the administration of stable iodide was investigated in chimpanzees aged 2 to 98 weeks. The uptake of iodide in the thyroid was measured with 123I-. The animals were subjected to a control measurement first, and subsequently the thyroid uptake of 123I- was determined twice; once at the start and once at the end of 11 days of ingestion of 0.5, 1.5 or 5.0 mg of stable iodide per kg body weight per day. The three doses of iodide reduced the control thyroid iodide uptake of 10 to 30% to lower than 1% when ingested 1 h before exposure to the tracer and to 2-4% when ingested 20 h before exposure. In the latter experiments 0.5 mg iodide/kg was less effective than doses of 1.5 mg/kg or higher. The physiological state of the thyroid of control infant chimpanzees does not differ from that of human infants. Incidentally, an increased level of TSH was found during the ingestion of iodide, but with unaltered thyroxine levels. Therefore, it is concluded that a daily dose of 1.5 mg stable iodide/kg body weight and higher offers optimal protection of the thyroid against exposure to radioactive iodine in infants and that, when used during 10 days, it leaves the thyroid unaffected.

  18. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge

    PubMed Central

    Pardi, Norbert; Secreto, Anthony J.; Shan, Xiaochuan; Debonera, Fotini; Glover, Joshua; Yi, Yanjie; Muramatsu, Hiromi; Ni, Houping; Mui, Barbara L.; Tam, Ying K.; Shaheen, Farida; Collman, Ronald G.; Karikó, Katalin; Danet-Desnoyers, Gwenn A.; Madden, Thomas D.; Hope, Michael J.; Weissman, Drew

    2017-01-01

    Monoclonal antibodies are one of the fastest growing classes of pharmaceutical products, however, their potential is limited by the high cost of development and manufacturing. Here we present a safe and cost-effective platform for in vivo expression of therapeutic antibodies using nucleoside-modified mRNA. To demonstrate feasibility and protective efficacy, nucleoside-modified mRNAs encoding the light and heavy chains of the broadly neutralizing anti-HIV-1 antibody VRC01 are generated and encapsulated into lipid nanoparticles. Systemic administration of 1.4 mg kg−1 of mRNA into mice results in ∼170 μg ml−1 VRC01 antibody concentrations in the plasma 24 h post injection. Weekly injections of 1 mg kg−1 of mRNA into immunodeficient mice maintain trough VRC01 levels above 40 μg ml−1. Most importantly, the translated antibody from a single injection of VRC01 mRNA protects humanized mice from intravenous HIV-1 challenge, demonstrating that nucleoside-modified mRNA represents a viable delivery platform for passive immunotherapy against HIV-1 with expansion to a variety of diseases. PMID:28251988

  19. Modulation of BDNF and TrkB expression in rat hippocampus in response to acute neurotoxicity by diethyldithiocarbamate.

    PubMed

    Micheli, M R; Bova, R; Laurenzi, M A; Bazzucchi, M; Grassi Zucconi, G

    2006-12-13

    In this study, we examined the expression profile of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in adult rat hippocampus following acute administration of diethyldithiocarbamate (DDTC), a neurotoxic compound which was previously shown to induce microglia activation and cell death. Semiquantitative RT-PCR analysis detected significant variations of BDNF mRNA levels in whole hippocampus homogenates, with a peak at 24h after DDTC injection. Increased BDNF protein expression was demonstrated by immunohistochemistry in various hippocampal subfields. The most relevant increase was observed in the hilus of the dentate gyrus where BDNF levels at 120h were found to be almost four times those of basal levels. Full-length TrkB (TrkB.FL) encoding mRNA was also shown to undergo an earlier increase in the hippocampus of DDTC-treated rats. TrkB immunostaining with an antibody binding both full-length and truncated (TrkB.T) isoforms was found to increase at 120h in the hippocampal CA2 and CA3 regions. These results demonstrate that DDTC modulates the expression of BDNF and its receptor in the adult rat hippocampus and suggest a possible involvement of this neurotrophin in the protective response to DDTC-induced neuronal damage.

  20. Neuroprotective effects of Bacopa monniera whole-plant extract against aluminum-induced hippocampus damage in rats: evidence from electron microscopic images.

    PubMed

    Nannepaga, John Sushma; Korivi, Mallikarjuna; Tirumanyam, Madhavi; Bommavaram, Mahitha; Kuo, Chia-Hua

    2014-10-31

    Impaired antioxidant system and structural changes in hippocampus are considered as key instigators of neurodegenerative diseases. The present study aimed to investigate the antioxidant and tissue protective properties of Bacopa monniera whole-plant extract (BME) against aluminum (Al)- induced oxidative stress and hippocampus damage in rats. Male Wistar rats were evenly divided into four groups, nine in each and labeled as control, Al treated (10 mg/kg), BME administered (40 mg/kg) and combination of both Al plus BME (Al+BME) treated groups. After one month of treatment by oral administration, antioxidant status was determined, and structural changes in the hippocampus were evaluated by electron microscopy. Al-induced increased oxidative damage in the hippocampus was revealed by elevated thiobarbituric acid reactive substances (TBARS). This increased lipid peroxidation was associated with significantly decreased antioxidant enzyme activities, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). However, aluminum intoxicated rats treated with BME for 30 days showed significantly restored antioxidant enzyme activities along with decreased TBARS (P < 0.01). Further evidences from electron micrographs clearly indicated that Al-induced vacuolation, lipofuscin deposition and pyramidal cell degeneration in the hippocampus was attenuated with co-administration of the whole-plant extract. Our results demonstrate that structural derangement in hippocampus by aluminum is directly proportionate with increased lipid peroxidation. Nevertheless, B. monniera treatment potentiates the antioxidant status and suppressed the tissue damage induced by Al-intoxication. These findings suggest that B. monniera whole-plant extracts can be considered as a possible remedy to counteract aluminum-associated neurological disorders.

  1. Protective Effects of Edaravone in Adult Rats with Surgery and Lipopolysaccharide Administration-Induced Cognitive Function Impairment

    PubMed Central

    Liu, Na; Ma, Li; Zhou, Xueyue; Zhang, Hong; Wang, Yongan

    2016-01-01

    Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterized by cognitive declines in patients after surgery. Previous studies have suggested that surgery contributed to such impairment. It has been proven that neuroinflammation may exacerbate surgery-induced cognitive impairment in aged rats. The free radical scavenger edaravone has high blood brain barrier permeability, and was demonstrated to effectively remove free radicals from the brain and alleviate the development of POCD in patients undergoing carotid endarterectomy, suggesting its potential role in preventing POCD. For this reason, this study was designed to determine whether edaravone is protective against POCD through its inhibitory effects on inflammatory cytokines and oxidative stress. First, Sprague Dawley adult male rats were administered 3 mg/kg edaravone intraperitoneally after undergoing a unilateral nephrectomy combined with lipopolysaccharide injection. Second, behavioral parameters related to cognitive function were recorded by fear conditioning and Morris Water Maze tests. Last, superoxide dismutase activities and malondialdehyde levels were measured in the hippocampi and prefrontal cortex on postoperative days 3 and 7, and microglial (Iba1) activation, p-Akt and p-mTOR protein expression, and synaptic function (synapsin 1) were also examined 3 and 7 days after surgery. Rats that underwent surgery plus lipopolysaccharide administration showed significant impairments in spatial and working memory, accompanied by significant reductions in hippocampal-dependent and independent fear responses. All impairments were attenuated by treatment with edaravone. Moreover, an abnormal decrease in superoxide dismutase activation, abnormal increase in malondialdehyde levels, significant increase in microglial reactivity, downregulation of p-Akt and p-mTOR protein expression, and a statistically significant decrease in synapsin-1 were observed in the hippocampi and prefrontal cortices of

  2. Effect of sub-acute oral cyanide administration in rats: protective efficacy of alpha-ketoglutarate and sodium thiosulfate.

    PubMed

    Tulsawani, R K; Debnath, M; Pant, S C; Kumar, Om; Prakash, A O; Vijayaraghavan, R; Bhattacharya, R

    2005-09-10

    Chronic toxicity of cyanide in humans and animals has been previously described. Alpha-ketoglutarate (alpha-KG) and sodium thiosulfate (STS) are known to confer remarkable protection against acute cyanide poisoning in rodents. Their efficacy against sub-acute or chronic cyanide exposure is not known. The objective of the present study was to assess the sub-acute toxicity of potassium cyanide (KCN) in female rats following oral administration of 7.0 mg/kg (0.5 LD50) for 14 d. The effect of alpha-KG (oral; 1.0 g/kg) and/or STS (intraperitoneal, 1.0 g/kg) on cyanide toxicity was also evaluated. Various hematological and biochemical indices were determined after 7 d of treatment and additional parameters like organ-body weight index (OBI) and histology of brain, heart, lung, liver, kidney and spleen were performed after 14 and 21 d (recovery group) of cyanide exposure. Sub-acute exposure of KCN did not produce any significant change in body weight of the animals, OBI, hematology and the levels of blood urea, creatinine, aspartate aminotransferase, triiodothyronine (T3) and tetraiodothyronine (T4). The levels of temporal glutathione disulfide (GSSG) and hepatic malondialdehyde (MDA), reduced glutathione (GSH) and GSSG were unaffected. However, in KCN treated animals elevated levels of blood glucose and reduced levels of alanine aminotransferase were observed. Activities of cytochrome c oxidase in the brain and rhodanese in the liver were diminished. Reduced levels of GSH and enhanced levels of MDA in brain were observed. Increased levels of blood thiocyanate were observed in all the treatments of KCN. Additionally, KCN also produced various histological changes in the brain, heart, liver and kidney. Although, treatment of alpha-KG and STS alone significantly blunted the toxicity of KCN, concomitant use of both interventions afforded to maximum protection. This study indicates a promising role of alpha-KG and STS for the treatment of prolonged cyanide exposures.

  3. Protection genes in nucleus accumbens shell affect vulnerability to nicotine self-administration across isogenic strains of adolescent rat.

    PubMed

    Chen, Hao; Luo, Rui; Gong, Suzhen; Matta, Shannon G; Sharp, Burt M

    2014-01-01

    Classical genetic studies show the heritability of cigarette smoking is 0.4-0.6, and that multiple genes confer susceptibility and resistance to smoking. Despite recent advances in identifying genes associated with smoking behaviors, the major source of this heritability and its impact on susceptibility and resistance are largely unknown. Operant self-administration (SA) of intravenous nicotine is an established model for smoking behavior. We recently confirmed that genetic factors exert strong control over nicotine intake in isogenic rat strains. Because the processing of afferent dopaminergic signals by nucleus accumbens shell (AcbS) is critical for acquisition and maintenance of motivated behaviors reinforced by nicotine, we hypothesized that differential basal gene expression in AcbS accounts for much of the strain-to-strain variation in nicotine SA. We therefore sequenced the transcriptome of AcbS samples obtained by laser capture microdissection from 10 isogenic adolescent rat strains and compared all RNA transcript levels with behavior. Weighted gene co-expression network analysis, a systems biology method, found 12 modules (i.e., unique sets of genes that covary across all samples) that correlated (p<0.05) with amount of self-administered nicotine; 9 of 12 correlated negatively, implying a protective role. PCR confirmed selected genes from these modules. Chilibot, a literature mining tool, identified 15 genes within 1 module that were nominally associated with cigarette smoking, thereby providing strong support for the analytical approach. This is the first report demonstrating that nicotine intake by adolescent rodents is associated with the expression of specific genes in AcbS of the mesolimbic system, which controls motivated behaviors. These findings provide new insights into genetic mechanisms that predispose or protect against tobacco addiction.

  4. Protective effects of intraperitoneal vitamin C, aprotinin and melatonin administration on retinal edema during experimental uveitis in the guinea pig.

    PubMed

    Kükner, A Sahap; Kükner, Aysel; Naziroğlu, Mustafa; Colakoğlu, Neriman; Celebi, Serdal; Yilmaz, Turgut; Aydemir, Orhan

    2004-01-01

    .05). In conclusion, this study demonstrated that oedematous effects of EU on the retina were reduced by the administration of intraperitoneal vitamin C, aprotinin and melatonin, i.e. these antioxidants had significant protective effects on the retina of guinea pigs against oedematous damage in EU. However, the reductive effect of vitamin C on EU was greater than that of aprotinin and melatonin. The intraperitoneal vitamin C, aprotinin and melatonin supplementations may strengthen the antioxidant defence system because of decreased ROS, and these agents may play a role in treating uveitis.

  5. Prior access to a sweet is more protective against cocaine self-administration in female rats than in male rats.

    PubMed

    Cason, Angie M; Grigson, Patricia S

    2013-03-15

    It is well established that female rats are more sensitive than male rats to the reinforcing effects of cocaine (Lynch, 2008 [42] for review). We hypothesized that greater preference for cocaine would support greater avoidance of a cocaine-paired taste cue in female vs. male rats. Moreover, at least in male rats, greater avoidance of the taste cue is associated with greater cocaine self-administration (Grigson and Twining, 2002 [3]). Thus, we anticipated that female rats would not only demonstrate greater avoidance of the drug-paired taste cue, but greater drug-taking as well. We tested these hypotheses by examining avoidance of a saccharin cue in male and female rats following several pairings with self-administered saline or cocaine (0.16, 0.33, or 0.66 mg/infusion). Contrary to expectations, the results showed that female rats exhibited less avoidance of the cocaine-associated saccharin cue than male rats and self-administered less, rather than more, cocaine, Thus, while female rats reportedly take more drug than male rats when the drug is presented in the absence of an alternative reward, they take less drug than male rats when the opportunity to self-administer cocaine is preceded by access to a palatable sweet. Females, then, may not simply be more sensitive to the rewarding properties of drug, but also to the reinforcing properties of natural rewards and this increase in sensitivity to sweets may serve to protect against drug-taking behavior.

  6. Nicotinic receptors in the dorsal and ventral hippocampus differentially modulate contextual fear conditioning.

    PubMed

    Kenney, Justin W; Raybuck, Jonathan D; Gould, Thomas J

    2012-08-01

    Nicotine administration alters various forms of hippocampus-dependent learning and memory. Increasing work has found that the dorsal and ventral hippocampus differentially contribute to multiple behaviors. Thus, the present study examined whether the effects of nicotine in the dorsal and ventral hippocampus have distinct influences on contextual fear learning in male C57BL/6J mice. Direct infusion of nicotine into the dorsal hippocampus resulted in an enhancement of contextual fear learning, whereas nicotine infused into the ventral hippocampus resulted in deficits. Nicotine infusions into the ventral hippocampus did not alter hippocampus-independent cued fear conditioning or time spent in the open arm of the elevated plus maze, a measure of anxiety, suggesting that the effects are due to alterations in contextual learning and not other general processes. Finally, results from using direct infusions of MLA, a low-affinity α7 nicotinic acetylcholine receptor (nAChR) antagonist, in conjunction with systemic nicotine, provide evidence that α7-nAChRs in the ventral hippocampus mediate the detrimental effect of ventral hippocampal nicotine on contextual fear learning. These results suggest that with systemic nicotine administration, competition exists between the dorsal and ventral hippocampus for behavioral control over contextual learning.

  7. The rat brain hippocampus proteome.

    PubMed

    Fountoulakis, Michael; Tsangaris, George T; Maris, Antony; Lubec, Gert

    2005-05-05

    The hippocampus is crucial in memory storage and retrieval and plays an important role in stress response. In humans, the CA1 area of hippocampus is one of the first brain areas to display pathology in Alzheimer's disease. A comprehensive analysis of the hippocampus proteome has not been accomplished yet. We applied proteomics technologies to construct a two-dimensional database for rat brain hippocampus proteins. Hippocampus samples from eight months old animals were analyzed by two-dimensional electrophoresis and the proteins were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The database comprises 148 different gene products, which are in the majority enzymes, structural proteins and heat shock proteins. It also includes 39 neuron specific gene products. The database may be useful in animal model studies of neurological disorders.

  8. Rapid and estrogen receptor beta mediated actions in the hippocampus mediate some functional effects of estrogen

    PubMed Central

    Walf, Alicia A.; Frye, Cheryl A.

    2008-01-01

    The steroid hormone, estradiol (E2), has numerous targets in the central nervous system, including the hippocampus, which plays a key role in cognition and affective behavior. This review focuses on our evidence from studies in rodents that E2 has diverse mechanisms in the hippocampus for its functional effects E2 has rapid, membrane-mediated effects in the hippocampus to enhance cognitive performance. Administration of E2 to the hippocampus of rats for 10 minutes following training enhances performance in a hippocampus-mediated task. Increased cell firing in the hippocampus occurs within this short time frame. Furthermore, administration of free E2 or an E2 conjugate, E2:bovine serum albumin (BSA), to the hippocampus produces similar performance-enhancing effects in this task, suggesting that E2 has membrane actions in the hippocampus for these effects. Further evidence that E2 has rapid, membrane-mediated effects is that co-administration of E2 and inhibitors of mitogen activated protein kinase (MAPK), rather than intracellular E2 receptors (ERs) or protein synthesis, attenuate the enhancing effects of E2 in this task. Despite these data that demonstrate E2 can have rapid and/or membrane-mediated effects in the hippocampus, there is clear evidence to suggest that intracellular ERs, particularly the β (rather than α) isoform of ERs, may be important targets for E2’s functional effects for hippocampal processes. Administration of ligands that are specific for ERβ, but not ERα, have enhancing effects on hippocampal processes similar to that of E2 (which has similar affinity for ERα and ERβ). These effects are attenuated when ERβ expression is knocked down in transgenic models or with central administration of antisense oligonucleotides. Thus, there may be a convergence of E2’s actions through rapid, membrane-mediated effects and intracellular ERs and in the hippocampus for these functional effects. PMID:18342348

  9. Neuronal loss and cytoskeletal disruption following intrahippocampal administration of the metabolic inhibitor malonate: lack of protection by MK-801.

    PubMed

    Pang, Z; Umberger, G H; Geddes, J W

    1996-02-01

    Impaired energy metabolism may contribute to the pathogenesis of late-onset neurodegenerative disorders such as Alzheimer's disease by increasing neuronal vulnerability to excitotoxic damage through the NMDA receptor. The effects of metabolic impairment on the striatum have been extensively examined, but relatively little is known regarding the vulnerability of the hippocampus. To examine the effect of metabolic impairment on the hippocampal formation, malonate (0.25-2.5 mumol), a reversible inhibitor of succinate dehydrogenase, was administered by stereotaxic injection into the hippocampus of male Sprague-Dawley rats. Neuronal loss was assessed by Nissl stain, and immunocytochemistry was used to examine cytoskeletal disruption. Malonate produced a dose-dependent lesion in which CA1 pyramidal neurons were most vulnerable, followed by CA3 and dentate gyrus. Cytoskeletal alterations included the loss of microtubule-associated protein 2 (MAP2) and dendritic MAP1B immunoreactivity, whereas axonal MAP1B and tau proteins were relatively spared. Spatially and temporally correlated with the loss of MAP2 was an increase in the immunoreactivity of calpain-cleaved spectrin. A similar pattern of neuronal damage and cytoskeletal disruption was produced by intrahippocampal injection of quinolinate (0.1 mumol), an NMDA agonist. Although these results are consistent with the hypothesis that metabolic impairment results in excitotoxic death, MK-801 (dizocilipine maleate), a noncompetitive NMDA receptor antagonist, did not attenuate the lesions produced by malonate but was effective against quinolinate. The results suggest that NMDA receptor activation is not required for malonate-induced damage in the hippocampal formation.

  10. Aging hippocampus and amygdala.

    PubMed

    Malykhin, Nikolai V; Bouchard, Thomas P; Camicioli, Richard; Coupland, Nicholas J

    2008-03-26

    Earlier studies suggest that the anterior hippocampus may show resilience to age-associated volume loss. This study compared high-resolution magnetic resonance images obtained from younger (n=28; age range: 22-50 years) and older (n=39; age range: 65-84 years) healthy right-handed individuals to determine whether age-related volume changes varied between the hippocampal head, body and tail. Volumetric reductions were progressively more severe from hippocampal head to tail. Amygdala volume differences were intermediate in size. Although limited by the cross-sectional design, these data suggest that hippocampal subregions show a gradient of volume reduction in healthy aging that contrasts with the preferential reduction of anterior hippocampal volumes in Alzheimer's and Parkinson's diseases.

  11. Nicotinic receptors, memory, and hippocampus.

    PubMed

    Kutlu, Munir Gunes; Gould, Thomas J

    2015-01-01

    Nicotinic acetylcholine receptors (nAChRs) modulate the neurobiological processes underlying hippocampal learning and memory. In addition, nicotine's ability to desensitize and upregulate certain nAChRs may alter hippocampus-dependent memory processes. Numerous studies have examined the effects of nicotine on hippocampus-dependent learning, as well as the roles of low- and high-affinity nAChRs in mediating nicotine's effects on hippocampus-dependent learning and memory. These studies suggested that while acute nicotine generally acts as a cognitive enhancer for hippocampus-dependent learning, withdrawal from chronic nicotine results in deficits in hippocampus-dependent memory. Furthermore, these studies demonstrated that low- and high-affinity nAChRs functionally differ in their involvement in nicotine's effects on hippocampus-dependent learning. In the present chapter, we reviewed studies using systemic or local injections of acute or chronic nicotine, nAChR subunit agonists or antagonists; genetically modified mice; and molecular biological techniques to characterize the effects of nicotine on hippocampus-dependent learning.

  12. Efficacy of polysaccharide from Alcaligenes xylosoxidans MSA3 administration as protection against γ-radiation in female rats

    PubMed Central

    Hassan, Amal I.; Ghoneim, Mona A. M.; Mahmoud, Manal G.; Asker, Mohsen M. S.; Mohamed, Saher S.

    2016-01-01

    Damage to normal tissues is a consequence of both therapeutic and accidental exposures to ionizing radiation. A water-soluble heteropolysaccharide called AXEPS, composed of glucose, galactose, rhamnose and glucouronic acid in a molar ratio of nearly 1.0:1.6:0.4:2.3, respectively, was isolated from culture medium of strain Alcaligenes xylosoxidans MSA3 by ethanol precipitation followed by freeze-drying. Chemical analysis, Fourier-transform infrared (FTIR) and chromatographic studies revealed that the molecular weight was 1.6 × 104 g mol−1. This study was designed to investigate the radioprotective and biological effects of AXEPS in alleviating the toxicity of ionizing radiation in female albino rats. A total of 32 female albino rats were divided into four groups. In the control group, rats were administered vehicle by tube for four weeks. The second group was administered AXEPS (100 mg/kg) orally by gavage for four weeks. Animals in the third group were exposed to whole-body γ-rays (5 Gy) and remained for 2 weeks without treatment. The fourth group received AXEPS (100 mg/kg) orally by gavage for two weeks before being exposed to whole-body γ-rays (5 Gy), then 24 h post γ-rays, they received AXEPS (100 mg/kg) in a treatment continuing till the end of the experiment (15 days after the whole–body γ-irradiation). Oral administration of AXEPS (100 mg/kg) significantly reversed the oxidative stress effects of radiation, as evidenced by the decrease in DNA damage in the bone marrow. Assessment of apoptosis and cell proliferation markers revealed that caspase-3 significantly increased in the irradiated group. Moreover, a significant decrease in the hematological constituents of peripheral blood, the chemotactic index and CD8+ T cells were observed in animals in the irradiation-only group, whereas an increase in the lymphocyte index was observed in animals in that group. In contrast, AXEPS treatment prevented these alterations. From our results, we conclude that

  13. Efficacy of polysaccharide from Alcaligenes xylosoxidans MSA3 administration as protection against γ-radiation in female rats.

    PubMed

    Hassan, Amal I; Ghoneim, Mona A M; Mahmoud, Manal G; Asker, Mohsen M S; Mohamed, Saher S

    2016-03-01

    Damage to normal tissues is a consequence of both therapeutic and accidental exposures to ionizing radiation. A water-soluble heteropolysaccharide called AXEPS, composed of glucose, galactose, rhamnose and glucouronic acid in a molar ratio of nearly 1.0:1.6:0.4:2.3, respectively, was isolated from culture medium of strain Alcaligenes xylosoxidans MSA3 by ethanol precipitation followed by freeze-drying. Chemical analysis, Fourier-transform infrared (FTIR) and chromatographic studies revealed that the molecular weight was 1.6 × 10(4) g mol(-1). This study was designed to investigate the radioprotective and biological effects of AXEPS in alleviating the toxicity of ionizing radiation in female albino rats. A total of 32 female albino rats were divided into four groups. In the control group, rats were administered vehicle by tube for four weeks. The second group was administered AXEPS (100 mg/kg) orally by gavage for four weeks. Animals in the third group were exposed to whole-body γ-rays (5 Gy) and remained for 2 weeks without treatment. The fourth group received AXEPS (100 mg/kg) orally by gavage for two weeks before being exposed to whole-body γ-rays (5 Gy), then 24 h post γ-rays, they received AXEPS (100 mg/kg) in a treatment continuing till the end of the experiment (15 days after the whole-body γ-irradiation). Oral administration of AXEPS (100 mg/kg) significantly reversed the oxidative stress effects of radiation, as evidenced by the decrease in DNA damage in the bone marrow. Assessment of apoptosis and cell proliferation markers revealed that caspase-3 significantly increased in the irradiated group. Moreover, a significant decrease in the hematological constituents of peripheral blood, the chemotactic index and CD8+ T cells were observed in animals in the irradiation-only group, whereas an increase in the lymphocyte index was observed in animals in that group. In contrast, AXEPS treatment prevented these alterations. From our results, we conclude that

  14. Vaccination with liposomal leishmanial antigens adjuvanted with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) confers long-term protection against visceral leishmaniasis through a human administrable route.

    PubMed

    Ravindran, Rajesh; Maji, Mithun; Ali, Nahid

    2012-01-01

    The development of a long-term protective subunit vaccine against visceral leishmaniasis depends on antigens and adjuvants that can induce an appropriate immune response. The immunization of leishmanial antigens alone shows limited efficacy in the absence of an appropriate adjuvant. Earlier we demonstrated sustained protection against Leishmania donovani with leishmanial antigens entrapped in cationic liposomes through an intraperitoneal route. However, this route is not applicable for human administration. Herein, we therefore evaluated the immune response and protection induced by liposomal soluble leishmanial antigen (SLA) formulated with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) through a subcutaneous route. Subcutaneous immunization of BALB/c mice with SLA entrapped in liposomes or with MPL-TDM elicited partial protection against experimental visceral leishmaniasis. In contrast, liposomal SLA adjuvanted with MPL-TDM induced significantly higher levels of protection in liver and spleen in BALB/c mice challenged 10 days post-vaccination. Protection conferred by this formulation was sustained up to 12 weeks of immunization, and infection was controlled for at least 4 months of the challenge, similar to liposomal SLA immunization administered intraperitoneally. An analysis of cellular immune responses of liposomal SLA + MPL-TDM immunized mice demonstrated the induction of IFN-γ and IgG2a antibody production not only 10 days or 12 weeks post-vaccination but also 4 months after the challenge infection and a down regulation of IL-4 production after infection. Moreover, long-term immunity elicited by this formulation was associated with IFN-γ production also by CD8⁺ T cells. Taken together, our results suggest that liposomal SLA + MPL-TDM represent a good vaccine formulation for the induction of durable protection against L. donovani through a human administrable route.

  15. Combined Administration of Levetiracetam and Valproic Acid Attenuates Age Related Hyperactivity of CA3 Place Cells, Reduces Place Field Area, and Increases Spatial Information Content in Aged Rat Hippocampus

    PubMed Central

    Robitsek, RJ; Ratner, MH; Stewart, TM; Eichenbaum, H; Farb, DH

    2015-01-01

    Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA. PMID:25941121

  16. Combined administration of levetiracetam and valproic acid attenuates age-related hyperactivity of CA3 place cells, reduces place field area, and increases spatial information content in aged rat hippocampus.

    PubMed

    Robitsek, Jonathan; Ratner, Marcia H; Stewart, Tara; Eichenbaum, Howard; Farb, David H

    2015-12-01

    Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of functional inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA.

  17. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors

    PubMed Central

    Kawahara, Tomohiro; Makizaki, Yutaka; Oikawa, Yosuke; Tanaka, Yoshiki; Maeda, Ayako; Shimakawa, Masaki; Komoto, Satoshi; Moriguchi, Kyoko; Ohno, Hiroshi; Taniguchi, Koki

    2017-01-01

    Human rotavirus (RV) infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1), which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in mice administered

  18. Brain-derived neurotrophic factor administration after traumatic brain injury in the rat does not protect against behavioral or histological deficits.

    PubMed

    Blaha, G R; Raghupathi, R; Saatman, K E; McIntosh, T K

    2000-01-01

    Brain-derived neurotrophic factor has been shown to be neuroprotective in models of excitotoxicity, axotomy and cerebral ischemia. The present study evaluated the therapeutic potential of brain-derived neurotrophic factor following traumatic brain injury in the rat. Male Sprague-Dawley rats (N=99) were anesthetized and subjected to lateral fluid percussion brain injury of moderate severity (2.4-2.8 atm) or sham injury. Four hours after injury, the animals were reanesthetized, an indwelling, intraparenchymal cannula was implanted, and infusion of brain-derived neurotrophic factor or phosphate-buffered saline vehicle was initiated from a mini-osmotic pump and continued for two weeks. In Study 1 (N=48), vehicle or 12 microg/day of brain-derived neurotrophic factor was infused into the dorsal hippocampus. In Study 2 (N=51), vehicle or brain-derived neurotrophic factor at a high (12 microg/day) or low dose (1.2 microg/day) was infused into the injured parietal cortex. All animals were evaluated for neurological motor function at two days, one week and two weeks post-injury. Cognitive function (learning and memory) was assessed at two weeks post-injury using a Morris Water Maze. At two weeks post-injury, neuronal loss in the hippocampal CA3 and dentate hilus and in the injured cortex was evaluated. In Study 2, neuronal loss was also quantified in the thalamic medial geniculate nucleus. All of the above outcome measures demonstrated significant deleterious effects of brain injury (P<0.05 compared to sham). However, post-traumatic brain-derived neurotrophic factor infusion did not significantly affect neuromotor function, learning, memory or neuronal loss in the hippocampus, cortex or thalamus when compared to vehicle infusion in brain-injured animals, regardless of the infusion site or infusion dose (P>0.05 for each). In contrast to previous studies of axotomy, ischemia and excitotoxicity, our data indicate that brain-derived neurotrophic factor is not protective against

  19. Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi

    PubMed Central

    Rocha, Joana N.; Cohen, Noah D.; Bordin, Angela I.; Brake, Courtney N.; Giguère, Steeve; Coleman, Michelle C.; Alaniz, Robert C.; Lawhon, Sara D.; Mwangi, Waithaka; Pillai, Suresh D.

    2016-01-01

    There is currently no licensed vaccine that protects foals against Rhodococcus equi–induced pneumonia. Oral administration of live, virulent R. equi to neonatal foals has been demonstrated to protect against subsequent intrabronchial challenge with virulent R. equi. Electron beam (eBeam)-inactivated R. equi are structurally intact and have been demonstrated to be immunogenic when administered orally to neonatal foals. Thus, we investigated whether eBeam inactivated R. equi could protect foals against developing pneumonia after experimental infection with live, virulent R. equi. Foals (n = 8) were vaccinated by gavaging with eBeam-inactivated R. equi at ages 2, 7, and 14 days, or gavaged with equal volume of saline solution (n = 4), and subsequently infected intrabronchially with live, virulent R. equi at age 21 days. The proportion of vaccinated foals that developed pneumonia following challenge was similar among the vaccinated (7/8; 88%) and unvaccinated foals (3/4; 75%). This vaccination regimen did not appear to be strongly immunogenic in foals. Alternative dosing regimens or routes of administration need further investigation and may prove to be immunogenic and protective. PMID:26828865

  20. Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi.

    PubMed

    Rocha, Joana N; Cohen, Noah D; Bordin, Angela I; Brake, Courtney N; Giguère, Steeve; Coleman, Michelle C; Alaniz, Robert C; Lawhon, Sara D; Mwangi, Waithaka; Pillai, Suresh D

    2016-01-01

    There is currently no licensed vaccine that protects foals against Rhodococcus equi-induced pneumonia. Oral administration of live, virulent R. equi to neonatal foals has been demonstrated to protect against subsequent intrabronchial challenge with virulent R. equi. Electron beam (eBeam)-inactivated R. equi are structurally intact and have been demonstrated to be immunogenic when administered orally to neonatal foals. Thus, we investigated whether eBeam inactivated R. equi could protect foals against developing pneumonia after experimental infection with live, virulent R. equi. Foals (n = 8) were vaccinated by gavaging with eBeam-inactivated R. equi at ages 2, 7, and 14 days, or gavaged with equal volume of saline solution (n = 4), and subsequently infected intrabronchially with live, virulent R. equi at age 21 days. The proportion of vaccinated foals that developed pneumonia following challenge was similar among the vaccinated (7/8; 88%) and unvaccinated foals (3/4; 75%). This vaccination regimen did not appear to be strongly immunogenic in foals. Alternative dosing regimens or routes of administration need further investigation and may prove to be immunogenic and protective.

  1. Diethanolamine alters neurogenesis and induces apoptosis in fetal mouse hippocampus

    PubMed Central

    Craciunescu, Corneliu N.; Wu, Renan; Zeisel, Steven H.

    2006-01-01

    Diethanolamine (DEA) is present in many consumer products such as shampoo. Dermal administration of DEA diminishes hepatic stores of the essential nutrient choline, and we previously reported that dietary choline deficiency during pregnancy reduces neurogenesis and increases apoptosis in the hippocampus of fetal rats and mice. Therefore, DEA could also alter brain development. Timed-pregnant C57BL/6 mice were dosed dermally from gestation day 7 through 17 with DEA at 0, 20, 80, 160, 320, and 640 mg/kg body/day. At doses of DEA > 80 mg/kg body/day, we observed decreased litter size. In fetuses (embryonic day 17) collected from dams treated dermally with 80 mg/kg body/day DEA, we observed decreased neural progenitor cell mitosis at the ventricular surface of the ventricular zone of the hippocampus [to 56±14% (SE) histone 3 (H3) phosphorylation as compared to controls; P < 0.01]. We also observed increased apoptosis in fetal hippocampus (to 170±10% of control measured using TUNEL and to 178±7% of control measured using activated caspase 3; P < 0.01). Thus, maternal exposure to DEA reduces the number of neural progenitor cells in hippocampus by two mechanisms, and this could permanently alter memory function in offspring of mothers exposed to this common ingredient of shampoos and soaps.—Craciunescu, C. N., Wu, R., Zeisel, S. H. Diethanolamine alters neurogenesis and induces apoptosis in fetal mouse hippocampus. PMID:16873886

  2. Protective effect of betulin on cognitive decline in streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Ma, Chunhua; Long, Hongyan

    2016-12-01

    Betulin is extracted from birch tree bark and exerts diverse pharmacological activities. The present study was designed to investigate the protective effect of betulin (BE) on cognitive decline in streptozotocin (STZ)-induced diabetic rats. The diabetic model was built by streptozotocin (STZ) (30mg/kg, ip). After 4 weeks, the diabetic rats were treated with vehicle or BE (20mg/kg, 40mg/kg) for 4 weeks. The oral glucose tolerance (OGTT) and serum insulin were detected. Three days later, Morris water maze (MWM) test was used to evaluate memory function. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in hippocampus were examined. Inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in serum and hippocampus were measured. The protein expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NF-κB pathways-related molecules in hippocampus were examined. As a results, BE could improve glucose intolerance and modify basal learning performance. Treatment with BE significantly restored SOD activity and decreased MDA content in hippocampus. BE also markedly reduced the contents of inflammatory cytokines in serum and hippocampus. Furthermore, administration of BE effectively upregulated the expressions of Nrf2, HO-1 and blocked the phosphorylations of IκB, NF-κB. In summary, BE might exhibit protective effect on cognitive decline in STZ-induced diabetic rats through HO-1/Nrf-2/NF-κB pathway.

  3. Acute but not chronic administration of pioglitazone promoted behavioral and neurochemical protective effects in the MPTP model of Parkinson's disease.

    PubMed

    Barbiero, Janaína K; Santiago, Ronise M; Lima, Marcelo M S; Ariza, Deborah; Morais, Lívia H; Andreatini, Roberto; Vital, Maria A B F

    2011-01-01

    The present study investigated the neurochemical, motor and cognitive effects of pioglitazone in a rat model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the first experiment, we administered MPTP, and 1h later administered a single oral dose of pioglitazone (5, 15 and 30 mg/kg). The following day, we performed the open-field test and neurochemical dose response curve. We demonstrated that 30 mg/kg of pioglitazone was capable of restoring striatal dopamine (DA) concentrations and motor behaviors. A second experiment was conducted to test the effects of two protocols (acute and chronic) of pioglitazone (30 mg/kg) administration in the open-field test, two-way active avoidance task and in the DA and metabolites levels. The acute protocol consisted of a single oral administration 1 h after MPTP, whereas the chronic protocol was performed with daily administrations starting 1 h after MPTP and ending 22 days after that. Results showed that neither protocol was able to reverse the cognitive impairment promoted by MPTP. We also demonstrated that acute treatment generated some level of neuroprotection, as confirmed by the absence of DA reduction in the group treated with pioglitazone in comparison to the sham group. By contrast, chronic treatment leaded to a reduction of striatal DA, close to MPTP administration alone. These findings suggest that acute administration of pioglitazone (30 mg/kg) was more efficient in generating beneficial effects on motor behaviors and in striatal DA levels. Nevertheless, we failed to demonstrate that pioglitazone administration improved performance on a dopamine-related cognitive task after MPTP.

  4. Intranasal Administration of an Inactivated Yersinia pestis Vaccine with Interleukin-12 Generates Protective Immunity against Pneumonic Plague ▿ #

    PubMed Central

    Kumar, Devender; Kirimanjeswara, Girish; Metzger, Dennis W.

    2011-01-01

    Inhalation of Yersinia pestis causes pneumonic plague, which rapidly progresses to death. A previously licensed killed whole-cell vaccine is presently unavailable due to its reactogenicity and inconclusive evidence of efficacy. The present study now shows that vaccination intranasally (i.n.) with inactivated Y. pestis CO92 (iYp) adjuvanted with interleukin-12 (IL-12) followed by an i.n. challenge with a lethal dose of Y. pestis CO92 prevented bacterial colonization and protected 100% of mice from pneumonic plague. Survival of the vaccinated mice correlated with levels of systemic and lung antibodies, reduced pulmonary pathology and proinflammatory cytokines, and the presence of lung lymphoid cell aggregates. Protection against pneumonic plague was partially dependent upon Fc receptors and could be transferred to naïve mice with immune mouse serum. On the other hand, protection was not dependent upon complement, and following vaccination, depletion of CD4 and/or CD8 T cells before challenge did not affect survival. In summary, the results demonstrate the safety, immunogenicity, and protective efficacy of i.n. administered iYp plus IL-12 in a mouse model of pneumonic plague. PMID:21880856

  5. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury

    SciTech Connect

    Rabbani, Zahid N.; Batinic-Haberle, Ines; Anscher, Mitchell S.; Huang Jie; Day, Brian J.; Alexander, Elaine; Dewhirst, Mark W.; Vujaskovic, Zeljko . E-mail: vujas@radonc.duke.edu

    2007-02-01

    Purpose: To determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin, AEOL 10150, with superoxide dismutase (SOD) mimetic properties, reduces the severity of radiation-induced injury to the lung from single-dose irradiation (RT) of 28 Gy. Methods and Materials: Rats were randomly divided into four different dose groups (0, 1, 10, and 30 mg/kg/day of AEOL 10150), receiving either short-term (1 week) or long-term (10 weeks) drug administration via osmotic pumps. Rats received single-dose irradiation (RT) of 28 Gy to the right hemithorax. Breathing rates, body weights, blood samples, histopathology, and immunohistochemistry were used to assess lung damage. Results: There was no significant difference in any of the study endpoints between the irradiated controls and the three groups receiving RT and short-term administration of AEOL 10150. For the long-term administration, functional determinants of lung damage 20 weeks postradiation were significantly worse for RT + phosphate-buffered saline (PBS) and RT + 1 mg/kg/day of AEOL 10150 as compared with the irradiated groups treated with higher doses of AEOL 10150 (10 or 30 mg/kg/day). Lung histology at 20 weeks revealed a significant decrease in structural damage and collagen deposition in rats receiving 10 or 30 mg/kg/day after radiation in comparison to the RT + PBS and 1 mg/kg/day groups. Immunohistochemistry demonstrated a significant reduction in macrophage accumulation, oxidative stress, and hypoxia in rats receiving AEOL 10150 (10 or 30 mg/kg/day) after lung irradiation compared with the RT + PBS and 1 mg/kg/day groups. Conclusions: The chronic administration of a novel catalytic antioxidant, AEOL 10150, demonstrates a significant protective effect from radiation-induced lung injury. AEOL 10150 has its primary impact on the cascade of events after irradiation, and adding the drug before irradiation and its short-term administration have no significant

  6. Administration of a probiotic associated with nasal vaccination with inactivated Lactococcus lactis-PppA induces effective protection against pneumoccocal infection in young mice.

    PubMed

    Vintiñi, E; Villena, J; Alvarez, S; Medina, M

    2010-03-01

    Streptococcus pneumoniae is a serious public health problem, especially in developing countries, where available vaccines are not part of the vaccination calendar. We evaluated different respiratory mucosa immunization protocols that included the nasal administration of Lactococcus lactis-pneumococcal protective protein A (PppA) live, inactivated, and in association with a probiotic (Lc) to young mice. The animals that received Lc by the oral and nasal route presented the highest levels of immunoglobulin (Ig)A and IgG anti-PppA antibodies in bronchoalveolar lavages (BAL) and IgG in serum, which no doubt contributed to the protection against infection. However, only the groups that received the live and inactivated vaccine associated with the oral administration of the probiotic were able to prevent lung colonization by S. pneumoniae serotypes 3 and 14 in a respiratory infection model. This would be related to a preferential stimulation of the T helper type 1 (Th1) cells at local and systemic levels and with a moderate Th2 and Th17 response, shown by the cytokine profile induced in BAL and by the results of the IgG1/IgG2a ratio at local and systemic levels. Nasal immunization with the inactivated recombinant strain associated with oral Lc administration was able to stimulate the specific cellular and humoral immune response and afford protection against the challenge with the two S. pneumoniae serotypes. The results obtained show the probiotic-inactivated vaccine association as a valuable alternative for application to human health, especially in at-risk populations, and are the first report of a safe and effective immunization strategy using an inactivated recombinant strain.

  7. Ginsenoside Rg1 prevents cognitive impairment and hippocampus senescence in a rat model of D-galactose-induced aging.

    PubMed

    Zhu, Jiahong; Mu, Xinyi; Zeng, Jin; Xu, Chunyan; Liu, Jun; Zhang, Mengsi; Li, Chengpeng; Chen, Jie; Li, Tinyu; Wang, Yaping

    2014-01-01

    Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose) induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d) for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally) or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally) for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the hippocampus.

  8. Ginsenoside Rg1 Prevents Cognitive Impairment and Hippocampus Senescence in a Rat Model of D-Galactose-Induced Aging

    PubMed Central

    Zeng, Jin; Xu, Chunyan; Liu, Jun; Zhang, Mengsi; Li, Chengpeng; Chen, Jie; Li, Tinyu; Wang, Yaping

    2014-01-01

    Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose) induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d) for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally) or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally) for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the hippocampus. PMID

  9. Systemic administration of the iron chelator deferiprone protects against light-induced photoreceptor degeneration in the mouse retina

    PubMed Central

    Song, Delu; Song, Ying; Hadziahmetovic, Majda; Zhong, Yong; Dunaief, Joshua L.

    2012-01-01

    Oxidative stress plays a key role in the light damage (LD) model of retinal degeneration as well as in age-related macular degeneration (AMD). Since iron can promote oxidative stress, the iron chelator Deferiprone (DFP) was tested for protection against light-induced retinal degeneration. To accomplish this, A/J mice were treated with or without DFP in drinking water, and then were placed in constant bright white fluorescent light (10,000 lux) for 20 hours. Retinas were evaluated at several time points after light exposure. Photoreceptor apoptosis was assessed using the TUNEL assay. Retinal degeneration was assessed by histology 10 days after exposure to damaging white light. Two genes upregulated by oxidative stress, heme oxygenase 1 (Hmox1) and ceruloplasmin (Cp), as well as complement component 3 (C3) were quantified by RT-qPCR. Cryosections were immunolabeled for oxidative stress marker (nitrotyrosine), a microglial marker (Iba1) as well as both heavy (H) and light (L) ferritin. Light exposure resulted in substantial photoreceptor-specific cell death. Dosing with DFP protected photoreceptors, decreasing the numbers of TUNEL-positive photoreceptors and increasing the number of surviving photoreceptors. The retinal mRNA levels of oxidative stress related genes and C3 were upregulated following light exposure and diminished by DFP treatment. Immunostaining for nitrotyrosine indicated that DFP reduced the nitrative stress caused by light exposure. Robust H/L-ferritin-containing microglial activation and migration to the outer retina occurred after light exposure and DFP treatment reduced microglial invasion. DFP is protective against light-induced retinal degeneration and has the potential to diminish oxidative stress in the retina. PMID:22579919

  10. Neural Representations of Location Outside the Hippocampus

    ERIC Educational Resources Information Center

    Knierim, James J.

    2006-01-01

    Place cells of the rat hippocampus are a dominant model system for understanding the role of the hippocampus in learning and memory at the level of single-unit and neural ensemble responses. A complete understanding of the information processing and computations performed by the hippocampus requires detailed knowledge about the properties of the…

  11. Co-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzi

    PubMed Central

    Sullivan, Nicole L.; Blazevic, Azra; Bruna-Romero, Oscar; Rodrigues, Mauricio M.; Hoft, Daniel F.

    2011-01-01

    Background Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. The goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone. Methodology We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-γ ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-γ, TNF-α, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-γ responses and survived a lethal challenge given within the first 3 months following immunization. The addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P<0.05). Improved protection correlated with significantly higher numbers of TS-specific IFN-γ producing total and CD8+ T cells detected>6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro re-stimulation. Conclusion Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi. PMID:21408124

  12. M30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration Induced by Corticosterone in the Hippocampus.

    PubMed

    Lam, Chun-Sing; Tipoe, George Lim; Wong, Johnny Kong-Ching; Youdim, Moussa B H; Fung, Man-Lung

    2016-01-01

    Monoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the turnover and homeostasis of monoamine neurotransmitters; yet, its pathophysiological role in monoamine deficiency, oxidative stress and neuroinflammation remains controversial. Protective effects of M30, a brain selective MAO inhibitor with iron-chelating antioxidant properties, have been shown in models of neurodegenerative diseases. This study aims to examine the neuroprotective mechanism of M30 against depressive-like behavior induced by corticosterone (CORT). Sprague-Dawley rats were given CORT subcutaneous injections with or without concomitant M30 administration for two weeks. CORT-treated rats exhibited depressive-like behavior with significant elevated levels of MAO activities, serotonin turnover, oxidative stress, neuroinflammation and apoptosis in the hippocampus with significant losses of synaptic proteins when compared to the control. The expression and activity of cytokine-responsive indoleamine 2,3-dioxygenase (IDO-1), a catabolic enzyme of serotonin and tryptophan, was significantly increased in the CORT-treated group with lowered levels of serotonin. Besides, CORT markedly reduced dendritic length and spine density. Remarkably, M30 administration neutralized the aberrant changes in the hippocampus and prevented the induction of depressive-like behavior induced by CORT. Our results suggest that M30 is neuroprotective against CORT-induced depression targeting elevated MAO activities that cause oxidative stress and neuroinflammation, resulting in IDO-1 activation, serotonin deficiency and neurodegeneration.

  13. M30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration Induced by Corticosterone in the Hippocampus

    PubMed Central

    Lam, Chun-Sing; Tipoe, George Lim; Wong, Johnny Kong-Ching; Youdim, Moussa B. H.; Fung, Man-Lung

    2016-01-01

    Monoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the turnover and homeostasis of monoamine neurotransmitters; yet, its pathophysiological role in monoamine deficiency, oxidative stress and neuroinflammation remains controversial. Protective effects of M30, a brain selective MAO inhibitor with iron-chelating antioxidant properties, have been shown in models of neurodegenerative diseases. This study aims to examine the neuroprotective mechanism of M30 against depressive-like behavior induced by corticosterone (CORT). Sprague-Dawley rats were given CORT subcutaneous injections with or without concomitant M30 administration for two weeks. CORT-treated rats exhibited depressive-like behavior with significant elevated levels of MAO activities, serotonin turnover, oxidative stress, neuroinflammation and apoptosis in the hippocampus with significant losses of synaptic proteins when compared to the control. The expression and activity of cytokine-responsive indoleamine 2,3-dioxygenase (IDO-1), a catabolic enzyme of serotonin and tryptophan, was significantly increased in the CORT-treated group with lowered levels of serotonin. Besides, CORT markedly reduced dendritic length and spine density. Remarkably, M30 administration neutralized the aberrant changes in the hippocampus and prevented the induction of depressive-like behavior induced by CORT. Our results suggest that M30 is neuroprotective against CORT-induced depression targeting elevated MAO activities that cause oxidative stress and neuroinflammation, resulting in IDO-1 activation, serotonin deficiency and neurodegeneration. PMID:27870896

  14. Protection of the maternal and fetal thyroid from radioactive contamination by the administration of stable iodide during pregnancy. An experimental evaluation in chimpanzees.

    PubMed

    Noteboom, J L; Hummel, W A; Broerse, J J; de Vijlder, J J; Vulsma, T; Jansen, J T; van Bekkum, D W

    1997-06-01

    The safety and efficacy of the administration of stable iodide to protect the fetal thyroid from exposure to radioactive iodide were investigated in chimpanzees in weeks 19 to 21 of pregnancy. The mean 24-h uptake of iodide in the fetal thyroid, determined with 123I-, was 1.8%. Administration of stable potassium iodide (KI), 0.65, 1.95 or 6.5 mg per kg body weight, 1 h before tracer injection reduced the fetal uptake satisfactorily. Only the higher doses were effective after 20 h. Excess iodide may impair a child's thyroid status. However, adverse effects were not found during the 11 days the animals ingested these doses. Tracer concentrations in the amniotic fluid were 30- to 130-fold lower than in the urine. The dose to the fetus from radioactivity in the maternal bladder was estimated by computer simulation. The potential increment of the risk from this dose during the ingestion of stable iodide is smaller than the reduction of risk achieved by inhibiting the uptake of radioactive iodide by the fetal thyroid. The conclusion of the experiments is that stable iodide can be used safely and effectively to protect the fetal thyroid against contamination with radioactive iodine.

  15. The bumps on the hippocampus

    NASA Astrophysics Data System (ADS)

    Gao, Yi; Ver Hoef, Lawrence

    2016-03-01

    The hippocampus has been the focus of more imaging research than any other subcortical structure in the human brain. However a feature that has been almost universally overlooked are the bumpy ridges on the inferior aspect of the hippocampus, which we refer to as hippocampal dentation. These bumps arise from folds in the CA1 layer of Ammon's horn. Similar to the folding of the cerebral cortex, hippocampal dentation allows for greater surface area in a confined space. However, while quantitative studies of radiologic brain images have been advancing for decades, examining numerous approaches to hippocampal segmentation and morphology analysis, virtually all published 3D renderings of the hippocampus show the under surface to be quite smooth or mildly irregular; we have rarely seen the characteristic bumpy structure in the reconstructed 3D scene, one exception being the 9.4T postmortem study. This is presumably due to the fact that, based on our experience with high resolution images, there is a dramatic degree of variability in hippocampal dentation between individuals from very smooth to highly dentated. An apparent question is, does this indicate that this specific morphological signature can only be captured using expensive ultra-high field techniques? Or, is such information buried in the data we commonly acquire, awaiting a computation technique that can extract and render it clearly? In this study, we propose a super-resolution technique that captures the fine scale morphometric features of the hippocampus based on common T1-weighted 3T MR images.

  16. Protective Effects of Co-Administration of Gallic Acid and Cyclosporine on Rat Myocardial Morphology Against Ischemia/Reperfusion

    PubMed Central

    Dianat, Mahin; Sadeghi, Najmeh; Badavi, Mohammad; Panahi, Marziyeh; Taheri Moghadam, Mahin

    2014-01-01

    Background: Irreversible myocardial ischemic injury begins 20 minutes after the onset of coronary occlusion. Then the infarcted cells show signs of necrosis and death. Objectives: This study investigated the effects of co-administration of Gallic acid (antioxidant) with cyclosporine (mitochondrial permeability transition pore [mPTP] inhibitor) on myocardial morphology of rats during ischemia and reperfusion. Materials and Methods: Fifty-four male Wistar rats (250-300 g), were randomly divided into 9 groups: sham, control (Ca received saline, 1 mL/kg, Cb: perfused with cyclosporine CsA 0.2 µM), 3 groups pretreated with Gallic acid in saline (G1a:7.5, G2a:15, and G3a: 30 mg/kg/day, and gavage daily for 10 days, n = 6), and the other three groups were pretreated with Gallic acid then perfused using CsA, (G1b:7.5, G2b:15, and G3b: 30 mg/kg/day) at the first 13 minutes of reperfusion period. After 10 days pretreatment, the rat hearts were isolated and transferred to Langendorff apparatus and exposed to 30 minutes ischemia following 60 minutes reperfusion. Afterward, the hearts were preserved in 10% formalin for histological studies at the end of the experiment. Finally, hematoxylin and eosin and Masson’s trichrome staining techniques were used for evaluating the changes in myocardial architecture, degradation of myofibers, and collagen integrity. The differences were analyzed using Pearson test. Results: Cell degenerative changes, pyknotic nuclei, contraction bands, edema, and loosening of collagen in between muscle fibers were observed during ischemia-reperfusion. Myocardial architecture and cellular morphology were recovered in co-administration groups, especially in (Gallic acid 15 mg/kg + CsA, P < 0.001). Conclusions: The results suggest the important role of the antioxidant system potentiation in the prevention of myocardial damage. PMID:25625048

  17. Acute Coronary Syndromes, Gastrointestinal Protection, and Recommendations Regarding Concomitant Administration of Proton-Pump Inhibitors (Omeprazol/Esomeprazole) and Clopidogrel.

    PubMed

    Lozano, Iñigo; Sanchez-Insa, Esther; de Leiras, Sergio Rodríguez; Carrillo, Pilar; Ruiz-Quevedo, Valeriano; Pinar, Eduardo; Gopar-Gopar, Silvia; Bayon, Jeremías; Mañas, Pilar; Lasa, Garikoitz; CruzGonzalez, Ignacio; Hernandez, Felipe; Fernandez-Portales, Javier; Fernandez-Fernandez, Javier; Pérez-Serradilla, Ana; de la Torre Hernandez, José M; Gomez-Jaume, Alfredo

    2016-02-01

    The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. The purpose is to know the gastroprotective approach in patients with acute coronary syndrome (ACS) and the level of follow-up of the alert. In 17 hospitals with catheterization laboratory in Spain, 1 per region, we studied 25 consecutive patients per hospital whose diagnosis of discharge since October 1, 2013, had been any type of ACS. We analyzed their baseline clinical profile, the gatroprotective agents at admission and discharge and the antiplatelet therapy at discharge. The number of patients included was 425: age 67.2 ± 12.5 years, women 29.8%, diabetes 36.5%. The patients presented unstable angina in 21.6%, non-ST-elevation myocardial infarction in 35.3% and ST-elevation myocardial infarction in 43.1%. Conservative approach was chosen in 17.9%, bare-metal stents 32.2%, ≥ 1 drug-eluting stent 48.5%, and surgery 1.4%. Aspirin was indicated in 1.9%, aspirin + clopidogrel 73.6%, aspirin + prasugrel 17.6%, and aspririn + ticagrelor 6.8%. Gastroprotective agents were present in 40.2% patients at admission and this percentage increased to 93.7% at discharge. Of the 313 (73.6%) on clopidogrel in 96 (30.6%) was combined with omeprazole and 3 (0.95%) with esomeprazole, whereas the most commonly used was pantoprazole with 190 patients (44.7%). In conclusion, almost the totality of the patients with an ACS receive gastroprotective agents at the moment of discharge, most of them with proton-pump inhibitors. In one every 3 cases of the patients who are on clopidogrel, the recommendation of the Food and Drug Administration and the European Medicines Agency is not followed.

  18. Methamphetamine transiently increases the blood-brain barrier permeability in the hippocampus: role of tight junction proteins and matrix metalloproteinase-9.

    PubMed

    Martins, Tânia; Baptista, Sofia; Gonçalves, Joana; Leal, Ermelindo; Milhazes, Nuno; Borges, Fernanda; Ribeiro, Carlos F; Quintela, Oscar; Lendoiro, Elena; López-Rivadulla, Manuel; Ambrósio, António F; Silva, Ana P

    2011-09-09

    Methamphetamine (METH) is a powerful stimulant drug of abuse that has steadily gained popularity worldwide. It is known that METH is highly neurotoxic and causes irreversible damage of brain cells leading to neurological and psychiatric abnormalities. Recent studies suggested that METH-induced neurotoxicity might also result from its ability to compromise blood-brain barrier (BBB) function. Due to the crucial role of BBB in the maintenance of brain homeostasis and protection against toxic molecules and pathogenic organisms, its dysfunction could have severe consequences. In this study, we investigated the effect of an acute high dose of METH (30mg/kg) on BBB permeability after different time points and in different brain regions. For that, young adult mice were sacrificed 1h, 24h or 72h post-METH administration. METH increased BBB permeability, but this effect was detected only at 24h after administration, being therefore a transitory effect. Interestingly, we also found that the hippocampus was the most susceptible brain region to METH, comparing to frontal cortex and striatum. Moreover, in an attempt to identify the key players in METH-induced BBB dysfunction we further investigated potential alterations in tight junction (TJ) proteins and matrix metalloproteinase-9 (MMP-9). METH was able to decrease the protein levels of zonula occludens (ZO)-1, claudin-5 and occludin in the hippocampus 24h post-injection, and increased the activity and immunoreactivity of MMP-9. The pre-treatment with BB-94 (30mg/kg), a matrix metalloproteinase inhibitor, prevented the METH-induced increase in MMP-9 immunoreactivity in the hippocampus. Overall, the present data demonstrate that METH transiently increases the BBB permeability in the hippocampus, which can be explained by alterations on TJ proteins and MMP-9.

  19. In ovo administration of CpG oligodeoxynucleotides and the recombinant microneme protein MIC2 protects against Eimeria infections.

    PubMed

    Dalloul, Rami A; Lillehoj, Hyun S; Klinman, Dennis M; Ding, Xicheng; Min, Wongi; Heckert, Robert A; Lillehoj, Erik P

    2005-05-02

    We have previously demonstrated that short oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) exert a positive effect on weight loss and oocyst shedding associated with Eimeria infection when injected in vivo. The present work investigated the effects of in ovo vaccination with CpG ODNs and an Eimeria recombinant microneme protein (MIC2), alone or in combination, on susceptibility to coccidiosis. In ovo injection of CpG ODNs alone enhanced resistance to experimental Eimeria acervulina infection as best exemplified by reduced oocyst shedding. Two CpG ODNs reduced the oocyst load, but did not affect weight gain. When co-administered with the recombinant microneme protein, both ODNs reduced oocyst shedding; however, only ODN D19 plus MIC2 consistently improved weight gain. Vaccinating with ODN 2006 or MIC2 protein curtailed oocyst shedding but did not enhance weight gain in Eimeria tenella-infected birds. Co-administration of CpG ODN and MIC2 did not have an additive effect in reducing the oocyst output; however, it resulted in the highest and lowest Ab response before and after Eimeria tenella infection, respectively. Collectively, CpG ODNs administered in ovo demonstrated immunoenhancing and adjuvant effects following Eimeria infections.

  20. [Protective effect of oral administration of several traditional Kampo-medicines on lethal Candida infection in immunosuppressed mice].

    PubMed

    Abe, S; Ishibashi, H; Tansho, S; Hanazawa, R; Komatsu, Y; Yamaguchi, H

    2000-01-01

    The protective effects of a "hozai" type of Kampo medicine, Juzen-taiho-to (Shi-quan-da-bu-tang, TJ-48), Hochu-ekki-to (Bu-zhong-yi-qi-tang, TJ-41) or Ninjin-yoei-to (Ren-shen-yang-rong-tang, TJ-108) on experimental candidiasis in immunosuppressed mice were investigated. ICR mice, which were immunosuppressed by injection of cyclophosphamide or prednisolone, were given these medicines orally andchallenged intravenously with Candida albicans (day 0). Treatments with a daily dose of 1 g/kg/day of TJ-48 or that of 1 or 2 g/kg/day of TJ-108 for 4 consecutive days from day-4 significantly prolonged the survival time of the Candida-infected mice pretreated with cyclophosphamide. Treatments with a daily dose of 1 g/kg/day of TJ-48 for 4 consecutive days from day 0, but not from day -4, significantly prolonged the life span of the Candida-infected mice pretreated with prednisolone. On the basis of these results and previous findings, characteristics of these kampo medicines as therapeutic agents against candidiasis in immunosuppressed hosts were discussed.

  1. Protection of Penaeus monodon against white spot syndrome by continuous oral administration of a low concentration of Bacillus subtilis spores expressing the VP28 antigen.

    PubMed

    Pham, K-C; Tran, H T T; Van Doan, C; Le, P H; Van Nguyen, A T; Nguyen, H A; Hong, H A; Cutting, S M; Phan, T-N

    2017-03-01

    In this study, Bacillus subtilis spores expressing a chimeric protein, CotB-VP28, were used as a probiotic vaccine to protect black tiger shrimps (Penaeus monodon) against white spot syndrome virus (WSSV) infection. Oral administration of pellets coated with CotB-VP28 spores (at ≥1 × 10(9 ) CFU per g pellet) to shrimps induced immune-relating phenoloxydase activity (PO) in shrimps after 14 days of feeding (prior challenge) and at day 3 post challenge (1·26 and 1·70 fold increase respectively). A 75% protection rate was obtained by continuous feeding of the spore-coated pellets at ≥1 × 10(9 ) CFU per g for 14 days prior to WSSV challenge and during all the postchallenge period. Even when the amount of CotB-VP28 spores in feed pellets was reduced down to ≥5 × 10(7)  CFU per g and ≥1 × 10(6)  CFU per g, relatively high protection rates of 70 and 67·5%, respectively, were still obtained. By contrast, feeding pellets without spores (untreated group) and with naked spores (PY79 group) at ≥1 × 10(9)  CFU per g could not protect shrimps against WSSV. These data suggest that supplementation of CotB-VP28 spores at low dose of ≥1 × 10(6)  CFU per g could be effective as a prophylactic treatment of WSS for black tiger shrimps.

  2. Hibiscus sabdariffa ethanolic extract protects against dyslipidemia and oxidative stress induced by chronic cholesterol administration in rabbits.

    PubMed

    Ekor, M; Adesanoye, O A; Udo, I E; Adegoke, O A; Raji, J; Farombi, E O

    2010-12-01

    Excessive intake of cholesterol (CHOL) and induction of free radical production play a critical role in the pathophysiology of several human diseases. Dietary therapy with plant products rich in flavonoids has been shown to provide benefits without the adverse effects of agents used in clinical practice. Hibiscus sabdariffa (HS) has been used for various purposes due to myriads of flavonoids present in it. In this study, the chemopreventive property of HS ethanolic extract (HSE) was investigated in dyslipidemia and oxidant stress associated with prolonged CHOL administration in rabbits. Twenty-five (25) adult male rabbits weighing between 1.5 and 1.7 kg were used and randomly divided into five groups of five rabbits per group. The CHOL-fed rabbits received 1 g/kg/day of CHOL suspended in 1 ml of corn oil for 8 weeks. Group 1 received 1 ml of corn oil and served as control. Group 2 was fed with CHOL only while groups 3, 4 and 5 received daily doses ofcholestyramine (questran, 260 mg/kg), HSE 200 mg/kg and HSE 300 mg/kg respectively along with CHOL. Animals were sacrificed by cervical dislocation 24-hours after last dose. Enzymic and non-enzymic markers of oxidative stress and lipid profile were analysed in serum, liver, kidney and heart of rabbits. HSE significantly attenuated the alteration in lipid levels and antioxidant status induced by high CHOL intake in rabbits in this study. Both serum and tissue levels of low density lipoprotein-CHOL, triglycerides, phospholipids, and total CHOL decreased with increase in high density lipoprotein-CHOL except in the heart, following treatment with HSE in CHOL-fed rabbits when compared with the untreated group (p<0.05). Similarly, HSE prevented CHOL-induced depletion of enzymic (superoxide dismutase, catalase) and non-enzymic (reduced glutathione, vitamin C) antioxidants with the attendant increases in lipid peroxidation and xanthine oxidase activity in these animals. The effectiveness of HSE in this condition was comparable

  3. Postchallenge Administration of Brincidofovir Protects Healthy and Immune-Deficient Mice Reconstituted with Limited Numbers of T Cells from Lethal Challenge with IHD-J-Luc Vaccinia Virus

    PubMed Central

    McCullough, Kevin Tyler; Cruz, Stephanie; Thomas, Antonia; Diaz, Claudia G.; Keilholz, Laurie; Grossi, Irma M.; Trost, Lawrence C.; Golding, Hana

    2015-01-01

    ABSTRACT Protection from lethality by postchallenge administration of brincidofovir (BCV, CMX001) was studied in normal and immune-deficient (nude, nu/nu) BALB/c mice infected with vaccinia virus (VACV). Whole-body bioluminescence imaging was used to record total fluxes in the nasal cavity, lungs, spleen, and liver and to enumerate pox lesions on tails of mice infected via the intranasal route with 105 PFU of recombinant IHD-J-Luc VACV expressing luciferase. Areas under the flux curve (AUCs) were calculated for individual mice to assess viral loads. A three-dose regimen of 20 mg/kg BCV administered every 48 h starting either on day 1 or day 2 postchallenge protected 100% of mice. Initiating BCV treatment earlier was more efficient in reducing viral loads and in providing protection from pox lesion development. All BCV-treated mice that survived challenge were also protected from rechallenge with IHD-J-Luc or WRvFire VACV without additional treatment. In immune-deficient mice, BCV protected animals from lethality and reduced viral loads while animals were on the drug. Viral recrudescence occurred within 4 to 9 days, and mice succumbed ∼10 to 20 days after treatment termination. Nude mice reconstituted with 105 T cells prior to challenge with 104 PFU of IHD-J-Luc and treated with BCV postchallenge survived the infection, cleared the virus from all organs, and survived rechallenge with 105 PFU of IHD-J-Luc VACV without additional BCV treatment. Together, these data suggest that BCV protects immunocompetent and partially T cell-reconstituted immune-deficient mice from lethality, reduces viral dissemination in organs, prevents pox lesion development, and permits generation of VACV-specific memory. IMPORTANCE Mass vaccination is the primary element of the public health response to a smallpox outbreak. In addition to vaccination, however, antiviral drugs are required for individuals with uncertain exposure status to smallpox or for whom vaccination is contraindicated

  4. The hippocampus in neurodegenerative disease.

    PubMed

    Moodley, K K; Chan, D

    2014-01-01

    AD is the commonest neurodegenerative disorder resulting ultimately in dementia, a stage during which there is a loss of previously acquired intellectual skill and independent occupational and social function. Neurodegenerative changes within the hippocampus and an extended neuronal network involving the medial temporal and medial parietal lobe result in the archetypal memory impairment seen in Alzheimer's disease (AD). As attention focuses increasingly on early diagnosis and treatment of dementia, this understanding of the hippocampal involvement in AD has helped to develop diagnostic tools for use in early disease. However, hippocampal damage is also a common feature among non-AD neurodegenerative dementias. Neuroimaging techniques, in conjunction with behavioral and pathological techniques, can be used to determine the involvement of the hippocampus in AD and other neurodegenerative diseases.

  5. Stress and the Developing Hippocampus

    PubMed Central

    Brunson, Kristen L.; Chen, Yuncai; Avishai-Eliner, Sarit; Baram, Tallie Z.

    2011-01-01

    The mechanisms that regulate neuronal function are a sum of genetically determined programs and experience. The effect of experience on neuronal function is particularly important during development, because early-life positive and adverse experience (stress) may influence the still “plastic” nervous system long-term. Specifically, for hippocampal-mediated learning and memory processes, acute stress may enhance synaptic efficacy and overall learning ability, and conversely, chronic or severe stress has been shown to be detrimental. The mechanisms that enable stress to act as this “double-edged sword” are unclear. Here, we discuss the molecular mediators of the stress response in the hippocampus with an emphasis on novel findings regarding the role of the neuropeptide known as corticotropin-releasing hormone (CRH). We highlight the physiological and pathological roles of this peptide in the developing hippocampus, and their relevance to the long-term effects of early-life experience on cognitive function during adulthood. PMID:12777683

  6. Long-term statin administration to dams on high-fat diet protects not only them but also their offspring from cardiovascular risk.

    PubMed

    Elahi, M M; Cagampang, F R; Ohri, S K; Hanson, M A

    2013-01-01

    We aimed to study the effects of long-term statin administration to high fat (HF)-fed female mice from the time they were weaned through to pregnancy and lactation on cardiovascular and metabolic risk factors in their HF-fed offspring. Female C57 mice on HF (45% kcal fat) were given pravastatin in their drinking water from the time they were weaned, during pregnancy and lactation. Weaned offspring were then fed an HF diet until adulthood generating the dam/offspring dietary groups HF/HF and HF plus pravastatin from the time dams were weaned, during pregnancy and lactation/HF (HF+S/HF). These groups were compared with offspring from mothers fed standard chow (control) which were then fed a control diet up to adulthood (control/control; C/C). HF+S dams showed significantly reduced total cholesterol concentrations and systolic blood pressure (SBP) versus HF dams. The reduction in total cholesterol and SBP in the HF+S dams did not restore values to those observed in the C group. Both male and female HF+S/HF offspring were significantly lighter in weight, and had lower SBP and serum cholesterol concentrations versus HF/HF. HF/HF offspring had elevated C-reactive protein levels but HF+S/HF animals of both sexes had reduced levels similar to those found in the C/C group. Long-term pravastatin administration to dams not only protects them from the deleterious effects of an HF diet, but this long-term maternal statin protection also has an equal and permanent effect in both male and female offspring up to their adult life, which is a novel finding.

  7. Role of amphotericin B upon enhancement of protective immunity elicited by oral administration with liposome-encapsulated-Japanese encephalitis virus nonstructural protein 1 (NS1) in mice.

    PubMed

    Lin, Tsung-Shun; Chuang, Chuan-Chang; Hsu, Hui-Ling; Liu, Yu-Tien; Lin, Wen-Po; Liang, Chung-Chih; Liu, Wen-Tssann

    2010-09-01

    Amphotericin B (AmB) is an antifungal antibiotic the activity of which has been associated with modulation of pro-inflammatory cytokines expression in cultured cells. Herein we reveal that co-administration with AmB enhances the immunogenicity of oral Lip-JENS1 vaccine which derived from liposomes functionalized with DSPC (distearoylphosphatidylcholine) and cholesterol (2:1, molar ratio)-bearing JE virus NS1 protein (600 microg ml(-1)). Oral single dose of Lip-JENS1 elicited a detectable serum NS1-specific IgG antibody response from a mouse model. Remarkably, the addition of AmB (125 microg per mouse), particularly, 2 h prior to, but not simultaneously with, the administration of Lip-JENS1 significantly enhanced the systemic antigen-specific antibody response, providing superior protection against lethal JEV challenges. Further, we observed AmB-induced the transcription of cytokine expression and translocation of transcriptional factor NF-kappaB from the cytoplasm to the nucleus for the murine macrophage J774A.1. Moreover, Peyer's-patch lymphocytes (PPL) from AmB-treated mice produced high levels of IL-1beta, IL-6 and TNF-alpha expression compared to the corresponding control of cells from non-treated mice. Taken together, the results suggest that AmB exerts a profound influence upon mucosal vaccination with Lip-JENS1, possibly playing an adjuvant-augmented role to "fine-tune" humoral as well as cellular immune response, thus conferring enhanced protective immunity for immunising individuals against JE infection.

  8. Eszopiclone and fluoxetine enhance the survival of newborn neurons in the adult rat hippocampus.

    PubMed

    Su, Xiaowei W; Li, Xiao-Yuan; Banasr, Mounira; Duman, Ronald S

    2009-11-01

    Clinical research has shown that co-administration of eszopiclone, a sedative-hypnotic sleeping agent, and fluoxetine, a serotonin uptake inhibitor, exerts an additive antidepressant action in treating patients with both depression and insomnia. Preclinical studies demonstrate that the behavioural actions of antidepressants are linked to neurogenesis in the adult hippocampus. To test the hypothesis that the additive effects of eszopiclone and fluoxetine could act via such a mechanism, the influence of combined administration of these agents on the proliferation and survival of bromodeoxyuridine (BrdU)-labelled newborn cells in the hippocampus of adult rats was determined. Chronic eszopiclone+fluoxetine co-administration significantly increased the survival, but not proliferation, of newborn neurons in dorsal hippocampus by approximately 50%, an effect greater than either drug alone. These findings are consistent with the hypothesis that eszopiclone enhances the antidepressant action of fluoxetine, in part via a novel mechanism that increases the survival of newborn neurons.

  9. Oral administration of the immunomodulator JBT-3002 induces endogenous interleukin 15 in intestinal macrophages for protection against irinotecan-mediated destruction of intestinal epithelium.

    PubMed

    Shinohara, H; Killion, J J; Bucana, C D; Yano, S; Fidler, I J

    1999-08-01

    We recently reported that p.o. administration of the new synthetic bacterial lipopeptide JBT-3002 can protect mice from irinotecan (CPT-11)-induced intestinal injury, but the mechanism was not known. Because interleukin-15 (IL-15) is associated with maintenance of intestinal epithelial cell integrity, we examined whether p.o. administration of JBT-3002 elevates expression of this monocyte-derived cytokine. Four daily i.p. injections of 100 mg/kg CPT-11 were effective against liver metastases produced by CT-26 murine colon cancer cells, but severe damage to the intestinal epithelium and early death of the mice also resulted. Three consecutive daily p.o. doses of JBT-3002 prior to i.p. injection of irinotecan prevented the undesirable side effects of irinotecan without reducing its ability to eradicate liver metastases. Immunohistochemical analyses of the intestines of mice treated with JBT-3002 and CPT-11 demonstrated an increase in the number of dividing cells in the crypts and enhanced expression of IL-15 in lamina propria cells; the increase correlated with increased expression of the IL-15 gene as determined by semiquantitative reverse transcriptase-PCR. In vitro studies demonstrated that JBT-3002 induced expression of IL-15 in peritoneal macrophages but not in normal intestinal epithelial cells (IEC-6). Moreover, the presence of IL-15 decreased irinotecan-mediated cytotoxicity of IEC-6 epithelial cells. These data show that the p.o. administration of JBT-3002 induces expression of IL-15 by macrophages in the lamina propria, which can prevent irinotecan-induced injury to the intestinal mucosa.

  10. Oral Administration of Lactobacillus plantarum Strain AYA Enhances IgA Secretion and Provides Survival Protection against Influenza Virus Infection in Mice

    PubMed Central

    Kikuchi, Yosuke; Kunitoh-Asari, Ayami; Hayakawa, Katsuyuki; Imai, Shinjiro; Kasuya, Kenji; Abe, Kimio; Adachi, Yu; Fukudome, Shin-ichi; Takahashi, Yoshimasa; Hachimura, Satoshi

    2014-01-01

    The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer’s patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer’s patch dendritic cells, with this production promoting IgA+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection. PMID:24466081

  11. Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

    PubMed

    Kikuchi, Yosuke; Kunitoh-Asari, Ayami; Hayakawa, Katsuyuki; Imai, Shinjiro; Kasuya, Kenji; Abe, Kimio; Adachi, Yu; Fukudome, Shin-Ichi; Takahashi, Yoshimasa; Hachimura, Satoshi

    2014-01-01

    The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+) B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.

  12. The protective effect of L-carnitine against hippocampal damage due to experimental formaldehyde intoxication in rats.

    PubMed

    Ozmen, E; Ozsoy, S Y; Donmez, N; Ozsoy, B; Yumuşak, N

    2014-07-01

    We investigated the protective effects of L-carnitine on hippocampus tissue damage in rats during experimental formaldehyde (FA) intoxication. Male Wistar albino rats were assigned into four groups: (1) control (C), (2) formaldehyde (FA), (3) formaldehyde + 0.5 g/kg of L-carnitine (FA + 0.5 LC) (4) formaldehyde + 1 g/kg L-carnitine (FA + 1 LC). At the end of the 14 day trial period, animals were sacrificed by decapitation under anesthesia. The hippocampus tissue samples were extracted to measure MDA, GSH and SOD activity. Neuronal degeneration was assessed based on histopathological (hematoxylin and eosin) and immunohistochemical (anti-ubiquitin) examination. To detect oxidative stress, specimens were reacted with anti-Cu/Zn-SOD antibody. After administering L-carnitine with FA to the animals, the activities of SOD and GSH increased, but the levels of MDA decreased in hippocampus tissue. Neuronal degeneration was observed in the FA group. L-carnitine administration reduced neuronal degeneration and histological structure was similar to controls. After FA application, degenerated hippocampus neurons were stained with anti-ubiquitin and Cu/Zn-SOD antibodies; weakly positive staining was observed in L- carnitine-treated groups. L-carnitine may be useful for preventing oxidative damage in the hippocampus tissue due to formaldehyde intoxication.

  13. Exercise protects against methamphetamine-induced aberrant neurogenesis.

    PubMed

    Park, Minseon; Levine, Harry; Toborek, Michal

    2016-09-28

    While no effective therapy is available for the treatment of methamphetamine (METH)-induced neurotoxicity, aerobic exercise is being proposed to improve depressive symptoms and substance abuse outcomes. The present study focuses on the effect of exercise on METH-induced aberrant neurogenesis in the hippocampal dentate gyrus in the context of the blood-brain barrier (BBB) pathology. Mice were administered with METH or saline by i.p. injections for 5 days with an escalating dose regimen. One set of mice was sacrificed 24 h post last injection of METH, and the remaining animals were either subjected to voluntary wheel running (exercised mice) or remained in sedentary housing (sedentary mice). METH administration decreased expression of tight junction (TJ) proteins and increased BBB permeability in the hippocampus. These changes were preserved post METH administration in sedentary mice and were associated with the development of significant aberrations of neural differentiation. Exercise protected against these effects by enhancing the protein expression of TJ proteins, stabilizing the BBB integrity, and enhancing the neural differentiation. In addition, exercise protected against METH-induced systemic increase in inflammatory cytokine levels. These results suggest that exercise can attenuate METH-induced neurotoxicity by protecting against the BBB disruption and related microenvironmental changes in the hippocampus.

  14. Exercise protects against methamphetamine-induced aberrant neurogenesis

    PubMed Central

    Park, Minseon; Levine, Harry; Toborek, Michal

    2016-01-01

    While no effective therapy is available for the treatment of methamphetamine (METH)-induced neurotoxicity, aerobic exercise is being proposed to improve depressive symptoms and substance abuse outcomes. The present study focuses on the effect of exercise on METH-induced aberrant neurogenesis in the hippocampal dentate gyrus in the context of the blood-brain barrier (BBB) pathology. Mice were administered with METH or saline by i.p. injections for 5 days with an escalating dose regimen. One set of mice was sacrificed 24 h post last injection of METH, and the remaining animals were either subjected to voluntary wheel running (exercised mice) or remained in sedentary housing (sedentary mice). METH administration decreased expression of tight junction (TJ) proteins and increased BBB permeability in the hippocampus. These changes were preserved post METH administration in sedentary mice and were associated with the development of significant aberrations of neural differentiation. Exercise protected against these effects by enhancing the protein expression of TJ proteins, stabilizing the BBB integrity, and enhancing the neural differentiation. In addition, exercise protected against METH-induced systemic increase in inflammatory cytokine levels. These results suggest that exercise can attenuate METH-induced neurotoxicity by protecting against the BBB disruption and related microenvironmental changes in the hippocampus. PMID:27677455

  15. Administration of thimerosal to infant rats increases overflow of glutamate and aspartate in the prefrontal cortex: protective role of dehydroepiandrosterone sulfate.

    PubMed

    Duszczyk-Budhathoki, Michalina; Olczak, Mieszko; Lehner, Malgorzata; Majewska, Maria Dorota

    2012-02-01

    Thimerosal, a mercury-containing vaccine preservative, is a suspected factor in the etiology of neurodevelopmental disorders. We previously showed that its administration to infant rats causes behavioral, neurochemical and neuropathological abnormalities similar to those present in autism. Here we examined, using microdialysis, the effect of thimerosal on extracellular levels of neuroactive amino acids in the rat prefrontal cortex (PFC). Thimerosal administration (4 injections, i.m., 240 μg Hg/kg on postnatal days 7, 9, 11, 15) induced lasting changes in amino acid overflow: an increase of glutamate and aspartate accompanied by a decrease of glycine and alanine; measured 10-14 weeks after the injections. Four injections of thimerosal at a dose of 12.5 μg Hg/kg did not alter glutamate and aspartate concentrations at microdialysis time (but based on thimerosal pharmacokinetics, could have been effective soon after its injection). Application of thimerosal to the PFC in perfusion fluid evoked a rapid increase of glutamate overflow. Coadministration of the neurosteroid, dehydroepiandrosterone sulfate (DHEAS; 80 mg/kg; i.p.) prevented the thimerosal effect on glutamate and aspartate; the steroid alone had no influence on these amino acids. Coapplication of DHEAS with thimerosal in perfusion fluid also blocked the acute action of thimerosal on glutamate. In contrast, DHEAS alone reduced overflow of glycine and alanine, somewhat potentiating the thimerosal effect on these amino acids. Since excessive accumulation of extracellular glutamate is linked with excitotoxicity, our data imply that neonatal exposure to thimerosal-containing vaccines might induce excitotoxic brain injuries, leading to neurodevelopmental disorders. DHEAS may partially protect against mercurials-induced neurotoxicity.

  16. Gastrointestinal protective efficacy of Kolaviron (a bi-flavonoid from Garcinia kola) following a single administration of sodium arsenite in rats: Biochemical and histopathological studies

    PubMed Central

    Akinrinde, Akinleye S.; Olowu, Ebunoluwa; Oyagbemi, Ademola A.; Omobowale, Olutayo T.

    2015-01-01

    Background: Arsenic intoxication is known to produce symptoms including diarrhea and vomiting, which are indications of gastrointestinal dysfunction. Objective: We investigated whether Kolaviron (KV) administration protected against sodium arsenite (NaAsO2)-induced damage to gastric and intestinal epithelium in rats. Materials and Methods: Control rats (Group I) were given a daily oral dose of corn oil. Rats in other groups were given a single dose of NaAsO2 (100 mg/kg; intraperitoneal) alone (Group II) or after pretreatment for 7 days with KV at 100 mg/kg (Group III) and 200 mg/kg (Group IV). Rats were sacrificed afterward and portions of the stomach, small intestine and colon were processed for histopathological examination. Hydrogen peroxide, reduced glutathione, malondialdehyde (MDA) concentrations as well as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione S-transferase (GST) and myeloperoxidase (MPO) were measured in the remaining portions of the different gastrointestinal tract (GIT) segments. Results: NaAsO2 caused significant increases (P < 0.05) in MDA levels and MPO activity, with significant reductions (P < 0.05) in GST, GPX, CAT and SOD activities in the stomach and intestines. KV significantly reversed the changes (P < 0.05) in a largely dose-dependent manner. The different segments had marked inflammatory cellular infiltration, with hyperplasia of the crypts, which occurred to much lesser degrees with KV administration. Conclusion: The present findings showed that KV might be a potent product for mitigating NaAsO2 toxicity in the GIT. PMID:26130939

  17. Prevention of delayed neuronal death in gerbil hippocampus by a novel vinca alkaloid derivative (vinconate).

    PubMed

    Araki, T; Kogure, K

    1989-08-01

    We investigated the effect of vinconate, a novel vinca alkaloid derivative, on delayed neuronal death using Mongolian gerbils. The animals were allowed to survive for 7 d after 3 or 5 min of forebrain ischemia induced by bilateral occlusion of the common carotid arteries. Morphological changes and calcium (45Ca) accumulation were evaluated in the CA1 sector of the hippocampus after ischemia. Vinconate (50, 100, and 300 mg/kg) showed protective effects against neuronal death in a dose-dependent manner when administered intraperitoneally (ip) 10 min before 5 min of ischemia. However, the administration of vinconate (100 and 300 mg/kg, ip) immediately after 5 min of ischemia showed no therapeutic effect, whereas a marked therapeutic effect of vinconate (50 and 100 mg/kg, ip) was observed when administered immediately after 3 min of ischemia. An anesthetic dose of pentobarbital (40 mg/kg, ip) also produced significant protection against neuronal death. Furthermore, a 45Ca autoradiographic study indicated that a marked calcium accumulation was found in the Ca1 sector at 7 d after 5 min of ischemia, which was consistent with the extent of histological neuronal damage. When vinconate (100 and 300 mg/kg, ip) was administered 10 min before 5 min of ischemia, the abnormal calcium accumulation was not detected in the CA1 sector. These data indicate that suppression of abnormal neuronal activity may be owing to the antagonistic action of vinconate on calcium accumulation.

  18. Proteomic analysis of the mice hippocampus after preconditioning induced by N-methyl-D-aspartate (NMDA).

    PubMed

    do Amaral e Silva Müller, Gabrielle; Vandresen-Filho, Samuel; Tavares, Carolina Pereira; Menegatti, Angela C O; Terenzi, Hernán; Tasca, Carla Inês; Severino, Patricia Cardoso

    2013-05-01

    Preconditioning induced by N-methyl-D-aspartate (NMDA) has been used as a therapeutic tool against later neuronal insults. NMDA preconditioning affords neuroprotection against convulsions and cellular damage induced by the NMDA receptor agonist, quinolinic acid (QA) with time-window dependence. This study aimed to evaluate the molecular alterations promoted by NMDA and to compare these alterations in different periods of time that are related to the presence or lack of neuroprotection. Putative mechanisms related to NMDA preconditioning were evaluated via a proteomic analysis by using a time-window study. After a subconvulsant and protective dose of NMDA administration mice, hippocampi were removed (1, 24 or 72 h) and total protein analyzed by 2DE gels and identified by MALDI-TOF. Differential protein expression among the time induction of NMDA preconditioning was observed. In the hippocampus of protected mice (24 h), four proteins: HSP70(B), aspartyl-tRNA synthetase, phosphatidylethanolamine binding protein and creatine kinase were found to be up-regulated. Two other proteins, HSP70(A) and V-type proton ATPase were found down-regulated. Proteomic analysis showed that the neuroprotection induced by NMDA preconditioning altered signaling pathways, cell energy maintenance and protein synthesis and processing. These events may occur in a sense to attenuate the excitotoxicity process during the activation of neuroprotection promoted by NMDA preconditioning.

  19. Protective Immunity against Murine Hepatitis Virus (MHV) Induced by Intranasal or Subcutaneous Administration of Hybrids of Tobacco Mosaic Virus That Carries an MHV Epitope

    NASA Astrophysics Data System (ADS)

    Koo, Moses; Bendahmane, Mohammed; Lettieri, Gerard A.; Paoletti, Alyssa D.; Lane, Thomas E.; Fitchen, John H.; Buchmeier, Michael J.; Beachy, Roger N.

    1999-07-01

    Hybrids of tobacco mosaic virus (TMV) were constructed with the use of fusion to the coat protein peptides of 10 or 15 amino acids, containing the 5B19 epitope from the spike protein of murine hepatitis virus (MHV) and giving rise to TMV-5B19 and TMV-5B19L, respectively. The TMV hybrids were propagated in tobacco plants, and the virus particles were purified. Immunogold labeling, with the use of the monoclonal MAb5B19 antibody, showed specific decoration of hybrid TMV particles, confirming the expression and display of the MHV epitope on the surface of the TMV. Mice were immunized with purified hybrid viruses after several regimens of immunization. Mice that received TMV-5B19L intranasally developed serum IgG and IgA specific for the 5B19 epitope and for the TMV coat protein. Hybrid TMV-5B19, administered by subcutaneous injections, elicited high titers of serum IgG that was specific for the 5B19 epitope and for coat protein, but IgA that was specific against 5B19 was not observed. Mice that were immunized with hybrid virus by subcutaneous or intranasal routes of administration survived challenge with a lethal dose (10 × LD50) of MHV strain JHM, whereas mice administered wild-type TMV died 10 d post challenge. Furthermore, there was a positive correlation between the dose of administered immunogen and protection against MHV infection. These studies show that TMV can be an effective vaccine delivery vehicle for parenteral and mucosal immunization and for protection from challenge with viral infection.

  20. Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus.

    PubMed

    Parker, Scott; Crump, Ryan; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Lanier, E Randall; Painter, George; Schriewer, Jill; Trost, Lawrence C; Buller, R Mark

    2014-11-01

    Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first-generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non-replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered

  1. Sublingual administration of a helper-dependent adenoviral vector expressing the codon-optimized soluble fusion glycoprotein of human respiratory syncytial virus elicits protective immunity in mice.

    PubMed

    Fu, Yuan-hui; Jiao, Yue-Ying; He, Jin-sheng; Giang, Gui-Yuan; Zhang, Wei; Yan, Yi-Fei; Ma, Yao; Hua, Ying; Zhang, Ying; Peng, Xiang-Lei; Shi, Chang-Xin; Hong, Tao

    2014-05-01

    Sublingual (s.l.) immunization has been described as a convenient and safe way to induce mucosal immune responses in the respiratory and genital tracts. We constructed a helper-dependent adenoviral (HDAd) vector expressing a condon-optimized soluble fusion glycoprotein (sFsyn) of respiratory syncytial virus (HDAd-sFsyn) and explored the potential of s.l. immunization with HDAd-sFsyn to stimulate immune responses in the respiratory mucosa. The RSV specific systemic and mucosal immune responses were generated in BALB/c mice, and the serum IgG with neutralizing activity was significantly elevated after homologous boost with s.l. application of HDAd-sFsyn. Humoral immune responses could be measured even 14weeks after a single immunization. Upon challenge, s.l. immunization with HDAd-sFsyn displayed an effective protection against RSV infection. These findings suggest that s.l. administration of HDAd-sFsyn acts as an effective and safe mucosal vaccine against RSV infection, and may be a useful tool in the prevention of RSV infection.

  2. Analysis of U.S. Food and Drug Administration food allergen recalls after implementation of the food allergen labeling and consumer protection act.

    PubMed

    Gendel, Steven M; Zhu, Jianmei

    2013-11-01

    To avoid potentially life-threatening reactions, food allergic consumers rely on information on food labels to help them avoid exposure to a food or ingredient that could trigger a reaction. To help consumers in the United States obtain the information that they need, the Food Allergen Labeling and Consumer Protection Act of 2004 defined a major food allergen as being one of eight foods or food groups and any ingredient that contains protein from one of these foods or food groups. A food that contains an undeclared major food allergen is misbranded under the U.S. Food, Drug, and Cosmetic Act and is subject to recall. Food allergen labeling problems are the most common cause of recalls for U.S. Food and Drug Administration (FDA)-regulated food products. To help understand why food allergen recalls continue to occur at a high rate, information on each food allergen recall that occurred in fiscal years 2007 through 2012 was obtained from the FDA recall database. This information was analyzed to identify the food, allergen, root cause, and mode of discovery for each food allergen recall. Bakery products were the most frequently recalled food type, and milk was the most frequently undeclared major food allergen. Use of the wrong package or label was the most frequent problem leading to food allergen recalls. These data are the first reported that indicate the importance of label and package controls as public health measures.

  3. Oral administration of heat-killed Lactobacillus plantarum L-137 enhances protection against influenza virus infection by stimulation of type I interferon production in mice.

    PubMed

    Maeda, Naoyoshi; Nakamura, Risa; Hirose, Yoshitaka; Murosaki, Shinji; Yamamoto, Yoshihiro; Kase, Tetsuo; Yoshikai, Yasunobu

    2009-08-01

    We have previously reported that heat-killed Lactobacillus plantarum L-137 (HK-LP) stimulates macrophage/dendritic cells to produce T helper (Th) 1-related cytokines in vitro and in vivo in mice. We here examined the effect of oral administration of HK-LP on protection against influenza virus infection in mice. C57BL/6 mice were orally given HK-LP from day -7 to 7 and intranasally infected with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) at 100 pfu on day 0. The survival time was significantly prolonged in mice treated with HK-LP than that in mice treated with PBS as controls. The viral titers in the lung were significantly lower in mice treated with HK-LP than controls at the early stage after influenza virus infection. An appreciable level of interferon (IFN)-beta was detected in the serum of mice treated with HK-LP, while no IFN-beta was detected in controls after influenza infection. Our results suggest that HK-LP, a potent IFN-beta inducer, is useful for prevention against influenza infection.

  4. Mnemonic convergence in the human hippocampus

    PubMed Central

    Backus, Alexander R.; Bosch, Sander E.; Ekman, Matthias; Grabovetsky, Alejandro Vicente; Doeller, Christian F.

    2016-01-01

    The ability to form associations between a multitude of events is the hallmark of episodic memory. Computational models have espoused the importance of the hippocampus as convergence zone, binding different aspects of an episode into a coherent representation, by integrating information from multiple brain regions. However, evidence for this long-held hypothesis is limited, since previous work has largely focused on representational and network properties of the hippocampus in isolation. Here we identify the hippocampus as mnemonic convergence zone, using a combination of multivariate pattern and graph-theoretical network analyses of functional magnetic resonance imaging data from humans performing an associative memory task. We observe overlap of conjunctive coding and hub-like network attributes in the hippocampus. These results provide evidence for mnemonic convergence in the hippocampus, underlying the integration of distributed information into episodic memory representations. PMID:27325442

  5. Glucocorticoids and the ageing hippocampus

    PubMed Central

    HIBBERD, CARINA; YAU, JOYCE L. W.; SECKL, JONATHAN R.

    2000-01-01

    Approximately 30% of human and mammalian populations develop cognitive impairments with ageing. Many of these impairments have been linked to dysfunction of the hippocampus, a well studied area of the medial-temporal lobe, which is involved in episodic memory and control of the hypothalamo-pituitary-adrenal stress axis and, thus, of glucocorticoid secretion. This paper reviews the growing body of studies which explore a possible relationship between lifetime exposure to glucocorticoids and hippocampal impairment. There is now strong evidence which associates hypercortisolemia in aged men with later cognitive dysfunction and this complements a wealth of rodent and other human data. We conclude with a discussion of possible pharmacological and behavioural interventions. PMID:11197528

  6. Prediction, sequences and the hippocampus

    PubMed Central

    Lisman, John; Redish, A.D.

    2009-01-01

    Recordings of rat hippocampal place cells have provided information about how the hippocampus retrieves memory sequences. One line of evidence has to do with phase precession, a process organized by theta and gamma oscillations. This precession can be interpreted as the cued prediction of the sequence of upcoming positions. In support of this interpretation, experiments in two-dimensional environments and on a cue-rich linear track demonstrate that many cells represent a position ahead of the animal and that this position is the same irrespective of which direction the rat is coming from. Other lines of investigation have demonstrated that such predictive processes also occur in the non-spatial domain and that retrieval can be internally or externally cued. The mechanism of sequence retrieval and the usefulness of this retrieval to guide behaviour are discussed. PMID:19528000

  7. Upregulation of miR-137 protects anesthesia-induced hippocampal neurodegeneration

    PubMed Central

    Huang, Changshun; Zhang, Xingcai; Zheng, Jungang; Chen, Chunru; Chen, Yijun; Yi, Juan

    2014-01-01

    Purpose: Ketamine is commonly used in pediatric anesthesia but may cause neurodegeneration in young brains. The aim of the study is to use an animal model to characterize the role of microRNA 137 (miR-137) in ketamine-induced neurodegeneration in neonatal hippocampus. Methods: Young Sprague-Dawley Rats (1 month old) was systemically administrated with ketamine (75 mg/kg) for 3 days. TUNEL assay was used to assess the ketamine-induced neurodegeneration of hippocampal CA1 neurons, quantitative real-time PCR (qRT-PCR) to assess the expression of miR-137 and Morris water maze test (MWM) to assess the damaged memory function. Alternatively, lentivirus over-expressing miR-137 was injected into hippocampus before ketamine administration, and the subsequent effects of miR-137 upregulation on ketamine-induced hippocampal neurodegeneration and memory dysfunction were investigated. Furthermore, the direct downstream target of miR-137, CDC42, was down-regulated by siRNA injection into hippocampus. The effects of CDC42 inhibition on hippocampal apoptosis and memory function were also investigated. Results: Excessive ketamine treatment resulted in severe apoptosis in hippocampal CA1 neurons, downregulation of miR-137 in hippocampus and significant long-term memory dysfunction. Conversely, pre-treatment of overexpressing miR-137 protected hippocampal neurodegeneration and memory loss. The molecular target of miR-137, CDC42 was down-regulated by ketamine in hippocampus. Knocking down hippocampal CDC42 exerted an apoptotic effect on hippocampal neurons and memory loss, similar to the effect of ketamine treatment. Conclusions: Our results demonstrated that miR-137 played an important role in regulating ketamine induced hippocampal neurodegeneration, possibly through CDC42. PMID:25197371

  8. Administrators: Nursing Home Administrator

    ERIC Educational Resources Information Center

    Kahl, Anne

    1976-01-01

    Responsibilities, skills needed, training needed, earnings, employment outlook, and sources of additional information are outlined for the administrator who holds the top management job in a nursing home. (JT)

  9. Systemic administration of an anti-tumor necrosis factor-alpha monoclonal antibody protects against endotoxin-induced uveitis in rats

    PubMed Central

    Ge, Qingman; Wang, Shaocheng; Zheng, Yuezhong

    2016-01-01

    Objective: This study was to evaluate the effect of systemic injection of an anti-tumor necrosis factor alpha (TNF-α) monoclonal antibody (mAb) on endotoxin-induced uveitis (EIU). Materials and Methods: Fifty-six male Wistar rats (6–8 weeks old) were randomly divided into three groups: EIU, anti-TNF-α mAb + EIU, and control. EIU was induced by injecting Escherichia coli O55:B5 lipopolysaccharide (LPS) into the hind footpad of the rats (150 μg/rat). The anti-TNF-α mAb (1 μg/kg) was administrated 30 min before LPS injection through one-time intravenous injection. The onset time and peak time of EIU were recorded. The serum and aqueous humor (AH) TNF-α, interleukin (IL)-6, and IL-10 levels were measured by ELISA at 4, 24, and 72 h post-LPS injection. Clinical manifestations of EIU and eye histopathology were scored. Results: Compared with the EIU rats, anti-TNF-α mAb + EIU rats showed significantly delayed onset of uveitis (t = 7.41, P < 0.001), lower clinical scores and histopathological grades (t = 3.18/2.22, P < 0.001), reduced levels of TNF-α (F = 15.06/59.43, P < 0.001) and IL-6 (F = 99.63/14.92, P < 0.001), and increased levels of IL-10 (F = 24.94/8.99, P < 0.001) in the serum and AH. AH TNF-α, serum IL-6, and AH IL-6 levels are positively correlated, whereas serum IL-10 levels were negatively correlated with EIU activity. Conclusion: Antagonizing TNF-α by system injection of the anti-TNF-α mAb protects against EIU in rats. Blocking TNF-α signaling could be a useful strategy for managing uveitis. PMID:28112125

  10. Noopept stimulates the expression of NGF and BDNF in rat hippocampus.

    PubMed

    Ostrovskaya, R U; Gudasheva, T A; Zaplina, A P; Vahitova, Ju V; Salimgareeva, M H; Jamidanov, R S; Seredenin, S B

    2008-09-01

    We studied the effect of original dipeptide preparation Noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) with nootropic and neuroprotective properties on the expression of mRNA for neurotropic factors NGF and BDNF in rat hippocampus. Expression of NGF and BDNF mRNA in the cerebral cortex and hippocampus was studied by Northern blot analysis. Taking into account the fact that pharmacological activity of Noopept is realized after both acute and chronic treatment, we studied the effect of single and long-term treatment (28 days) with this drug. Expression of the studied neurotropic factors in the cerebral cortex was below the control after single administration of Noopept, while chronic administration caused a slight increase in BDNF expression. In the hippocampus, expression of mRNA for both neurotrophins increased after acute administration of Noopept. Chronic treatment with Noopept was not followed by the development of tolerance, but even potentiated the neurotrophic effect. These changes probably play a role in neuronal restoration. We showed that the nootropic drug increases expression of neurotrophic factors in the hippocampus. Our results are consistent with the hypothesis that neurotrophin synthesis in the hippocampus determines cognitive function, particularly in consolidation and delayed memory retrieval. Published data show that neurotrophic factor deficiency in the hippocampus is observed not only in advanced Alzheimer's disease, but also at the stage of mild cognitive impairment (pre-disease state). In light of this our findings suggest that Noopept holds much promise to prevent the development of Alzheimer's disease in patients with mild cognitive impairment. Moreover, therapeutic effectiveness of Noopept should be evaluated at the initial stage of Alzheimer's disease.

  11. Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice.

    PubMed

    Antunes, Michelle S; Ruff, Jossana Rodrigues; de Oliveira Espinosa, Dieniffer; Piegas, Manuela Bastos; de Brito, Maicon Lenon Otenio; Rocha, Kellen Athaíde; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Souza, Leandro Cattelan; Donato, Franciele; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    Depression is one of the most common mental disorders and a primary cause of disability. To better treat patients suffering this illness, elucidation of the underlying psychopathological and neurobiological mechanisms is urgently needed. Based on the above-mentioned evidence, we sought to investigate the effects of neuropeptide Y (NPY) treatment in tricyclic antidepressant treatment-resistant depression induced by adrenocorticotropic hormone (ACTH) administration. Mice were treated with NPY (5.84, 11.7 or 23.4mmol/μl) intracerebroventricularly (i.c.v.) for one or five days. The levels of serum corticosterone, tryptophan (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and indoleamine 2,3-dioxygenase (IDO) activity in the hippocampus were analyzed. The behavioral parameters (depressive-like and locomotor activity) were also verified. This study demonstrated that ACTH administration increased serum corticosterone levels, KYN, 5-HIAA levels, IDO activity (hippocampus), immobility in the forced swimming test (FST) and the latency to feed in the novelty suppressed feeding test (NSFT). In addition, ACTH administration decreased the BDNF and NGF levels in the hippocampus of mice. NPY treatment was effective in preventing these hormonal, neurochemical and behavioral alterations. It is suggested that the main target of NPY is the modulation of corticosterone and neuronal plasticity protein levels, which may be closely linked with pharmacological action in a model of tricyclic antidepressant treatment-resistant depression. Thus, this study demonstrated a protective effect of NPY on the alterations induced by ACTH administration in mice, indicating that it could be useful as a therapy for the treatment of tricyclic antidepressant treatment-resistant depression.

  12. Glycyrrhizin ameliorates oxidative stress and inflammation in hippocampus and olfactory bulb in lithium/pilocarpine-induced status epilepticus in rats.

    PubMed

    González-Reyes, Susana; Santillán-Cigales, Juan Jair; Jiménez-Osorio, Angélica Saraí; Pedraza-Chaverri, José; Guevara-Guzmán, Rosalinda

    2016-10-01

    Glycyrrhizin (GL) is a triterpene present in the roots and rhizomes of Glycyrrhiza glabra that has anti-inflammatory, hepatoprotective and neuroprotective effects. Recently, it was demonstrated that GL produced neuroprotective effects on the postischemic brain as well as on the kainic acid injury model in rats. In addition to this, GL also prevented excitotoxic effects on primary cultures. The aims of the present study were to evaluate GL scavenging properties and to investigate GL's effect on oxidative stress and inflammation in the lithium/pilocarpine-induced seizure model in two cerebral regions, hippocampus and olfactory bulb, at acute time intervals (3 or 24h) after status epilepticus (SE). Fluorometric methods showed that GL scavenged three reactive oxygen species: hydrogen peroxide, peroxyl radicals and superoxide anions. In contrast, GL was unable to scavenge peroxynitrite, hydroxyl radicals, singlet oxygen and 2,2-diphenil-1-picrylhydrazyl (DPPH) radicals suggesting that GL is a weak scavenger. Additionally, administration of GL (50mg/kg, i.p.) 30min before pilocarpine administration significantly suppressed oxidative stress. Moreover, malondialdehyde levels were diminished and glutathione levels were maintained at control values in both cerebral regions at 3 and 24 after SE. At 24h after SE, glutathione S-transferase and superoxide dismutase activity increased in the hippocampus, while both glutathione reductase and glutathione peroxidase activity were unchanged in the olfactory bulb at that time. In addition, GL suppressed the induction of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in both cerebral regions evaluated. These results suggest that GL confers protection against pilocarpine damage via antioxidant and anti-inflammatory effects.

  13. Protective Mechanisms of Nitrone Antioxidants in Kanic Acid Induced Neurodegeneration

    DTIC Science & Technology

    2004-01-01

    L., Hong, J.S. (1996) Expression of) FosB in the rat hippocampus and striatum after systemic administration of kainic acid. Neurosci. Abstr. 22...gene expression in the hippocampus . Immunohistochemical methods and electromobility gel shift assays (EMSAs) demonstrate the concerted activation of...acid-induced neurodegenerative diseases. The major focus will be on the pathophysiological changes in the hippocampus . Special attention will be given

  14. Neurogenic Effects of Ghrelin on the Hippocampus

    PubMed Central

    Kim, Chanyang; Kim, Sehee; Park, Seungjoon

    2017-01-01

    Mammalian neurogenesis continues throughout adulthood in the subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus in the hippocampus. It is well known that hippocampal neurogenesis is essential in mediating hippocampus-dependent learning and memory. Ghrelin, a peptide hormone mainly synthesized in the stomach, has been shown to play a major role in the regulation of energy metabolism. A plethora of evidence indicates that ghrelin can also exert important effects on neurogenesis in the hippocampus of the adult brain. The aim of this review is to discuss the current role of ghrelin on the in vivo and in vitro regulation of neurogenesis in the adult hippocampus. We will also discuss the possible role of ghrelin in dietary restriction-induced hippocampal neurogenesis and the link between ghrelin-induced hippocampal neurogenesis and cognitive functions. PMID:28282857

  15. Neurogenic Effects of Ghrelin on the Hippocampus.

    PubMed

    Kim, Chanyang; Kim, Sehee; Park, Seungjoon

    2017-03-08

    Mammalian neurogenesis continues throughout adulthood in the subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus in the hippocampus. It is well known that hippocampal neurogenesis is essential in mediating hippocampus-dependent learning and memory. Ghrelin, a peptide hormone mainly synthesized in the stomach, has been shown to play a major role in the regulation of energy metabolism. A plethora of evidence indicates that ghrelin can also exert important effects on neurogenesis in the hippocampus of the adult brain. The aim of this review is to discuss the current role of ghrelin on the in vivo and in vitro regulation of neurogenesis in the adult hippocampus. We will also discuss the possible role of ghrelin in dietary restriction-induced hippocampal neurogenesis and the link between ghrelin-induced hippocampal neurogenesis and cognitive functions.

  16. Chewing Maintains Hippocampus-Dependent Cognitive Function

    PubMed Central

    Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2015-01-01

    Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research. PMID:26078711

  17. Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

    PubMed Central

    Galinato, Melissa H.; Orio, Laura; Mandyam, Chitra D.

    2014-01-01

    Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1 h/day) or extended access (6 h/day) paradigm for 17 days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of NMDA receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct allostatic changes in

  18. Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus.

    PubMed

    Galinato, M H; Orio, L; Mandyam, C D

    2015-02-12

    Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1h/day) or extended access (6h/day) paradigm for 17days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of N-methyl-d-aspartate (NMDA) receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct

  19. Synergistic deleterious effect of chronic stress and sodium azide in the mouse hippocampus.

    PubMed

    Delgado-Cortés, María José; Espinosa-Oliva, Ana M; Sarmiento, Manuel; Argüelles, Sandro; Herrera, Antonio J; Mauriño, Raquel; Villarán, Ruth F; Venero, José L; Machado, Alberto; de Pablos, Rocío M

    2015-04-20

    Alzheimer's disease is the most common cause of dementia in the elderly. Although the primary cause of the disease is presently unknown, to date several risk factors have been described. Evidence suggests that one of these risk factors could be chronic stress. The aim of this work is to demonstrate that chronic stress is able to induce Alzheimer's disease features after the administration of nontoxic doses of sodium azide. We found that chronic stress increases the levels of several proteins involved in Alzheimer's disease pathogenesis, such as presenilin 1, presenilin 2, and S100β, besides inducing the aggregation of Tau, ubiquitin, and β-amyloid proteins in the hippocampus. More important, our work shows a synergistic effect of stress and sodium azide treatment leading to significant neuronal death in the mouse hippocampus. Our results point out that chronic stress is a risk factor contributing to amplify and accelerate Alzheimer's disease features in the hippocampus.

  20. Effect of taurine on the concentrations of glutamate, GABA, glutamine and alanine in the rat striatum and hippocampus.

    PubMed

    Molchanova, Svetlana M; Oja, Simos S; Saransaari, Pirjo

    2007-01-01

    Taurine, a non-protein amino acid, acts as an osmoregulator and inhibitory neuromodulator in the brain. Here we studied the effects of intraperitoneal injections of taurine on the concentrations of glutamate and GABA, and their precursors, glutamine and alanine, in the rat striatum and hippocampus. Injections of 0.25, 0.5 and 1 g/kg taurine led to a gradual increase in taurine tissue concentrations in both hippocampus and striatum. Glutamate and GABA also increased in the hippocampus, but not in the striatum. Glutamine increased and alanine decreased markedly in both brain structures. The results corroborate the neuromodulatory role of taurine in the brain. Taurine administration results in an imbalance in inhibitory and excitatory neurotransmission in the glutamatergic (hippocampus) and GABAergic (striatum) brain structures, affecting more markedly the neurotransmitter precursors.

  1. The expression of contextual fear conditioning involves activation of a NMDA receptor-nitric oxide-cGMP pathway in the dorsal hippocampus of rats.

    PubMed

    Fabri, Denise R S; Hott, Sara C; Reis, Daniel G; Biojone, Caroline; Corrêa, Fernando M A; Resstel, Leonardo B M

    2014-10-01

    The dorsal portion of the hippocampus is a limbic structure that is involved in fear conditioning modulation in rats. Moreover, evidence shows that the local dorsal hippocampus glutamatergic system, nitric oxide (NO) and cGMP modulate behavioral responses during aversive situations. Therefore, the present study investigated the involvement of dorsal hippocampus NMDA receptors and the NO/cGMP pathway in contextual fear conditioning expression. Male Wistar rats were submitted to an aversive contextual conditioning session and 48 h later they were re-exposed to the aversive context in which freezing, cardiovascular responses (increase of both arterial pressure and heart rate) and decrease of tail temperature were recorded. The intra-dorsal hippocampus administration of the NMDA receptor antagonist AP7, prior to the re-exposure to the aversive context, attenuated fear-conditioned responses. The re-exposure to the context evoked an increase in NO concentration in the dorsal hippocampus of conditioned animals. Similar to AP7 administration, we observed a reduction of contextual fear conditioning after dorsal hippocampus administration of either the neuronal NO synthase inhibitor N-propyl-L-arginine, the NO scavenger c-PTIO or the guanylate cyclase inhibitor ODQ. Therefore, the present findings suggest the possible existence of a dorsal hippocampus NMDA/NO/cGMP pathway modulating the expression of contextual fear conditioning in rats.

  2. 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.

  3. Impact of colostrum and plasma immunoglobulin intake on hippocampus structure during early postnatal development in pigs.

    PubMed

    Pierzynowski, Stefan; Ushakova, Galyna; Kovalenko, Tatiana; Osadchenko, Iryna; Goncharova, Kateryna; Gustavsson, Per; Prykhodko, Olena; Wolinski, Jarek; Slupecka, Monika; Ochniewicz, Piotr; Weström, Björn; Skibo, Galina

    2014-06-01

    The first milk, colostrum, is an important source of nutrients and an exclusive source of immunoglobulins (Ig), essential for the growth and protection from infection of newborn pigs. Colostrum intake has also been shown to affect the vitality and behaviour of neonatal pigs. The objective of this study was to evaluate the effects of feeding colostrum and plasma immunoglobulin on brain development in neonatal pigs. Positive correlations were found between growth, levels of total protein and IgG in blood plasma and hippocampus development in sow-reared piglets during the first 3 postnatal days. In piglets fed an elemental diet (ED) for 24h, a reduced body weight, a lower plasma protein level and a decreased level of astrocyte specific protein in the hippocampus was observed, as compared to those that were sow-reared. The latter was coincident with a reduced microgliogenesis and an essentially diminished number of neurons in the CA1 area of the hippocampus after 72h. Supplementation of the ED with purified plasma Ig, improved the gliogenesis and supported the trophic and immune status of the hippocampus. The data obtained indicate that the development of the hippocampus structure is improved by colostrum or an Ig-supplemented elemental diet in order to stimulate brain protein synthesis and its development during the early postnatal period.

  4. Protective effects of tryptophan on neuro-inflammation in rats after administering lipopolysaccharide.

    PubMed

    Del Angel-Meza, A R; Dávalos-Marín, A J; Ontiveros-Martinez, L L; Ortiz, G G; Beas-Zarate, C; Chaparro-Huerta, V; Torres-Mendoza, B M; Bitzer-Quintero, O K

    2011-06-01

    Tryptophan (TRP), which plays an important role in immune system regulation, protein synthesis, serotonin (5-HT) and melatonin production, is a potent endogenous free radical scavenger and antioxidant. The aim of this work was to determine the efficacy of TRP in neuro-inflammation induced by systemic administration of lipopolysacharide (LPS, 20mg/kg) which promotes the synthesis of free radical (LPO: MDA and 4-HDA), and pro-inflammatory cytokine Interferon-γ (IFN-γ) in different brain regions (cerebral cortex and hippocampus) of rats. Experiments were performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein), cerebral cortex and hippocampus were evaluated for lipid peroxidation (LPO) products, nitrites, nitrates and plasmatic concentration of IFN-γ. LPO levels in LPS+TRP groups were significantly decreased than that obtained in the LPS group. However, there were no observed differences in plasmatic levels of nitrites and nitrates as well as IFN-γ, neither in the cerebral cortex or hippocampus. The TRP has protective effect in the oxidative damage in a model of endotoxic shock in the breading nurslings induced by the systemic administration of LPS, acting as a scavenger of free radicals. So, it can be proposed as an innocuous protector agent in the endotoxic shock process.

  5. ADMINISTRATION OF A SUBSTITUTED ADAMANTLY-UREA INHIBITOR OF THE SOLUBLE EPOXIDE HYDROLASE PROTECTS THE KIDNEY FROM DAMAGE IN HYPERTENSIVE GOTO-KAKIZAKI RATS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hypertension and type II diabetes are co-morbid diseases that lead to the development of nephropathy. Soluble epoxide hydrolase (sEH) inhibitors are reported to provide protection from renal injury. We hypothesized that the sEH inhibitor 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) protects ...

  6. SCLM, total saponins extracted from Chaihu-jia-longgu-muli-tang, reduces chronic mild stress-induced apoptosis in the hippocampus in mice.

    PubMed

    Liu, Yadong; Ma, Shiping; Qu, Rong

    2010-08-01

    Increasing evidence demonstrates that stress or depression can lead to atrophy and cell loss in the hippocampus. In contrast, antidepressant treatment significantly reduces apoptosis in the dentate granule cell layer and subgranular zone in animal models of depression. In the present study, we investigated the neuroprotective action of SCLM, the total saponins extracted from Chaihu-jia-longgu-muli-tang, a traditional Chinese medicinal formula which was prescribed 1000 years ago, in the reduction of apoptosis in hippocampal neurons using an experimental chronic mild stress (CMS) model. Mice were subjected to the CMS procedure for a period of 21 consecutive days. SCLM (100 mg/kg, p.o.) or fluoxetine (20 mg/ kg, p.o.) was administered during the stress periods. CMS mice showed a decreased sucrose intake over 21 days, and an increase in the number of TUNEL-positive neurons as well as up-regulation of the apoptotic-related factors, such as Bax and caspase-3 in the hippocampus, compared with control mice. On the other hand, the administration of SCLM (100 mg/kg) and fluoxetine (20 mg/kg) reversed these effects induced by CMS, showing a significant increase of sucrose intake and a dramatic reduction of TUNEL-positive neurons and decreased expression of Bax and caspase-3 proteins. The present results suggest that SCLM possesses a significant antidepressant-like property, and this effect may be through protection against stress-induced neuronal apoptosis by affecting the expression of Bax and caspase-3 proteins in the hippocampus. These findings provide important information that the anti-apoptotic effect of herbal medicine therapy may be beneficial for the treatment of depression.

  7. Cocaine- or stress-induced metaplasticity of LTP in the dorsal and ventral hippocampus.

    PubMed

    Keralapurath, Madhusudhanan M; Clark, Jason K; Hammond, Sherri; Wagner, John J

    2014-05-01

    Despite the well documented role of the hippocampus in various modes of drug reinstatement behavior, the persisting effects of in vivo cocaine exposure on hippocampal synaptic plasticity are not sufficiently understood. In this report we investigated the effects of cocaine conditioning on long-term potentiation (LTP) in the CA1 region of hippocampus along its septotemporal axis. Male Sprague-Dawley rats experienced a behavioral protocol, in which locomotor activity was monitored in response to various conditioning treatments. LTP was measured in ex vivo slice preparations taken 1-2 weeks after the last behavioral session from the ventral (vH) and dorsal (dH) sectors of hippocampus. Unexpectedly, experiencing the minor intermittent stimuli of the behavioral protocol caused stress-induced metaplastic changes in both vH (increased LTP) and dH (decreased LTP) in the saline conditioned rats relative to behaviorally naïve controls. These stress effects in the vH and dH were blocked by conditioning with either mineralocorticoid (spironolactone) or glucocorticoid (mifepristone) antagonists, respectively. Stress-induced metaplasticity in the vH was also prevented by prior administration of the kappa opioid antagonist nor-binaltorphimine. Cocaine conditioning induced locomotor sensitization and significantly increased LTP in the vH without causing significant change in LTP in the dH. Cocaine-induced metaplasticity in the vH was prevented by co-administration of the dopamine D2-like antagonist eticlopride during cocaine conditioning, but not by co-administration of the D1/5 antagonist SCH 23390. Our results suggest that the functional connectivity of hippocampus is altered by metaplastic triggers such as exposure to drugs of abuse and/or stressors, thereby shifting the efferent output of hippocampus from dH (cortical) toward vH (limbic) influenced circuits.

  8. Increased calcium/calmodulin-dependent protein kinase II activity by morphine-sensitization in rat hippocampus.

    PubMed

    Kadivar, Mehdi; Farahmandfar, Maryam; Ranjbar, Faezeh Esmaeli; Zarrindast, Mohammad-Reza

    2014-07-01

    Repeated exposure to drugs of abuse, such as morphine, elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect long-lasting changes in some of the important molecules involved in memory processing such as calcium/calmodulin-dependent protein kinase II (CaMKII). In the present study, we investigated the effect of morphine sensitization on mRNA expression of α and β isoforms and activity of CaMKII in the hippocampus of male rats. Animals were treated for 3 days with saline or morphine (20mg/kg) and following a washout period of 5 days, a challenge dose of morphine (5mg/kg) were administered. The results indicate that morphine administration in pre-treated animals produces behavioral sensitization, as determined by significant increase in locomotion and oral stereotypy behavior. In addition, repeated morphine treatment increased mRNA expression of both α and β isoforms of CaMKII in the hippocampus. The present study also showed that induction of morphine sensitization significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus. However, acute administration of morphine (5mg/kg) did not alter either α and β CaMKII mRNA expression or CaMKII activity in the hippocampus. The stimulation effects of morphine sensitization on mRNA expression and activity of CaMKII were completely abolished by administration of naloxone, 30min prior to s.c. injections of morphine (20mg/kg/day×3 days). Our data demonstrated that induction of morphine sensitization could effectively modulate the activity and the mRNA expression of CaMKII in the hippocampus and this effect of morphine was exerted by the activation of opioid receptors.

  9. Distinct roles of the hippocampus and perirhinal cortex in GABAA receptor blockade-induced enhancement of object recognition memory.

    PubMed

    Kim, Jong Min; Kim, Dong Hyun; Lee, Younghwan; Park, Se Jin; Ryu, Jong Hoon

    2014-03-13

    It is well known that the hippocampus plays a role in spatial and contextual memory, and that spatial information is tightly regulated by the hippocampus. However, it is still highly controversial whether the hippocampus plays a role in object recognition memory. In a pilot study, the administration of bicuculline, a GABAA receptor antagonist, enhanced memory in the passive avoidance task, but not in the novel object recognition task. In the present study, we hypothesized that these different results are related to the characteristics of each task and the different roles of hippocampus and perirhinal cortex. A region-specific drug-treatment model was employed to clarify the role of the hippocampus and perirhinal cortex in object recognition memory. After a single habituation in the novel object recognition task, intra-perirhinal cortical injection of bicuculline increased and intra-hippocampal injection decreased the exploration time ratio to novel object. In addition, when animals were repeatedly habituated to the context, intra-perirhinal cortical administration of bicuculline still increased exploration time ratio to novel object, but the effect of intra-hippocampal administration disappeared. Concurrent increases of c-Fos expression and ERK phosphorylation were observed in the perirhinal cortex of the object with context-exposed group either after single or repeated habituation to the context, but no changes were noted in the hippocampus. Altogether, these results suggest that object recognition memory formation requires the perirhinal cortex but not the hippocampus, and that hippocampal activation interferes with object recognition memory by the information encoding of unfamiliar environment.

  10. Obama Administration Takes Historic Action on Climate Change/Clean Power Plan to protect public health, spur clean energy investments and strengthen U.S. leadership

    EPA Pesticide Factsheets

    WASHINGTON -President Obama announced the U.S. Environmental Protection Agency's final Clean Power Plan today, which will cut U.S. carbon pollution from the power sector by 870 million tons, or 32 percent

  11. Insulin Reduces Cerebral Ischemia/Reperfusion Injury in the Hippocampus of Diabetic Rats

    PubMed Central

    Collino, Massimo; Aragno, Manuela; Castiglia, Sara; Tomasinelli, Chiara; Thiemermann, Christoph; Boccuzzi, Giuseppe; Fantozzi, Roberto

    2009-01-01

    OBJECTIVE—There is evidence that insulin reduces brain injury evoked by ischemia/reperfusion (I/R). However, the molecular mechanisms underlying the protective effects of insulin remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3β (GSK-3β). Here, we investigate the role of GSK-3β inhibition on I/R-induced cerebral injury in a rat model of insulinopenic diabetes. RESEARCH DESIGN AND METHODS—Rats with streptozotocin-induced diabetes were subjected to 30-min occlusion of common carotid arteries followed by 1 or 24 h of reperfusion. Insulin (2–12 IU/kg i.v.) or the selective GSK-3β inhibitor TDZD-8 (0.2–3 mg/kg i.v.) was administered during reperfusion. RESULTS—Insulin or TDZD-8 dramatically reduced infarct volume and levels of S100B protein, a marker of cerebral injury. Both drugs induced phosphorylation of the Ser9 residue, thereby inactivating GSK-3β in the rat hippocampus. Insulin, but not TDZD-8, lowered blood glucose. The hippocampi of the drug-treated animals displayed reduced oxidative stress at 1 h of reperfusion as shown by the decreased generation of reactive oxygen species and lipid peroxidation. I/R-induced activation of nuclear factor-κB was attenuated by both drug treatments. At 24 h of reperfusion, TDZD-8 and insulin significantly reduced plasma levels of tumor necrosis factor-α; neutrophil infiltration, measured as myeloperoxidase activity and intercellular-adhesion-molecule-1 expression; and cyclooxygenase-2 and inducible-NO-synthase expression. CONCLUSIONS—Acute administration of insulin or TDZD-8 reduced cerebral I/R injury in diabetic rats. We propose that the inhibitory effect on the activity of GSK-3β contributes to the protective effect of insulin independently of any effects on blood glucose. PMID:18840784

  12. Dietary flavonoid fisetin regulates aluminium chloride-induced neuronal apoptosis in cortex and hippocampus of mice brain.

    PubMed

    Prakash, Dharmalingam; Sudhandiran, Ganapasam

    2015-12-01

    Dietary flavonoids have been suggested to promote brain health by protecting brain parenchymal cells. Recently, understanding the possible mechanism underlying neuroprotective efficacy of flavonoids is of great interest. Given that fisetin exerts neuroprotection, we have examined the mechanisms underlying fisetin in regulating Aβ aggregation and neuronal apoptosis induced by aluminium chloride (AlCl3) administration in vivo. Male Swiss albino mice were induced orally with AlCl3 (200 mg/kg. b.wt./day/8 weeks). Fisetin (15 mg/Kg. b.wt. orally) was administered for 4 weeks before AlCl3-induction and administered simultaneously for 8 weeks during AlCl3-induction. We found aggregation of Amyloid beta (Aβ 40-42), elevated expressions of Apoptosis stimulating kinase (ASK-1), p-JNK (c-Jun N-terminal Kinase), p53, cytochrome c, caspases-9 and 3, with altered Bax/Bcl-2 ratio in favour of apoptosis in cortex and hippocampus of AlCl3-administered mice. Furthermore, TUNEL and fluoro-jade C staining demonstrate neurodegeneration in cortex and hippocampus. Notably, treatment with fisetin significantly (P<0.05) reduced Aβ aggregation, ASK-1, p-JNK, p53, cytochrome c, caspase-9 and 3 protein expressions and modulated Bax/Bcl-2 ratio. TUNEL-positive and fluoro-jade C stained cells were also significantly reduced upon fisetin treatment. We have identified the involvement of fisetin in regulating ASK-1 and p-JNK as possible mediator of Aβ aggregation and subsequent neuronal apoptosis during AlCl3-induced neurodegeneration. These findings define the possibility that fisetin may slow or prevent neurodegneration and can be utilised as neuroprotective agent against Alzheimer's and Parkinson's disease.

  13. Neuroprotective effects of various doses of topiramate against methylphenidate induced oxidative stress and inflammation in rat isolated hippocampus.

    PubMed

    Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

    2016-03-01

    Methylphenidate (MPH) abuse causes neurodegeneration. The neuroprotective effects of topiramate (TPM) have been reported but its putative mechanism remains unclear. The current study evaluates the role of various doses of TPM on protection of rat hippocampal cells from MPH-induced oxidative stress and inflammation in vivo. Seventy adult male rats were divided into six groups. Group 1 received normal saline (0.7 mL/rat) and group 2 was injected with MPH (10 mg/kg) for 21 days. Groups 3, 4, 5, 6 and 7 concurrently were treated by MPH (10 mg/kg) and TPM (10, 30, 50, 70 and 100 mg/kg, intraperitoneally (i.p.)), respectively for 21 days. After drug administration, the open field test (OFT) was used to investigate motor activity. Oxidative, antioxidant and inflammatory factors were measured in isolated hippocampus. Also, the brain-derived neurotrophic factor (BDNF) level was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Cresyl violet staining of Dentate Gyrus (DG) and CA1 cell layers of the hippocampus were also performed. MPH significantly disturbs motor activity in OFT and TPM (70 and 100 mg/kg) decreased this disturbance. Also MPH significantly increased lipid peroxidation, mitochondrial reduced state of glutathione (GSH) level, interleukin (IL)-1β and tumour necrosis factor (TNF)-α and BDNF level in isolated hippocampal cells. Also superoxide dismutase, glutathione peroxidase and glutathione reductase activity significantly decreased. Various doses of TPM attenuated these effects and significantly decreased MPH-induced oxidative damage, inflammation and hippocampal cell loss and increased BDNF level. This study suggests that TPM has the potential to be used as a neuroprotective agent against oxidative stress and neuroinflammation induced by frequent use of MPH.

  14. On the delay-dependent involvement of the hippocampus in object recognition memory.

    PubMed

    Hammond, Rebecca S; Tull, Laura E; Stackman, Robert W

    2004-07-01

    The role of the hippocampus in object recognition memory processes is unclear in the current literature. Conflicting results have been found in lesion studies of both primates and rodents. Procedural differences between studies, such as retention interval, may explain these discrepancies. In the present study, acute lidocaine administration was used to temporarily inactivate the hippocampus prior to training in the spontaneous object recognition task. Male C57BL/6J mice were administered bilateral lidocaine (4%, 0.5 microl/side) or aCSF (0.5 microl/side) directly into the CA1 region of the dorsal hippocampus 5 min prior to sample object training, and object recognition memory was tested after a short ( 5 min) or long (24 h) retention interval. There was no effect of intra-hippocampal lidocaine on the time needed for mice to accumulate sample object exploration, suggesting that inactivation of the hippocampus did not affect sample session activity or the motivation to explore objects. Lidocaine-treated mice exhibited impaired object recognition memory, measured as reduced novel object preference, after a 24 h but not a 5 min retention interval. These data support a delay-dependent role for the hippocampus in object recognition memory, an effect consistent with the results of hippocampal lesion studies conducted in rats. However, these data are also consistent with the view that the hippocampus is involved in object recognition memory regardless of retention interval, and that object recognition processes of parahippocampal structures (e.g., perirhinal cortex) are sufficient to support object recognition memory over short retention intervals.

  15. Role of NMDA receptors in noise-induced tau hyperphosphorylation in rat hippocampus and prefrontal cortex.

    PubMed

    Li, Kang; Jia, Hengchuan; She, Xiaojun; Cui, Bo; Zhang, Na; Chen, Xuewei; Xu, Chuanxiang; An, Gaihong; Ma, Qiang

    2014-05-15

    Chronic noise exposure has been associated with abnormalities in glutamate (Glu)-NMDAR signaling and tau hyperphosphorylation. However, further studies are necessary to clarify potential causal relationships. The aim of the present study was to evaluate the role of NMDA receptors in noise-induced tau hyperphosphorylation in the rat hippocampus and prefrontal cortex. Male Wistar rats were randomly divided into three groups in the present study: control with isotonic saline instillation (n=10); noise exposure (100 dB SPL white noise, 4h/d × 14d) and treated with saline (n=10); and noise exposure and treated with MK-801 (0.5mg/kg, intraperitoneally; n=10). The levels of tau phosphorylated at Ser202 and Ser396, and proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A), were measured in the hippocampus and prefrontal cortex (PFC) after the last noise exposure. We showed that phosphorylated tau levels were enhanced in noise-exposed-rat hippocampus and PFC. MK-801 decreased the hyperphosphorylation of tau at Ser202 and Ser396 sites in the hippocampus and PFC. Furthermore, MK-801 reversed noise-induced GSK3β overexpression but had no significant effect on PP2A levels. This suggests that MK-801 protects against chronic-noise-induced tau hyperphosphorylation in the hippocampus and PFC. These findings demonstrate that Glu-NMDAR signaling may be involved in triggering aberrant tau hyperphosphorylation in the hippocampus and PFC after chronic noise exposure.

  16. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

    PubMed Central

    Varela-Nallar, Lorena; Arredondo, Sebastian B.; Tapia-Rojas, Cheril; Hancke, Juan; Inestrosa, Nibaldo C.

    2015-01-01

    Andrographolide (ANDRO) is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β), a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected. PMID:26798521

  17. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus.

    PubMed

    Varela-Nallar, Lorena; Arredondo, Sebastian B; Tapia-Rojas, Cheril; Hancke, Juan; Inestrosa, Nibaldo C

    2015-01-01

    Andrographolide (ANDRO) is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β), a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected.

  18. Neurofunctional topography of the human hippocampus

    PubMed Central

    Robinson, Jennifer L.; Barron, Daniel S.; Kirby, Lauren A. J.; Bottenhorn, Katherine L.; Hill, Ashley C.; Murphy, Jerry E.; Katz, Jeffrey S.; Salibi, Nouha; Eickhoff, Simon B.; Fox, Peter T.

    2015-01-01

    Much of what we assume about the functional topography of the hippocampus was derived from a single case study over half a century ago. Given advances in the imaging sciences, a new era of discovery is underway, with potential to transform our understanding of healthy processing as well as our ability to treat disorders. We employed coactivation based parcellation, a meta-analytic approach, and ultra-high field, high-resolution functional and structural neuroimaging to characterize the neurofunctional topography of the hippocampus. Data revealed strong support for an evolutionarily preserved topography along the long-axis. Specifically, the left hippocampus was segmented into three distinct clusters: an emotional processing cluster supported by structural and functional connectivity to the amygdala and parahippocampal gyrus, a cognitive operations cluster, with functional connectivity to the anterior cingulate and inferior frontal gyrus, and a posterior perceptual cluster with distinct structural connectivity patterns to the occipital lobe coupled with functional connectivity to the precuneus and angular gyrus. The right hippocampal segmentation was more ambiguous, with plausible 2- and 5-cluster solutions plausible. Segmentations shared connectivity with brain regions known to support the correlated processes. This represents the first neurofunctional topographic model of the hippocampus using a robust, bias-free, multi-modal approach. PMID:26350954

  19. Unconscious relational encoding depends on hippocampus

    PubMed Central

    Duss, Simone B.; Reber, Thomas P.; Hänggi, Jürgen; Schwab, Simon; Wiest, Roland; Müri, René M.; Brugger, Peter; Gutbrod, Klemens

    2014-01-01

    Textbooks divide between human memory systems based on consciousness. Hippocampus is thought to support only conscious encoding, while neocortex supports both conscious and unconscious encoding. We tested whether processing modes, not consciousness, divide between memory systems in three neuroimaging experiments with 11 amnesic patients (mean age = 45.55 years, standard deviation = 8.74, range = 23–60) and 11 matched healthy control subjects. Examined processing modes were single item versus relational encoding with only relational encoding hypothesized to depend on hippocampus. Participants encoded and later retrieved either single words or new relations between words. Consciousness of encoding was excluded by subliminal (invisible) word presentation. Amnesic patients and controls performed equally well on the single item task activating prefrontal cortex. But only the controls succeeded on the relational task activating the hippocampus, while amnesic patients failed as a group. Hence, unconscious relational encoding, but not unconscious single item encoding, depended on hippocampus. Yet, three patients performed normally on unconscious relational encoding in spite of amnesia capitalizing on spared hippocampal tissue and connections to language cortex. This pattern of results suggests that processing modes divide between memory systems, while consciousness divides between levels of function within a memory system. PMID:25273998

  20. NASA Fire Protection

    NASA Technical Reports Server (NTRS)

    Clark, Theodore

    2001-01-01

    This viewgraph presentation provides information on fire protection operations and administration at Stennis Space Center (SSC). The presentation also lists innovative practices and recent improvements.

  1. Administration of zinc complex of acetylsalicylic acid after the onset of myocardial injury protects the heart by upregulation of antioxidant enzymes.

    PubMed

    Korkmaz-Icöz, Sevil; Atmanli, Ayhan; Radovits, Tamás; Li, Shiliang; Hegedüs, Peter; Ruppert, Mihály; Brlecic, Paige; Yoshikawa, Yutaka; Yasui, Hiroyuki; Karck, Matthias; Szabó, Gábor

    2016-03-01

    We recently demonstrated that the pre-treatment of rats with zinc and acetylsalicylic acid complex in the form of bis(aspirinato)zinc(II) [Zn(ASA)2] is superior to acetylsalicylic acid in protecting the heart from acute myocardial ischemia. Herein, we hypothesized that Zn(ASA)2 treatment after the onset of an acute myocardial injury could protect the heart. The rats were treated with a vehicle or Zn(ASA)2 after an isoproterenol injection. Isoproterenol-induced cardiac damage [inflammatory infiltration into myocardial tissue, DNA-strand breakage evidenced by TUNEL-assay, increased 11-dehydro thromboxane (TX)B2-levels, elevated ST-segment, widened QRS complex and prolonged QT-interval] was prevented by the Zn(ASA)2 treatment. In isoproterenol-treated rats, load-independent left ventricular contractility parameters were significantly improved after Zn(ASA)2. Furthermore, Zn(ASA)2 significantly increased the myocardial mRNA-expression of superoxide dismutase-1, glutathione peroxidase-4 and decreased the level of Na(+)/K(+)/ATPase. Postconditioning with Zn(ASA)2 protects the heart from acute myocardial ischemia. Its mechanisms of action might involve inhibition of pro-inflammatory prostanoids and upregulation of antioxidant enzymes.

  2. Restoration of Calbindin After Fetal Hippocampal CA3 Cell Grafting Into the Injured Hippocampus in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Shetty, Ashok K.; Hattiangady, Bharathi

    2013-01-01

    Degeneration of the CA3 pyramidal and dentate hilar neurons in the adult rat hippocampus after an intracerebroventricular kainic acid (KA) administration, a model of temporal lobe epilepsy, leads to permanent loss of the calcium binding protein calbindin in major fractions of dentate granule cells and CA1 pyramidal neurons. We hypothesize that the enduring loss of calbindin in the dentate gyrus and the CA1 subfield after CA3-lesion is due to disruption of the hippocampal circuitry leading to hyperexcitability in these regions; therefore, specific cell grafts that are capable of both reconstructing the disrupted circuitry and suppressing hyper-excitability in the injured hippocampus can restore calbindin. We compared the effects of fetal CA3 or CA1 cell grafting into the injured CA3 region of adult rats at 45 days after KA-induced injury on the hippocampal calbindin. The calbindin immunoreactivity in the dentate granule cells and the CA1 pyramidal neurons of grafted animals was evaluated at 6 months after injury (i.e. at 4.5 months post-grafting). Compared with the intact hippocampus, the calbindin in “lesion-only” hippocampus was dramatically reduced at 6 months post-lesion. However, calbindin expression was restored in the lesioned hippocampus receiving CA3 cell grafts. In contrast, in the lesioned hippocampus receiving CA1 cell grafts, calbindin expression remained less than the intact hippocampus. Thus, specific cell grafting restores the injury-induced loss of calbindin in the adult hippocampus, likely via restitution of the disrupted circuitry. Since loss of calbindin after hippocampal injury is linked to hyperexcitability, re-expression of calbindin in both dentate gyrus and CA1 subfield following CA3 cell grafting may suggest that specific cell grafting is efficacious for ameliorating injury-induced hyperexcitability in the adult hippocampus. However, electrophysiological studies of KA-lesioned hippocampus receiving CA3 cell grafts are required in future

  3. Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats.

    PubMed

    Kishi, Takuya; Hirooka, Yoshitaka; Nagayama, Tomomi; Isegawa, Kengo; Katsuki, Masato; Takesue, Ko; Sunagawa, Kenji

    2015-01-01

    In metabolic syndrome (MetS), previous studies have suggested that cognitive decline is worsened. Among the factors associated with cognition, decreased brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. We previously reported that exercise training with calorie restriction yielded protection against cognitive decline via BDNF in the hippocampus of hypertensive rats. The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). After treatment for 28 days, body weight, insulin, fasting blood glucose, adiponectin, systolic blood pressure, and oxidative stress in the hippocampus were significantly lower, and BDNF expression in the hippocampus was significantly higher in CR and CR+A than in HF. Cognitive performance determined by the Morris water maze test was significantly higher in CR than in HF, whereas the benefit was attenuated in CR+A. In conclusion, calorie restriction protects against cognitive decline via up-regulation of BDNF/TrkB through an antioxidant effect in the hippocampus of dietary-induced obesity rats.

  4. First records of Hippocampus algiricus in the Canary Islands (north-east Atlantic Ocean) with an observation of hybridization with Hippocampus hippocampus.

    PubMed

    Otero-Ferrer, F; Herrera, R; López, A; Socorro, J; Molina, L; Bouza, C

    2015-10-01

    Morphometric and genetic analyses confirmed the first records of the West African seahorse Hippocampus algiricus at Gran Canaria Island (north-east Atlantic Ocean), and also the first evidence of interspecific hybridization in seahorses. These results provide additional data on the distribution of H. algiricus that may help to establish future conservation strategies, and uncover a new potential sympatric scenario between H. algiricus and Hippocampus hippocampus.

  5. Enriched environment induces higher CNPase positive cells in aged rat hippocampus.

    PubMed

    Zhao, Yuan-Yu; Shi, Xiao-Yan; Zhang, Lei; Wu, Hong; Chao, Feng-Lei; Huang, Chun-Xia; Gao, Yuan; Qiu, Xuan; Chen, Lin; Lu, Wei; Tang, Yong

    2013-10-25

    It had been reported that enriched environment was beneficial for the brain cognition and for the neurons and synapses in hippocampus. Previous study reported that the oligodendrocyte density in hippocampus was increased when the rats were reared in the enriched environment from weaning to adulthood. However, biological conclusions based on density were difficult to interpret because the changes in density could be due to an alteration of total quantity and/or an alteration in the reference volume. In the present study, we used unbiased stereological methods to investigate the effect of enriched environment on the total number of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) positive cells in CA1 and dentate gyrus (DG) of the hippocampus in aged rats. Our results indicated that there was significant difference in the total numbers of CNPase positive cells in both CA1 and DG between enriched environment group and standard environment group. The present study provided the first evidence for the protective effects of enriched environment on the CNPase positive cells in aged hippocampus.

  6. Combined administration of synthetic RNA and a conventional vaccine improves immune responses and protection against foot-and-mouth disease virus in swine.

    PubMed

    Borrego, Belén; Blanco, Esther; Rodríguez Pulido, Miguel; Mateos, Francisco; Lorenzo, Gema; Cardillo, Sabrina; Smitsaart, Eliana; Sobrino, Francisco; Sáiz, Margarita

    2017-03-16

    Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease and a major concern in animal health worldwide. We have previously reported the use of RNA transcripts mimicking structural domains in the non-coding regions of the FMDV RNA as potent type-I interferon (IFN) inducers showing antiviral effect in vivo, as well as their immunomodulatory properties in combination with an FMD vaccine in mice. Here, we describe the enhancing effect of RNA delivery on the immunogenicity and protection induced by a suboptimal dose of a conventional FMD vaccine in pigs. Animals receiving the RNA developed earlier and higher levels of neutralizing antibodies against homologous and heterologous isolates, compared to those immunized with the vaccine alone, and had higher anti-FMDV titers at late times post-vaccination. RNA delivery also induced higher specific T-cell response and protection levels against FMDV challenge. Peripheral blood mononuclear cells from pigs inoculated with RNA and the vaccine had a higher IFN-γ specific response than those from pigs receiving the vaccine alone. When challenged with FMDV, all three animals immunized with the conventional vaccine developed antibodies to the non-structural viral proteins 3ABC and two of them developed severe signs of disease. In the group receiving the vaccine together with the RNA, two pigs were fully protected while one showed delayed and mild signs of disease. Our results support the immunomodulatory effect of these RNA molecules in natural hosts and suggest their potential use for improvement of FMD vaccines strategies.

  7. Protection against Rift Valley fever virus infection in mice upon administration of interferon-inducing RNA transcripts from the FMDV genome.

    PubMed

    Lorenzo, Gema; Rodríguez-Pulido, Miguel; López-Gil, Elena; Sobrino, Francisco; Borrego, Belén; Sáiz, Margarita; Brun, Alejandro

    2014-09-01

    In this work we have addressed the effect of synthetic, non-infectious, RNA transcripts, mimicking structural domains of the non-coding regions (NCRs) of the foot-and-mouth disease virus (FMDV) genome on the infection of mice with Rift Valley fever virus (RVFV). Groups of 5 mice were inoculated intraperitoneally (i.p.) with 200 μg of synthetic RNA resembling the 5'-terminal S region, the internal ribosome entry site (IRES) or the 3'-NCR of the FMDV genome. RNA inoculation was performed 24h before (-24 h), 24 h after (+24 h) or simultaneously to the challenge with a lethal dose of RVFV. Administration of the IRES RNA afforded higher survival rates than administration of S or 3'NCR transcripts either at -24h or +24h after challenge. In contrast, when RNA inoculation and viral challenge were performed simultaneously, all mice survived in both IRES- and 3'NCR-inoculated groups, with an 80% survival in mice receiving the S RNA. Among survivors, a complete correlation between significant anti-RVFV circulating antibody titers and resistance to a second lethal challenge with the virus was observed, supporting a limited viral replication in the RNA-inoculated animals upon the first challenge. All three RNA transcripts were able to induce the production of systemic antiviral and pro-inflammatory cytokines. These data show that triggering of intracellular pathogen sensing pathways constitutes a promising approach towards development of novel RVF preventive or therapeutic strategies.

  8. Balance between oxidative damage and proliferative potential in an experimental rat model of CCl4-induced cirrhosis: protective role of adenosine administration.

    PubMed

    Hernández-Muñoz, R; Díaz-Muñoz, M; López, V; López-Barrera, F; Yáñez, L; Vidrio, S; Aranda-Fraustro, A; Chagoya de Sánchez, V

    1997-11-01

    Oxidative stress and its consequent lipid peroxidation (LP) exert harmful effects, which have been currently involved in the generation of carbon tetrachloride-induced cirrhosis. However, the recent report that "physiological" LP can be associated with liver regeneration (LR) makes it necessary to discriminate between oxidative stress-induced and LR-associated LP. In rats rendered cirrhotic by continuous CCl4 administration for 4 weeks, moderate cell necrosis and fine fatty infiltration were found. The histological abnormalities were accompanied by increased LP, mainly accounted for by the microsomal and cytosolic fractions and evidence of oxidative stress (decreased hepatic glutathione content and changes in xanthine oxidase and pentose phosphate pathway activities). After 8 weeks, a micronodular cirrhosis developed, but oxidative stress was greatly attenuated, only persisting in the enhanced LP confined to microsomes. Simultaneous administration of adenosine, a reliable hepatoprotector that readily prevents the onset of liver fibrosis, was able to block the oxidative stress induced by the long-term CCl4 treatment but elicited a selective subcellular distribution of increased LP, similar to that found during LR. The adenosine-induced changes in liver LP (mainly in the nuclear fraction) correlated with an increased activity of thymidine kinase. Therefore, data suggest that adenosine-mediated preservation of energy availability and mitochondrial function could participate in preventing the onset of oxidative stress in cirrhotic rats. The latter could induce a successful liver recovery, curtailing the sequence of events leading to fibrogenesis.

  9. Proteome Analysis of Rat Hippocampus Following Morphine-induced Amnesia and State-dependent Learning.

    PubMed

    Jafarinejad-Farsangi, Saeideh; Farazmand, Ali; Rezayof, Ameneh; Darbandi, Niloufar

    2015-01-01

    Morphine's effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in morphine-induced amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of morphine can change the expression level of rat hippocampal proteins during learning of a passive avoidance task. A step-through type passive avoidance task was used for the assessment of memory retention. To identify the complex pattern of protein expression induced by morphine, we compared rat hippocampal proteome either in morphine-induced amnesia or in state-dependent learning by two-dimensional gel electerophoresis and combined mass spectrometry (MS and MS/MS). Post-training administration of morphine decreased step-through latency. Pre-test administration of morphine induced state-dependent retrieval of the memory acquired under post-training morphine influence. In the hippocampus, a total of 18 proteins were identified whose MASCOT (Modular Approach to Software Construction Operation and Test) scores were inside 95% confidence level. Of these, five hippocampal proteins altered in morphine-induced amnesia and ten proteins were found to change in the hippocampus of animals that had received post-training and pre-test morphine. These proteins show known functions in cytoskeletal architecture, cell metabolism, neurotransmitter secretion and neuroprotection. The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level. In addition, our proteomicscreensuggests that morphine induces memory impairment and state-dependent learning through modulating neuronal plasticity.

  10. Administrative Synergy

    ERIC Educational Resources Information Center

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2012-01-01

    One of the biggest obstacles to overcome in creating and sustaining an administrative professional learning community (PLC) is time. Administrators are constantly deluged by the tyranny of the urgent. It is a Herculean task to carve out time for PLCs, but it is imperative to do so. In this article, the authors describe how an administrative PLC…

  11. Comparative effects of repeated administration of cadmium chloride during pregnancy and lactation and selenium protection against cadmium toxicity on some organs in immature rats' offsprings.

    PubMed

    Bekheet, Souad H M

    2011-12-01

    This research comprises studies on the transfer of cadmium (CdCl(2)) from the lactating dam to the pup via milk and absorbed in the suckling, showing that cadmium is transferred to the testes, ovary, cerebellum, and thyroid gland during development. The present studies were carried out in order to assess the protective effects of selenium against cadmium toxicity in pregnant rats. On the sixth day of gestation, the females were dosed subcutaneously either with cadmium or with cadmium and selenium in the following doses (mg/kg of body weight): 0, 1 Cd, 1 Cd + 1 Se, 2 Cd, 2 Cd + 2 Se. In groups treated with cadmium, no maternal or embryonic toxicities were observed; however, an increase in testes diameters of seminiferous tubules, a progressive sloughing of germ cells, vacuolization of Sertoli cells, and Leydig cells hyperplasia were noted. The reduction in the ovary size and inhibited folliculogenesis resulted in diminution of the numbers of primordial, growing, and tertiary follicles. The pathological change in the cerebellum, the migration of granular cells from the external germinal layer to the internal granular layer, was strongly retarded. Also, the formation of many microfollicles in the thyroid gland which mimic the changes was seen in thyrotoxicosis. It also appears that selenium used at a low-enough dose could be a very effective protection against cadmium-induced developmental toxicity in the testes, ovary, cerebellum, and thyroid gland but not in the higher dose in the ovary and cerebellum.

  12. Lack of protective effect of local administration of triamcinolone or systemic treatment with methylprednisolone against damages caused by optic nerve crush in rats.

    PubMed

    Huang, Tzu Lun; Chang, Chung Hsing; Lin, Kung Hung; Sheu, Min Muh; Tsai, Rong Kung

    2011-02-01

    The purpose of the present study was to investigate the effects of administrations of triamcinolone acetonide and systemic methylprednisolone sodium succinate on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of optic nerve crush. The treated groups either received triamcinolone immediately in the form of two pieces of soaked-gelform surrounding retrobulbar optic nerves (0.5 mg/per gelform) or methylprednisolone via peritoneal injection, and control group received intra-peritoneal injection with phosphate-buffered saline (PBS) after crush experiments. RGC density was counted by retrograde labeling with Fluorogold, and visual function was assessed by flash visual-evoked potentials. Terminal transferase dUTP nick end-labeling (TUNEL) assays, Western blot analysis of serine/threonine kinase (p-Akt), extracellular signal-regulated kinases (p-ERK) and signal transducer and activator of transcription 3 (p-STAT3) and immunohistochemistry of ED1, marker of macrophage/microglia in the optic nerve were conducted. Two and four weeks after optic nerve crush experiments, neither triamcinolone nor methylprednisolone treatment rescued the RGC from death in the central and mid-peripheral retinas compared with those of the corresponding optic nerve-crushed and PBS-treated rats. Visual-evoked potentials measurements showed a prolonged latency of the P(1) wave in all treated groups (triamcinolone-treated: 123 ± 23 ms, methylprednisolone-treated: 133 ± 25 ms and PBS-treated: 151 ± 55 ms) after two weeks. TUNEL assays showed that there was no decrease in apoptotic cells in the RGC layers of both triamcinolone treated and methylprednisolone-treated retinas. Western blot analysis showed that p-AKT, p-ERK and p-Stat3 were not up-regulated in either retina of the triamcinolone or methylprednisolone treated rats. In addition, the number of ED1-positive cells was not attenuated at the lesion sites of the ON in either treatment group. Based upon these results

  13. Electrophysiological and neurochemical changes in the rat hippocampus after in vitro and in vivo treatments with cocaine

    SciTech Connect

    Yasuda, R.P.

    1986-01-01

    The in vitro and in vivo effects of cocaine in the noradrenergic pathway in the rat hippocampus were examined. Although the blockade of (/sup 3/H)-norepinephrine-uptake by cocaine has been well-characterized in both the central and peripheral nervous systems, investigations characterizing the electrophysiological effects of cocaine in the central nervous system have been limited. The first part of this thesis examines the relationship between the ability of cocaine to potentiate the electrophysiological response to norepinephrine (NE) and the ability of cocaine to block noradrenergic high affinity uptake in rat hippocampal slices. The second part of this thesis examines the effects of the repeated administration of cocaine on noradrenergic pre- and postsynaptic function and receptors of the rat hippocampus. These studies demonstrate that after repeated administration of cocaine (10 mg/kg/day) for 8 and 14 days there is a 50% decrease in NE high affinity uptake in the rat hippocampus. This was accompanied by a 40% increase in a binding site for NE uptake inhibitors at 14 days. In contrast to these effects, there was no effect on ..beta..-adrenergic receptor number or the isoproterenol induced electrophysiological responsiveness in the rat hippocampus. The conclusion of these studies is that the repeated administration of cocaine has a greater effect on presynaptic targets in the noradrenergic system than on postsynaptic neurons.

  14. Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus.

    PubMed

    Stanojlović, Miloš; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša; Zlatković, Jelena; Horvat, Anica; Drakulić, Dunja

    2016-08-01

    Although a substantial number of pre-clinical and experimental studies have investigated effects of 17β-estradiol, its precise molecular mechanism of action in the early state of chronic cerebral hypoperfusion remains controversial. The present study attempted to verify whether post-ischemic estradiol treatment (33.3 μg/kg for seven consecutive days) affects previously reported number of hippocampal apoptotic cells and amount of DNA fragmentation characteristic for apoptosis as well as the expression of key elements within synaptosomal Akt and Erk signal transduction pathways (NF-κB, Bax, Bcl-2, cytochrome C, caspase 3, and PARP). Additionally, alterations of aforementioned molecules linked to protection in various neurodegenerative disorders were monitored in the cytosolic, mitochondrial, and nuclear fractions associating investigated kinases and NF-κB with gene expression of their downstream effectors-Bcl-2, Bax, and caspase 3. The results revealed that an initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by chronic cerebral hypoperfusion was significantly reduced by 17β-estradiol. In synaptic regions, an altered profile with respect to the protein expression of Bcl-2 and phosphorylated Akt was detected, although the level of other examined proteins was not modified. In other investigated sub-cellular fractions, 17β-estradiol elicited phosphorylation and translocation of Akt and Erk along with modulation of the expression of their subsequent effectors. Our findings support the concept that repeated post-ischemic 17β-estradiol treatment attenuates neurodegeneration induced by chronic cerebral hypoperfusion in hippocampus through the activation of investigated kinases and regulation of their downstream molecules in sub-cellular manner indicating a time window and regime of its administration as a valid therapeutic intervention.

  15. Neurotoxic kynurenine metabolism is increased in the dorsal hippocampus and drives distinct depressive behaviors during inflammation

    PubMed Central

    Parrott, J M; Redus, L; Santana-Coelho, D; Morales, J; Gao, X; O'Connor, J C

    2016-01-01

    The kynurenine pathway of tryptophan metabolism has an important role in mediating the behavioral effects of inflammation, which has implications in understanding neuropsychiatric comorbidity and for the development of novel therapies. Inhibition of the rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), prevents the development of many of these inflammation-induced preclinical behaviors. However, dysregulation in the balance of downstream metabolism, where neuroactive kynurenines are generated, is hypothesized to be a functionally important pathogenic feature of inflammation-induced depression. Here we utilized two novel transgenic mouse strains to directly test the hypothesis that neurotoxic kynurenine metabolism causes depressive-like behavior following peripheral immune activation. Wild-type (WT) or kynurenine 3-monooxygenase (KMO)-deficient (KMO−/−) mice were administered either lipopolysaccharide (LPS, 0.5 mg kg−1) or saline intraperitoneally. Depressive-like behavior was measured across multiple domains 24 h after immune challenge. LPS precipitated a robust depressive-like phenotype, but KMO−/− mice were specifically protected from LPS-induced immobility in the tail suspension test (TST) and reduced spontaneous alternations in the Y-maze. Direct administration of 3-hydroxykynurenine, the metabolic product of KMO, caused a dose-dependent increase in depressive-like behaviors. Mice with targeted deletion of 3-hydroxyanthranilic acid dioxygenase (HAAO), the enzyme that generates quinolinic acid, were similarly challenged with LPS. Similar to KMO−/− mice, LPS failed to increase immobility during the TST. Whereas kynurenine metabolism was generally increased in behaviorally salient brain regions, a distinct shift toward KMO-dependent kynurenine metabolism occurred in the dorsal hippocampus in response to LPS. Together, these results demonstrate that KMO is a pivotal mediator of hippocampal-dependent depressive-like behaviors induced by

  16. Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure.

    PubMed

    Fiedorowicz, A; Figiel, I; Kamińska, B; Zaremba, M; Wilk, S; Oderfeld-Nowak, B

    2001-09-07

    We investigated the effect of trimethyltin (TMT), a well-known neurotoxicant, on murine hippocampal neurons and glial cells. Three days following intraperitoneal (i.p.) injection of TMT into 1-month-old Balb/c mice at a dose of 2.5 mg/kg body weight we detected damage of the dentate gyrus granular neurons. The dying cells displayed chromatin condensation and internucleosomal DNA fragmentation, which are the most characteristic features of apoptosis. To study, if prolyl oligopeptidase is engaged in neuronal apoptosis following TMT administration, we pretreated mice with the specific inhibitor--Fmoc-Pro-ProCN in doses of 5 and 10 mg/kg body weight (i.p. injection). Three days following injection we did not observe any attenuation of neurotoxic damage, regardless of inhibitor dose, indicating the lack of prolyl oligopeptidase contribution to neuronal injury caused by TMT. The neurodegeneration was associated with reactive astrogliosis in whole hippocampus, but particularly in injured dentate gyrus. The reactive astrocytes showed an increased nerve growth factor (NGF) expression in ventral as well as dorsal hippocampal parts. NGF immunoreactivity was also augmented in neurons of CA3/CA4 areas, which were almost totally spared after TMT intoxication. It suggested a role for this neurotrophin in protection of pyramidal cells from loss of connection between CA3/CA4 and dentate gyrus fields. The granule neurons' death was accompanied by increased histochemical staining with isolectin B4, a marker of microglia, in the region of neurodegeneration. The microglial cells displayed ramified and ameboid morphology, characteristic of their reactive forms. Activated microglia were the main source of interleukin 1beta (IL-1beta). It is possible that this cytokine may participate in neurodegeneration of granule cells. Alternatively, IL-1beta elaborated by microglia could play a role in increasing NGF expression, both in astroglia and in CA3/CA4 neurons.

  17. Memory, scene construction, and the human hippocampus.

    PubMed

    Kim, Soyun; Dede, Adam J O; Hopkins, Ramona O; Squire, Larry R

    2015-04-14

    We evaluated two different perspectives about the function of the human hippocampus--one that emphasizes the importance of memory and another that emphasizes the importance of spatial processing and scene construction. We gave tests of boundary extension, scene construction, and memory to patients with lesions limited to the hippocampus or large lesions of the medial temporal lobe. The patients were intact on all of the spatial tasks and impaired on all of the memory tasks. We discuss earlier studies that associated performance on these spatial tasks to hippocampal function. Our results demonstrate the importance of medial temporal lobe structures for memory and raise doubts about the idea that these structures have a prominent role in spatial cognition.

  18. Does the hippocampus keep track of time?

    PubMed

    Palombo, D J; Keane, M M; Verfaellie, M

    2016-03-01

    In the present study, we examined the role of the medial temporal lobe (MTL) in prospective time estimation at short and long timescales using a novel behavioral paradigm adapted from rodent work. Amnesic patients with MTL damage and healthy control participants estimated the duration of nature-based video clips that were either short (≤ 90 s) or long (more than 4 min). Consistent with previous work in rodents, we found that amnesic patients were impaired at making estimations for long, but not for short durations. Critically, these effects were observed in patients who had lesions circumscribed to the hippocampus, suggesting that the pattern observed was not attributable to the involvement of extra-hippocampal structures. That the MTL, and more specifically the hippocampus, is critical for prospective temporal estimation only at long intervals suggests that multiple neurobiological mechanisms support prospective time estimation.

  19. Functional neurogenesis in the adult hippocampus

    NASA Astrophysics Data System (ADS)

    van Praag, Henriette; Schinder, Alejandro F.; Christie, Brian R.; Toni, Nicolas; Palmer, Theo D.; Gage, Fred H.

    2002-02-01

    There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.

  20. Development of short-snouted seahorse (Hippocampus hippocampus, L. 1758): osteological and morphological aspects.

    PubMed

    Novelli, B; Otero-Ferrer, F; Socorro, J A; Caballero, M J; Segade-Botella, A; Molina Domínguez, L

    2017-01-25

    Information about early development after male release lags behind studies of juveniles and adult seahorses, and newborn seahorses, similar in shape to adults, are considered juveniles or fry. During early life, Hippocampus hippocampus present behavioural (shift in habitat, from planktonic to benthic) and morphological changes; for this reasons, the aims of this study are to define the stage of development of H. hippocampus after they are expelled from the male brood pouch and to establish direct or indirect development through an osteological analysis. The ossification process was studied in 120 individuals, from their release to 30 days after birth. To analyse the osteological development, Alcian Blue-Alizarin Red double staining technique for bone and cartilage was adapted to this species. At birth, H. hippocampus presents a mainly cartilaginous structure that ossifies in approximately 1 month. The bony armour composed of bony rings and plates develops in 10 days. The caudal fin, a structure absent in juveniles and adult seahorses, is present at birth and progressively disappears with age. The absence of adult osteological structure in newborns, like coronet, bony rings and plates, head spines and components allowing tail prehensile abilities, suggests a metamorphosis before the juvenile stage. During the indirect development, the metamorphic stage started inside brood pouch and followed outside and leads up to reconsider the status of H. hippocampus newborns.

  1. Hippocampus responds to auditory change in rabbits.

    PubMed

    Ruusuvirta, T; Astikainen, P; Wikgren, J; Nokia, M

    2010-09-29

    Any change or novelty in the auditory environment is potentially important for survival. The cortex has been implicated in the detection of auditory change whereas the hippocampus has been associated with the detection of auditory novelty. Local field potentials (LFPs) were recorded from the CA1 area of the hippocampus in waking rabbits. In the oddball condition, a rare tone of one frequency (deviant) randomly replaced a repeated tone of another frequency (standard). In the equal-probability condition, the standard was replaced by a set of tones of nine different frequencies in order to remove the repetitive auditory background of the deviant (now labelled as control-deviant) while preserving its temporal probability. In the oddball condition, evoked potentials at 36-80 ms post-stimulus were found to have greater amplitude towards negative polarity for the deviant relative to the standard. No significant differences in response amplitudes were observed between the control-deviant and the standard. These findings suggest that the hippocampus plays a role in auditory change detection.

  2. Glucocorticoid effects on memory retrieval require concurrent noradrenergic activity in the hippocampus and basolateral amygdala.

    PubMed

    Roozendaal, Benno; Hahn, Emily L; Nathan, Sheila V; de Quervain, Dominique J-F; McGaugh, James L

    2004-09-15

    Previous findings indicate that administration of abeta-adrenoceptor antagonist systemically blocks glucocorticoid impairment of memory retrieval. Here, we report that beta-adrenoceptor activation in the hippocampus and the basolateral complex of the amygdala (BLA) is implicated in the impairing effects of glucocorticoids on memory retrieval. The specific glucocorticoid receptor (GR) agonist 11beta,17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362) (15 ng) infused into the hippocampus of male Sprague Dawley rats 60 min before water maze retention testing, 24 hr after training, impaired probe trial retention performance, as assessed by quadrant search time and initial latency to cross the platform location. Because we found previously that RU 28362 infused into the hippocampus does not affect water maze acquisition or immediate recall, the findings suggest that the GR agonist-induced retention impairment was attributable to a selective influence on long-term memory retrieval. Likewise, systemic injections of the beta1-adrenoceptor partial agonist xamoterol (3.0 or 10.0 mg/kg, s.c.) 60 min before the probe trial dose-dependently impaired retention performance. The beta-adrenoceptor antagonist propranolol (2.0 mg/kg) administered subcutaneously before retention testing did not affect retention performance alone, but blocked the memory retrieval impairment induced by concurrent intrahippocampal infusions of RU 28362. Pretest infusions of the beta1-adrenoceptor antagonist atenolol into either the hippocampus (1.25 microg in 0.5 microl) or the BLA (0.5 microg in 0.2 microl) also prevented the GR agonist-induced memory retrieval impairment. These findings suggest that glucocorticoids impair retrieval of long-term spatial memory by facilitating noradrenergic mechanisms in the hippocampus, and additionally, that norepinephrine-mediated BLA activity is critical in enabling hippocampal glucocorticoid effects on memory retrieval.

  3. Sulfite leads to neuron loss in the hippocampus of both normal and SOX-deficient rats.

    PubMed

    Kocamaz, Erdogan; Adiguzel, Esat; Er, Buket; Gundogdu, Gulşah; Kucukatay, Vural

    2012-08-01

    Sulfites are compounds commonly used as preservatives in foods, beverages and pharmaceuticals. Sulfite is also endogenously generated during the metabolism of sulfur-containing amino acids and drugs. It has been shown that sulfite is a highly toxic molecule. Many studies have examined the effects of sulfite toxicity, but the effect of ingested sulfite on the number of neurons in the hippocampus has not yet been reported. The present study was undertaken to investigate the effect of ingested sulfite on pyramidal neurons by counting cells in CA1 and CA3-2 subdivisions of the rat hippocampus. For this purpose, rats were assigned to one of four groups (6 rats per group): control (C), sulfite (S), deficient (D) and deficient+sulfite (DS). Sulfite oxidase deficiency was established by feeding rats a low molybdenum diet and adding 200ppm tungsten (W) to their drinking water. Sulfite (70mg/kg) was also administered to the animals via their drinking water. At the end of the experimental period, the rats were sacrificed by exsanguination under anesthesia, and their brains and livers quickly removed. The livers were used for a SOX activity assay, and the brains were used for neuronal counts in a known fraction of the CA1 and CA3-2 subdivisions of the left hippocampus using the optical fractionator method, which is a stereological method. The results showed that sulfite treatment caused a significant decrease in the total number of pyramidal neurons in three subdivisions of the hippocampus (CA1 and CA3-2) in the S, D and DS groups compared with the control group. It is concluded that exogenous administration of sulfite causes loss of pyramidal neurons in CA1 and CA3-2 subdivisions in both normal and SOX deficient rat hippocampus. This finding provides supporting evidence that sulfite is a neurotoxic molecule.

  4. The effect of morphine sensitization on extracellular concentrations of GABA in dorsal hippocampus of male rats.

    PubMed

    Farahmandfar, Maryam; Zarrindast, Mohammad-Reza; Kadivar, Mehdi; Karimian, Seyed Morteza; Naghdi, Nasser

    2011-11-01

    Repeated, intermittent exposure to drugs of abuse, such as morphine results in response enhancements to subsequent drug treatments, a phenomenon referred to as behavioral sensitization. As persistent neuronal sensitization may contribute to the long-lasting consequences of drug abuse, characterizing the neurochemical mechanisms of sensitization is providing insights into addiction. Although it has been shown that GABAergic systems in the CA1 region of dorsal hippocampus are involved in morphine sensitization, the alteration of extracellular level of GABA in this area in morphine sensitization has not been investigated. In the present study, using the in vivo microdialysis technique, we investigated the effect of morphine sensitization on extracellular GABA concentration in CA1 region of dorsal hippocampus of freely moving rats. Sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days free of the opioid treatment. The results showed that extracellular GABA concentration in CA1 was decreased following acute administration of morphine in non-sensitized rats. However, morphine-induced behavioral sensitization significantly increased the extracellular GABA concentration in this area. The enhancement of GABA in morphine sensitized rats was inhibited by administration of naloxone 30 min before each of three daily doses of morphine. These results suggest an adaptation of the GABAergic neuronal transmission in dorsal hippocampus induced by morphine sensitization and it is implied that opioid receptors may play an important role in this effect.

  5. Morphine and yohimbine regulate midkine gene expression in the rat hippocampus.

    PubMed

    Ezquerra, Laura; Pérez-García, Carmen; Garrido, Elisa; Díez-Fernández, Carmen; Deuel, Thomas F; Alguacil, Luis F; Herradón, Gonzalo

    2007-02-28

    Pleiotrophin and midkine are two recently discovered growth factors that promote survival and differentiation of catecholaminergic neurons. Chronic opioid stimulation has been reported to induce marked alterations of the locus coeruleus-hippocampus noradrenergic pathway, an effect that is prevented when opioids are coadministered with the alpha2-adrenoceptor antagonist yohimbine. The present work tries to examine a possible link between yohimbine reversal of morphine effects and pleiotrophin/midkine activation in the rat hippocampus by studying the levels of expression of pleiotrophin and midkine in response to acute and chronic administration of morphine, yohimbine and combinations of both drugs. Pleiotrophin gene expression was not altered by any treatment; however midkine mRNA levels were increased after chronic treatment with morphine. Chronic administration of yohimbine alone also increased midkine expression levels, whereas yohimbine and morphine administered together exhibited summatory effects on the upregulation of midkine expression levels. The data suggest that midkine could play a role in the prevention of opioid-induced neuroadaptations in hippocampus by yohimbine.

  6. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus.

    PubMed

    Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanan; Leksomboon, Ratana; Chaichun, Amnart; Wigmore, Peter; Welbat, Jariya Umka

    2015-10-05

    Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.

  7. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus

    PubMed Central

    Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanan; Leksomboon, Ratana; Chaichun, Amnart; Wigmore, Peter; Umka Welbat, Jariya

    2015-01-01

    Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis. PMID:26445061

  8. Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer's disease (APP/PS1) transgenic mice.

    PubMed

    Lin, Tzu-Wei; Shih, Yao-Hsiang; Chen, Shean-Jen; Lien, Chi-Hsiang; Chang, Chia-Yuan; Huang, Tung-Yi; Chen, Shun-Hua; Jen, Chauying J; Kuo, Yu-Min

    2015-02-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disease. Post-mortem examination and brain imaging studies indicate that neurodegeneration is evident in the hippocampus and amygdala of very early stage AD patients. Exercise training is known to enhance hippocampus- and amygdala-associated neuronal function. Here, we investigated the effects of exercise (running) on the neuronal structure and function of the hippocampus and amygdala in APP/PS1 transgenic (Tg) mice. At 4-months-old, an age before amyloid deposition, the amygdala-associated, but not the hippocampus-associated, long-term memory was impaired in the Tg mice. The dendritic complexities of the amygdalar basolateral neurons, but not those in the hippocampal CA1 and CA3 neurons, were reduced. Furthermore, the levels of BDNF/TrkB signaling molecules (i.e. p-TrkB, p-Akt and p-PKC) were reduced in the amygdala, but not in the hippocampus of the 4-month-old Tg mice. The concentrations of Aβ40 and Aβ42 in the amygdala were higher than those in the hippocampus. Ten weeks of treadmill training (from 1.5- to 4-month-old) increased the hippocampus-associated memory and dendritic arbor of the CA1 and CA3 neurons, and also restored the amygdala-associated memory and the dendritic arbor of amygdalar basolateral neurons in the Tg mice. Similarly, exercise training also increased the levels of p-TrkB, p-AKT and p-PKC in the hippocampus and amygdala. Furthermore, exercise training reduced the levels of soluble Aβ in the amygdala and hippocampus. Exercise training did not change the levels of APP or RAGE, but significantly increased the levels of LRP-1 in both brain regions of the Tg mice. In conclusion, our results suggest that tests of amygdala function should be incorporated into subject selection for early prevention trials. Long-term exercise protects neurons in the amygdala and hippocampus against AD-related degeneration, probably via enhancements of BDNF signaling pathways and Aβ clearance. Physical

  9. Ketamine regulates the presynaptic release machinery in the hippocampus.

    PubMed

    Müller, Heidi Kaastrup; Wegener, Gregers; Liebenberg, Nico; Zarate, Carlos A; Popoli, Maurizio; Elfving, Betina

    2013-07-01

    In the search for new drug targets, that may help point the way to develop fast-acting treatments for mood disorders, we have explored molecular pathways regulated by ketamine, an NMDA receptor antagonist, which has consistently shown antidepressant response within a few hours of administration. Using Sprague-Dawley rats we investigated the effects of ketamine on the presynaptic release machinery responsible for neurotransmitter release at 1, 2 and 4 h as well as 7 days after administration of a single subanesthetic dose of ketamine (15 mg/kg). A large reduction in the accumulation of SNARE complexes was observed in hippocampal synaptic membranes after 1, 2 and 4 h of ketamine administration. In parallel, we found a selective reduction in the expression of the synaptic vesicle protein synaptotagmin I and an increase in the levels of synapsin I in hippocampal synaptosomes suggesting a mechanism by which ketamine reduces SNARE complex formation, in part, by regulating the number of synaptic vesicles in the nerve terminals. Moreover, ketamine reduced Thr(286)-phosphorylated αCaMKII and its interaction with syntaxin 1A, which identifies CaMKII as a potential target for second messenger-mediated actions of ketamine. In addition, despite previous reports of ketamine-induced inhibition of GSK-3, we were unable to detect regulation of its activity after ketamine administration. Our findings demonstrate that ketamine rapidly induces changes in the hippocampal presynaptic machinery similar to those that are obtained only with chronic treatments with traditional antidepressants. This suggests that reduction of neurotransmitter release in the hippocampus has possible relevance for the rapid antidepressant effect of ketamine.

  10. Ketamine regulates the presynaptic release machinery in the hippocampus

    PubMed Central

    Müller, Heidi Kaastrup; Wegener, Gregers; Liebenberg, Nico; Zarate, Carlos A.; Popoli, Maurizio; Elfving, Betina

    2013-01-01

    In the search for new drug targets, that may help point the way to develop fast-acting treatments for mood disorders, we have explored molecular pathways regulated by ketamine, an NMDA receptor antagonist, which has consistently shown antidepressant response within a few hours of administration. Using Sprague-Dawley rats we investigated the effects of ketamine on the presynaptic release machinery responsible for neurotransmitter release at 1, 2 and 4 h as well as 7 days after administration of a single subanesthetic dose of ketamine (15 mg/kg). A large reduction in the accumulation of SNARE complexes was observed in hippocampal synaptic membranes after 1, 2 and 4 h of ketamine administration. In parallel, we found a selective reduction in the expression of the synaptic vesicle protein synaptotagmin I and an increase in the levels of synapsin I in hippocampal synaptosomes suggesting a mechanism by which ketamine reduces SNARE complex formation, in part, by regulating the number of synaptic vesicles in the nerve terminals. Moreover, ketamine reduced Thr286-phosphorylated αCaMKII and its interaction with syntaxin 1A, which identifies CaMKII as a potential target for second messenger-mediated actions of ketamine. In addition, despite previous reports of ketamine-induced inhibition of GSK-3, we were unable to detect regulation of its activity after ketamine administration. Our findings demonstrate that ketamine rapidly induces changes in the hippocampal presynaptic machinery similar to those that are obtained only with chronic treatments with traditional antidepressants. This suggests that reduction of neurotransmitter release in the hippocampus has possible relevance for the rapid antidepressant effect of ketamine. PMID:23548331

  11. Red wine interferes with oestrogen signalling in rat hippocampus.

    PubMed

    Monteiro, Rosário; Faria, Ana; Mateus, Nuno; Calhau, Conceição; Azevedo, Isabel

    2008-07-01

    Oestrogens have neuroprotective properties, resulting in memory and learning preservation. Red wine (RW) has been linked to neuroprotection, but mechanisms are largely unknown. The aim of this work was to test the effect of RW or 13% ethanol solution consumption on the expression of aromatase and estrogen receptors (ER) in the rat hippocampus. Beverages were supplied to male Wistar rats and after 8 weeks of treatment animals were euthanised, hippocampus was removed, aromatase expression assessed by western blotting and aromatase and ER transcription determined by RT-PCR. The effects of treatments on hippocampal aromatase activity were also determined, as well as the effect of several red wine polyphenols in hippocampal homogenates from untreated animals. Aromatase transcription was increased by ethanol (to 158+/-7%) but only significantly by RW (to 180+/-9%). No difference was found in ERalpha expression among groups, whereas RW significantly decreased ERbeta expression (to 63+/-10%). Resveratrol, quercetin, myricetin and kaempferol had no effect on aromatase activity and catechin (300 microM), epicatechin (200 microM), procyanidin extract (200 mg/L) and fractioned procyanidins (FI and FII; 200 mg/L) significantly decreased aromatase activity. The contribution of procyanidins in wine to the effect observed in aromatase was investigated in animals treated for the same period with these compounds (200 mg/L), although no effect was seen in aromatase activity, mRNA or protein levels, meaning that this group of compounds had little contribution, if any, to the effects observed. Nevertheless, the increase in aromatase expression induced by RW may corroborate the neuroprotective ability attributed to this beverage. Alterations in the relative abundance of ER expression may also play an important role in the protection.

  12. Oral administration of Lactococcus lactis subsp. lactis JCM5805 enhances lung immune response resulting in protection from murine parainfluenza virus infection.

    PubMed

    Jounai, Kenta; Sugimura, Tetsu; Ohshio, Konomi; Fujiwara, Daisuke

    2015-01-01

    When activated by viral infection, plasmacytoid dendritic cells (pDCs) play a primary role in the immune response through secretion of IFN-α. Lactococcus lactis subsp. lactis JCM5805 (JCM5805) is a strain of lactic acid bacteria (LAB) that activates murine and human pDCs to express type I and type III interferons (IFNs). JCM5805 has also been shown to activate pDCs via a Toll-like receptor 9 (TLR9) dependent pathway. In this study, we investigated the anti-viral effects of oral administration of JCM5805 using a mouse model of murine parainfluenza virus (mPIV1) infection. JCM5805-fed mice showed a drastic improvement in survival rate, prevention of weight loss, and reduction in lung histopathology scores compared to control mice. We further examined the mechanism of anti-viral effects elicited by JCM5805 administration using naive mice. Microscopic observations showed that JCM5805 was incorporated into CD11c+ immune cells in Peyer's patches (PP) and PP pDCs were significantly activated and the expression levels of IFNs were significantly increased. Interestingly, nevertheless resident pDCs at lung were not activated and expressions levels of IFNs at whole lung tissue were not influenced, the expressions of anti-viral factors induced by IFNs, such as Isg15, Oasl2, and Viperin, at lung were up-regulated in JCM5805-fed mice compared to control mice. Therefore expressed IFNs from intestine might be delivered to lung and IFN stimulated genes might be induced. Furthermore, elevated expressions of type I IFNs from lung lymphocytes were observed in response to mPIV1 ex vivo stimulation in JCM5805-fed mice compared to control. This might be due to increased ratio of pDCs located in lung were significantly increased in JCM5805 group. Taken together, a specific LAB strain might be able to affect anti-viral immunological profile in lung via activation of intestinal pDC leading to enhanced anti-viral phenotype in vivo.

  13. Protection of the Librarian.

    ERIC Educational Resources Information Center

    Sable, M. H.

    1984-01-01

    Explores three potential sources of harrassment from whom the librarian requires protection--patrons, lower-echelon supervisors, and library administrators. Types of protection provided by library associations, the courts, unionization, librarians' professional goals, actions of progressive administrators, collective bargaining, and public and…

  14. 40 CFR 72.12 - Administrative appeals.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Administrative appeals. 72.12 Section 72.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Program General Provisions § 72.12 Administrative appeals. The procedures...

  15. 40 CFR 72.12 - Administrative appeals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Administrative appeals. 72.12 Section 72.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Program General Provisions § 72.12 Administrative appeals. The procedures...

  16. 40 CFR 72.12 - Administrative appeals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Administrative appeals. 72.12 Section 72.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Program General Provisions § 72.12 Administrative appeals. The procedures...

  17. 40 CFR 72.12 - Administrative appeals.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Administrative appeals. 72.12 Section 72.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Program General Provisions § 72.12 Administrative appeals. The procedures...

  18. 40 CFR 72.12 - Administrative appeals.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Administrative appeals. 72.12 Section 72.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Program General Provisions § 72.12 Administrative appeals. The procedures...

  19. 40 CFR 30.47 - Contract administration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Contract administration. 30.47 Section 30.47 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER...

  20. 40 CFR 30.47 - Contract administration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Contract administration. 30.47 Section 30.47 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER...

  1. 40 CFR 30.47 - Contract administration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Contract administration. 30.47 Section 30.47 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER...

  2. 40 CFR 30.47 - Contract administration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Contract administration. 30.47 Section 30.47 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER...

  3. 40 CFR 108.7 - Hearing before Administrator.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Hearing before Administrator. 108.7 Section 108.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS EMPLOYEE PROTECTION HEARINGS § 108.7 Hearing before Administrator. At his option, the Administrator...

  4. 40 CFR 108.7 - Hearing before Administrator.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Hearing before Administrator. 108.7 Section 108.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS EMPLOYEE PROTECTION HEARINGS § 108.7 Hearing before Administrator. At his option, the Administrator...

  5. Intranasal Administration of GDNF Protects Against Neural Apoptosis in a Rat Model of Parkinson's Disease Through PI3K/Akt/GSK3β Pathway.

    PubMed

    Yue, Peijian; Gao, Lin; Wang, Xuejing; Ding, Xuebing; Teng, Junfang

    2017-02-28

    Glial cell line-derived neurotrophic factor (GDNF) plays important roles in protecting the damaged or dying dopamine neurons in the animal models of Parkinson's disease (PD). This study was to determine the effect and mechanisms of GDNF on the apoptosis of neurons in 6-hydroxydopamine (6-OHDA) induced Parkinson's disease model of rats. Healthy male Sprague-Dawley rats (220-240 g) were randomly divided into six groups (n = 10). 6-OHDA was used to establish the PD rat model. Tyrosine hydroxylase (TH) immunohistochemistry was used to assess the neuron loss in 6-OHDA-lesioned rats. TUNEL and western blot were used to identify the effects and mechanisms of GDNF in the rat model of PD. The numbers of TH-positive neurons in the 6-OHDA-injected lesioned substantia nigra (SN) decreased significantly compared with the Sham group. GDNF treatment effectively ameliorated the apoptosis of neuronal cells in SN induced by 6-OHDA. In addition, GDNF significantly increased serine protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK3β) phosphorylation induced by 6-OHDA. In contrast, application of LY294002 or triciribine reversed the roles of GDNF in PD models. The results implicated that the anti-apoptosis effects of GDNF in neurons might be mediated through PI3K/Akt/GSK3β pathway. Therefore, GDNF may be a promising agent for PD treatment.

  6. Protection against Foot-and-Mouth Disease Virus in Guinea Pigs via Oral Administration of Recombinant Lactobacillus plantarum Expressing VP1

    PubMed Central

    Wang, Miao; Pan, Li; Zhou, Peng; Lv, Jianliang; Zhang, Zhongwang; Wang, Yonglu; Zhang, Yongguang

    2015-01-01

    Mucosal vaccination is an effective strategy for generating antigen-specific immune responses against mucosal infections of foot-and-mouth disease virus (FMDV). In this study, Lactobacillus plantarum strains NC8 and WCFS1 were used as oral delivery vehicles containing a pSIP411-VP1 recombinant plasmid to initiate mucosal and systemic immune responses in guinea pigs. Guinea pigs were orally vaccinated (three doses) with NC8-pSIP411, NC8-pSIP411-VP1, WCFS1-pSIP411, WCFS1-pSIP411-VP1 or milk. Animals immunized with NC8-pSIP411-VP1 and WCFS1-pSIP411-VP1 developed high levels of antigen-specific serum IgG, IgA, IgM, mucosal secretory IgA (sIgA) and neutralizing antibodies, and revealed stronger cell-mediated immune responses and enhanced protection against FMDV challenge compared with control groups. The recombinant pSIP411-VP1 effectively improved immunoprotection against FMDV in guinea pigs. PMID:26629822

  7. Protection against Foot-and-Mouth Disease Virus in Guinea Pigs via Oral Administration of Recombinant Lactobacillus plantarum Expressing VP1.

    PubMed

    Wang, Miao; Pan, Li; Zhou, Peng; Lv, Jianliang; Zhang, Zhongwang; Wang, Yonglu; Zhang, Yongguang

    2015-01-01

    Mucosal vaccination is an effective strategy for generating antigen-specific immune responses against mucosal infections of foot-and-mouth disease virus (FMDV). In this study, Lactobacillus plantarum strains NC8 and WCFS1 were used as oral delivery vehicles containing a pSIP411-VP1 recombinant plasmid to initiate mucosal and systemic immune responses in guinea pigs. Guinea pigs were orally vaccinated (three doses) with NC8-pSIP411, NC8-pSIP411-VP1, WCFS1-pSIP411, WCFS1-pSIP411-VP1 or milk. Animals immunized with NC8-pSIP411-VP1 and WCFS1-pSIP411-VP1 developed high levels of antigen-specific serum IgG, IgA, IgM, mucosal secretory IgA (sIgA) and neutralizing antibodies, and revealed stronger cell-mediated immune responses and enhanced protection against FMDV challenge compared with control groups. The recombinant pSIP411-VP1 effectively improved immunoprotection against FMDV in guinea pigs.

  8. Protein profiling reveals antioxidant and signaling activities of NAP (Davunetide) in rodent hippocampus exposed to hypobaric hypoxia.

    PubMed

    Sethy, Niroj Kumar; Sharma, Narendra Kumar; Das, Mainak; Bhargava, Kalpana

    2014-11-01

    NAP (davunetide) is a clinical octapeptide and reportedly possesses neuroprotective, neurotrophic and cognitive protective properties. The information for NAP-mediated neuroproteome changes and associated signaling pathways during hypoxia will help in drug development programmes across the world. In the present study, we have evaluated the antioxidant activities of NAP in rat hippocampus exposed to hypobaric hypoxia (25,000 ft, 282 mm Hg) for 3, 6 and 12 h respectively. Using 2D-gel electrophoresis (2D-GE) with matrix-assisted laser desorption ionization time of flight (MALDI-TOF/TOF) mass spectrometry, we have identified altered expression of 80 proteins in NAP-supplemented hippocampus after hypoxia. Pathway analysis revealed that NAP supplementation significantly regulated oxidative stress response, oxidoreductase activity and cellular response to stress pathways during hypoxia. Additionally, NAP supplementation also regulated energy production pathways along with AMP-activated protein kinase (AMPK) signaling and signaling by Rho family GTPases pathways. We observed higher expression of antioxidant Sod1, Eno1, Prdx2 and Prdx5 proteins that were subsequently validated by Western blotting. A higher level of Prdx2 was also observed by immunohistochemistry in NAP-supplemented hippocampus during hypoxia. In corroboration, we are able to detect significant lower level of protein carbonyls in NAP-supplemented hypoxic hippocampus suggesting amelioration of oxidant molecules by NAP supplementation. These results emphasize the antioxidant and signaling properties of NAP in rodent hippocampus during hypobaric hypoxia.

  9. Mucosal vaccination with a live recombinant rhinovirus followed by intradermal DNA administration elicits potent and protective HIV-specific immune responses

    PubMed Central

    Tomusange, Khamis; Wijesundara, Danushka; Gummow, Jason; Wesselingh, Steve; Suhrbier, Andreas; Gowans, Eric J.; Grubor-Bauk, Branka

    2016-01-01

    Mucosal immunity is deemed crucial to control sexual transmission of human immunodeficiency virus (HIV). Herein we report the efficacy of a mucosal HIV vaccine strategy comprising intranasal (IN) vaccination with a cocktail of live recombinant human rhinoviruses (HRVs) encoding overlapping fragments of HIV Gag and full length Tat (rHRV-Gag/Tat) followed by intradermal (ID) vaccination with DNA vaccines encoding HIV Gag and Tat (pVAX-Gag-Tat). This heterologous prime-boost strategy will be referred to hereafter as rHRV-DNA. As a control, IN vaccination with wild type (wt)-HRV-A1 followed by a single ID dose of pVAX (wt-HRV-A1/pVAX vaccination) was included. rHRV-DNA vaccination elicited superior multi-functional CD8+T cell responses in lymphocytes harvested from mesenteric lymph nodes and spleens, and higher titres of Tat-specific antibodies in blood and vaginal lavages, and reduced the viral load more effectively after challenge with EcoHIV, a murine HIV challenge model, in peritoneal macrophages, splenocytes and blood compared compared with wt-HRV-A1/pVAX vaccination or administration of 3 ID doses of pVAX-Gag-Tat (3X pVAX-Gag-Tat vaccination). These data provide the first evidence that a rHRV-DNA vaccination regimen can induce HIV-specific immune responses in the gut, vaginal mucosa and systemically, and supports further testing of this regimen in the development of an effective mucosally-targeted HIV-1 vaccine. PMID:27853256

  10. Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats.

    PubMed

    Allagui, Mohamed Salah; Feriani, Anouer; Bouoni, Zouhour; Alimi, Hichem; Murat, Jean Claud; El Feki, Abdelfattah

    2014-09-01

    The present study aimed to investigate the potential effects of vitamins (C and E)/melatonin co-administration on the hematologic and hepatic functions and oxidative stress in alloxan-induced diabetic rats. The intraperitoneal injection of alloxan (120 mg/kg b.w. for 2 days) induced a significant increase of blood glucose levels (hyperglycemia) associated with serious hematologic disorders (P < 0.01) evidenced by the decrease in the levels of red blood cell count (RBC) (-18%), hematocrit (Ht) (-18%), hemoglobin content (Hb) (-36%), mean corpuscular hemoglobin (MCH) (-17%), and mean corpuscular hemoglobin concentration (MCHC) (-16%). The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and the plasmatic levels of total cholesterol and triglyceride contents of diabetic rats were, however, noted to undergo significant increases by 42% (P < 0.01), 134% (P < 0.001), 27.5% (P < 0.01), 147% (P < 0.001), and 67% (P < 0.01), respectively, as compared to the control animals. Furthermore, a significant increase in malondialdehyde (MDA) content and a significant decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were observed in the plasma and hepatic tissues of diabetic rats when compared to the controls. Interestingly, the treatment with vitamins (C, E) in combination with melatonin was noted to reduce the plasma levels of glucose, lower the MDA levels, and restore the hematologic parameters and biochemical and antioxidant levels of diabetic rats back to normal values, alleviating diabetes metabolic disorders in rats.

  11. Pleiotrophin as a central nervous system neuromodulator, evidences from the hippocampus.

    PubMed

    González-Castillo, Celia; Ortuño-Sahagún, Daniel; Guzmán-Brambila, Carolina; Pallàs, Mercè; Rojas-Mayorquín, Argelia Esperanza

    2014-01-01

    Pleiotrophin (PTN) is a secreted growth factor, and also a cytokine, associated with the extracellular matrix, which has recently starting to attract attention as a significant neuromodulator with multiple neuronal functions during development. PTN is expressed in several tissues, where its signals are generally related with cell proliferation, growth, and differentiation by acting through different receptors. In Central Nervous System (CNS), PTN exerts post-developmental neurotrophic and -protective effects, and additionally has been involved in neurodegenerative diseases and neural disorders. Studies in Drosophila shed light on some aspects of the different levels of regulatory control of PTN invertebrate homologs. Specifically in hippocampus, recent evidence from PTN Knock-out (KO) mice involves PTN functioning in learning and memory. In this paper, we summarize, discuss, and contrast the most recent advances and results that lead to proposing a PTN as a neuromodulatory molecule in the CNS, particularly in hippocampus.

  12. Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection.

    PubMed

    Chitradevi, Sekar Tamil Selvi; Kaur, Gurpreet; Uppalapati, Sivaramakrishna; Yadav, Anandprakash; Singh, Dependrapratap; Bansal, Anju

    2015-11-01

    Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-γ) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%-70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%-85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants.

  13. Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

    PubMed

    Piloni, Natacha E; Perazzo, Juan C; Fernandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2016-02-01

    This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(•))/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(•))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation.

  14. Evaluation of Safety and Protective Effect of Combined Extract of Cissampelos pareira and Anethum graveolens (PM52) against Age-Related Cognitive Impairment.

    PubMed

    Thukham-Mee, Wipawee; Wattanathorn, Jintanaporn

    2012-01-01

    The present study aimed to determine acute toxicity, the protective effect, and underlying mechanism of PM52, a combined extract of Cissampelos pareira and Anethum graveolens, against age-related cognitive impairment in animal model of age-related cognitive impairment. PM52 was determined as acute toxicity according to OECD guideline. Male Wistar rats, weighing 180-220 g, were orally given PM52 at doses of 2, 10, and 50 mg/kg at a period of 14 days before and 7 days after the bilateral administration of AF64A via intracerebroventricular route. All animals were assessed according to spatial memory, neuron density, MDA level, the activities of SOD, CAT, GSH-Px, and AChEI effect in hippocampus. It was found that all doses of PM52 could attenuate memory impairment and neurodegeneration in hippocampus. The possible mechanisms might occur via the suppression of AChE and the decreased oxidative stress in hippocampus. Therefore, our data suggest that PM52 may serve as food supplement to protect against age-related cognitive impairment such as mild cognitive impairment (MCI) and early phase of Alzheimer's disease. However, further researches are still essential.

  15. Administrative Ecology

    ERIC Educational Resources Information Center

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  16. Recombinant fowlpox viruses coexpressing chicken type I IFN and Newcastle disease virus HN and F genes: influence of IFN on protective efficacy and humoral responses of chickens following in ovo or post-hatch administration of recombinant viruses.

    PubMed

    Karaca, K; Sharma, J M; Winslow, B J; Junker, D E; Reddy, S; Cochran, M; McMillen, J

    1998-10-01

    We have constructed recombinant (r) fowl pox viruses (FPVs) coexpressing chicken type I interferon (IFN) and/or hemagglutinin-neuraminidase (HN) and fusion (F) proteins of Newcastle disease virus (NDV). We administered rFPVs and FPV into embryonated chicken eggs at 17 days of embryonation or in chickens after hatch. Administration of FPV or rFPVs did not influence hatchability and survival of hatched chicks. In ovo or after hatch vaccination of chickens with the recombinant viruses resulted in protection against challenge with virulent FPV and NDV. Chickens vaccinated with FPV or FPV-NDV recombinant had significantly lower body weight 2 weeks following vaccination. This loss in body weight was not detected in chickens receiving FPV-IFN and FPV-NDV-IFN recombinants. Chickens vaccinated with FPV coexpressing IFN and NDV genes produced less antibodies against NDV in comparison with chickens vaccinated with FPV expressing NDV genes.

  17. Reversion of BDNF, Akt and CREB in Hippocampus of Chronic Unpredictable Stress Induced Rats: Effects of Phytochemical, Bacopa Monnieri

    PubMed Central

    Hazra, Somoday; Kumar, Sourav; Saha, Goutam Kumar

    2017-01-01

    Objective The aims of the present study were to explore the behavioural effects and to understand the possible mode of action of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced depressive model and the biochemical alterations such as brain derived neurotrophic factor (BDNF), Akt, cyclic-AMP response element binding (CREB) protein level in the hippocampus of rats. Methods We examined the effects of chronic administration of BME on CUS exposed rats for 28 days. Behavioural changes were assessed by sucrose consumption and open field test to assess the effect of BME on CUS-induced depression. The mechanisms underlying antidepressant like action of BME was further evaluated by measuring levels of BDNF, Akt, and CREB in the hippocampus of rat brain and compared with the standard tricyclic antidepressant drug imipramine (20 mg/kg body weight). Results Exposure to CUS for 28 days produced depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity including decreased BDNF, Akt and CREB levels in the hippocampus. Daily administration of BME at a dose of (80 mg/kg body weight) significantly reverses the behavioral alteration and restored the normal level of BDNF, total and phospho-Akt, total and phospho CREB in the hippocampus of CUS induced rats as compared to vehicle treated control rats. Conclusion These findings suggest that BME ameliorates CUS induced behavioural depression in rats and that can be used as a potent therapeutic agent in treating depressive like behavior. PMID:28096878

  18. LTP enhances synaptogenesis in the developing hippocampus

    PubMed Central

    Watson, Deborah J.; Ostroff, Linnaea; Cao, Guan; Parker, Patrick H.; Smith, Heather

    2015-01-01

    ABSTRACT In adult hippocampus, long‐term potentiation (LTP) produces synapse enlargement while preventing the formation of new small dendritic spines. Here, we tested how LTP affects structural synaptic plasticity in hippocampal area CA1 of Long‐Evans rats at postnatal day 15 (P15). P15 is an age of robust synaptogenesis when less than 35% of dendritic spines have formed. We hypothesized that LTP might therefore have a different effect on synapse structure than in adults. Theta‐burst stimulation (TBS) was used to induce LTP at one site and control stimulation was delivered at an independent site, both within s. radiatum of the same hippocampal slice. Slices were rapidly fixed at 5, 30, and 120 min after TBS, and processed for analysis by three‐dimensional reconstruction from serial section electron microscopy (3DEM). All findings were compared to hippocampus that was perfusion‐fixed (PF) in vivo at P15. Excitatory and inhibitory synapses on dendritic spines and shafts were distinguished from synaptic precursors, including filopodia and surface specializations. The potentiated response plateaued between 5 and 30 min and remained potentiated prior to fixation. TBS resulted in more small spines relative to PF by 30 min. This TBS‐related spine increase lasted 120 min, hence, there were substantially more small spines with LTP than in the control or PF conditions. In contrast, control test pulses resulted in spine loss relative to PF by 120 min, but not earlier. The findings provide accurate new measurements of spine and synapse densities and sizes. The added or lost spines had small synapses, took time to form or disappear, and did not result in elevated potentiation or depression at 120 min. Thus, at P15 the spines formed following TBS, or lost with control stimulation, appear to be functionally silent. With TBS, existing synapses were awakened and then new spines formed as potential substrates for subsequent plasticity. © 2015 The Authors Hippocampus

  19. GABAergic cell types in the lizard hippocampus.

    PubMed

    Guirado, S; Dávila, J C

    1999-04-01

    The neurochemical classification of GABAergic cells in the lizard hippocampus resulted in a further division into four major, non-overlapping subtypes. Each GABAergic cell subtype displays specific targets on the principal hippocampal neurons. The synaptic targets of the GABA/neuropeptide subtype are the distal apical dendrites of principal neurons. Calretinin- and parvalbumin-containing GABAergic cells synapse on the cell body and proximal dendrites of principal cells. Calbindin is expressed in a distinct group of interneurons, the synapses of which are directed to the dendrites of principal neurons. Finally, another subtype displays NADPH-diaphorase activity, but its synaptic target has not been established.

  20. Navigating the human hippocampus without a GPS.

    PubMed

    Zucker, Halle R; Ranganath, Charan

    2015-06-01

    The award of the Nobel Prize to Professors John O'Keefe, May-Britt Moser, and Edvard Moser brings global recognition to one of the most significant success stories in modern neuroscience. Here, we consider how their findings, along with related studies of spatial cognition in rodents, have informed our understanding of the human hippocampus. Rather than identifying a "GPS" in the brain, we emphasize that these researchers helped to establish a fundamental role for cortico-hippocampal networks in the guidance of behavior based on a representation of the current place, time, and situation. We conclude by highlighting the major questions that remain to be addressed in future research.

  1. Hippocampus and neocortex: recognition and spatial memory.

    PubMed

    Vann, Seralynne D; Albasser, Mathieu M

    2011-06-01

    Recognition and spatial memory are typically associated with the perirhinal cortex and hippocampal formation, respectively. Solely focusing on these structures for these specific mnemonic functions may, however, be limiting progress in the field. The distinction between these subdivisions of memory is becoming less defined as, for example, hippocampal cells traditionally considered to encode locations also encode place-object associations. There is increasing evidence for the involvement of overlapping networks of brain structures for aspects of both spatial and recognition memory. Future models of spatial and recognition memory will have to extend beyond the hippocampus and perirhinal cortex to incorporate a wider network of cortical and subcortical structures.

  2. Key Obama officials leave administration

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2013-01-01

    Secretary of the Interior Ken Salazar is one of the latest members of the Obama administration to announce that he is leaving his position near the start of President Obama's second term in office. Salazar, who has served as interior secretary since January 2009, intends to leave the department by the end of March, the department noted on 16 January. Salazar joins a number of other key officials who are planning to leave the administration. They include Environmental Protection Agency administrator Lisa Jackson, National Oceanic and Atmospheric Administration administrator Jane Lubchenco, and U.S. Geological Survey director Marcia McNutt.

  3. Modulation of memory with septal injections of morphine and glucose: effects on extracellular glucose levels in the hippocampus.

    PubMed

    McNay, Ewan C; Canal, Clinton E; Sherwin, Robert S; Gold, Paul E

    2006-02-28

    The concentration of glucose in the extracellular fluid (ECF) of the hippocampus decreases substantially during memory testing on a hippocampus-dependent memory task. Administration of exogenous glucose, which enhances task performance, prevents this decrease, suggesting a relationship between hippocampal glucose availability and memory performance. In the present experiment, spontaneous alternation performance and task-related changes in hippocampal ECF glucose were assessed in rats after intraseptal administration of morphine, which impairs memory on a spontaneous alternation task, and after co-administration of intraseptal glucose, which attenuates that impairment. Consistent with previous findings, spontaneous alternation testing resulted in a decrease in hippocampal ECF glucose levels in control rats. However, rats that received intraseptal morphine prior to testing showed memory impairments and an absence of the task-related decrease in hippocampal ECF glucose levels. Intraseptal co-administration of glucose with morphine attenuated the memory impairment, and ECF glucose levels in the hippocampus decreased in a manner comparable to that seen in control rats. These data suggest that fluctuations in hippocampal ECF glucose levels may be a marker of mnemonic processing and support the view that decreases in extracellular glucose during memory testing reflect increased glucose demand during memory processing.

  4. Hippocampus Segmentation Based on Local Linear Mapping

    PubMed Central

    Pang, Shumao; Jiang, Jun; Lu, Zhentai; Li, Xueli; Yang, Wei; Huang, Meiyan; Zhang, Yu; Feng, Yanqiu; Huang, Wenhua; Feng, Qianjin

    2017-01-01

    We propose local linear mapping (LLM), a novel fusion framework for distance field (DF) to perform automatic hippocampus segmentation. A k-means cluster method is propose for constructing magnetic resonance (MR) and DF dictionaries. In LLM, we assume that the MR and DF samples are located on two nonlinear manifolds and the mapping from the MR manifold to the DF manifold is differentiable and locally linear. We combine the MR dictionary using local linear representation to present the test sample, and combine the DF dictionary using the corresponding coefficients derived from local linear representation procedure to predict the DF of the test sample. We then merge the overlapped predicted DF patch to obtain the DF value of each point in the test image via a confidence-based weighted average method. This approach enabled us to estimate the label of the test image according to the predicted DF. The proposed method was evaluated on brain images of 35 subjects obtained from SATA dataset. Results indicate the effectiveness of the proposed method, which yields mean Dice similarity coefficients of 0.8697, 0.8770 and 0.8734 for the left, right and bi-lateral hippocampus, respectively. PMID:28368016

  5. The Hippocampus and Disambiguation of Overlapping Sequences

    PubMed Central

    Agster, Kara L.; Fortin, Norbert J.; Eichenbaum, Howard

    2010-01-01

    Recent models of hippocampal function emphasize its potential role in disambiguating sequences of events that compose distinct episodic memories. In this study, rats were trained to distinguish two overlapping sequences of odor choices. The capacity to disambiguate the sequences was measured by the critical odor choice after the overlapping elements of the sequences. When the sequences were presented in rapid alternation, damage to the hippocampus, produced either by infusions of the neurotoxin ibotenic acid or by radiofrequency current, produced a severe deficit, although animals with radiofrequency lesions relearned the task. When the sequences were presented spaced apart and in random order, animals with radiofrequency hippocampal lesions could perform the task. However, they failed when a memory delay was imposed before the critical choice. These findings support the hypothesis that the hippocampus is involved in representing sequences of nonspatial events, particularly when interference between the sequences is high or when animals must remember across a substantial delay preceding items in a current sequence. PMID:12097529

  6. Hippocampus Segmentation Based on Local Linear Mapping.

    PubMed

    Pang, Shumao; Jiang, Jun; Lu, Zhentai; Li, Xueli; Yang, Wei; Huang, Meiyan; Zhang, Yu; Feng, Yanqiu; Huang, Wenhua; Feng, Qianjin

    2017-04-03

    We propose local linear mapping (LLM), a novel fusion framework for distance field (DF) to perform automatic hippocampus segmentation. A k-means cluster method is propose for constructing magnetic resonance (MR) and DF dictionaries. In LLM, we assume that the MR and DF samples are located on two nonlinear manifolds and the mapping from the MR manifold to the DF manifold is differentiable and locally linear. We combine the MR dictionary using local linear representation to present the test sample, and combine the DF dictionary using the corresponding coefficients derived from local linear representation procedure to predict the DF of the test sample. We then merge the overlapped predicted DF patch to obtain the DF value of each point in the test image via a confidence-based weighted average method. This approach enabled us to estimate the label of the test image according to the predicted DF. The proposed method was evaluated on brain images of 35 subjects obtained from SATA dataset. Results indicate the effectiveness of the proposed method, which yields mean Dice similarity coefficients of 0.8697, 0.8770 and 0.8734 for the left, right and bi-lateral hippocampus, respectively.

  7. Pattern Separation Deficits Following Damage to the Hippocampus

    ERIC Educational Resources Information Center

    Kirwan, C. Brock; Hartshorn, Andrew; Stark, Shauna M.; Goodrich-Hunsaker, Naomi J.; Hopkins, Ramona O.; Stark, Craig E. L.

    2012-01-01

    Computational models of hippocampal function propose that the hippocampus is capable of rapidly storing distinct representations through a process known as pattern separation. This prediction is supported by electrophysiological data from rodents and neuroimaging data from humans. Here, we test the prediction that damage to the hippocampus would…

  8. Role of the Dorsal Hippocampus in Object Memory Load

    ERIC Educational Resources Information Center

    Sannino, Sara; Russo, Fabio; Torromino, Giulia; Pendolino, Valentina; Calabresi, Paolo; De Leonibus, Elvira

    2012-01-01

    The dorsal hippocampus is crucial for mammalian spatial memory, but its exact role in item memory is still hotly debated. Recent evidence in humans suggested that the hippocampus might be selectively involved in item short-term memory to deal with an increasing memory load. In this study, we sought to test this hypothesis. To this aim we developed…

  9. Coumarin effects on amino acid levels in mice prefrontal cortex and hippocampus.

    PubMed

    Pereira, Elaine Cristina; Lucetti, Daniel Luna; Barbosa-Filho, José Maria; de Brito, Eliane Magalhães; Monteiro, Valdécio Silvano; Patrocínio, Manoel Cláudio Azevedo; de Moura, Rebeca Ribeiro; Leal, Luzia Kalyne Almeida Moreira; Macedo, Danielle Silveira; de Sousa, Francisca Cléa Florenço; de Barros Viana, Glauce Socorro; Vasconcelos, Silvânia Maria Mendes

    2009-04-24

    Coumarin is a compound known to be present in a wide variety of plants, microorganisms and animal species. Most of its effects were studied in organs and systems other than the central nervous system. The present work evaluated the effect of coumarin administration on the levels of gamma-aminobutyric acid (GABA), glutamate (GLU), glycine (GLY) and taurine (TAU) in the prefrontal cortex and hippocampus of mice. Male Swiss mice were treated with distilled water (controls), coumarin (20 or 40 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). Results showed that in the prefrontal cortex, coumarin at the lowest dose increased the levels of GLU and TAU, while GABA increased with both doses studied and GLY had its levels increased only at the dose of 40 mg/kg. Diazepam (DZP) increased the levels of GABA and TAU and decreased the levels of GLU and GLY in this area. In the hippocampus, only glutamate had its levels decreased after coumarin treatment, while diazepam increased the levels of GABA and TAU and decreased the levels of GLU in this brain region. We concluded that coumarin stimulates the release of endogenous amino acids, increasing the levels of inhibitory and excitatory amino acids in the prefrontal cortex, and decreasing glutamate levels in the hippocampus. Together, these results are of interest, considering that some neurodegenerative diseases and seizures are related to the imbalance of the amino acid levels in the CNS suggesting a perspective of a therapeutic use of coumarins in these disorders.

  10. Morphine conditioned place preference depends on glucocorticoid receptors in both hippocampus and nucleus accumbens.

    PubMed

    Dong, Zhifang; Han, Huili; Wang, Meina; Xu, Lin; Hao, Wei; Cao, Jun

    2006-01-01

    Learned association between drugs of abuse and context is essential for the formation of drug conditioned place preference (CPP), which is believed to engage many brain regions including hippocampus and nucleus accumbens (NAc). The underlying mechanisms are not fully understood. Here, we examined whether glucocorticoid receptors (GRs) of hippocampus and NAc influenced the formation of morphine CPP in Sprague Dawley rats. We found that systemic or intrahippocampal infused DMSO vehicle (DMSO 20% in saline) 30 min before daily morphine (10 mg/kg, s.c.) conditioning did not affect the formation of morphine CPP. In contrast, systemic administration (5 mg/kg, s.c.) or intrahippocampal infusion (0, 0.1, 1.0, 10, 20 microg per side) of the GR antagonist RU38486 blocked or impaired the formation of CPP in a dose-dependent manner, respectively. Furthermore, intra-NAc infused RU38486 (10 microg per side) but not DMSO vehicle also prevented the formation of CPP. These results demonstrate that both the GRs of hippocampus and NAc are necessary for the formation of morphine CPP, suggesting a neural network function of the GRs in forming the opiate-associated memory.

  11. Harmine and Imipramine Promote Antioxidant Activities in Prefrontal Cortex and Hippocampus

    PubMed Central

    Réus, Gislaine Z.; Stringari, Roberto B.; de Souza, Bruna; Petronilho, Fabrícia; Dal-Pizzol, Felipe; Hallak, Jaime E.; Zuardi, Antônio W.; Crippa, José A.; Quevedo, João

    2010-01-01

    A growing body of evidence has suggested that reactive oxygen species (ROS) may play an important role in the physiopathology of depression. Evidence has pointed to the β-carboline harmine as a potential therapeutic target for the treatment of depression. The present study we evaluated the effects of acute and chronic administration of harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) or saline in lipid and protein oxidation levels and superoxide dismutase (SOD) and catalase (CAT) activities in rat prefrontal cortex and hippocampus. Acute and chronic treatments with imipramine and harmine reduced lipid and protein oxidation, compared to control group in prefrontal cortex and hippocampus. The SOD and CAT activities increased with acute and chronic treatments with imipramine and harmine, compared to control group in prefrontal cortex and hippocampus. In conclusion, our results indicate positive effects of imipramine antidepressant and β-carboline harmine of oxidative stress parameters, increasing SOD and CAT activities and decreasing lipid and protein oxidation. PMID:21150338

  12. Hippocampus and amygdala volumes in patients with vaginismus

    PubMed Central

    Atmaca, Murad; Baykara, Sema; Ozer, Omer; Korkmaz, Sevda; Akaslan, Unsal; Yildirim, Hanefi

    2016-01-01

    AIM: To compare hippocampus and amygdala volumes of patients with vaginismus with those of healthy control subjects. METHODS: Magnetic resonance imaging was performed on ten patients with vaginismus and ten control subjects matched for age and gender. Volumes of the hippocampus and amygdala were blindly measured. RESULTS: We found that the mean right amygdala volume of patients with vaginismus were smaller than that of the healthy controls. With regard to hippocampus volumes, the mean left and right hippocampus volumes were smaller than those of the healthy controls. CONCLUSION: Our present findings suggest that there have been hippocampus and amygdala structural abnormalities in patients with vaginismus. These changes provide the notion that vaginismus may be a fear-related condition. PMID:27354964

  13. Luteinizing hormone acts at the hippocampus to dampen spatial memory.

    PubMed

    Burnham, Veronica; Sundby, Christopher; Laman-Maharg, Abigail; Thornton, Janice

    2017-03-01

    Luteinizing hormone (LH) rises dramatically during and after menopause, and has been correlated with an increased incidence of Alzheimer's disease and decreased memory performance in humans and animal models. To test whether LH acts directly on the dorsal hippocampus to affect memory, ovariectomized female rats were infused with either the LH-homologue human chorionic gonadotropin (hCG) or the LH receptor antagonist deglycosylated-hCG (dg-hCG). Infusion of hCG into either the lateral ventricle or the dorsal hippocampus caused significant memory impairments in ovariectomized estradiol-treated females. Consistent with this, infusion of the LH antagonist dg-hCG into the dorsal hippocampus caused an amelioration of memory deficits in ovariectomized females. Furthermore, the gonadotropin-releasing hormone antagonist Antide, failed to act in the hippocampus to affect memory. These findings demonstrate a significant role for LH action in the dorsal hippocampus in spatial memory dysfunction.

  14. Overactivation of NR2B-containing NMDA receptors through entorhinal-hippocampal connection initiates accumulation of hyperphosphorylated tau in rat hippocampus after transient middle cerebral artery occlusion.

    PubMed

    Xu, Cheng-Shi; Liu, An-Chun; Chen, Juan; Pan, Zhi-Yong; Wan, Qi; Li, Zhi-Qiang; Wang, Ze-Fen

    2015-08-01

    Middle cerebral artery occlusion (MCAO) induces secondary damages in the hippocampus that is remote from primary ischemic regions. Tau hyperphosphorylation is an important risk for neurodegenerative diseases. Increased tau phosphorylation has been identified in ischemic cortex, but little is known regarding the changes in the hippocampus. We showed that unilateral transient MCAO induced accumulation of hyperphosphorylated tau and concurrent dephosphorylation of glycogen synthase kinase-3β at Ser 9 in the ipsilateral hippocampus. These MCAO-induced changes were not reproduced when glutamatergic inputs from the entorhinal cortex to the hippocampus were transected; however, the changes were mimicked by intrahippocampal N-methyl-d-aspartate (NMDA) administration. Inhibition of NMDA receptor (NMDAR) subunit NR2B, but not NR2A activity in the hippocampus attenuated the accumulation of hyperphosphorylated tau and spatial cognitive impairment in MCAO rats. Together, our data suggest that overactivation of NR2B-containing NMDARs through entorhinal-hippocampal connection plays an important role in the accumulation of hyperphosphorylated tau in the hippocampus following MCAO. Glycogen synthase kinase-3β is an important protein kinase involved in NMDARs-mediated tau hyperphosphorylation. This study indicates that early inhibition of NR2B-containing NMDARs may represent a potential strategy to prevent or delay the occurrence of post-stroke dementia. Middle cerebral artery occlusion induces secondary damage in the hippocampus that is remote from primary ischemic regions. We propose that excessive activation of NR2B-containing NMDA receptors through entorhinal-hippocampal connection initiated the accumulation of hyperphosphorylated tau in the hippocampus, which subsequently induced cognitive deficit. This study provides new insights into the prospects of NR2B inhibition in stoke therapy.

  15. Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus.

    PubMed

    Nomura, Toshihiro; Oyamada, Yoshihiro; Fernandes, Herman B; Remmers, Christine L; Xu, Jian; Meltzer, Herbert Y; Contractor, Anis

    2016-01-01

    Repeated administration of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) to rodents causes long-lasting deficits in cognition and memory, and has effects on behaviors that have been suggested to be models of the cognitive impairment associated with schizophrenia (CIAS). Despite this being a widely studied animal model, little is known about the long lasting changes in synapses and circuits that underlie the altered behaviors. Here we examined synaptic transmission ex-vivo in the hippocampus of mice after a subchronic PCP (scPCP) administration regime. We found that after at least one week of drug free washout period when mice have impaired cognitive function, the threshold for long-term potentiation (LTP) of CA1 excitatory synapses was elevated. This elevated LTP threshold was directly related to increased inhibitory input to CA1 pyramidal cells through increased activity of GABAergic neurons. These results suggest repeated PCP administration causes a long-lasting metaplastic change in the inhibitory circuits in the hippocampus that results in impaired LTP, and could contribute to the deficits in hippocampal-dependent memory in PCP-treated mice. Changes in GABA signaling have been described in patients with schizophrenia, therefore our results support using scPCP as a model of CIAS. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.

  16. Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus

    PubMed Central

    Nomura, Toshihiro; Oyamada, Yoshihiro; Fernandes, Herman B.; Remmers, Christine; Xu, Jian; Meltzer, Herbert; Contractor, Anis

    2015-01-01

    Repeated administration of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) to rodents causes long-lasting deficits in cognition and memory, and has effects on behaviors that have been suggested to be models of the cognitive impairment associated with schizophrenia (CIAS). Despite this being a widely studied animal model, little is known about the long lasting changes in synapses and circuits that underlie the altered behaviors. Here we examined synaptic transmission ex-vivo in the hippocampus of mice after a subchronic PCP (scPCP) administration regime. We found that after at least one week of drug free washout period when mice have impaired cognitive function, the threshold for long term potentiation (LTP) of CA1 excitatory synapses was elevated. This elevated LTP threshold was directly related to increased inhibitory input to CA1 pyramidal cells through increased activity of GABAergic neurons. These results suggest repeated PCP administration causes a long-lasting metaplastic change in the inhibitory circuits in the hippocampus that results in impaired LTP, and could contribute to the deficits in hippocampal-dependent memory in PCP-treated mice. Changes in GABA signaling have been described in patients with schizophrenia, therefore our results support using scPCP as a model of CIAS. PMID:25937215

  17. Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus.

    PubMed

    Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui

    2016-04-15

    Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.

  18. Selective 5-hydroxytryptamine2 receptor antagonists protect against the neurotoxicity of methylenedioxymethamphetamine in rats.

    PubMed

    Schmidt, C J; Abbate, G M; Black, C K; Taylor, V L

    1990-11-01

    The serotonergic deficits resulting from methylenedioxymethamphetamine (MDMA)-induced neurotoxicity were prevented by the simultaneous administration of 5-hydroxytryptamine2 (5-HT2) receptor antagonists such as MDL 11,939 or ritanserin. This effect was not region specific as protection was observed in the cortex, hippocampus and striatum 1 week after the administration of a single dose of MDMA. MDL 11,939 also showed some efficacy at reducing the deficits in 5-HT concentrations and tryptophan hydroxylase activity produced by multiple administrations of MDMA. Protection against the neurotoxicity required the administration of MDL 11,939 within 1 hr of MDMA indicating 5-HT2 receptor activation was an early event in the process leading to terminal damage. Examination of the effect of the 5-HT2 receptor blockade on the early neurochemical alterations induced by MDMA revealed an inhibitory effect on MDMA-stimulated dopamine synthesis. Analysis of these data and the associated changes in dopamine metabolites indicates that 5-HT2 receptor antagonists block MDMA-induced neurotoxicity by interfering with the ability of the dopamine neuron to maintain its cytoplasmic pool of transmitter and thereby sustain carrier-mediated dopamine release.

  19. [Cell signaling in the epileptic hippocampus].

    PubMed

    Ferrer, I

    Cell signaling commanding death or survival in human epileptic hippocampus is difficult to trace because of the long interval between the beginning of symptoms and the sampling of damaged cerebral tissue for neuropathological examination. Intraperitoneal injection of the glutamate analogue kainic acid (KA) is a useful tool to analyze the effects of seizures and the excitotoxic damage in the rodent hippocampus. KA acts on NMDA and KA receptors, whereas it has little impact on AMPA receptors. Neurons of the hilus and CA3 neurons are primary targets of KA, although parvalbumin containing GABAergic neurons are less vulnerable than glutamatergic neurons. Immediate responses to KA are hsp 70 mRNA induction and HSP 70/72 protein expression, as well as c fos and c jun mRNA, and c Fos and c Jun protein expression in the hippocampus. Yet increased c Fos and c Jun expression is not a predictor of cell death or cell survival. In contrast, the tissular plasminogen activator (tPA) and the membrane Fas/Fas L signaling pathway probably have a role in facilitating cell death following KA injection. The involvement of other pathways remains controversial. Increased expression of the pro apoptotic Bax together with decreased Bcl 2 suggests Bax mediated apoptosis. Activation of the mitochondrial pathway includes leakage of citochrome c to the cytosol and activation of the caspase cascade leading to apoptosis. However, other studies have emphasized the limited expression of caspase 3, the main executioner of apoptosis, and the relevance of necrosis as the main form of cell death following KA excitotoxicity. Phosphorylation dependent activation of several kinases, including MAPK, p 38 and JNK/SAPK, and their substrates has been found in KA treated animals. Decreased CREBp expression is associated with cell death whereas increased ATF 2P and Elk 1P are associated with cell survival. Trophic factors probably do not play a significant role during the early stages of hippocanmpal damage but

  20. Effect of Gingko biloba extract on scopolamine-induced apoptosis in the hippocampus of rats.

    PubMed

    Jahanshahi, M; Nickmahzar, E G; Babakordi, F

    2013-09-01

    Apoptosis, known as programmed cell death, plays a crucial role in normal development and tissue homeostasis. Apoptosis is also involved in neurodegenerative diseases such as Alzheimer's disease. Amnesia refers to the loss of memory and can also be a warning sign of neurodegenerative diseases. The antioxidant properties of Ginkgo biloba extract was known previously. Therefore, the aim of this study was to examine the effects of Ginkgo biloba extract on the rat's hippocampal apoptotic neurons number after Scopolamine based amnesia. Thirty-six adult male Wistar rats were used. Rats were randomly divided into control, sham, protective and treatment groups. The rats in the sham group received only scopolamine hydrobromide (3 mg/kg) intraperitoneally. The rats in the protective and treatment groups received Ginkgo biloba extract (40, 80 mg/kg) for 7 days intraperitoneally before/after scopolamine injection. Then 48 h after the last injection, the brains of rats were withdrawn and fixed with paraformaldehyde, and then, after histological processing, the slices were stained with the TUNEL kit for apoptotic neurons. Data were compared by the ANOVA Post Hoc Tukey test; P < 0.05 was considered significant. Our results showed that Scopolamine (in the sham group) increased significantly the number of apoptotic neurons in all areas of the hippocampus compared with the control. Whereas, Ginkgo biloba extract reduce the neuronal apoptosis in the hippocampus before and/or after encounter with scopolamine. We concluded that pretreatment and treatment injection of Ginkgo biloba extract can have a protective effect for neurons and it can limit apoptosis in all area of the hippocampus.

  1. Supplemental choline during the periweaning period protects against trace conditioning impairments attributable to post-training ethanol exposure in adolescent rats.

    PubMed

    Hunt, Pamela S

    2012-08-01

    Supplemental choline during early stages of development can result in long-lasting improvements to memory function. In addition, pre- or postnatal choline has been shown to be protective against some of the adverse effects of early alcohol exposure. The present experiment examined whether supplemental choline given to rats would protect against the effects of posttraining alcohol administration on trace fear conditioning. Posttraining alcohol exposure in adolescent rats results in poor performance in this hippocampus-dependent task, although delay conditioning is unaffected. Here, rats were given an s.c. injection of either saline or choline chloride daily on postnatal days (PD) 15-26. On PD 30 subjects were trained in a trace fear conditioning procedure. For the next 3 days animals were administered 2.5 g/kg ethanol or water control, and conditional stimulus (CS)-elicited freezing was measured on PD 34. Results indicated that posttraining alcohol disrupted the expression of trace conditioning and that supplemental choline on PD 15-26 was protective against this effect. That is, choline-treated animals subsequently given posttraining ethanol performed as well as animals not given ethanol. These results indicate that supplemental choline given during the periweaning period protects against ethanol-induced impairments in a hippocampus-dependent learning task. Findings contribute to the growing literature showing improvements in learning and memory in subjects given extra dietary choline during critical periods of brain development.

  2. Collaboration with Environmental Protection Administration Taiwan (EPAT)

    EPA Pesticide Factsheets

    Through this partnership, U.S. and Taiwan environmental authorities have developed a strong capacity to reduce pollution and manage the environment through joint projects, innovate research, and knowledge exchange.

  3. Memory, scene construction, and the human hippocampus

    PubMed Central

    Kim, Soyun; Dede, Adam J. O.; Hopkins, Ramona O.; Squire, Larry R.

    2015-01-01

    We evaluated two different perspectives about the function of the human hippocampus–one that emphasizes the importance of memory and another that emphasizes the importance of spatial processing and scene construction. We gave tests of boundary extension, scene construction, and memory to patients with lesions limited to the hippocampus or large lesions of the medial temporal lobe. The patients were intact on all of the spatial tasks and impaired on all of the memory tasks. We discuss earlier studies that associated performance on these spatial tasks to hippocampal function. Our results demonstrate the importance of medial temporal lobe structures for memory and raise doubts about the idea that these structures have a prominent role in spatial cognition. PMID:25825712

  4. NEUROINFLAMMATION IN THE NORMAL AGING HIPPOCAMPUS

    PubMed Central

    BARRIENTOS, R. M.; KITT, M. M.; WATKINS, L. R.; MAIER, S. F.

    2015-01-01

    A consequence of normal aging is a greater susceptibility to memory impairments following an immune challenge such as infection, surgery, or traumatic brain injury. The neuroinflammatory response, produced by these challenges results in increased and prolonged production of pro-inflammatory cytokines in the otherwise healthy aged brain. Here we discuss the mechanisms by which long-lasting elevations in pro-inflammatory cytokines in the hippocampus produce memory impairments. Sensitized microglia are a primary source of this exaggerated neuroinflammatory response and appear to be a hallmark of the normal aging brain. We review the current understanding of the causes and effects of normal aging-induced microglial sensitization, including dysregulations of the neuroendocrine system, potentiation of neuroinflammatory responses following an immune challenge, and the impairment of memories. We end with a discussion of therapeutic approaches to prevent these deleterious effects. PMID:25772789

  5. The hippocampus as a cognitive graph

    PubMed Central

    Muller, RU; Stead, M; Pach, J

    1996-01-01

    preexisting barrier, respectively. We argue that the ability to solve such problems qualifies the proposed hippocampal object as a cognitive map. Graph theory thus provides a sort of existence proof demonstrating that the hippocampus contains the necessary information to function as a map, in the sense postulated by others (O'Keefe, J., and L. Nadel. 1978. The Hippocampus as a Cognitive Map. Clarendon Press, Oxford, UK). It is also possible that the cognitive mapping functions of the hippocampus are carried out by parallel graph searching algorithms implemented as neural processes. This possibility has the great attraction that the hippocampus could then operate in much the same way to find paths in general problem space; it would only be necessary for pyramidal cells to exhibit a strong nonpositional firing correlate. PMID:8783070

  6. 40 CFR 97.508 - Administrative appeal procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Administrative appeal procedures. 97.508 Section 97.508 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Trading Program § 97.508 Administrative appeal procedures. The administrative appeal procedures...

  7. 40 CFR 97.508 - Administrative appeal procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Administrative appeal procedures. 97.508 Section 97.508 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Trading Program § 97.508 Administrative appeal procedures. The administrative appeal procedures...

  8. LTP enhances synaptogenesis in the developing hippocampus.

    PubMed

    Watson, Deborah J; Ostroff, Linnaea; Cao, Guan; Parker, Patrick H; Smith, Heather; Harris, Kristen M

    2016-05-01

    In adult hippocampus, long-term potentiation (LTP) produces synapse enlargement while preventing the formation of new small dendritic spines. Here, we tested how LTP affects structural synaptic plasticity in hippocampal area CA1 of Long-Evans rats at postnatal day 15 (P15). P15 is an age of robust synaptogenesis when less than 35% of dendritic spines have formed. We hypothesized that LTP might therefore have a different effect on synapse structure than in adults. Theta-burst stimulation (TBS) was used to induce LTP at one site and control stimulation was delivered at an independent site, both within s. radiatum of the same hippocampal slice. Slices were rapidly fixed at 5, 30, and 120 min after TBS, and processed for analysis by three-dimensional reconstruction from serial section electron microscopy (3DEM). All findings were compared to hippocampus that was perfusion-fixed (PF) in vivo at P15. Excitatory and inhibitory synapses on dendritic spines and shafts were distinguished from synaptic precursors, including filopodia and surface specializations. The potentiated response plateaued between 5 and 30 min and remained potentiated prior to fixation. TBS resulted in more small spines relative to PF by 30 min. This TBS-related spine increase lasted 120 min, hence, there were substantially more small spines with LTP than in the control or PF conditions. In contrast, control test pulses resulted in spine loss relative to PF by 120 min, but not earlier. The findings provide accurate new measurements of spine and synapse densities and sizes. The added or lost spines had small synapses, took time to form or disappear, and did not result in elevated potentiation or depression at 120 min. Thus, at P15 the spines formed following TBS, or lost with control stimulation, appear to be functionally silent. With TBS, existing synapses were awakened and then new spines formed as potential substrates for subsequent plasticity.

  9. Engineering Administration.

    ERIC Educational Resources Information Center

    Naval Personnel Program Support Activity, Washington, DC.

    This book is intended to acquaint naval engineering officers with their duties in the engineering department. Standard shipboard organizations are analyzed in connection with personnel assignments, division operations, and watch systems. Detailed descriptions are included for the administration of directives, ship's bills, damage control, training…

  10. Administrative IT

    ERIC Educational Resources Information Center

    Grayson, Katherine, Ed.

    2006-01-01

    When it comes to Administrative IT solutions and processes, best practices range across the spectrum. Enterprise resource planning (ERP), student information systems (SIS), and tech support are prominent and continuing areas of focus. But widespread change can also be accomplished via the implementation of campuswide document imaging and sharing,…

  11. Database Administrator

    ERIC Educational Resources Information Center

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  12. [Interhemisphere asymmetry of hippocampus and neocortex in correlates of active and passive behavioural strategy in negative emotional situations].

    PubMed

    Pavlova, I V; Rysakova, M P; Ziablintseva, E A

    2010-12-01

    The interhemisphere interaction of neurons in bilateral derivations from parietal and sensomotor areas of neocortex and the area CA1 of hippocampus were studied in rabbits with active and passive behavioural strategy in the open field by plotting histograms of crosscorrelation. In passive animals, there was asymmetry in bilateral neuronal interaction: with right-sided dominance in the neocortex and with left-sided that--in the hippocampus. On the contrary, in active rabbits, the left-sided dominance was observed in the neocortex, and the lateralization was not revealed in the hippocampus. The brain laterality was reflected in motor asymmetry of animals in preferring left or right turns in the open field. Passive rabbits made relatively more left turns, and the active animals--right turns. Systemic administration of agonist GABA(B) receptors phenibut decreased behavioural responses to emotional stimuli and eliminated interhemisphere asymmetry observed usually in negative emotional situations. Thus the interhemisphere asymmetry of the neocortex and hippocampus is correlated with individual typological characteristics of animals and reflects the readiness to preferential forms of behavioural responses in active and passive rabbits.

  13. Radiation Protection Handbook

    NASA Technical Reports Server (NTRS)

    1972-01-01

    A handbook which sets forth the Kennedy Space Center radiation protection policy is presented. The book also covers administrative direction and guidance on organizational and procedural requirements of the program. Only ionizing radiation is covered.

  14. Spatial memory and the avian hippocampus: research in zebra finches.

    PubMed

    Mayer, Uwe; Watanabe, Shigeru; Bischof, Hans-Joachim

    2013-01-01

    The aim of the present review is to show that spatial learning and memory is not a specialty of just a few avian species, and to describe the role of the avian hippocampus in spatial learning, memory and orientation. Based on our own research in zebra finches, we try to give an (not complete and probably biased) overview of this topic, and we also discuss the question of functional equivalence of hippocampus in birds and in mammals in that we question how far theories developed for mammalian hippocampus can also be applied to the avian hippocampal formation.

  15. 40 CFR 108.4 - Investigation by Regional Administrator.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Investigation by Regional Administrator. 108.4 Section 108.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS EMPLOYEE PROTECTION HEARINGS § 108.4 Investigation by Regional Administrator. Upon receipt of...

  16. 40 CFR 108.4 - Investigation by Regional Administrator.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Investigation by Regional Administrator. 108.4 Section 108.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS EMPLOYEE PROTECTION HEARINGS § 108.4 Investigation by Regional Administrator. Upon receipt of...

  17. Caffeine and modafinil given during 48 h sleep deprivation modulate object recognition memory and synaptic proteins in the hippocampus of the rat.

    PubMed

    Wadhwa, M; Sahu, S; Kumari, P; Kauser, H; Ray, K; Panjwani, U

    2015-11-01

    We aimed to evaluate the effect of caffeine/modafinil on sleep deprivation (SD) induced alterations in recognition memory and synaptic proteins. The data revealed a beneficial effect of caffeine/modafinil against deficit in the familiar object retrieval performance and object exploration ratio after 48 h SD. Caffeine treatment prevented the SD induced down-regulation of synaptophysin and synapsin I proteins with no change in PSD-95 protein in hippocampus. However, modafinil administration improved the down-regulation of synaptophysin, synapsin I and PSD-95 proteins in hippocampus. Hence, caffeine/modafinil can serve as counter measures in amelioration of SD induced consequences at behavioural and protein levels.

  18. The protective effect of Borago Officinalis extract on amyloid β (25-35)-induced long term potentiation disruption in the dentate gyrus of male rats.

    PubMed

    Zargooshnia, Somayeh; Shahidi, Siamak; Ghahremanitamadon, Fatemeh; Nikkhah, Ali; Mehdizadeh, Mehdi; Soleimani Asl, Sara

    2015-02-01

    Alzheimer's disease (AD) begins with impairment in synaptic functions before developing into later neurodegeneration and neural loss. In the present study we have examined the protective effects of Borago Officinalis (borage) extract on amyloid β (Aβ)--Induced long term potentiation (LTP) disruption in hippocampal dentate gyrus (DG). Wistar male rats received intrahippocampal (IHP) injection of the Aβ (25-35) and borage extract throughout gestation (100 mg/kg). LTP in perforant path- DG synapses was assessed using electrophysiology method and field excitatory post- synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured by 400 Hz tetanization. Finally, the total thiol content of hippocampus was measured using colorimetric reaction based on the Ellman's method. The results showed that Aβ (25-35) significantly decreased fEPSP slope and SP amplitude comparing with the control and sham group, whereas borage extract administration increased these parameters compared to the Aβ group. Aβ induced a remarkable decrease in total thiol content of hippocampus and borage prevented the decrease of the hippocampal total sulfhydryl (SH) groups. This data suggest that Aβ (25-35) can effectively inhibit LTP in the granular cells of the DG in hippocampus, and borage supplementation reverse the synaptic plasticity in DG following Aβ treatment and that borage consumption may lead to an improvement of AD-induced cognitive dysfunction.

  19. Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex.

    PubMed

    Sanchez, Diego; Bajo-Grañeras, Raquel; Del Caño-Espinel, Manuela; Garcia-Centeno, Rosa; Garcia-Mateo, Nadia; Pascua-Maestro, Raquel; Ganfornina, Maria D

    2015-07-01

    A detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in the cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in the cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of the cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism.

  20. Statistical learning of temporal community structure in the hippocampus.

    PubMed

    Schapiro, Anna C; Turk-Browne, Nicholas B; Norman, Kenneth A; Botvinick, Matthew M

    2016-01-01

    The hippocampus is involved in the learning and representation of temporal statistics, but little is understood about the kinds of statistics it can uncover. Prior studies have tested various forms of structure that can be learned by tracking the strength of transition probabilities between adjacent items in a sequence. We test whether the hippocampus can learn higher-order structure using sequences that have no variance in transition probability and instead exhibit temporal community structure. We find that the hippocampus is indeed sensitive to this form of structure, as revealed by its representations, activity dynamics, and connectivity with other regions. These findings suggest that the hippocampus is a sophisticated learner of environmental regularities, able to uncover higher-order structure that requires sensitivity to overlapping associations.

  1. Fall Protection in Construction

    DTIC Science & Technology

    1998-01-01

    Fall Protection in Construction U.S. Department of Labor Occupational Safety and Health Administration OSHA 3146 1998(Revised) Report Documentation...Department of Labor Occupational Safety & Health Administration 200 Constitution Avenue Washington, DC 20210 Performing Organization Report Number OSHA 3146...compliance responsibili- ties, which are set forth in OSHA standards themselves, and the Occupational Safety and Health Act. Moreover, because

  2. Hippocampus and Amygdala Morphology in Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Plessen, Kerstin J.; Bansal, Ravi; Zhu, Hongtu; Whiteman, Ronald; Amat, Jose; Quackenbush, Georgette A.; Martin, Laura; Durkin, Kathleen; Blair, Clancy; Royal, Jason; Hugdahl, Kenneth; Peterson, Bradley S.

    2008-01-01

    Context Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. Objective To study the morphology of the hippocampus and amygdala in children with ADHD. Design A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. Settings University research institute. Patients One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. Main Outcome Measures Volumes and measures of surface morphology for the hippocampus and amygdala. Results The hippocampus was larger bilaterally in the ADHD group than in the control group (t=3.35; P<.002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. Conclusions The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD. PMID:16818869

  3. A quantitative transcriptome reference map of the normal human hippocampus.

    PubMed

    Caracausi, Maria; Rigon, Vania; Piovesan, Allison; Strippoli, Pierluigi; Vitale, Lorenza; Pelleri, Maria Chiara

    2016-01-01

    We performed an innovative systematic meta-analysis of 41 gene expression profiles of normal human hippocampus to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 30,739 known mapped and the 16,258 uncharacterized (unmapped) transcripts. For this aim, we used the software called TRAM (Transcriptome Mapper), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the hippocampus with the whole brain transcriptome map to identify a typical expression pattern of this subregion compared with the whole organ. Finally, due to the fact that the hippocampus is one of the main brain region to be severely affected in trisomy 21 (the best known genetic cause of intellectual disability), a particular attention was paid to the expression of chromosome 21 (chr21) genes. Data were downloaded from microarray databases, processed, and analyzed using TRAM software. Among the main findings, the most over-expressed loci in the hippocampus are the expressed sequence tag cluster Hs.732685 and the member of the calmodulin gene family CALM2. The tubulin folding cofactor B (TBCB) gene is the best gene at behaving like a housekeeping gene. The hippocampus vs. the whole brain differential transcriptome map shows the over-expression of LINC00114, a long non-coding RNA mapped on chr21. The hippocampus transcriptome map was validated in vitro by assaying gene expression through several magnitude orders by "Real-Time" reverse transcription polymerase chain reaction (RT-PCR). The highly significant agreement between in silico and experimental data suggested that our transcriptome map may be a useful quantitative reference benchmark for gene expression studies related to human hippocampus. Furthermore, our analysis yielded biological insights about those genes that have an intrinsic over-/under-expression in the hippocampus.

  4. Hippocampus, delay discounting, and vicarious trial-and-error.

    PubMed

    Bett, David; Murdoch, Lauren H; Wood, Emma R; Dudchenko, Paul A

    2015-05-01

    In decision-making, an immediate reward is usually preferred to a delayed reward, even if the latter is larger. We tested whether the hippocampus is necessary for this form of temporal discounting, and for vicarious trial-and-error at the decision point. Rats were trained on a recently developed, adjustable delay-discounting task (Papale et al. (2012) Cogn Affect Behav Neurosci 12:513-526), which featured a choice between a small, nearly immediate reward, and a larger, delayed reward. Rats then received either hippocampus or sham lesions. Animals with hippocampus lesions adjusted the delay for the larger reward to a level similar to that of sham-lesioned animals, suggesting a similar valuation capacity. However, the hippocampus lesion group spent significantly longer investigating the small and large rewards in the first part of the sessions, and were less sensitive to changes in the amount of reward in the large reward maze arm. Both sham- and hippocampus-lesioned rats showed a greater amount of vicarious trial-and-error on trials in which the delay was adjusted. In a nonadjusting version of the delay discounting task, animals with hippocampus lesions showed more variability in their preference for a larger reward that was delayed by 10 s compared with sham-lesioned animals. To verify the lesion behaviorally, rat were subsequently trained on a water maze task, and rats with hippocampus lesions were significantly impaired compared with sham-lesioned animals. The findings on the delay discounting tasks suggest that damage to the hippocampus may impair the detection of reward magnitude.

  5. Protection and Safety.

    ERIC Educational Resources Information Center

    American School Board Journal, 1964

    1964-01-01

    Several aspects of school safety and protection are presented for school administrators and architects. Among those topics discussed are--(1) life safety, (2) vandalism controlled through proper design, (3) personal protective devices, and (4) fire alarm systems. Another critical factor in providing a complete school safety program is proper…

  6. Musical Training Induces Functional Plasticity in Human Hippocampus

    PubMed Central

    Esposito, Fabrizio; di Salle, Francesco; Boller, Christian; Hilti, Caroline C.; Habermeyer, Benedikt; Scheffler, Klaus; Wetzel, Stephan; Seifritz, Erich; Cattapan-Ludewig, Katja

    2010-01-01

    Training can change the functional and structural organization of the brain, and animal models demonstrate that the hippocampus formation is particularly susceptible to training-related neuroplasticity. In humans, however, direct evidence for functional plasticity of the adult hippocampus induced by training is still missing. Here, we used musicians' brains as a model to test for plastic capabilities of the adult human hippocampus. By using functional magnetic resonance imaging optimized for the investigation of auditory processing, we examined brain responses induced by temporal novelty in otherwise isochronous sound patterns in musicians and musical laypersons, since the hippocampus has been suggested previously to be crucially involved in various forms of novelty detection. In the first cross-sectional experiment, we identified enhanced neural responses to temporal novelty in the anterior left hippocampus of professional musicians, pointing to expertise-related differences in hippocampal processing. In the second experiment, we evaluated neural responses to acoustic temporal novelty in a longitudinal approach to disentangle training-related changes from predispositional factors. For this purpose, we examined an independent sample of music academy students before and after two semesters of intensive aural skills training. After this training period, hippocampal responses to temporal novelty in sounds were enhanced in musical students, and statistical interaction analysis of brain activity changes over time suggests training rather than predisposition effects. Thus, our results provide direct evidence for functional changes of the adult hippocampus in humans related to musical training. PMID:20107063

  7. Relating Hippocampus to Relational Memory Processing across Domains and Delays

    PubMed Central

    Monti, Jim M.; Cooke, Gillian E.; Watson, Patrick D.; Voss, Michelle W.; Kramer, Arthur F.; Cohen, Neal J.

    2015-01-01

    The hippocampus has been implicated in a diverse set of cognitive domains and paradigms, including cognitive mapping, long-term memory, and relational memory, at long or short study–test intervals. Despite the diversity of these areas, their association with the hippocampus may rely on an underlying commonality of relational memory processing shared among them. Most studies assess hippocampal memory within just one of these domains, making it difficult to know whether these paradigms all assess a similar underlying cognitive construct tied to the hippocampus. Here we directly tested the commonality among disparate tasks linked to the hippocampus by using PCA on performance from a battery of 12 cognitive tasks that included two traditional, long-delay neuropsychological tests of memory and two laboratory tests of relational memory (one of spatial and one of visual object associations) that imposed only short delays between study and test. Also included were different tests of memory, executive function, and processing speed. Structural MRI scans from a subset of participants were used to quantify the volume of the hippocampus and other subcortical regions. Results revealed that the 12 tasks clustered into four components; critically, the two neuropsychological tasks of long-term verbal memory and the two laboratory tests of relational memory loaded onto one component. Moreover, bilateral hippocampal volume was strongly tied to performance on this component. Taken together, these data emphasize the important contribution the hippocampus makes to relational memory processing across a broad range of tasks that span multiple domains. PMID:25203273

  8. Relating hippocampus to relational memory processing across domains and delays.

    PubMed

    Monti, Jim M; Cooke, Gillian E; Watson, Patrick D; Voss, Michelle W; Kramer, Arthur F; Cohen, Neal J

    2015-02-01

    The hippocampus has been implicated in a diverse set of cognitive domains and paradigms, including cognitive mapping, long-term memory, and relational memory, at long or short study-test intervals. Despite the diversity of these areas, their association with the hippocampus may rely on an underlying commonality of relational memory processing shared among them. Most studies assess hippocampal memory within just one of these domains, making it difficult to know whether these paradigms all assess a similar underlying cognitive construct tied to the hippocampus. Here we directly tested the commonality among disparate tasks linked to the hippocampus by using PCA on performance from a battery of 12 cognitive tasks that included two traditional, long-delay neuropsychological tests of memory and two laboratory tests of relational memory (one of spatial and one of visual object associations) that imposed only short delays between study and test. Also included were different tests of memory, executive function, and processing speed. Structural MRI scans from a subset of participants were used to quantify the volume of the hippocampus and other subcortical regions. Results revealed that the 12 tasks clustered into four components; critically, the two neuropsychological tasks of long-term verbal memory and the two laboratory tests of relational memory loaded onto one component. Moreover, bilateral hippocampal volume was strongly tied to performance on this component. Taken together, these data emphasize the important contribution the hippocampus makes to relational memory processing across a broad range of tasks that span multiple domains.

  9. Impaired hippocampal-dependent learning and functional abnormalities in the hippocampus in mice lacking serotonin1A receptors

    PubMed Central

    Sarnyai, Zoltán; Sibille, Etienne L.; Pavlides, Constantine; Fenster, Robert J.; McEwen, Bruce S.; Tóth, Miklós

    2000-01-01

    The hippocampus is a major limbic target of the brainstem serotonergic neurons that modulate fear, anxiety, and learning through postsynaptic serotonin1A receptors (5-HT1A receptors). Because chronic stress selectively down-regulates the 5-HT1A receptors in the hippocampus, we hypothesized that mice lacking these receptors may exhibit abnormalities reminiscent of symptoms of stress-related psychiatric disorders. In particular, a hippocampal deficit in the 5-HT1A receptor could contribute to the cognitive abnormalities often seen in these disorders. To test whether a deficit in 5-HT1A receptors impairs hippocampus-related functions, we studied hippocampal-dependent learning and memory, synaptic plasticity in the hippocampus, and limbic neuronal excitability in 5-HT1A-knockout (KO) mice. 5-HT1A-KO animals showed a deficit in hippocampal-dependent learning and memory tests, such as the hidden platform (spatial) version of the Morris water maze and the delayed version of the Y maze. The performance of KO mice was not impaired in nonhippocampal memory tasks such as the visible platform (nonspatial) version of the Morris water maze, the immediate version of the Y maze, and the spontaneous-alternation test of working memory. Furthermore, paired-pulse facilitation in the dentate gyrus of the hippocampus was impaired in 5-HT1A-KO mice. Finally, 5-HT1A-KO mice, as compared with wild-type animals, displayed higher limbic excitability manifested as lower seizure threshold and higher lethality in response to kainic acid administration. These results demonstrate that 5-HT1A receptors are required for maintaining normal hippocampal functions and implicate a role for the 5-HT1A receptor in hippocampal-related symptoms, such as cognitive disturbances, in stress-related disorders. PMID:11121072

  10. Education mediates microstructural changes in bilateral hippocampus.

    PubMed

    Piras, Fabrizio; Cherubini, Andrea; Caltagirone, Carlo; Spalletta, Gianfranco

    2011-02-01

    Education has been extensively considered an influential factor in the modulation of interindividual differences in cognitive performance and cerebral structure. Consequently, education has been linked to the concept of reserve, which refers to an unspecified aspect of brain structure or function that enables people with more education to cope better with brain pathology or age-related changes. Nevertheless, the education-related neural mechanisms involved in reserve are still not completely understood. In this study, 150 healthy subjects were submitted to a comprehensive sociodemographic, clinical and cognitive assessment, and a high-resolution structural MRI and diffusion tensor imaging scan protocol. Data of micro- (mean diffusivity, MD) and macro- (volume) structural changes of six bilateral deep gray matter structures (thalamus, caudate nucleus, putamen, hippocampus, amygdala, and globus pallidus) were analyzed with reference to years of formal education. Results show that decreased MD in both left and right hippocampi was the only structural parameter that, along with decreasing age, significantly correlated with higher education. The present findings suggest that the hippocampal formation might be one site where education-mediated microstructural changes occur, possibly compensating for cognitive decline.

  11. Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline.

    PubMed

    Kang, Yunxiao; Yan, Wensheng; Fang, Hui; Zhang, Guoliang; Du, Yakun; Wang, Lei; Cui, Huixian; Shi, Geming

    2017-01-01

    The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients.

  12. Pretreatment with minocycline restores neurogenesis in the subventricular zone and subgranular zone of the hippocampus after ketamine exposure in neonatal rats.

    PubMed

    Lu, Yang; Giri, P K; Lei, Shan; Zheng, Juan; Li, Weisong; Wang, Ning; Chen, Xinlin; Lu, Haixia; Zuo, Zhiyi; Liu, Yong; Zhang, Pengbo

    2017-04-05

    Ketamine is commonly used for anesthesia in pediatric patients. Recent studies indicated that ketamine exposure in the developing brain can induce neuroapoptosis and disturb normal neurogenesis, which will result in long-lasting cognitive impairment. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative diseases models. In the present study, we investigated whether the disturbed neurogenesis and behavioural deficits after ketamine neonatal exposure could be alleviated by minocycline. Postnatal day(PND)7 Sprague-Dawley rat pups randomly received either normal saline, ketamine, or minocycline 30min prior to ketamine administration, respectively. The rats were decapitated at PND14 for the detection of neurogenesis in the subventricularzone(SVZ) and subgranular zone (SGZ) of the hippocampus by immunostaining. The protein expression of p-Akt, p-GSK-3β in the SVZ and SGZ at 12h after anesthesia, PND10 and PND14 were assessed by western blotting analysis. At PND 42-47, spatial learning and memory abilities were measured by the Morris water maze in all groups. Our data showed that ketamine exposure in neonatal rats resulted in neurogenetic damage and persistent cognitive deficits, and that pretreatment with minocycline eliminated the brain development damage and improved the behavioral function in adult rats. Moreover, the protection of minocycline is associated with the PI3K/Akt signaling pathway.

  13. Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

    PubMed Central

    Yan, Wensheng; Fang, Hui; Zhang, Guoliang; Du, Yakun; Wang, Lei; Cui, Huixian

    2017-01-01

    The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients. PMID:28386312

  14. 40 CFR 179.130 - Administrative record.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Administrative record. 179.130 Section 179.130 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS... closed: (1) With respect to the taking of evidence, when specified by the presiding officer. (2)...

  15. Protective effect of glutathione on kainic acid-induced neuropathological changes in the rat brain.

    PubMed

    Saija, A; Princi, P; Pisani, A; Lanza, M; Scalese, M; Aramnejad, E; Ceserani, R; Costa, G

    1994-01-01

    1. Glutathione (GSH), injected by slow intravenous (i.v.) infusion (7.9 microliters/min, for 4 hr; total dose: 1.5 g/kg), starting 10 min after i.v. injection of kainic acid (KA; 12 mg/kg) in the rat reduced the decrease in local cerebral glucose utilization observed 48 hr following the administration of the neurotoxin. 2. Furthermore, it blocked the neuronal loss in hippocampal CA1 and CA3 regions, and prevented, in the hippocampus, the development of edema and the marked depletion in the endogenous brain GSH pool. 3. One can speculate that this protective effect of exogenous GSH is correlated to its capacity to scavenge free radicals, thus preventing the accumulation of oxidant chemical species and the consequent reduction of cellular antioxidant defense.

  16. The protective effects of long-term oral administration of marine collagen hydrolysate from chum salmon on collagen matrix homeostasis in the chronological aged skin of Sprague-Dawley male rats.

    PubMed

    Liang, Jiang; Pei, Xinrong; Zhang, Zhaofeng; Wang, Nan; Wang, Junbo; Li, Yong

    2010-10-01

    To investigate the long-term effects of marine collagen hydrolysate (MCH) from Chum Salmon skin on the aberrant collagen matrix homeostasis in chronological aged skin, Sprague-Dawley male rats of 4-wk-old were orally administrated with MCH at the diet concentrations of 2.25% and 4.5% for 24 mo. Histological and biochemical analysis revealed that MCH had the potential to inhibit the collagen loss and collagen fragmentation in chronological aged skin. Based on immunohistochemistry and western blot analysis, collagen type I and III protein expression levels in MCH-treated groups significantly increased as compared with the aged control group. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed MCH was able to increase the expressions of procollagen type I and III mRNA (COL1A2 and COL3A1) through activating Smad signaling pathway with up-regulated TGF-βRII (TβRII) expression level. Meanwhile, MCH was shown to inhibit the age-related increased collagen degradation through attenuating MMP-1 expression and increasing tissue inhibitor of metalloproteinases-1 expression in a dose-dependent manner. Moreover, MCH could alleviate the oxidative stress in chronological aged skin, which was revealed from the data of superoxide dismutase activity and the thiobarbituric acid reactive substances level in skin homogenates. Therefore, MCH was demonstrated to have the protective effects on chronological skin aging due to the influence on collagen matrix homeostasis. And the antioxidative property of MCH might play an important role in the process.

  17. Two waves of proteasome-dependent protein degradation in the hippocampus are required for recognition memory consolidation.

    PubMed

    Figueiredo, Luciana S; Dornelles, Arethuza S; Petry, Fernanda S; Falavigna, Lucio; Dargél, Vinicius A; Köbe, Luiza M; Aguzzoli, Cristiano; Roesler, Rafael; Schröder, Nadja

    2015-04-01

    Healthy neuronal function and synaptic modification require a concert of synthesis and degradation of proteins. Increasing evidence indicates that protein turnover mediated by proteasome activity is involved in long-term synaptic plasticity and memory. However, its role in different phases of memory remains debated, and previous studies have not examined the possible requirement of protein degradation in recognition memory. Here, we show that the proteasome inhibitor, lactacystin (LAC), infused into the CA1 area of the hippocampus at two specific time points during consolidation, impairs 24-retention of memory for object recognition in rats. Administration of LAC after retrieval did not affect retention. These findings provide the first evidence for a requirement of proteasome activity in recognition memory, indicate that protein degradation in the hippocampus is necessary during selective time windows of memory consolidation, and further our understanding of the role of protein turnover in memory formation.

  18. Standardised extract of Bacopa monniera (CDRI-08) improves contextual fear memory by differentially regulating the activity of histone acetylation and protein phosphatases (PP1α, PP2A) in hippocampus.

    PubMed

    Preethi, Jayakumar; Singh, Hemant K; Venkataraman, Jois Shreyas; Rajan, Koilmani Emmanuvel

    2014-05-01

    Contextual fear conditioning is a paradigm for investigating cellular mechanisms involved in hippocampus-dependent memory. Earlier, we showed that standardised extract of Bacopa monniera (CDRI-08) improves hippocampus-dependent learning in postnatal rats by elevating the level of serotonin (5-hydroxytryptamine, 5-HT), activate 5-HT3A receptors, and cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein. In this study, we have further examined the molecular mechanism of CDRI-08 in hippocampus-dependent memory and compared to the histone deacetylase (HDACs) inhibitor sodium butyrate (NaB). To assess the hippocampus-dependent memory, wistar rat pups were subjected to contextual fear conditioning (CFC) following daily (postnatal days 15-29) administration of vehicle solution (0.5 % gum acacia + 0.9 % saline)/CDRI-08 (80 mg/kg, p.o.)/NaB (1.2 g/kg in PBS, i.p.). CDRI-08/NaB treated group showed enhanced freezing behavior compared to control group when re-exposed to the same context. Administration of CDRI-08/NaB resulted in activation of extracellular signal-regulated kinase ERK/CREB signaling cascade and up-regulation of p300, Ac-H3 and Ac-H4 levels, and down-regulation of HDACs (1, 2) and protein phosphatases (PP1α, PP2A) in hippocampus following CFC. This would subsequently result in an increased brain-derived neurotrophic factor (Bdnf) (exon IV) mRNA in hippocampus. Altogether, our results indicate that CDRI-08 enhances hippocampus-dependent contextual memory by differentially regulating histone acetylation and protein phosphatases in hippocampus.

  19. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    PubMed

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2015-05-01

    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment.

  20. Hippocampus and epilepsy: findings from human tissues

    PubMed Central

    Huberfeld, Gilles; Blauwblomme, Thomas; Miles, Richard

    2015-01-01

    Surgical removal of the epileptogenic zone provides an effective therapy for several epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including (1) temporal lobe epilepsies with hippocampal sclerosis, (2) cortical dysplasias, (3) epilepsies associated with tumors and (4) developmental malformations. Slices of tissue from patient with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum an output region which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide, restores intracellular chloride and thus hyperpolarizing GABAergic actions so suppressing interictal activity. PMID

  1. Investigating the functions of subregions within anterior hippocampus

    PubMed Central

    Zeidman, Peter; Lutti, Antoine; Maguire, Eleanor A.

    2015-01-01

    Previous functional MRI (fMRI) studies have associated anterior hippocampus with imagining and recalling scenes, imagining the future, recalling autobiographical memories and visual scene perception. We have observed that this typically involves the medial rather than the lateral portion of the anterior hippocampus. Here, we investigated which specific structures of the hippocampus underpin this observation. We had participants imagine novel scenes during fMRI scanning, as well as recall previously learned scenes from two different time periods (one week and 30 min prior to scanning), with analogous single object conditions as baselines. Using an extended segmentation protocol focussing on anterior hippocampus, we first investigated which substructures of the hippocampus respond to scenes, and found both imagination and recall of scenes to be associated with activity in presubiculum/parasubiculum, a region associated with spatial representation in rodents. Next, we compared imagining novel scenes to recall from one week or 30 min before scanning. We expected a strong response to imagining novel scenes and 1-week recall, as both involve constructing scene representations from elements stored across cortex. By contrast, we expected a weaker response to 30-min recall, as representations of these scenes had already been constructed but not yet consolidated. Both imagination and 1-week recall of scenes engaged anterior hippocampal structures (anterior subiculum and uncus respectively), indicating possible roles in scene construction. By contrast, 30-min recall of scenes elicited significantly less activation of anterior hippocampus but did engage posterior CA3. Together, these results elucidate the functions of different parts of the anterior hippocampus, a key brain area about which little is definitely known. PMID:26478961

  2. Evolution of the hippocampus in reptiles and birds.

    PubMed

    Striedter, Georg F

    2016-02-15

    Although the hippocampus is structurally quite different among reptiles, birds, and mammals, its function in spatial memory is said to be highly conserved. This is surprising, given that structural differences generally reflect functional differences. Here I review this enigma in some detail, identifying several evolutionary changes in hippocampal cytoarchitecture and connectivity. I recognize a lepidosaurid pattern of hippocampal organization (in lizards, snakes, and the tuatara Sphenodon) that differs substantially from the pattern of organization observed in the turtle/archosaur lineage, which includes crocodilians and birds. Although individual subdivisions of the hippocampus are difficult to homologize between these two patterns, both lack a clear homolog of the mammalian dentate gyrus. The strictly trilaminar organization of the ancestral amniote hippocampus was gradually lost in the lineage leading to birds, and birds expanded the system of intrahippocampal axon collaterals, relative to turtles and lizards. These expanded collateral axon branches resemble the extensive collaterals in CA3 of the mammalian hippocampus but probably evolved independently of them. Additional examples of convergent evolution between birds and mammals are the loss of direct inputs to the hippocampus from the primary olfactory cortex and the general expansion of telencephalic regions that communicate reciprocally with the hippocampus. Given this structural convergence, it seems likely that some similarities in the function of the hippocampus between birds and mammals, notably its role in the ability to remember many different locations without extensive training, likewise evolved convergently. The currently available data do not allow for a strong test of this hypothesis, but the hypothesis itself suggests some promising new research directions.

  3. View from the Administrator's Office.

    ERIC Educational Resources Information Center

    Shaub, Walter M.

    1999-01-01

    Discusses Environmental Protection Agency (EPA) administrator Carol Browner's views on facilitating practical approaches that address major environmental issues in the United States. Examines issues of helping local communities, climate impact and prevention, water quality and quantity, and the EPA's changing role in society. (WRM)

  4. The role of the hippocampus in generalizing configural relationships.

    PubMed

    Berens, Sam C; Bird, Chris M

    2017-03-01

    The hippocampus has been implicated in integrating information across separate events in support of mnemonic generalizations. These generalizations may be underpinned by processes at both encoding (linking similar information across events) and retrieval ("on-the-fly" generalization). However, the relative contribution of the hippocampus to encoding- and retrieval-based generalizations is poorly understood. Using fMRI in humans, we investigated the hippocampal role in gradually learning a set of spatial discriminations and subsequently generalizing them in an acquired equivalence task. We found a highly significant correlation between individuals' performance on a generalization test and hippocampal activity during the test, providing evidence that hippocampal processes support on-the-fly generalizations at retrieval. Within the same hippocampal region there was also a correlation between activity during the final stage of learning (when all associations had been learnt but no generalization was required) and subsequent generalization performance. We suggest that the hippocampus spontaneously retrieves prior events that share overlapping features with the current event. This process may also support the creation of generalized representations during encoding. These findings are supportive of the view that the hippocampus contributes to both encoding- and retrieval-based generalization via the same basic mechanism; retrieval of similar events sharing common features. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

  5. Contextual learning requires synaptic AMPA receptor delivery in the hippocampus.

    PubMed

    Mitsushima, Dai; Ishihara, Kouji; Sano, Akane; Kessels, Helmut W; Takahashi, Takuya

    2011-07-26

    The hippocampus plays a central role in learning and memory. Although synaptic delivery of AMPA-type glutamate receptors (AMPARs) contributes to experience-dependent synaptic strengthening, its role in hippocampus-dependent learning remains elusive. By combining viral-mediated in vivo gene delivery with in vitro patch-clamp recordings, we found that the inhibitory avoidance task, a hippocampus-dependent contextual fear-learning paradigm, delivered GluR1-containing AMPARs into CA3-CA1 synapses of the dorsal hippocampus. To block the synaptic delivery of endogenous AMPARs, we expressed a fragment of the GluR1-cytoplasmic tail (the 14-aa GluR1 membrane-proximal region with two serines mutated to phospho-mimicking aspartates: MPR-DD). MPR-DD prevented learning-driven synaptic AMPAR delivery in CA1 neurons. Bilateral expression of MPR-DD in the CA1 region of the rat impaired inhibitory avoidance learning, indicating that synaptic GluR1 trafficking in the CA1 region of the hippocampus is required for encoding contextual fear memories. The fraction of CA1 neurons that underwent synaptic strengthening positively correlated with the performance in the inhibitory avoidance fear memory task. These data suggest that the robustness of a contextual memory depends on the number of hippocampal neurons that participate in the encoding of a memory trace.

  6. The role of the hippocampus in generalizing configural relationships

    PubMed Central

    2017-01-01

    ABSTRACT The hippocampus has been implicated in integrating information across separate events in support of mnemonic generalizations. These generalizations may be underpinned by processes at both encoding (linking similar information across events) and retrieval (“on‐the‐fly” generalization). However, the relative contribution of the hippocampus to encoding‐ and retrieval‐based generalizations is poorly understood. Using fMRI in humans, we investigated the hippocampal role in gradually learning a set of spatial discriminations and subsequently generalizing them in an acquired equivalence task. We found a highly significant correlation between individuals’ performance on a generalization test and hippocampal activity during the test, providing evidence that hippocampal processes support on‐the‐fly generalizations at retrieval. Within the same hippocampal region there was also a correlation between activity during the final stage of learning (when all associations had been learnt but no generalization was required) and subsequent generalization performance. We suggest that the hippocampus spontaneously retrieves prior events that share overlapping features with the current event. This process may also support the creation of generalized representations during encoding. These findings are supportive of the view that the hippocampus contributes to both encoding‐ and retrieval‐based generalization via the same basic mechanism; retrieval of similar events sharing common features. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27933668

  7. The rodent hippocampus is essential for nonspatial object memory.

    PubMed

    Cohen, Sarah J; Munchow, Alcira H; Rios, Lisa M; Zhang, Gongliang; Asgeirsdóttir, Herborg N; Stackman, Robert W

    2013-09-09

    Elucidating the role of the rodent hippocampus in object recognition memory is critical for establishing the appropriateness of rodents as models of human memory and for their use in the development of memory disorder treatments. In mammals, spatial memory and nonspatial memory depend upon the hippocampus and associated medial temporal lobe (MTL) structures. Although well established in humans, the role of the rodent hippocampus in object memory remains highly debated due to conflicting findings across temporary and permanent hippocampal lesion studies and evidence that the perirhinal cortex may support object memory. In the current studies, we used intrahippocampal muscimol microinfusions to transiently inactivate the male C57BL/6J mouse hippocampus at distinct stages during the novel object recognition (NOR) task: during object memory encoding and consolidation, just consolidation, and/or retrieval. We also assessed the effect of temporary hippocampal inactivation when objects were presented in different contexts, thus eliminating the spatial or contextual components of the task. Lastly, we assessed extracellular dorsal hippocampal glutamate efflux and firing properties of hippocampal neurons while mice performed the NOR task. Our results reveal a clear and compelling role of the rodent hippocampus in nonspatial object memory.

  8. Neocortical activation of the hippocampus during sleep in infant rats.

    PubMed

    Mohns, Ethan J; Blumberg, Mark S

    2010-03-03

    We recently reported that the majority of hippocampal neurons in newborn rats increase their activity in association with myoclonic twitches, which are indicative of active sleep. Because spindle bursts in the developing somatosensory neocortex occur in response to sensory feedback from myoclonic twitching, we hypothesized that the state-dependent activity of the newborn hippocampus arises from sensory feedback that sequentially activates the neocortex and then hippocampus, constituting an early form of neocortical-hippocampal communication. Here, in unanesthetized 5- to 6-d-old rats, we test this hypothesis by recording simultaneously from forelimb and barrel regions of somatosensory neocortex and dorsal hippocampus during periods of spontaneous sleep and wakefulness and in response to peripheral stimulation. Myoclonic twitches were consistently followed by neocortical spindle bursts, which were in turn consistently followed by bursts of hippocampal unit activity; moreover, spindle burst power was positively correlated with hippocampal unit activity. In addition, exogenous stimulation consistently evoked this neocortical-to-hippocampal sequence of activation. Finally, parahippocampal lesions that disrupted functional connections between the neocortex and hippocampus effectively disrupted the transmission of both spontaneous and evoked neocortical activity to the hippocampus. These findings suggest that sleep-related motor activity contributes to the development of neocortical and hippocampal circuits and provides a foundation on which coordinated activity between these two forebrain structures develops.

  9. Oral administration of grape seed polyphenol extract restores memory deficits in chronic cerebral hypoperfusion rats.

    PubMed

    Chen, Chen; Zheng, Yake; Wu, Tianwen; Wu, Chuanjie; Cheng, Xuan

    2017-04-01

    Chronic cerebral hypoperfusion (CCH) has been recognized as an important cause of both vascular dementia and Alzheimer's disease (AD), the two most prominent neurodegenerative diseases causing memory impairment in the elderly. However, an effective therapy for CCH-induced memory impairment has not yet been established. Grape seed polyphenol extract (GSPE) has powerful antioxidant properties and protects neurons and glia during ischemic injury, but its potential use in the prevention of CCH-induced memory impairment has not yet been investigated. Here, CCH-related memory impairment was modeled in rats using permanent bilateral occlusion of the common carotid artery. A Morris water maze task was used to evaluate memory, the levels of acetylcholinesterase, choline acetyltransferase, acetylcholine were used to evaluate cholinergic function, and oxidative stress was assessed by measuring the enzyme activity of superoxide dismutase, glutathione peroxidase, malonic dialdehyde, and catalase. We found that oral administration of GSPE for 1 month can rescue memory deficits. We also found that GSPE restores cholinergic neuronal function and represses oxidative damage in the hippocampus of CCH rats. We propose that GSPE protects memory in CCH rats by reducing ischemia-induced oxidative stress and cholinergic dysfunction. These findings provide a novel application of GSPE in CCH-related memory impairments.

  10. 40 CFR 1620.3 - Administrative claim; who may file.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Administrative claim; who may file. 1620.3 Section 1620.3 Protection of Environment CHEMICAL SAFETY AND HAZARD INVESTIGATION BOARD ADMINISTRATIVE CLAIMS ARISING UNDER THE FEDERAL TORT CLAIMS ACT § 1620.3 Administrative claim; who may file....

  11. 40 CFR 1620.2 - Administrative claim; when presented.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Administrative claim; when presented. 1620.2 Section 1620.2 Protection of Environment CHEMICAL SAFETY AND HAZARD INVESTIGATION BOARD ADMINISTRATIVE CLAIMS ARISING UNDER THE FEDERAL TORT CLAIMS ACT § 1620.2 Administrative claim; when presented....

  12. Radiation Protection

    MedlinePlus

    Jump to main content US EPA United States Environmental Protection Agency Search Search Radiation Protection Share Facebook Twitter Google+ Pinterest Contact Us Radiation Protection Document Library View ...

  13. Impact of chronic morphine on delta opioid receptor expressing neurons in the mouse hippocampus

    PubMed Central

    Eric, Erbs; Lauren, Faget; Alice, Ceredig Rhian; Audrey, Matifas; Jean-Luc, Vonesch; L., Kieffer Brigitte; Dominique, Massotte

    2015-01-01

    Delta opioid receptors participate to the control of chronic pain and emotional responses. Recent data also identified their implication in spatial memory and drug-context associations pointing to a critical role of hippocampal delta receptors. To better appreciate the impact of repeated drug exposure on their modulatory activity, we used fluorescent knock-in mice that express a functional delta receptor fused at its carboxy-terminus with the green fluorescent protein in place of the native receptor. We then tested the impact of chronic morphine treatment on the density and distribution of delta receptor-expressing cells in the hippocampus. A decrease in delta receptor positive cell density was observed in the CA1, CA3 and dentate gyrus without alteration of the distribution across the different GABAergic populations that mainly express delta receptors. This effect partly persisted after four weeks of morphine abstinence. In addition, we observed increased delta opioid receptor expression at the cell surface compared to saline treated animals. In the hippocampus, chronic morphine administration thus induces delta opioid receptor cellular redistribution and durably decreases delta receptor-expressing cell density. Such modifications are likely to alter hippocampal physiology, and to contribute to long-term cognitive deficits. PMID:26480813

  14. Acupuncture suppresses kainic acid-induced neuronal death and inflammatory events in mouse hippocampus.

    PubMed

    Kim, Seung-Tae; Doo, Ah-Reum; Kim, Seung-Nam; Kim, Song-Yi; Kim, Yoon Young; Kim, Jang-Hyun; Lee, Hyejung; Yin, Chang Shik; Park, Hi-Joon

    2012-09-01

    The administration of kainic acid (KA) causes seizures and produces neurodegeneration in hippocampal CA3 pyramidal cells. The present study investigated a possible role of acupuncture in reducing hippocampal cell death and inflammatory events, using a mouse model of kainic acid-induced epilepsy. Male C57BL/6 mice received acupuncture treatments at acupoint HT8 or in the tail area bilaterally once a day for 2 days and again immediately after an intraperitoneal injection of KA (30 mg/kg). HT8 is located on the palmar surface of the forelimbs, between the fourth and fifth metacarpal bones. Twenty-four hours after the KA injection, neuronal cell survival, the activations of microglia and astrocytes, and mRNA expression of two proinflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were measured in the hippocampus. Acupuncture stimulation at HT8, but not in the tail area, significantly reduced the KA-induced seizure, neuron death, microglial and astrocyte activations, and IL-1β mRNA expression in the hippocampus. The acupuncture stimulation also decreased the mRNA expression of TNF-α, but it was not significant. These results indicate that acupuncture at HT8 can inhibit hippocampal cell death and suppress KA-induced inflammatory events, suggesting a possible role for acupuncture in the treatment of epilepsy.

  15. Impact of chronic morphine on delta opioid receptor-expressing neurons in the mouse hippocampus.

    PubMed

    Erbs, E; Faget, L; Ceredig, R A; Matifas, A; Vonesch, J-L; Kieffer, B L; Massotte, D

    2016-01-28

    Delta opioid (DOP) receptors participate to the control of chronic pain and emotional responses. Recent data also identified their implication in spatial memory and drug-context associations pointing to a critical role of hippocampal delta receptors. To better appreciate the impact of repeated drug exposure on their modulatory activity, we used fluorescent knock-in mice that express a functional delta receptor fused at its carboxy-terminus with the green fluorescent protein in place of the native receptor. We then tested the impact of chronic morphine treatment on the density and distribution of delta receptor-expressing cells in the hippocampus. A decrease in delta receptor-positive cell density was observed in the CA1, CA3 and dentate gyrus without alteration of the distribution across the different GABAergic populations that mainly express delta receptors. This effect partly persisted after four weeks of morphine abstinence. In addition, we observed increased DOP receptor expression at the cell surface compared to saline-treated animals. In the hippocampus, chronic morphine administration thus induces DOP receptor cellular redistribution and durably decreases delta receptor-expressing cell density. Such modifications are likely to alter hippocampal physiology, and to contribute to long-term cognitive deficits.

  16. Histopathological, Ultrastructural, and Immunohistochemical Assessment of Hippocampus Structures of Rats Exposed to TCDD and High Doses of Tocopherol and Acetylsalicylic Acid

    PubMed Central

    Rosińczuk, Joanna; Całkosiński, Ireneusz

    2015-01-01

    The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on central nervous system consists of changing expression of estrogen receptors, whereas the result of chronic inflammatory reaction caused by dioxin is occurrence of destructive changes in various organs connected with disturbed metabolism of connective tissue and damage of cells. The aim of the study was to determine the effect of dioxins on function, ultrastructure, and cytological and histological structure of hippocampus, particularly on expression of estrogen receptors in central nervous system as well as to define protective influence of tocopherol (TCP) and acetylsalicylic acid (ASA) on the decrease in activity of proinflammatory effects in central nervous system. It was shown that TCDD contributes to destructive and inflammatory changes along with demyelization of myelin sheaths and atrophy of estrogen receptors in hippocampus. Dioxin contributes to atrophy of estrogen receptors in hippocampus, in which also destructive and inflammatory changes were found along with demyelination of myelin sheaths. Histopathological and ultrastructural image of hippocampus areas in rats, in which both TCP and ASA were used, is characterized by poorly expressed degenerative changes and smaller inflammatory reactivity. Using both TCP and ASA has a protective effect on functions of central nervous system. PMID:25879034

  17. 40 CFR 211.111 - Testing by the Administrator.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Testing by the Administrator. 211.111 Section 211.111 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS PRODUCT NOISE LABELING General Provisions § 211.111 Testing by the Administrator. (a)(1)...

  18. 40 CFR 147.2929 - Administrative permitting procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Administrative permitting procedures. 147.2929 Section 147.2929 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER... Mineral Reserve-Class II Wells § 147.2929 Administrative permitting procedures. (a) Completeness...

  19. 40 CFR 231.6 - Administrator's final determinations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Administrator's final determinations. 231.6 Section 231.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING SECTION 404(c) PROCEDURES § 231.6 Administrator's final determinations. After reviewing...

  20. 40 CFR 1.27 - Offices of the Associate Administrators.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... 1.27 Section 1.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL STATEMENT OF... Executive Secretary of the U.S. side of the US-USSR/PRC agreements on environmental protection and of the U... Administrator coordinates Regional issues, organizes Regional Administrator meetings and work groups;...

  1. 40 CFR 231.6 - Administrator's final determinations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Administrator's final determinations. 231.6 Section 231.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING SECTION 404(c) PROCEDURES § 231.6 Administrator's final determinations. After reviewing...

  2. Dopamine regulates stimulus generalization in the human hippocampus.

    PubMed

    Kahnt, Thorsten; Tobler, Philippe N

    2016-02-02

    The ability to generalize previously learned information to novel situations is fundamental for adaptive behavior. However, too wide or too narrow generalization is linked to neuropsychiatric disorders. Previous research suggests that interactions between the dopaminergic system and the hippocampus may play a role in generalization, but whether and how the degree of generalization can be modulated via these pathways is currently unknown. Here, we addressed this question in humans using pharmacology, functional magnetic resonance imaging, and computational modeling. Blocking dopamine D2-receptors (D2R) altered generalization behavior as revealed by an increased kurtosis of the generalization gradient, and a decreased width of model-derived generalization parameters. Moreover, D2R-blockade modulated similarity-based responses in the hippocampus and decreased midbrain-hippocampal connectivity, which in turn correlated with individual differences in generalization. These results suggest that dopaminergic activity in the hippocampus may relate to the degree of generalization and highlight a potential target for treatment.

  3. PPARα signaling in the hippocampus: crosstalk between fat and memory.

    PubMed

    Roy, Avik; Pahan, Kalipada

    2015-03-01

    Major functions of the hippocampus are to generate, organize and store memory. This is a complex process, which is orchestrated by a group of molecules, called plasticity-related molecules. To control these various plasticity-related molecules at the transcriptional level, we have been endowed with cAMP response element-binding protein (CREB), also known as a master regulator of memory. Interestingly, we have seen that this master regulator is regulated at the transcriptional level in the hippocampus by peroxisome proliferator-activated receptor α (PPARα), a nuclear hormone receptor family transcription factor that is known to control the metabolism of fatty acids in the liver, underlying a possible crosstalk between fat and memory. Although liver PPARα does not directly control hippocampal CREB, this opens up an important possibility to improve hippocampal functions and to be resistant to memory loss by PPARα ligands and maintaining normal levels of PPARα in the hippocampus.

  4. Age effects on atrophy rates of entorhinal cortex and hippocampus

    PubMed Central

    Du, An-Tao; Schuff, Norbert; Chao, Linda L.; Kornak, John; Jagust, William J.; Kramer, Joel H.; Reed, Bruce R.; Miller, Bruce L.; Norman, David; Chui, Helena C.; Weiner, Michael W.

    2007-01-01

    The effects of age, subcortical vascular disease, apolipoprotein E (APOE) ɛ4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes were assessed on MR images. Age was significantly associated with increased atrophy rates of 0.04 ± 0.02% per year for ERC and 0.05 ± 0.02% per year for hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with presence of lacunes, in addition to age. WMH, APOE ɛ4 and hypertension had no significant effect on atrophy rates. In conclusion, age and presence of lacunes should be taken into consideration in imaging studies of CN subjects and AD patients to predict AD progression and assess the response to treatment trials. PMID:15961190

  5. Direct and indirect activation of the hippocampus by tubocurarine

    PubMed Central

    Feldberg, W.; Lotti, V. J.

    1970-01-01

    1. In cats anaesthetized with intravenous chloralose, tubocurarine was either perfused through the inferior horn of a lateral ventricle or applied by micro-injection into the hippocampus, and the electrical activity was recorded from the surfaces of the occipital cortices and from the cannulae used for the perfusion or injection which, insulated except at their tips, served as recording electrodes as well. 2. With both methods, the hippocampus became activated by tubocurarine acting directly on the hippocampus. The activation resulted in an abnormal spike discharge interrupted from time to time by short bursts of fast activity, termed episodes, followed by periods of electrical silence during which no abnormal activity was recorded. This abnormal discharge was recorded in all leads. The spikes were negative when recorded from the surface of the hippocampus, but changed polarity when the electrode was lowered and penetrated the pyramidal cell layer, and on further lowering the electrode the positive spikes increased in voltage up to 15 mV and then decreased. 3. With both methods, signs of indirect activation of the hippocampus were observed when the tubocurarine set up foci of excitation in one of the following three areas of cerebral cortex which lie ventral to the hippocampus, the Area entorhinica, the Area perirhinica and the Area post-splenialis. The foci of excitation resulted in a continuous discharge of negative spikes which were recorded in the leads from these areas only. A characteristic feature of the indirect hippocampal activation arising from the continuous discharge set up in the Area post-splenialis was the periodicity. Activation lasting 20-60 sec occurred every few minutes or at shorter intervals, often leading to an episode. PMID:5499820

  6. Suppression of synaptic plasticity by fullerenol in rat hippocampus in vitro

    PubMed Central

    Wang, Xin-Xing; Zha, Ying-Ying; Yang, Bo; Chen, Lin; Wang, Ming

    2016-01-01

    Fullerenol, a water-soluble fullerene derivative, has attracted much attention due to its bioactive properties, including the antioxidative properties and free radical scavenging ability. Due to its superior nature, fullerenol represents a promising diagnostic, therapeutic, and protective agent. Therefore, elucidation of the possible side effects of fullerenol is important in determining its potential role. In the present study, we investigated the acute effects of 5 μM fullerenol on synaptic plasticity in hippocampal brain slices of rats. Incubation with fullerenol for 20 minutes significantly decreased the peak of paired-pulse facilitation and long-term potentiation, indicating that fullerenol suppresses the short- and long-term synaptic plasticity of region I of hippocampus. We found that fullerenol depressed the activity and the expression of nitric oxide (NO) synthase in hippocampus. In view of the important role of NO in synaptic plasticity, the inhibition of fullerenol on NO synthase may contribute to the suppression of synaptic plasticity. These findings may facilitate the evaluation of the side effects of fullerenol. PMID:27729790

  7. MDMA administration decreases serotonin but not N-acetylaspartate in the rat brain

    PubMed Central

    Perrine, Shane A.; Ghoddoussi, Farhad; Michaels, Mark S.; Hyde, Elisabeth M.; Kuhn, Donald M.; Galloway, Matthew P.

    2010-01-01

    In animals, repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) reduces markers of serotonergic activity and studies show similar serotonergic deficits in human MDMA users. Using proton magnetic resonance spectroscopy (1H-MRS) at 11.7 Tesla, we measured the metabolic neurochemical profile in intact, discrete tissue punches taken from prefrontal cortex, anterior striatum, and hippocampus of rats administered MDMA (5 mg/kg IP, 4× q 2 h) or saline and euthanized 7 days after the last injection. Monoamine content was measured with HPLC in contralateral punches from striatum and hippocampus to compare the MDMA-induced loss of 5HT innervation with constituents in the 1H-MRS profile. When assessed 7 days after the last MDMA injection, levels of hippocampal and striatal serotonin (5HT) were significantly reduced, consistent with published animal studies. N-acetylaspartate (NAA) levels were significantly increased in prefrontal cortex and not affected in anterior striatum or hippocampus; myo-inositol (INS) levels were increased in prefrontal cortex and hippocampus but not anterior striatum. Glutamate levels were increased in prefrontal cortex and decreased in hippocampus, while GABA levels were decreased only in hippocampus. The data suggest that NAA may not reliably reflect MDMA-induced 5HT neurotoxicity. However, the collective pattern of changes in 5HT, INS, glutamate and GABA is consistent with persistent hippocampal neuroadaptations caused by MDMA. PMID:20800616

  8. Zinc Selectively Blocks Neurosteroid-Sensitive Extrasynaptic δGABAA Receptors in the Hippocampus

    PubMed Central

    Carver, Chase Matthew; Chuang, Shu-Hui

    2016-01-01

    hippocampus circuits. Zn2+ inhibits synaptic GABAA receptors, but its interaction is less well appreciated at the extrasynaptic receptors, which respond sensitively to endogenous neurosteroids. Here, we describe selective functional blockade by Zn2+ of neurosteroid-sensitive, extrasynaptic GABAA receptors in the mouse hippocampus dentate gyrus, a key region associated with epilepsy and memory disorders. By demonstrating that extracellular Zn2+ prevents neurosteroid augmentation of tonic current and protection against limbic seizures, our findings provide novel implications of this potential antagonistic interaction in a variety of neurological conditions. PMID:27488628

  9. Early histological maturation in the hippocampus of the guinea pig.

    PubMed

    Nacher, J; Palop, J J; Ramirez, C; Molowny, A; Lopez-Garcia, C

    2000-06-01

    The vesicular zinc-rich synaptic systems of the principal neurons of the hippocampus are well developed in newborn guinea pigs, a precocial species. In addition, alvear and fimbrial myelinated fibers as well as significant inhibitory interneurons (i.e. somatostatin, parvalbumin and opioid immunoreactive hippocampal interneurons) are also well developed. On the contrary, neither vesicular zinc synapses nor myelinated fibers nor the above mentioned immunoreactive interneurons are detectable in newborn specimens of other related altricial species such as rats or rabbits. These data suggest that early maturation of a highly integrative center related to cognitive map building such as the hippocampus is characteristic of precocial species.

  10. Anterior hippocampus: the anatomy of perception, imagination and episodic memory

    PubMed Central

    Zeidman, Peter; Maguire, Eleanor A.

    2017-01-01

    The brain creates a model of the world around us. We can use this representation to perceive and comprehend what we see at any given moment, but also to vividly re-experience scenes from our past and imagine future (or even fanciful) scenarios. Recent work has shown that these cognitive functions — perception, imagination and recall of scenes and events — all engage the anterior hippocampus. Here we capitalise on new findings from functional neuroimaging to propose a model that links high-level cognitive functions to specific structures within the anterior hippocampus. PMID:26865022

  11. H.R. 1589: A Bill to amend the Clean Air Act to authorize the Administrator of the Environmental Protection Agency to grant a waiver of the oxygenated fuels requirement, and for other purposes. Introduced in the House of Representatives, One Hundred Third Congress, First Session, April 1, 1993

    SciTech Connect

    1993-12-31

    The report H.R. 1589 is a bill to amend the Clean Air Act to authorize the Administrator of the Environmental Protection Agency to grant a waiver of the oxygenated fuels requirement. The use of methy tertiary butyl ether oxygenated fuels is referred to as M-T-B-E oxygenated fuels and at issue is a risk assessment of the health hazards of these ethanol fuels, particularly at low temperatures.

  12. Changes in CREB activation in the prefrontal cortex and hippocampus blunt ethanol-induced behavioral sensitization in adolescent mice

    PubMed Central

    Soares-Simi, Sabrina L.; Pastrello, Daniel M.; Ferreira, Zulma S.; Yonamine, Mauricio; Marcourakis, Tania; Scavone, Cristoforo; Camarini, Rosana

    2013-01-01

    Drug dependence is a major health problem in adults and has been recognized as a significant problem in adolescents. We previously demonstrated that repeated treatment with a behaviorally sensitizing dose of ethanol in adult mice induced tolerance or no sensitization in adolescents and that repeated ethanol-treated adolescents expressed lower Fos and Egr-1 expression than adult mice in the prefrontal cortex (PFC). In the present work, we investigated the effects of acute and repeated ethanol administration on cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) DNA-binding activity using the electrophoretic mobility shift assay (EMSA) and the phosphorylated CREB (pCREB)/CREB ratio using immunoblotting in both the PFC and hippocampus in adolescent and adult mice. Adult mice exhibited typical locomotor sensitization after 15 days of daily treatment with 2.0 g/kg ethanol, whereas adolescent mice did not exhibit sensitization. Overall, adolescent mice displayed lower CREB binding activity in the PFC compared with adult mice, whereas opposite effects were observed in the hippocampus. The present results indicate that ethanol exposure induces significant and differential neuroadaptive changes in CREB DNA-binding activity in the PFC and hippocampus in adolescent mice compared with adult mice. These differential molecular changes may contribute to the blunted ethanol-induced behavioral sensitization observed in adolescent mice. PMID:24379765

  13. Nicotine versus 6-hydroxy-l-nicotine against chlorisondamine induced memory impairment and oxidative stress in the rat hippocampus.

    PubMed

    Hritcu, Lucian; Ionita, Radu; Motei, Diana Elena; Babii, Cornelia; Stefan, Marius; Mihasan, Marius

    2017-02-01

    6-Hydroxy-l-nicotine (6HLN), a nicotine derivative from nicotine degradation by Arthrobacter nicotinovorans pAO1 strain was found to improve behavioral deficits and to reverse oxidative stress in the rat hippocampus. Rats were given CHL (10mg/kg, i.p.) were used as an Alzheimer's disease-like model. The nicotine (0.3mg/kg) and 6HLN (0.3mg/kg) were administered alone or in combination in the CHL-treated rats. Memory-related behaviors were evaluated using Y-maze and radial arm-maze tests. The antioxidant enzymes activity and the levels of the biomarkers of oxidative stress were measured in the hippocampus. Statistical analyses were performed using two-way ANOVA and Tukey's post hoc test. F values for which p<0.05 were regarded as statistically significant. CHL-caused memory deficits and oxidative stress enhancing were observed. Both nicotine and 6HLN administration attenuated the cognitive deficits and recovered the antioxidant capacity in the rat hippocampus of the CHL rat model. Our results suggest that 6HLN versus nicotine confers anti-amnesic properties in the CHL-induced a rat model of memory impairment via reversing cholinergic function and decreasing brain oxidative stress, suggesting the use of this compound as an alternative agent in AD treatment.

  14. Prenatal methamphetamine exposure induces long-lasting alterations in memory and development of NMDA receptors in the hippocampus.

    PubMed

    Šlamberová, R; Vrajová, M; Schutová, B; Mertlová, M; Macúchová, E; Nohejlová, K; Hrubá, L; Puskarčíková, J; Bubeníková-Valešová, V; Yamamotová, A

    2014-01-01

    Since close relationship was shown between drug addiction and memory formation, the aim of the present study was to investigate the effects of interaction between prenatal methamphetamine (MA) exposure and MA treatment in adulthood on spatial and non-spatial memory and on the structure of the N-methyl-D-aspartate (NMDA) receptors in the hippocampus. Adult male rats prenatally exposed to MA (5 mg/kg) or saline were tested in adulthood. Non-spatial memory was examined in the Object Recognition Test (ORT) and spatial memory in the Object Location Test (OLT) and in the Memory Retention Test (MRT) conducted in the Morris Water Maze (MWM), respectively. Based on the type of the memory test animals were injected either acutely (ORT, OLT) or long-term (MWM) with MA (1 mg/kg). After each testing, animals were sacrificed and brains were removed. The hippocampus was then examined in Western Blot analysis for occurrence of different NMDA receptors' subtypes. Our results demonstrated that prenatal MA exposure affects the development of the NMDA receptors in the hippocampus that might correspond with improvement of spatial memory tested in adulthood in the MWM. On the other hand, the effect of prenatal MA exposure on non-spatial memory examined in the ORT was the opposite. In addition, we showed that the effect of MA administration in adulthood on NMDA receptors is influenced by prenatal MA exposure, which seems to correlate with the spatial memory examined in the OLT.

  15. Expression of brain-derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs.

    PubMed

    Bai, Ou; Chlan-Fourney, Jennifer; Bowen, Rudy; Keegan, David; Li, Xin-Min

    2003-01-01

    Typical and atypical antipsychotic drugs, though both effective, act on different neurotransmitter receptors and are dissimilar in some clinical effects and side effects. The typical antipsychotic drug haloperidol has been shown to cause a decrease in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal cell survival, differentiation, and neuronal connectivity. However, it is still unknown whether atypical antipsychotic drugs similarly regulate BDNF expression. We examined the effects of chronic (28 days) administration of typical and atypical antipsychotic drugs on BDNF mRNA expression in the rat hippocampus using in situ hybridization. Quantitative analysis revealed that the typical antipsychotic drug haloperidol (1 mg/kg) down-regulated BDNF mRNA expression in both CA1 (P < 0.05) and dentate gyrus (P < 0.01) regions compared with vehicle control. In contrast, the atypical antipsychotic agents clozapine (10 mg/kg) and olanzapine (2.7 mg/kg) up-regulated BDNF mRNA expression in CA1, CA3, and dentate gyrus regions of the rat hippocampus compared with their respective controls (P < 0.01). These findings demonstrate that the typical and atypical antipsychotic drugs differentially regulate BDNF mRNA expression in rat hippocampus.

  16. Acute stress enhances the expression of neuroprotection- and neurogenesis-associated genes in the hippocampus of a mouse restraint model

    PubMed Central

    Sannino, Giuseppina; Pasqualini, Lorenza; Ricciardelli, Eugenia; Montilla, Patricia; Soverchia, Laura; Ruggeri, Barbara; Falcinelli, Silvia; Renzi, Alessandra; Ludka, Colleen; Kirchner, Thomas; Grünewald, Thomas G. P.; Ciccocioppo, Roberto; Ubaldi, Massimo; Hardiman, Gary

    2016-01-01

    Stress arises from an external demand placed on an organism that triggers physiological, cognitive and behavioural responses in order to cope with that request. It is thus an adaptive response useful for the survival of an organism. The objective of this study was to identify and characterize global changes in gene expression in the hippocampus in response to acute stress stimuli, by employing a mouse model of short-term restraint stress. In our experimental design mice were subjected to a one time exposure of restraint stress and the regulation of gene expression in the hippocampus was examined 3, 12 and 24 hours thereafter. Microarray analysis revealed that mice which had undergone acute restraint stress differed from non-stressed controls in global hippocampal transcriptional responses. An up-regulation of transcripts contributing directly or indirectly to neurogenesis and neuronal protection including, Ttr, Rab6, Gh, Prl, Ndufb9 and Ndufa6, was observed. Systems level analyses revealed a significant enrichment for neurogenesis, neuron morphogenesis- and cognitive functions-related biological process terms and pathways. This work further supports the hypothesis that acute stress mediates a positive action on the hippocampus favouring the formation and the preservation of neurons, which will be discussed in the context of current data from the literature. PMID:26863456

  17. Glucocorticoids and the expression of mRNAs for neurotrophins, their receptors and GAP-43 in the rat hippocampus.

    PubMed

    Chao, H M; McEwen, B S

    1994-10-01

    The genes encoding brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and basic fibroblast growth factor (bFGF) are all expressed in the adult rat hippocampus. The colocalization of the these factors with the receptors to which they bind, namely trkB, trkC and the bFGF receptor, respectively, suggests that in the hippocampus they may exert their putative protective and trophic effects through an autocrine mechanism. The morphology and survival of hippocampal neurons are also affected by glucocorticoids, which can act as transcriptional activators of gene expression. In this study we have used in situ hybridization to investigate the adrenal steroid regulation of the mRNAs encoding the neurotrophic factors BDNF, NT-3, and bFGF, their respective receptors, and the growth-associated protein GAP-43. After 7 days of adrenalectomy (ADX), there was an increase in the level of GAP-43 mRNA expression in the CA1 and CA3 pyramidal cell layers of the hippocampus, that was prevented by corticosterone replacement to the ADX animals. In the CA2 subregion, adrenalectomy resulted in a decrease in bFGF mRNA expression, that was reversed by steroid treatment. There was evidence for glucocorticoid modulation of the BDNF and NT-3 mRNAs in pyramidal cell layers and in the dentate gyrus, but not of the mRNAs encoding the trkB, trk C or bFGF receptors.

  18. Morphine sensitization increases the extracellular level of glutamate in CA1 of rat hippocampus via μ-opioid receptor.

    PubMed

    Farahmandfar, Maryam; Karimian, Seyed Morteza; Zarrindast, Mohammad-Reza; Kadivar, Mehdi; Afrouzi, Hossein; Naghdi, Nasser

    2011-04-25

    Repeated administration of abuse drugs such as morphine elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect plastic changes requiring regulation of glutamatergic system in the brain. In this study, we investigated the effect of morphine sensitization on extracellular glutamate concentration in the hippocampus, a brain region rich in glutamatergic neurons. Sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days free of the opioid treatment. The results showed that extracellular glutamate concentration in the CA1 was decreased following administration of morphine in non-sensitized rats. However, morphine-induced behavioral sensitization significantly increased the extracellular glutamate concentration in this area. The enhancement of glutamate in morphine sensitized rats was prevented by administration of naloxone 30 min before each of three daily doses of morphine. These results suggest an adaptation of the glutamatergic neuronal transmission in the hippocampus after morphine sensitization and it is postulated that opioid receptors may play an important role in this effect.

  19. Inflammation-induced dysfunction of the low-density lipoprotein receptor-related protein-1 at the blood-brain barrier: protection by the antioxidant N-acetylcysteine.

    PubMed

    Erickson, Michelle A; Hansen, Kim; Banks, William A

    2012-10-01

    Impairment in two blood-brain barrier (BBB) efflux transporters, p-glycoprotein (Pgp) and low-density lipoprotein receptor-related protein-1 (LRP-1) are thought to contribute to the progression of Alzheimer's disease (AD) by resulting in the brain accumulation of their substrate amyloid beta peptide (Aβ). The initial cause of impaired efflux, however, is unknown. We have shown that induction of systemic inflammation by intraperitoneal administration of lipopolysaccharide impairs the efflux of Aβ from the brain, suggesting that systemic inflammation could be one such initiator. In this study, we determined whether pre-administration of the antioxidant N-aceytlcysteine (Nac) has a protective effect against LPS-induced Aβ transporter dysfunction. Our findings were that Nac protected against LPS-induced Aβ transport dysfunction at the BBB through an LRP-1-dependent and Pgp-independent mechanism. This was associated with Nac exerting antioxidant effects in the periphery but not the brain, despite an increased rate of entry of Nac into the brain following LPS. We also found that Nac pre-administration resulted in lower blood levels of the cytokines and chemokines interferon-γ, interleukin-10, CCL2, CCL4, and CCL5, but only lowered CCL4 in the cerebral cortex and hippocampus. Finally, we observed that hippocampal cytokine responses to LPS were decreased compared to cortex. These findings demonstrate a novel mechanism by which antioxidants prevent Aβ accumulation in the brain caused by inflammation, and therefore protect against AD.

  20. Topiramate Confers Neuroprotection Against Methylphenidate-Induced Neurodegeneration in Dentate Gyrus and CA1 Regions of Hippocampus via CREB/BDNF Pathway in Rats.

    PubMed

    Motaghinejad, Majid; Motevalian, Manijeh; Abdollahi, Mohammad; Heidari, Mansour; Madjd, Zahra

    2017-04-01

    Methylphenidate (MPH) abuse can cause serious neurological damages. The neuroprotective effects of topiramate (TPM) have been reported already, but its mechanism of action still remains unclear. The current study evaluates in vivo role of CREB/BDNF in TPM protection of the rat hippocampal cells from methylphenidate-induced apoptosis, oxidative stress, and inflammation. A total of 60 adult male rats were divided into six groups. Groups 1 and 2 received normal saline (0.7 ml/rat) and MPH (10 mg/kg) respectively for 14 days. Groups 3 and 4 were concurrently treated with MPH (10 mg/kg) and TPM 50 and 100 mg/kg respectively for 14 days. Groups 5 and 6 were treated with 50 and 100 mg/kg TPM only respectively. After drug administration, open field test (OFT) was used to investigate motor activity. The hippocampus was then isolated and the apoptotic, antiapoptotic, oxidative, antioxidant, and inflammatory factors were measured. Expression of the total and phosphorylated CREB and BDNF in gene and protein levels, and gene expression of Ak1, CaMK4, MAPK3, PKA, and c-Fos levels were also measured. MPH significantly decreased motor activity in OFT. TPM (50 and 100 mg/kg) decreased MPH-induced motor activity disturbance. Additionally, MPH significantly increased Bax protein level, CaMK4 gene expression, lipid peroxidation, catalase activity, mitochondrial GSH, IL-1β, and TNF-α levels in isolated hippocampal cells. Also CREB, in total and phosphorylated forms, BDNF and Bcl-2 protein levels, Ak1, MAPK3, PKA and c-Fos gene expression, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities decreased significantly by MPH. TPM (50 and 100 mg/kg), both in the presence and absence of MPH, attenuated the effects of MPH. Immunohistochemistry data showed that TPM increased localization of the total and phosphorylated forms of CREB in dentate gyrus (DG) and CA1 areas of the hippocampus. It seems that TPM can be used as a neuroprotective agent against

  1. Involvement of brain-derived neurotrophic factor and neurogenesis in oestradiol neuroprotection of the hippocampus of hypertensive rats.

    PubMed

    Pietranera, L; Lima, A; Roig, P; De Nicola, A F

    2010-10-01

    The hippocampus of spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats shows decreased cell proliferation and astrogliosis as well as a reduced number of hilar cells. These defects are corrected after administration of 17β-oestradiol (E(2) ) for 2 weeks. The present work investigated whether E(2) treatment of SHR and of hypertensive DOCA-salt male rats modulated the expression of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in hippocampal neurogenesis. The neurogenic response to E(2) was simultaneously determined by counting the number of doublecortin-immunopositive immature neurones in the subgranular zone of the dentate gyrus. Both hypertensive models showed decreased expression of BDNF mRNA in the granular zone of the dentate gyrus, without changes in CA1 or CA3 pyramidal cell layers, decreased BDNF protein levels in whole hippocampal tissue, low density of doublecortin (DCX)-positive immature neurones in the subgranule zone and decreased length of DCX+ neurites in the dentate gyrus. After s.c. implantation of a single E(2) pellet for 2 weeks, BDNF mRNA in the dentate gyrus, BDNF protein in whole hippocampus, DCX immunopositive cells and the length of DCX+ neurites were significantly raised in both SHR and DOCA-salt-treated rats. These results indicate that: (i) low BDNF expression and deficient neurogenesis distinguished the hippocampus of SHR and DOCA-salt hypertensive rats and (ii) E(2) was able to normalise these biologically important functions in the hippocampus of hypertensive animals.

  2. Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus.

    PubMed

    Jangra, Ashok; Kasbe, Prajapati; Pandey, Surya Narayan; Dwivedi, Shubham; Gurjar, Satendra S; Kwatra, Mohit; Mishra, Murli; Venu, Athira K; Sulakhiya, Kunjbihari; Gogoi, Ranadeep; Sarma, Nitul; Bezbaruah, Babul K; Lahkar, Mangala

    2015-12-01

    Mounting evidence suggests that long-term aluminum exposure results in severe toxic effects, including neurobehavioral and neurochemical anomalies. The present study was performed to examine the neuroprotective potential of hesperidin and silibinin against aluminum chloride (AlCl3)-induced neurotoxicity in mice. AlCl3 (100 mg/kg/day) was injected daily through oral gavage for 42 days. Concomitantly, hesperidin (50 and 100 mg/kg/day, p.o.) and silibinin (100 and 200 mg/kg/day, p.o.) was administered for 42 days in different groups. The extent of cognitive impairment was assessed by Morris water maze and novel object recognition test on the 43rd day. Neurotoxicity was assessed by measuring oxido-nitrosative stress and proinflammatory cytokines in the hippocampus of mice. Six weeks treatment with AlCl3 caused cognitive impairment as indicated by an increase in the retention latency time and reduction in the percentage of recognition index. AlCl3-treated group showed oxido-nitrosative stress as indicated by increase in the level of lipid peroxidation, nitrite and depleted reduced glutathione, catalase activity in the hippocampus. Moreover, the chronic AlCl3 administration raised the proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) level and increased acetylcholinesterase activity and reduced the BDNF content in the hippocampus of AlCl3-treated animals. However, chronic treatment with hesperidin and silibinin at higher doses significantly ameliorated the AlCl3-induced cognitive impairment and hippocampal biochemical anomalies. The present study clearly indicated that hesperidin and silibinin exert neuroprotective effects against AlCl3-induced cognitive impairment and neurochemical changes. Amelioration of cognitive impairment may be attributed to the impediment of oxido-nitrosative stress and inflammation in the hippocampus.

  3. Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning.

    PubMed

    Ueda, S; Sakakibara, S; Yoshimoto, K

    2005-01-01

    The dentate gyrus of the hippocampal formation produces new neurons throughout adulthood in mammalian species. Several experimental statuses and factors regulating to neurogenesis have been identified in the adult dentate gyrus. For example, exposure to an enriched environment enhances neurogenesis in the dentate gyrus and improves hippocampus-dependent spatial learning. Furthermore, serotonin is known to influence adult neurogenesis, and learning and memory. However, the effects of long-lasting depletion of serotonin over the developing period on neurogenesis have not been investigated. Thus, we examined the influence of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis and spatial memory performance. As reported previously, environmental enrichment significantly increased new neurons in the dentate gyrus. However, there was no improvement of the spatial learning test in adult rats in standard and in environmental enrichment housings. Intracisternal administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine, on postnatal day 3 apparently reduced serotonin content in the adult hippocampus without regeneration. This experimental depletion of serotonin in the hippocampus of rats housed in an enriched environment had no effect on spatial memory performance, but produced significant decreases in the number of bromodeoxyuridine-labeled new cells in the dentate gyrus. These findings indicate that newly generated cells stimulated by environmental enrichment are not critical for improvements in hippocampus-dependent learning. Furthermore, numbers of bromodeoxyuridine-labeled cells in the dentate gyrus of 5,7-dihydroxytryptamine-injected rats did not differ between 1 day and 4 weeks after bromodeoxyuridine injection. These data suggest that survival of newly generated dentate gyrus cells remains relatively constant under long-lasting serotonin depletion.

  4. Developing an Animal Model of Human Amnesia: The Role of the Hippocampus

    ERIC Educational Resources Information Center

    Kesner, Raymond P.; Goodrich-Hunsaker, Naomi J.

    2010-01-01

    This review summarizes a series of experiments aimed at answering the question whether the hippocampus in rats can serve as an animal model of amnesia. It is recognized that a comparison of the functions of the rat hippocampus with human hippocampus is difficult, because of differences in methodology, differences in complexity of life experiences,…

  5. Taurine counteracts the suppressive effect of lipopolysaccharide on neurogenesis in the hippocampus of rats.

    PubMed

    Wu, Gaofeng; Matsuwaki, Takashi; Tanaka, Yoshinori; Yamanouchi, Keitaro; Hu, Jianmin; Nishihara, Masugi

    2013-01-01

    Neurogenesis has been generally accepted to happen in the subventricular zone lining the lateral ventricular and subgranular zone (SGZ) in the hippocampus of adult mammalian brain. Recent studies have reported that inflammatory stimuli, such as injection of lipopolysaccharide (LPS), impair neurogenesis in the SGZ. Taurine, a sulfur-containing β-amino acid, is a major free intracellular amino acid in many tissues of mammals and having various supplementary effects on the mammalian body functions including the brain. Recently, it has been also reported that taurine levels in the brain significantly increase under stressful conditions. The present study was aimed to evaluate the possible beneficial effects of taurine on the neurogenesis in the SGZ under the condition of acute inflammatory stimuli by LPS. Adult male rats were intraperitoneally injected with taurine once a day for 39 days. Twenty-four hours before the animals were sacrificed on the last day of taurine treatment, LPS was injected simultaneously with bromodeoxyuridine (BrdU). Immunohistochemistry for BrdU, Ki67, and Iba-1 in the brain was performed, and serum levels of TNF-α and IL-1β 2 h after LPS injection were determined. The results showed that LPS significantly decreased the number of immunoreactive cells for both BrdU and Ki67 in the SGZ, while increased that for Iba-1, all of which were restored by taurine administration. Meanwhile, the serum concentrations of TNF-α and IL-1β were significantly increased, which were significantly attenuated by taurine administration. These results suggest that taurine effectively maintains neurogenesis in the SGZ under the acute infectious condition by attenuating the increase of microgliosis in the hippocampus as well as proinflammatory cytokines in the peripheral circulation.

  6. Effects of Short-Term Exposure to Lithium on Antiapoptotic Bcl-xL Protein Expression in Cortex and Hippocampus of Rats after Acute Stress.

    PubMed

    Dygalo, N N; Bannova, A V; Sukhareva, E V; Shishkina, G T; Ayriyants, K A; Kalinina, T S

    2017-03-01

    The antiapoptotic protein Bcl-xL is involved in development of neurobiological resilience to stress; hence, the possibility of use of psychotropic drugs to increase its expression in brain in response to stress is of considerable interest. Lithium is a neurotropic drug widely used in psychiatry. In work, we studied effects of lithium administration (for 2 or 7 days) on the expression of Bcl-xL mRNA and protein in the hippocampi and cortices of rats subjected to stress that induced depression-like behavior in the animals. In contrast to the brain-derived neurotrophic factor (BDNF), whose expression decreased in the hippocampus in response to acute stress, stress increased the level of Bcl-xL mRNA in the hippocampus, but decreased it in the frontal cortex. Treatment of stressed animals with lithium for 2 or 7 days increased Bcl-xL protein levels 1.5-fold in the hippocampus, but it decreased them in the cortex. Therefore, Bcl-xL expression in the brain can be modulated by both stress and psychotropic drugs, and the effects of these factors are brain region-specific: both stress exposure and lithium administration activated Bcl-xL expression in the hippocampus and suppressed it in the frontal cortex. The activation of Bcl-xL expression in the hippocampus by lithium, demonstrated for the first time in this study, suggests an important role of this protein in the therapeutic effects of lithium in the treatment of stress-induced psychoemotional disorders.

  7. Sub-chronic exposure to the insecticide dimethoate induces a proinflammatory status and enhances the neuroinflammatory response to bacterial lypopolysaccharide in the hippocampus and striatum of male mice

    SciTech Connect

    Astiz, Mariana Diz-Chaves, Yolanda Garcia-Segura, Luis M.

    2013-10-15

    Dimethoate is an organophosphorus insecticide extensively used in horticulture. Previous studies have shown that the administration of dimethoate to male rats, at a very low dose and during a sub-chronic period, increases the oxidation of lipids and proteins, reduces the levels of antioxidants and impairs mitochondrial function in various brain regions. In this study, we have assessed in C57Bl/6 adult male mice, whether sub-chronic (5 weeks) intoxication with a low dose of dimethoate (1.4 mg/kg) affects the expression of inflammatory molecules and the reactivity of microglia in the hippocampus and striatum under basal conditions and after an immune challenge caused by the systemic administration of lipopolysaccharide. Dimethoate increased mRNA levels of tumor necrosis factor α (TNFα) and interleukin (IL) 6 in the hippocampus, and increased the proportion of Iba1 immunoreactive cells with reactive phenotype in dentate gyrus and striatum. Lipopolysaccharide caused a significant increase in the mRNA levels of IL1β, TNFα, IL6 and interferon-γ-inducible protein 10, and a significant increase in the proportion of microglia with reactive phenotype in the hippocampus and the striatum. Some of the effects of lipopolysaccharide (proportion of Iba1 immunoreactive cells with reactive phenotype and IL6 mRNA levels) were amplified in the animals treated with dimethoate, but only in the striatum. These findings indicate that a sub-chronic period of administration of a low dose of dimethoate, comparable to the levels of the pesticide present as residues in food, causes a proinflammatory status in the brain and enhances the neuroinflammatory response to the lipopolysaccharide challenge with regional specificity. - Highlights: • The dose of pesticide used was comparable to the levels of residues found in food. • Dimethoate administration increased cytokine expression and microglia reactivity. • Hippocampus and striatum were differentially affected by the treatment.

  8. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    ERIC Educational Resources Information Center

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  9. Behavioral Functions of the CA3 Subregion of the Hippocampus

    ERIC Educational Resources Information Center

    Kesner, Raymond P.

    2007-01-01

    From a behavioral perspective, the CA3a,b subregion of the hippocampus plays an important role in the encoding of new spatial information within short-term memory with a duration of seconds and minutes. This can easily be observed in tasks that require rapid encoding, novelty detection, one-trial short-term or working memory, and one-trial cued…

  10. The Learning Hippocampus: Education and Experience-Dependent Plasticity

    ERIC Educational Resources Information Center

    Wenger, Elisabeth; Lövdén, Martin

    2016-01-01

    The hippocampal formation of the brain plays a crucial role in declarative learning and memory while at the same time being particularly susceptible to environmental influences. Education requires a well-functioning hippocampus, but may also influence the development of this brain structure. Understanding these bidirectional influences may have…

  11. A case of hypertensive intraventricular hemorrhage bled from the hippocampus.

    PubMed

    Furuse, Motomasa; Kuroda, Kenji; Miyashita, Minoru; Saura, Ryuichi; Kuroiwa, Toshihiko

    2012-04-01

    The hippocampus is not a usual origin of bleeding due to hypertension. A 66-year-old male suffered from headache and abnormal behavior. Computed tomographic images showed an intraventricular hemorrhage predominantly located in the right lateral ventricle. His arterial blood pressure was 198/92 mmHg on admission. No apparent vascular anomaly was demonstrated on a digital subtraction angiogram. Two months after the onset, his mini-mental status examination showed full recovery from the score of 19 at onset, and most of his memory disturbances were improved except for visual memory disturbance. A follow-up magnetic resonance image revealed that the hemosiderin was stained in the atrophic right hippocampus, and the final diagnosis was hypertensive intraventricular hemorrhage bled from the right hippocampus. It is difficult to diagnose hippocampal hemorrhage immediately when it is combined with intraventricular hemorrhage, because the hippocampus is covered with hematoma in the inferior horn. Moreover, with regard to neurologic examination, the patients do not show any focal sign such as hemiparesis or aphasia. In elderly patients with compensatory ventricular dilatation, one must also be attentive to a misdiagnosis of obstructive hydrocephalus due to intraventricular hemorrhage.

  12. An event map of memory space in the hippocampus

    PubMed Central

    Deuker, Lorena; Bellmund, Jacob LS; Navarro Schröder, Tobias; Doeller, Christian F

    2016-01-01

    The hippocampus has long been implicated in both episodic and spatial memory, however these mnemonic functions have been traditionally investigated in separate research strands. Theoretical accounts and rodent data suggest a common mechanism for spatial and episodic memory in the hippocampus by providing an abstract and flexible representation of the external world. Here, we monitor the de novo formation of such a representation of space and time in humans using fMRI. After learning spatio-temporal trajectories in a large-scale virtual city, subject-specific neural similarity in the hippocampus scaled with the remembered proximity of events in space and time. Crucially, the structure of the entire spatio-temporal network was reflected in neural patterns. Our results provide evidence for a common coding mechanism underlying spatial and temporal aspects of episodic memory in the hippocampus and shed new light on its role in interleaving multiple episodes in a neural event map of memory space. DOI: http://dx.doi.org/10.7554/eLife.16534.001 PMID:27710766

  13. Clitoria ternatea root extract enhances acetylcholine content in rat hippocampus.

    PubMed

    Rai, K S; Murthy, K D; Karanth, K S; Nalini, K; Rao, M S; Srinivasan, K K

    2002-12-01

    Treatment with 100 mg/kg of Clitoria ternatea aqueous root extract (CTR), for 30 days in neonatal and young adult age groups of rat, significantly increased acetylcholine (ACh) content in their hippocampi as compared to age matched controls. Increase in ACh content in their hippocampus may be the neurochemical basis for their improved learning and memory.

  14. Stress Effects on the Hippocampus: A Critical Review

    ERIC Educational Resources Information Center

    Kim, Eun Joo; Pellman, Blake; Kim, Jeansok J.

    2015-01-01

    Uncontrollable stress has been recognized to influence the hippocampus at various levels of analysis. Behaviorally, human and animal studies have found that stress generally impairs various hippocampal-dependent memory tasks. Neurally, animal studies have revealed that stress alters ensuing synaptic plasticity and firing properties of hippocampal…

  15. Cooperation between the Hippocampus and the Striatum during Episodic Encoding

    ERIC Educational Resources Information Center

    Sadeh, Talya; Shohamy, Daphna; Levy, Dana Rubi; Reggev, Niv; Maril, Anat

    2011-01-01

    The hippocampus and the striatum are thought to play distinct roles in learning and memory, each supporting an independent memory system. A fundamental question is whether, and how, these systems interact to jointly contribute to learning and memory. In particular, it remains unknown whether the striatum contributes selectively to implicit,…

  16. CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS.

    EPA Science Inventory

    CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS. ME Gilbert1, ME Kelly2, S. Salant3, T Shafer1, J Goodman3 1Neurotoxicology Div, US EPA, RTP, NC, 27711, 2Children's Hospital, Philadelphia, PA, 19104, 3Helen Hayes Hospital, Haverstraw, NY, 10993.
    ...

  17. A Cognitive Map for Object Memory in the Hippocampus

    ERIC Educational Resources Information Center

    Manns, Joseph R.; Eichenbaum, Howard

    2009-01-01

    The hippocampus has been proposed to support a cognitive map, a mental representation of the spatial layout of an environment as well as the nonspatial items encountered in that environment. In the present study, we recorded simultaneously from 43 to 61 hippocampal pyramidal cells as rats performed an object recognition memory task in which novel…

  18. Amygdala and Hippocampus Enlargement during Adolescence in Autism

    ERIC Educational Resources Information Center

    Groen, Wouter; Teluij, Michelle; Buitelaar, Jan; Tendolkar, Indira

    2010-01-01

    Objective: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse.…

  19. Representation of odor habituation and timing in the hippocampus.

    PubMed

    Deshmukh, Sachin S; Bhalla, Upinder S

    2003-03-01

    We performed simultaneous single-neuron recordings from the hippocampus and the olfactory bulb of anesthetized, freely breathing rats. Odor response properties of neurons in the olfactory bulb and hippocampus were characterized as firing rate changes or respiration-coupled changes. A panel of five odors was used. The rats had not been exposed to the odors on the panel before the experiment. The olfactory bulb and hippocampal neurons responded to repeated odor presentations in two ways: first, by changes in firing rate, and second, by respiratory tuning changes. Approximately 60% of bulbar neurons, 48% of hippocampal CA1 neurons, and 12% of hippocampal CA3 neurons showed statistically significant responses. None of the odor-responsive neurons in either the bulb or hippocampus responded to all of the odors on the panel. Repeated 10 sec odor stimuli presented at the intervals of 20, 30, 60, 110, and 160 sec were used to analyze the effect of the interval on odor response properties of the recorded neurons. Bulbar neurons were relatively nonselective for odor interval. Hippocampal neurons showed unexpected selectivity for the interval between repeated odor presentations. CA1 and CA3 neurons responded to only one to three of the intervals in the range. On the basis of these findings, we postulate that the hippocampus has the ability to keep track of the time elapsed between consecutive odor stimuli. This may act as a neuronal substrate for habituation and for complex tasks such as odor-guided navigation.

  20. Antioxidation Effect of Simvastatin in Aorta and Hippocampus: A Rabbit Model Fed High-Cholesterol Diet

    PubMed Central

    Zhang, Guangyin; Li, Ming; Xu, Yinzhi; Peng, Li; Yang, Cui; Zhou, Yanan; Zhang, Junping

    2016-01-01

    We show that hypercholesterolemia contributes to oxidative stress injury progression in brain and simvastatin counteracts the cholesterol-induced peroxidation injury in rabbit hippocampus, and we demonstrate for the first time that the simvastatin is a critical role in brain protection and identify HO-1 and other related antioxidant enzymes as molecular target for active redox compounds. Second, our experiments have pointed out an association between statin treatment and a decrease in the risk of having peroxidation damage of brain. The balance effects of simvastatin to ROS and antioxidants enzymes network are most probably due to improved SOD functional activity, increase in GSH-Px, increase in HO-1 expression, and decrease of MDA generation. PMID:26798426

  1. GFAP and S100beta expression in the cortex and hippocampus in response to mild cortical contusion.

    PubMed

    Hinkle, D A; Baldwin, S A; Scheff, S W; Wise, P M

    1997-10-01

    We studied the acute response of glial fibrillary acidic protein (GFAP) and S100beta gene expression in the cerebral cortex and hippocampus to mild unilateral cortical contusion. Our goal was to evaluate and compare the expression patterns of each gene in the early stages of the astrocytic response to brain injury. RNA was extracted from the cerebral cortex and hippocampus of male rats at 0, 3, 12, 24, or 96 h after lesion or sham-operation, then quantified using an RNase protection assay. Contusion produced a robust elevation in GFAP mRNA by 12 h in both brain regions on the ipsilateral side to the contusion. In the cortex, but not the hippocampus, this elevation was sustained at 96 h. S100beta mRNA levels were elevated bilaterally in lesioned animals at 24 h in both brain regions. However, these data are difficult to interpret because sham mRNA levels decreased with time, making it unclear whether contusion stimulates S100beta gene expression or whether it mitigates the inhibitory effect of sham. We further analyzed the effect of contusion on GFAP and S100beta immunoreactive astrocyte density at 96 h postlesion or postsham by double-label immunocytochemistry. All detectable astrocytes under all conditions were S100beta immunoreactive in both brain regions. Furthermore, all S100beta immunoreactive astrocytes in the lesioned ipsilateral cortex were also GFAP immunoreactive, whereas only about 11% of S100beta positive cells were also GFAP labeled in the contralateral lesioned or the ipsilateral sham cortex. In the hippocampus, all S100beta immunoreactive cells were also GFAP immunoreactive under all conditions. These data correlate with the gene expression data at 96 h, and suggest that, at least in the cortex, resident S100beta-expressing astrocytes produce GFAP at levels that are undetectable by immunocytochemistry until they are activated in response to injury.

  2. 48 CFR 828.106 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Administration. 828.106 Section 828.106 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 828.106 Administration....

  3. 48 CFR 1328.106 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Administration. 1328.106 Section 1328.106 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 1328.106 Administration....

  4. 48 CFR 28.106 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Administration. 28.106 Section 28.106 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 28.106 Administration....

  5. 48 CFR 428.106 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Administration. 428.106 Section 428.106 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 428.106 Administration....

  6. 48 CFR 1328.106 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Administration. 1328.106 Section 1328.106 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 1328.106 Administration....

  7. 48 CFR 828.106 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Administration. 828.106 Section 828.106 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 828.106 Administration....

  8. 48 CFR 1228.106 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Administration. 1228.106 Section 1228.106 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 1228.106 Administration....

  9. 48 CFR 1228.106 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Administration. 1228.106 Section 1228.106 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 1228.106 Administration....

  10. 48 CFR 428.106 - Administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Administration. 428.106 Section 428.106 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds and Other Financial Protections 428.106 Administration....

  11. Galantamine potentiates the protective effect of rofecoxib and caffeic acid against intrahippocampal Kainic acid-induced cognitive dysfunction in rat.

    PubMed

    Kumar, Anil; Prakash, Atish; Pahwa, Deeksha

    2011-05-30

    Role of neuroinflammatory mediators particularly cyclooxygenase (COX), lipoxygenase (LOX), have been well suggested in the pathophysiology of neurodegenerative disorders. Rofecoxib is a selective cyclooxygenase 2 enzymes belongs to non-steroidal anti-inflammatory drug, commonly called as coxibs. Whereas, caffeic acid (3,4-dihydroxycinnamic acid) is one of the natural phenolic compounds and reported to inhibit 5-lipoxygenase (5-LOX) activity as one of mechanisms. Present study has been designed to investigate the effects of rofecoxib, caffeic acid and its potentiation by galantamine against intrahippocampal kainic acid-induced cognitive impairment, oxidative damage and mitochondrial respiratory enzyme alterations in rats. Kainic acid (KA) was administrated in the hippocampus region of rat brain. Various behavioral (locomotor activity and memory performances were assessed by using actophotometer and Morris water maze respectively) followed by oxidative stress, mitochondrial enzyme complex were assessed. Intrahippocampal administration of KA significantly impaired locomotor activity, memory performance, mitochondrial enzyme complexes and caused oxidative stress as compared to sham treatment. Rofecoxib (5 and 10mg/kg), caffeic acid (5 and 10mg/kg), Gal (2.5 and 5mg/kg) treatment for 14 days significantly improved locomotor activity, memory retention and oxidative defense (as evidenced by decrease lipid peroxidation, nitrite, increased superoxide dismutase activity and redox ratio) in hippocampus. Besides, alterations in the levels of mitochondrial enzymes and acetylcholine esterase enzyme were significantly restored by rofecoxib and caffeic acid as compared to control. Further, combination of rofecoxib (5mg/kg) with caffeic acid (5mg/kg) and lower dose of gal (2.5mg/kg) with rofecoxib (5mg/kg) treatments significantly potentiated their protective effect which was significant as compared to their effect per se. The results of the present study suggest that galantamine

  12. EPA Administrator Signs New Policy to Enhance Tribal Treaty Rights

    EPA Pesticide Factsheets

    WASHINGTON -Today, U.S. Environmental Protection Agency (EPA) Administrator Gina McCarthy took an important step in helping protect the environment on tribal lands by issuing the EPA Policy on Consultation and Coordination with Indian Tribes: Guidan

  13. Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus

    PubMed Central

    Greenwood, Benjamin N.; Strong, Paul V.; Foley, Teresa E.; Thompson, Robert; Fleshner, Monika

    2007-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus have been implicated in human affective disorders and behavioral stress responses. The current studies examined the role of BDNF in the behavioral consequences of inescapable stress, or learned helplessness. Inescapable stress decreased BDNF mRNA and protein in the hippocampus of sedentary rats. Rats allowed voluntary access to running wheels for either 3 or 6 weeks prior to exposure to stress were protected against stress-induced reductions of hippocampal BDNF protein. The observed prevention of stress-induced deceases in BDNF, however, occurred in a time course inconsistent with the prevention of learned helplessness by wheel running, which is evident following 6 weeks, but not 3 weeks, of wheel running. BDNF suppression in physically active rats was produced by administering a single injection of the selective serotonin reuptake inhibitor fluoxetine (10 mg/kg) just prior to stress. Despite reduced levels of hippocampal BDNF mRNA following stress, physically active rats given the combination of fluoxetine and stress remained resistant against learned helplessness. Sedentary rats given both fluoxetine and stress still demonstrated typical learned helplessness behaviors. Fluoxetine by itself reduced BDNF mRNA in sedentary rats only, but did not affect freezing or escape learning 24 hours later. Finally, bilateral injections of BDNF (1 μg) into the dentate gyrus prior to stress prevented stress-induced reductions of hippocampal BDNF but did not prevent learned helplessness in sedentary rats. These data indicate that learned helplessness behaviors are independent of the presence or absence of hippocampal BDNF because blocking inescapable stress-induced BDNF suppression does not always prevent learned helplessness, and learned helplessness does not always occur in the presence of reduced BDNF. Results also suggest that the prevention of stress-induced hippocampal BDNF suppression is not

  14. N-acetyl cysteine (NAC) treatment reduces mercury-induced neurotoxicity in the developing rat hippocampus

    PubMed Central

    Falluel-Morel, Anthony; Lin, Lulu; Sokolowski, Katie; McCandlish, Elizabeth; Buckley, Brian; DiCicco-Bloom, Emanuel

    2011-01-01

    Mercury is an environmental toxicant that can disrupt brain development. However, while progress has been made in defining its neurotoxic effects, we know far less about available therapies that can effectively protect brain in exposed individuals. We previously developed an animal model in which we defined the sequence of events underlying neurotoxicity: Methylmercury (MeHg) injection in postnatal rat acutely induced inhibition of mitosis and stimulated apoptosis in the hippocampus, that later resulted in intermediate term deficits in structure size and cell number. NAC is the N-acetyl derivative of L-cysteine used clinically for treatment of drug intoxication. Here, based on its known efficacy in promoting MeHg urinary excretion, we evaluated NAC for protective effects in the developing brain. In immature neurons and precursors MeHg (3µM) induced a >50% decrease in DNA synthesis at 24hr, an effect that was completely blocked by NAC co-incubation. In vivo, injection of MeHg (5µg/gbw) into 7 day-old rats induced a 22% decrease in DNA synthesis in whole hippocampus and a 4-fold increase in activated caspase-3 immunoreactive cells at 24hr, and reduced total cell numbers by 13% at 3 weeks. Treatment of MeHg exposed rats with repeated injections of NAC abolished MeHg toxicity. NAC prevented the reduction in DNA synthesis and the marked increase in caspase-3 immunoreactivity. Moreover, the intermediate term decrease in hippocampal cell number provoked by MeHg was fully blocked by NAC. Altogether, these results suggest that MeHg toxicity in the perinatal brain can be ameliorated by using NAC, opening potential avenues for therapeutic intervention. PMID:22420031

  15. Modulation of age-related changes in oxidative stress markers and energy status in the rat heart and hippocampus: a significant role for ozone therapy.

    PubMed

    El-Sawalhi, Maha M; Darwish, Hebatallah A; Mausouf, Mohamed N; Shaheen, Amira A

    2013-08-01

    Oxidative stress emerges as a key player in the ageing process. Controlled ozone administration is known to promote an oxidative preconditioning or adaptation to oxidative stress. The present study investigated whether prophylactic ozone administration could interfere with the age-related changes in the heart and the hippocampus of rats. Four groups of rats, aged about 3 months old, were used. Group 1 (Prophylactic ozone group) received ozone/oxygen mixture by rectal insufflations (0.6 mg/kg) twice/week for the first 3 months, then once/week till the age of 15 months. Group 2 (Oxygen group) received oxygen as vehicle for ozone in a manner similar to group 1. Group 3 (Aged control group) was kept without any treatment until the age of 15 months. A fourth group of rats (Adult control group) was evaluated at 3 months of age to provide baseline data. Ozone alleviated age-associated redox state imbalance as evidenced by reduction of lipid and protein oxidation markers, lessening of lipofuscin deposition, restoration of glutathione levels in both tissues and normalization of glutathione peroxidase activity in the heart tissue. Ozone also mitigated age-associated energy failure in the heart and the hippocampus, improved cardiac cytosolic Ca(2+) homeostasis and restored the attenuated Na(+) , K(+) -ATPase activity in the hippocampus of aged rats. These data provide new evidence concerning the anti-ageing potential of prophylactic ozone administration.

  16. [Effect of semax on the temporary dynamics of brain-derived neurotrophic factor and nerve growth factor gene expression in the rat hippocampus and frontal cortex].

    PubMed

    Agapova, T Iu; Agniullin, Ia V; Silachev, D N; Shadrina, M I; Slominskiĭ, P A; Shram, S I; Limborskaia, S A; Miasoedov, N F

    2008-01-01

    Semax is a synthetic peptide, which consists of the N-terminal adrenocorticotropic hormone fragment (4-7) (ACTH4-7) and C-terminal Pro-Gly-Pro peptide. Semax promotes neuron survival in hypoxia, increases selective attention and memory storage. It was shown that this synthetic peptide exerted a number of gene expressions, especially brain derived neurotrophic factor gene (Bdnf) and nerve growth factor gene (Ngf). Temporary dynamics of Bdnf and Ngf ex- pression in rat hippocampus and frontal cortex under Semax action (50 mg/kg, single intranasal administration) was studied in this work. It was shown that the studied gene expression levels changed significantly both in the hippocampus and the frontal cortex tissues 20 minutes after the peptide preparation application. The expression levels decreased in the hippocampus and increased in the frontal cortex. Forty minutes after Semax administration both gene expression levels returned to the level typical of control tissues. After that they increased significantly by 90 minutes after experiment start. Bdnf and Ngf expression levels decreased up to the control levels by 8 hours after medicine applying maximum gene expression levels were attained. Thus, Semax administration results in rapid, long-term, and specific activation of Bdnf and Ngf expression changes in different rat brain departments.

  17. Comparison of automated and manual segmentation of hippocampus MR images

    NASA Astrophysics Data System (ADS)

    Haller, John W.; Christensen, Gary E.; Miller, Michael I.; Joshi, Sarang C.; Gado, Mokhtar; Csernansky, John G.; Vannier, Michael W.

    1995-05-01

    The precision and accuracy of area estimates from magnetic resonance (MR) brain images and using manual and automated segmentation methods are determined. Areas of the human hippocampus were measured to compare a new automatic method of segmentation with regions of interest drawn by an expert. MR images of nine normal subjects and nine schizophrenic patients were acquired with a 1.5-T unit (Siemens Medical Systems, Inc., Iselin, New Jersey). From each individual MPRAGE 3D volume image a single comparable 2-D slice (matrix equals 256 X 256) was chosen which corresponds to the same coronal slice of the hippocampus. The hippocampus was first manually segmented, then segmented using high dimensional transformations of a digital brain atlas to individual brain MR images. The repeatability of a trained rater was assessed by comparing two measurements from each individual subject. Variability was also compared within and between subject groups of schizophrenics and normal subjects. Finally, the precision and accuracy of automated segmentation of hippocampal areas were determined by comparing automated measurements to manual segmentation measurements made by the trained rater on MR and brain slice images. The results demonstrate the high repeatability of area measurement from MR images of the human hippocampus. Automated segmentation using high dimensional transformations from a digital brain atlas provides repeatability superior to that of manual segmentation. Furthermore, the validity of automated measurements was demonstrated by a high correlation with manual segmentation measurements made by a trained rater. Quantitative morphometry of brain substructures (e.g. hippocampus) is feasible by use of a high dimensional transformation of a digital brain atlas to an individual MR image. This method automates the search for neuromorphological correlates of schizophrenia by a new mathematically robust method with unprecedented sensitivity to small local and regional differences.

  18. Weak and nondiscriminative responses to conspecifics in the rat hippocampus.

    PubMed

    von Heimendahl, Moritz; Rao, Rajnish P; Brecht, Michael

    2012-02-08

    Little is known about how hippocampal neurons in rodents respond to and represent conspecifics. To address this question, we let rats interact while quantifying hippocampal neuronal activation patterns with extracellular recordings and immediate-early gene (c-Fos) expression. A total of 319 single putative pyramidal neurons was recorded in dorsal hippocampus. In sessions with multiple stimulus rats, no cell responded differentially to individual rats (N = 267 cells). We did find, however, that the presence of other rats induced a significant enhancement or suppression of firing in a fraction of neurons (n = 22 of 319; 7%). As expected, a large fraction of neurons (n = 170; 53%) had place fields. There was no evidence for place-independent responses to rats. Rather, the modulations were linked to the spatial responses. While neurons did not discriminate between individual rats, they did discriminate between rats and inanimate objects. Surprisingly, neuronal responses were more strongly modulated by objects than by rats, even though subjects spent more time near their conspecifics. Consistent with the low fraction of rat-modulated cells, social encounters did not induce c-Fos expression in the hippocampus, while there was a social interaction-specific expression in the basolateral amygdala. In both interacting and non-interacting rats, the fraction of c-Fos-expressing cells in the hippocampus was very low. Our investigation of social coding in the rat hippocampus, along with other recent work, showed that social responses were rare and lacked individual specificity, altogether speaking against a role of rodent dorsal hippocampus in social memory.

  19. Hippocampus Is Place of Interaction between Unconscious and Conscious Memories

    PubMed Central

    Züst, Marc Alain; Colella, Patrizio; Reber, Thomas Peter; Vuilleumier, Patrik; Hauf, Martinus; Ruch, Simon; Henke, Katharina

    2015-01-01

    Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus—the key structure also recruited for conscious relational (episodic) memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked) combinations of unfamiliar faces and written occupations (“actor” or “politician”). At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation—actor or politician—would facilitate or inhibit the subsequent conscious retrieval of a celebrity’s occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity’s occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious

  20. 45 CFR 164.308 - Administrative safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... business processes for protection of the security of electronic protected health information while... Information § 164.308 Administrative safeguards. (a) A covered entity or business associate must, in accordance with § 164.306: (1)(i) Standard: Security management process. Implement policies and procedures...

  1. 45 CFR 164.308 - Administrative safeguards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... business processes for protection of the security of electronic protected health information while... Information § 164.308 Administrative safeguards. (a) A covered entity or business associate must, in accordance with § 164.306: (1)(i) Standard: Security management process. Implement policies and procedures...

  2. 40 CFR 35.6815 - Administrative requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Section 35.6815 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL... must comply with the following requirements regarding financial administration: (1) Payment. The State....6285(c). The State may not pay for its cost share using in-kind services, unless the State has...

  3. 40 CFR 35.6815 - Administrative requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Section 35.6815 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL... must comply with the following requirements regarding financial administration: (1) Payment. The State....6285(c). The State may not pay for its cost share using in-kind services, unless the State has...

  4. Protective role of Cynodon dactylon in ameliorating the aluminium-induced neurotoxicity in rat brain regions.

    PubMed

    Sumathi, Thangarajan; Shobana, Chandrasekar; Kumari, Balasubramanian Rathina; Nandhini, Devarajulu Nisha

    2011-12-01

    Cynodon dactylon (Poaceae) is a creeping grass used as a traditional ayurvedic medicine in India. Aluminium-induced neurotoxicity is well known and different salts of aluminium have been reported to accelerate damage to biomolecules like lipids, proteins and nucleic acids. The objective of the present study was to investigate whether the aqueous extract of C. dactylon (AECD) could potentially prevent aluminium-induced neurotoxicity in the cerebral cortex, hippocampus and cerebellum of the rat brain. Male albino rats were administered with AlCl(3) at a dose of 4.2 mg/kg/day i.p. for 4 weeks. Experimental rats were given C. dactylon extract in two different doses of 300 mg and 750 mg/keg/day orally 1 h prior to the AlCl(3) administration for 4 weeks. At the end of the experiments, antioxidant status and activities of ATPases in cerebral cortex, hippocampus and cerebellum of rat brain were measured. Aluminium administration significantly decreased the level of GSH and the activities of SOD, GPx, GST, Na(+)/K(+) ATPase, and Mg(2+) ATPase and increased the level of lipid peroxidation (LPO) in all the brain regions when compared with control rats. Pre-treatment with AECD at a dose of 750 mg/kg b.w increased the antioxidant status and activities of membrane-bound enzymes (Na(+)/K(+) ATPase and Mg(2+) ATPase) and also decreased the level of LPO significantly, when compared with aluminium-induced rats. The results of this study indicated that AECD has potential to protect the various brain regions from aluminium-induced neurotoxicity.

  5. Methamphetamine reversed maternal separation-induced decrease in nerve growth factor in the ventral hippocampus.

    PubMed

    Dimatelis, J J; Russell, V A; Stein, D J; Daniels, W M

    2014-06-01

    Stress has been suggested to predispose individuals to drug abuse. The early life stress of maternal separation (MS) is known to alter the response to drugs of abuse later in life. Exposure to either stress or methamphetamine has been shown to alter neurotrophic factors in the brain. Changes in neurotrophin levels may contribute to the underlying molecular mechanisms responsible for drug use- and stress-induced behaviours. The purpose of the present study was to investigate the individual effects of MS and methamphetamine administration during adolescence and the combined effects of both stressors on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the dorsal and ventral hippocampus (HC) in adulthood. Methamphetamine administration (1 mg/kg, daily from postnatal day (PND) 33 to 36 and from PND 39 to 42), MS and the combination of the two stressors resulted in decreased BDNF levels in both the dorsal and ventral HC. MS decreased NGF levels in the ventral HC which was restored by methamphetamine administration in adolescence. In the dorsal HC, NGF remained unaltered by either stressor alone or in combination. We propose that the restoration of NGF levels in the ventral HC may reflect a possible compensatory mechanism in response to methamphetamine exposure in adolescence following the early life stress of MS.

  6. Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model.

    PubMed

    Soerensen, Jonna; Pekcec, Anton; Fuest, Christina; Nickel, Astrid; Potschka, Heidrun

    2009-12-01

    Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.

  7. Dexmedetomidine alleviates cerebral ischemia-induced short-term memory impairment by inhibiting the expression of apoptosis-related molecules in the hippocampus of gerbils

    PubMed Central

    Choi, In-Young; Hwang, Lakkyong; Jin, Jun-Jang; Ko, Il-Gyu; Kim, Sung-Eun; Shin, Mal-Soon; Shin, Key-Moon; Kim, Chang-Ju; Park, Sung-Wook; Han, Jin-Hee; Yi, Jae-Woo

    2017-01-01

    Cerebral ischemia results from cerebrovascular occlusion, which leads to neuronal cell death and eventually causes neurological impairments. Dexmedetomidine is a potent and highly selective α2-adrenoreceptor agonist with actions such as sedation, anxiolysis, analgesia and anesthetic-sparing effects. We investigated the effect of dexmedetomidine on apoptosis in the hippocampus after transient global ischemia in gerbils. Transient global ischemia was induced by ligation of both common carotid arteries. Dexmedetomidine was administrated intraperitoneally at three respective doses (0.1, 1 and 10 µg/kg) once per day for 14 consecutive days beginning a day after surgery. Short-term memory was assessed by use of a step-down avoidance task. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, immunohistochemistry for caspase-3, and western blot analysis of Bcl-2-associated X protein, B-cell lymphoma 2, Bid, cytochrome c, apoptotic protease activating factor-1 and caspase-9 in the hippocampus. Induction of global ischemia deteriorated short-term memory by enhancing the expression of apoptosis-related molecules in the hippocampus. Treatment with dexmedetomidine suppressed the expression of apoptosis-related molecules under ischemic conditions, resulting in short-term memory improvement. Under normal conditions, dexmedetomidine exerted no significant effect on apoptosis in the hippocampus. The present results suggest that the α2-adrenoceptor agonist dexmedetomidine may be a useful therapeutic agent for the treatment of ischemic brain diseases. PMID:28123477

  8. Amyloid-β peptide absence in short term effects on kinase activity of energy metabolism in mice hippocampus and cerebral cortex.

    PubMed

    Ianiski, Francine R; Rech, Virginia C; Nishihira, Vivian S K; Alves, Catiane B; Baldissera, Matheus D; Wilhelm, Ethel A; Luchese, Cristiane

    2016-01-01

    Considering that Alzheimer's disease is a prevalent neurodegenerative disease worldwide, we investigated the activities of three key kinases: creatine kinase, pyruvate kinase and adenylate kinase in the hippocampus and cerebral cortex in Alzheimer's disease model. Male adult Swiss mice received amyloid-β or saline. One day after, mice were treated with blank nanocapsules (17 ml/kg) or meloxicam-loaded nanocapsules (5 mg/kg) or free meloxicam (5 mg/kg). Treatments were performed on alternating days, until the end of the experimental protocol. In the fourteenth day, kinases activities were performed. Amyloid-β did not change the kinases activity in the hippocampus and cerebral cortex of mice. However, free meloxicam decrease the creatine kinase activity in mitochondrial-rich fraction in the group induced by amyloid-β, but for the cytosolic fraction, it has raised in the activity of pyruvate kinase activity in cerebral cortex. Further, meloxicam-loaded nanocapsules administration reduced adenylate kinase activity in the hippocampus of mice injected by amyloid-β. In conclusion we observed absence in short-term effects in kinases activities of energy metabolism in mice hippocampus and cerebral cortex using amyloid-β peptide model. These findings established the foundation to further study the kinases in phosphoryltransfer network changes observed in the brains of patients post-mortem with Alzheimer's disease.

  9. Cannabinoid CB1 receptors of the dorsal hippocampus are important for induction of conditioned place preference (CPP) but do not change morphine CPP.

    PubMed

    Zarrindast, Mohammad-Reza; Nouri, Maryam; Ahmadi, Shamseddin

    2007-08-13

    Interactions between cannabinoid and opioid systems have been reported in many studies. In the present study, we have investigated influence of cannabinoid CB1 receptor mechanism on the acquisition of conditioned place preference (CPP) induced by morphine in male Wistar rats. The cannabinoid CB1 receptor agonist (WIN55,212-2) and antagonist (AM251) were injected bilaterally into the dorsal hippocampus. Morphine and naloxone were injected subcutaneously (s.c.). The conditioning treatments with injections of morphine (6 and 9 mg/kg) induced a CPP for the drug-associated place. When administered into the dorsal hippocampus, WIN55,212-2 (1 microg/rat) induced CPP, but significantly did not alter CPP induced by a sub-effective dose of morphine (3 mg/kg). Moreover, administration of different doses of AM251 (50 and 100 ng/rat) into the dorsal hippocampus induced CPP, while did not change CPP by the sub-effective dose of morphine. Naloxone alone (1 mg/kg) induced conditioned place aversion (CPA). The drug (0.5 and 1 mg/kg) also caused CPA when co-administered with WIN55,212-2 (1 microg/rat). These results suggest that endocannabinoid system in the dorsal hippocampus is important for the CPP paradigm. However, agents did not alter morphine-induced CPP.

  10. Senior Administrators Should Have Administrative Contracts.

    ERIC Educational Resources Information Center

    Posner, Gary J.

    1987-01-01

    Recognizing that termination is viewed by the employee as the equivalent to capital punishment of a career, an administrative contract can reduce the emotional and financial entanglements that often result. Administrative contracts are described. (MLW)

  11. Prior regular exercise reverses the decreased effects of sleep deprivation on brain-derived neurotrophic factor levels in the hippocampus of ovariectomized female rats.

    PubMed

    Saadati, Hakimeh; Sheibani, Vahid; Esmaeili-Mahani, Saeed; Darvishzadeh-Mahani, Fatemeh; Mazhari, Shahrzad

    2014-11-01

    Previous studies indicated that brain-derived neurotrophic factor (BDNF) is the main candidate to mediate the beneficial effects of exercise on cognitive function in sleep deprived male rats. In addition, our previous findings demonstrate that female rats are more vulnerable to the deleterious effects of sleep deprivation on cognitive performance and synaptic plasticity. Therefore, the current study was designed to investigate the effects of treadmill exercise and/or sleep deprivation (SD) on the levels of BDNF mRNA and protein in the hippocampus of female rats. Intact and ovariectomized (OVX) female Wistar rats were used in the present experiment. The exercise protocol was four weeks treadmill running and sleep deprivation was accomplished using the multiple platform method. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis were used to evaluate the level of BDNF mRNA and protein in the rat hippocampus respectively. Our results showed that protein and mRNA expression of BDNF was significantly (p<0.05) decreased after 72 h SD in OVX rats in compared with other groups. Furthermore, sleep deprived OVX rats under exercise conditions had a significant (p<0.05) up-regulation of the BDNF protein and mRNA in the hippocampus. These findings suggest that regular exercise can exert a protective effect against hippocampus-related functions and impairments induced by sleep deprivation probably by inducing BDNF expression.

  12. "Unforgettable" - a pictorial essay on anatomy and pathology of the hippocampus.

    PubMed

    Dekeyzer, Sven; De Kock, Isabelle; Nikoubashman, Omid; Vanden Bossche, Stephanie; Van Eetvelde, Ruth; De Groote, Jeroen; Acou, Marjan; Wiesmann, Martin; Deblaere, Karel; Achten, Eric

    2017-04-01

    The hippocampus is a small but complex anatomical structure that plays an important role in spatial and episodic memory. The hippocampus can be affected by a wide range of congenital variants and degenerative, inflammatory, vascular, tumoral and toxic-metabolic pathologies. Magnetic resonance imaging is the preferred imaging technique for evaluating the hippocampus. The main indications requiring tailored imaging sequences of the hippocampus are medically refractory epilepsy and dementia. The purpose of this pictorial review is threefold: (1) to review the normal anatomy of the hippocampus on MRI; (2) to discuss the optimal imaging strategy for the evaluation of the hippocampus; and (3) to present a pictorial overview of the most common anatomic variants and pathologic conditions affecting the hippocampus.

  13. 77 FR 71641 - NASA Advisory Council; Science Committee; Planetary Protection Subcommittee; Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-03

    ... SPACE ADMINISTRATION NASA Advisory Council; Science Committee; Planetary Protection Subcommittee; Meeting AGENCY: National Aeronautics and Space Administration. ACTION: Notice of meeting. SUMMARY: In... and Space Administration (NASA) announces a meeting of the Planetary Protection Subcommittee of...

  14. 77 FR 20851 - NASA Advisory Council; Science Committee; Planetary Protection Subcommittee; Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ... SPACE ADMINISTRATION NASA Advisory Council; Science Committee; Planetary Protection Subcommittee; Meeting AGENCY: National Aeronautics and Space Administration. ACTION: Notice of meeting. SUMMARY: In... and Space Administration (NASA) announces a meeting of the Planetary Protection Subcommittee of...

  15. Differences in relative hippocampus volume and number of hippocampus neurons among five corvid species.

    PubMed

    Gould, Kristy L; Gilbertson, Karl E; Hrvol, Andrew J; Nelson, Joseph C; Seyfer, Abigail L; Brantner, Rose M; Kamil, Alan C

    2013-01-01

    The relative size of the avian hippocampus (Hp) has been shown to be related to spatial memory and food storing in two avian families, the parids and corvids. Basil et al. [Brain Behav Evol 1996;47:156-164] examined North American food-storing birds in the corvid family and found that Clark's nutcrackers had a larger relative Hp than pinyon jays and Western scrub jays. These results correlated with the nutcracker's better performance on most spatial memory tasks and their strong reliance on stored food in the wild. However, Pravosudov and de Kort [Brain Behav Evol 2006;67:1-9] raised questions about the methodology used in the 1996 study, specifically the use of paraffin as an embedding material and recalculation for shrinkage. Therefore, we measured relative Hp volume using gelatin as the embedding material in four North American species of food-storing corvids (Clark's nutcrackers, pinyon jays, Western scrub jays and blue jays) and one Eurasian corvid that stores little to no food (azure-winged magpies). Although there was a significant overall effect of species on relative Hp volume among the five species, subsequent tests found only one pairwise difference, blue jays having a larger Hp than the azure-winged magpies. We also examined the relative size of the septum in the five species. Although Shiflett et al. [J Neurobiol 2002;51:215-222] found a difference in relative septum volume amongst three species of parids that correlated with storing food, we did not find significant differences amongst the five species in relative septum. Finally, we calculated the number of neurons in the Hp relative to body mass in the five species and found statistically significant differences, some of which are in accord with the adaptive specialization hypothesis and some are not.

  16. Testimony of E. Ramona Trovato, Deputy Assistant Administrator, Office of Environmental Information, U.S. Environmental Protection Agency before the Committee on Environment and Public Works, United States Senate.

    ERIC Educational Resources Information Center

    2002

    This testimony provides an overview of health and environmental issues in U.S. schools and describes efforts by the Environmental Protection Agency (EPA), in concert with other federal agencies, to help schools address environmental issues. These include the Clear Skies Initiative, Indoor Air Quality Tools for Schools, High Performance Schools,…

  17. Nuclear factor kappa B-dependent Zif268 expression in hippocampus is required for recognition memory in mice.

    PubMed

    Zalcman, Gisela; Federman, Noel; de la Fuente, Verónica; Romano, Arturo

    2015-03-01

    Long-term memory formation requires gene expression after acquisition of new information. The first step in the regulation of gene expression is the participation of transcription factors (TFs) such as nuclear factor kappa B (NF-кB), which are present before the neuronal activity induced by training. It was proposed that the activation of these types of TFs allows a second step in gene regulation by induction of immediate-early genes (IEGs) whose protein products are, in turn, TFs. Between these IEGs, zif268 has been found to play a critical role in long-term memory formation and reprocessing after retrieval. Here we found in mice hippocampus that, on one hand, NF-кB was activated 45 min after training in a novel object recognition (NOR) task and that inhibiting NF-кB immediately after training by intrahippocampal administration of NF-кB Decoy DNA impaired NOR memory consolidation. On the other hand, Zif268 protein expression was induced 45 min after NOR training and the administration of DNA antisense to its mRNA post-training impaired recognition memory. Finally, we found that the inhibition of NF-кB by NF-кB Decoy DNA reduced significantly the training-induced Zif268 increment, indicating that NF-кB is involved in the regulation of Zif268 expression. Thus, the present results support the involvement of NF-кB activity-dependent Zif268 expression in the hippocampus during recognition memory consolidation.

  18. Decreased Fast Ripples in the Hippocampus of Rats with Spontaneous Recurrent Seizures Treated with Carbenoxolone and Quinine

    PubMed Central

    Ventura-Mejía, Consuelo

    2014-01-01

    Background. In models of temporal lobe epilepsy and in patients with this pathology, high frequency oscillations called fast ripples (FRs, 250–600 Hz) can be observed. FRs are considered potential biomarkers for epilepsy and, in the light of many in vitro and in silico studies, we thought that electrical synapses mediated by gap junctions might possibly modulate FRs in vivo. Methods. Animals with spontaneous recurrent seizures induced by pilocarpine administration were implanted with movable microelectrodes in the right anterior and posterior hippocampus to evaluate the effects of gap junction blockers administered in the entorhinal cortex. The effects of carbenoxolone (50 nmoles) and quinine (35 pmoles) on the mean number of spontaneous FR events (occurrence of FRs), as well as on the mean number of oscillation cycles per FR event and their frequency, were assessed using a specific algorithm to analyze FRs in intracranial EEG recordings. Results. We found that these gap junction blockers decreased the mean number of FRs and the mean number of oscillation cycles per FR event in the hippocampus, both during and at different times after carbenoxolone and quinine administration. Conclusion. These data suggest that FRs may be modulated by gap junctions, although additional experiments in vivo will be necessary to determine the precise role of gap junctions in this pathological activity associated with epileptogenesis. PMID:25276773

  19. Veterans Health Administration

    MedlinePlus

    ... code here VA » Veterans Health Administration Veterans Health Administration Marine Continues to Serve by Serving Veterans David ... Read more » VA Medical Centers The Veterans Health Administration is home to the United States’ largest integrated ...

  20. 40 CFR 23.2 - Timing of Administrator's action under Clean Water Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Timing of Administrator's action under Clean Water Act. 23.2 Section 23.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL JUDICIAL REVIEW UNDER EPA-ADMINISTERED STATUTES § 23.2 Timing of Administrator's action under Clean Water Act. Unless the Administrator...

  1. 40 CFR 23.2 - Timing of Administrator's action under Clean Water Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Timing of Administrator's action under Clean Water Act. 23.2 Section 23.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL JUDICIAL REVIEW UNDER EPA-ADMINISTERED STATUTES § 23.2 Timing of Administrator's action under Clean Water Act. Unless the Administrator...

  2. 40 CFR 23.2 - Timing of Administrator's action under Clean Water Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Timing of Administrator's action under Clean Water Act. 23.2 Section 23.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL JUDICIAL REVIEW UNDER EPA-ADMINISTERED STATUTES § 23.2 Timing of Administrator's action under Clean Water Act. Unless the Administrator...

  3. The Hippocampus and Imagining the Future: Where Do We Stand?

    PubMed Central

    Addis, Donna Rose; Schacter, Daniel L.

    2011-01-01

    Recent neuroimaging work has demonstrated that the hippocampus is engaged when imagining the future, in some cases more than when remembering the past. It is possible that this hippocampal activation reflects recombining details into coherent scenarios and/or the encoding of these scenarios into memory for later use. However, inconsistent findings have emerged from recent studies of future simulation in patients with memory loss and hippocampal damage. Thus, it remains an open question as to whether the hippocampus is necessary for future simulation. In this review, we consider the findings from patient studies and the neuroimaging literature with respect to a new framework that highlights three component processes of simulation: accessing episodic details, recombining details, and encoding simulations. We attempt to reconcile these discrepancies between neuroimaging and patient studies by suggesting that different component processes of future simulation may be differentially affected by hippocampal damage. PMID:22291625

  4. Ketamine selectively suppresses synchronized afterdischarges in immature hippocampus.

    PubMed

    Brady, R J; Swann, J W

    1986-08-29

    The role of excitatory amino acid neurotransmission in epileptogenesis was investigated in the developing hippocampus. Bath application of ketamine blocked penicillin-induced, synchronized afterdischarges in immature rat CA3 hippocampal neurons. Ketamine also decreased the duration of the preceding intracellularly recorded depolarization shift but had no measurable effect on the resting membrane potential or input impedance of pyramidal cells. Concentrations of ketamine that blocked afterdischarge generation dramatically depressed intracellular depolarizations produced by iontophoretic application of N-methyl-D-aspartate (NMDA) but not quisqualate. The effects of the NMDA antagonist 2-amino-7-phosphonoheptanoic acid on epileptiform discharges were identical to those of ketamine. These results suggest that an endogenous excitatory amino acid acting on an NMDA receptor plays a key role in the pronounced capacity of immature hippocampus for seizures.

  5. Dual role of GABA in the neonatal rat hippocampus.

    PubMed

    Khalilov, I; Dzhala, V; Ben-Ari, Y; Khazipov, R

    1999-11-01

    The effects of modulators of GABA-A receptors on neuronal network activity were studied in the neonatal (postnatal days 0-5) rat hippocampus in vitro. Under control conditions, the physiological pattern of activity of the neonatal hippocampal network was characterized by spontaneous network-driven giant depolarizing potentials (GDPs). The GABA-A receptor agonist isoguvacine (1-2 microM) and the allosteric modulator diazepam (2 microM) induced biphasic responses: initially the frequency of GDPs increased 3 to 4 fold followed by blockade of GDPs and desynchronization of the network activity. The GABA-A receptor antagonists bicuculline (10 microM) and picrotoxin (100 microM) blocked GDPs and induced glutamate (AMPA and NMDA)-receptor-mediated interictal- and ictal-like activities in the hippocampal slices and the intact hippocampus. These data suggest that at early postnatal ages GABA can exert a dual - both excitatory and inhibitory - action on the network activity.

  6. Prospective representation of navigational goals in the human hippocampus.

    PubMed

    Brown, Thackery I; Carr, Valerie A; LaRocque, Karen F; Favila, Serra E; Gordon, Alan M; Bowles, Ben; Bailenson, Jeremy N; Wagner, Anthony D

    2016-06-10

    Mental representation of the future is a fundamental component of goal-directed behavior. Computational and animal models highlight prospective spatial coding in the hippocampus, mediated by interactions with the prefrontal cortex, as a putative mechanism for simulating future events. Using whole-brain high-resolution functional magnetic resonance imaging and multi-voxel pattern classification, we tested whether the human hippocampus and interrelated cortical structures support prospective representation of navigational goals. Results demonstrated that hippocampal activity patterns code for future goals to which participants subsequently navigate, as well as for intervening locations along the route, consistent with trajectory-specific simulation. The strength of hippocampal goal representations covaried with goal-related coding in the prefrontal, medial temporal, and medial parietal cortex. Collectively, these data indicate that a hippocampal-cortical network supports prospective simulation of navigational events during goal-directed planning.

  7. Lasting neuropathological changes in rat brain after intermittent neonatal administration of thimerosal.

    PubMed

    Olczak, Mieszko; Duszczyk, Michalina; Mierzejewski, Paweł; Wierzba-Bobrowicz, Teresa; Majewska, Maria D

    2010-01-01

    Thimerosal, an organomercurial added as a preservative to some vaccines, is a suspected iatrogenic factor, possibly contributing to paediatric neurodevelopmental disorders including autism. We examined the effects of early postnatal administration of thimerosal (four i.m. injections, 12 or 240 μg THIM-Hg/kg, on postnatal days 7, 9, 11 and 15) on brain pathology in Wistar rats. Numerous neuropathological changes were observed in young adult rats which were treated postnatally with thimerosal. They included: ischaemic degeneration of neurons and "dark" neurons in the prefrontal and temporal cortex, the hippocampus and the cerebellum, pathological changes of the blood vessels in the temporal cortex, diminished synaptophysin reaction in the hippocampus, atrophy of astroglia in the hippocampus and cerebellum, and positive caspase-3 reaction in Bergmann astroglia. These findings document neurotoxic effects of thimerosal, at doses equivalent to those used in infant vaccines or higher, in developing rat brain, suggesting likely involvement of this mercurial in neurodevelopmental disorders.

  8. Self-generated theta oscillations in the hippocampus.

    PubMed

    Goutagny, Romain; Jackson, Jesse; Williams, Sylvain

    2009-12-01

    Hippocampal theta rhythm is crucial for spatial memory and is thought to be generated by extrinsic inputs. In contrast, using a complete rat hippocampus in vitro, we found several intrinsic, atropine-resistant theta generators in CA1. These oscillators were organized along the septotemporal axis and arose independently from CA3. Our results suggest that CA1 theta rhythm can emerge from the coupling of multiple autonomous hippocampal theta oscillators.

  9. Allergy Enhances Neurogenesis and Modulates Microglial Activation in the Hippocampus

    PubMed Central

    Klein, Barbara; Mrowetz, Heike; Thalhamer, Josef; Scheiblhofer, Sandra; Weiss, Richard; Aigner, Ludwig

    2016-01-01

    Allergies and their characteristic TH2-polarized inflammatory reactions affect a substantial part of the population. Since there is increasing evidence that the immune system modulates plasticity and function of the central nervous system (CNS), we investigated the effects of allergic lung inflammation on the hippocampus—a region of cellular plasticity in the adult brain. The focus of the present study was on microglia, the resident immune cells of the CNS, and on hippocampal neurogenesis, i.e., the generation of new neurons. C57BL/6 mice were sensitized with a clinically relevant allergen derived from timothy grass pollen (Phl p 5). As expected, allergic sensitization induced high serum levels of allergen-specific immunoglobulins (IgG1 and IgE) and of TH2 cytokines (IL-5 and IL-13). Surprisingly, fewer Iba1+ microglia were found in the granular layer (GL) and subgranular zone (SGZ) of the hippocampal dentate gyrus and also the number of Iba1+MHCII+ cells was lower, indicating a reduced microglial surveillance and activation in the hippocampus of allergic mice. Neurogenesis was analyzed by labeling of proliferating cells with bromodeoxyuridine (BrdU) and determining their fate 4 weeks later, and by quantitative analysis of young immature neurons, i.e., cells expressing doublecortin (DCX). The number of DCX+ cells was clearly increased in the allergy animals. Moreover, there were more BrdU+ cells present in the hippocampus of allergic mice, and these newly born cells had differentiated into neurons as indicated by a higher number of BrdU+NeuN+ cells. In summary, allergy led to a reduced microglia presence and activity and to an elevated level of neurogenesis in the hippocampus. This effect was apparently specific to the hippocampus, as we did not observe these alterations in the subventricular zone (SVZ)/olfactory bulb (OB) system, also a region of high cellular plasticity and adult neurogenesis. PMID:27445696

  10. The ventral hippocampus is necessary for expressing a spatial memory.

    PubMed

    Loureiro, Michael; Lecourtier, Lucas; Engeln, Michel; Lopez, Joëlle; Cosquer, Brigitte; Geiger, Karin; Kelche, Christian; Cassel, Jean-Christophe; Pereira de Vasconcelos, Anne

    2012-01-01

    Current views posit the dorsal hippocampus (DHipp) as contributing to spatial memory processes. Conversely, the ventral hippocampus (VHipp) modulates stress, emotions and affects. Arguments supporting this segregation include differences in (i) connectivity: the DHipp is connected with the entorhinal cortex which receives visuospatial neocortical inputs; the VHipp is connected with both the amygdala and hypothalamus, (ii) electrophysiological characteristics: there is a larger proportion of place cells in the DHipp than in the VHipp, and an increasing dorsoventral gradient in the size of place fields, suggesting less refined spatial coding in the VHipp, and (iii) consequences of lesions: spatial memory is altered after DHipp lesions, less dramatically, sometimes not, after VHipp lesions. Using reversible inactivation, we report in rats, that lidocaine infusions into the DHipp or VHipp right before a probe trial impair retrieval performance in a water-maze task. This impairment was found at two post-acquisition delays compatible with recent memory (1 and 5 days). Pre-training blockade of the VHipp did not prevent task acquisition and drug-free retrieval, on the contrary to pre-training blockade of DHipp, which altered performance in a subsequent drug-free probe trial. Complementary experiments excluded possible locomotor, sensorimotor, motivational or anxiety-related biases from data interpretation. Our conclusion is that a spatial memory can be acquired with the DHipp, less efficiently with the VHipp, and that the retrieval of such a memory and/or the expression of its representation engages the dorsoventral axis of the hippocampus when the task has been learnt with an entirely functional hippocampus.

  11. Gene expression in cortex and hippocampus during acute pneumococcal meningitis

    PubMed Central

    Coimbra, Roney S; Voisin, Veronique; de Saizieu, Antoine B; Lindberg, Raija LP; Wittwer, Matthias; Leppert, David; Leib, Stephen L

    2006-01-01

    Background Pneumococcal meningitis is associated with high mortality (~30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i) a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI) and (ii) the self-organizing map (SOM), a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05), 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy. PMID

  12. Early-Life Stress and Neurometabolites of the Hippocampus

    PubMed Central

    Coplan, Jeremy D.; Mathew, Sanjay J.; Abdallah, Chadi G.; Mao, Xiangling; Kral, John G.; Smith, Eric L. P.; Rosenblum, Leonard A.; Perera, Tarique D.; Dwork, Andrew J.; Hof, Patrick R.; Gorman, Jack M.; Shungu, Dikoma C.

    2010-01-01

    We tested the hypothesis that early life stress would persistently compromise neuronal viability of the hippocampus of the grown nonhuman primate. Neuronal viability was assessed through ascertainment of N-acetyl aspartate (NAA) – an amino acid considered reflective of neuronal density/functional integrity – using in vivo proton magnetic resonance spectroscopic imaging (MRSI). The subjects reported herein represent a re-analysis of a sample of nineteen adult male bonnet macaques that had been reared in infancy under induced stress by maternal variable foraging demand (VFD) (N = 10) or control rearing conditions (N = 9). The MRSI spectral readings were recorded using a GE 1.5 Tesla machine under anesthesia. Relative NAA values were derived using NAA as numerator and both choline (Cho) or creatine (Cr) as denominators. Left medial temporal lobe (MTL) NAA/Cho but not NAA/Cr was decreased in VFD subjects versus controls. An MTL NAA/Cho ratio deficit remained significant when controlling for multiple confounding variables. Regression analyses suggested that the NAA/Choline finding was due to independently low left NAA and high left choline. Right MTL showed no rearing effects for NAA, but right NAA was positively related to body mass, irrespective of denominator. The current data indicate that decreased left MTL NAA/Cho may reflect low neuronal viability of the hippocampus following early life stress in VFD-reared versus normally-reared subjects. Given the importance of the hippocampus in stress-mediated toxicity, validation of these data using absolute quantification is suggested and correlative neurohistological studies of hippocampus are warranted. PMID:20713023

  13. Effect of ethanol on the development and maturation of synapses in the rat hippocampus: A quantitative electron-microscopic study

    SciTech Connect

    Kuge, Takashi; Asayama, Tohru; Kakuta, Sachiko; Murakami, Kunio; Ishikawa, Yohichi; Kuroda, Masaru; Imai, Tsunehiko; Seki, Kumiko; Omoto, Miyako; Kishi, Kiyoshi )

    1993-07-01

    The effects of chronic ethanol administration on the development and maturation of synapses in the strata radiatum and lacunosum-moleculare of CA1 in the hippocampus were quantitatively examined in rates exposed to ethanol for the entire period of fetal life as well as the whole period of postnatal life. Synapse densities in the strata radiatum and lacunosum-moleculare of the ethanol-treated group were significantly lower than those of the control group at 2, 14, 21, and 70 days of age. However, the rates of density reduction did not change between either of the strata that receive different groups of afferent fibers. The ratio of axospinous to axoshaftic synapses also did not change between control and ethanol-treated groups. These data suggest that chronic administration of ethanol reduces the density of synapses in this area and that this effect is not specific to neither the type of afferent fibers nor the type of synapses. 35 refs., 6 figs.

  14. A fundamental oscillatory state of isolated rodent hippocampus.

    PubMed

    Wu, Chiping; Shen, Hui; Luk, Wah Ping; Zhang, Liang

    2002-04-15

    Population neuronal rhythms of various frequencies are observed in the rodent hippocampus during distinct behavioural states. However, the question of whether the hippocampus exhibits properties of spontaneous rhythms and population synchrony in isolation has not been definitively answered. To address this, we developed a novel preparation for studying neuronal rhythms in a relatively large hippocampal tissue in vitro. We isolated the whole hippocampus from mice up to 28 days postnatal age, removing the dentate gyrus while preserving the functional CA3-to-CA1 connections. Placing the hippocampal isolate in a perfusion chamber for electrophysiological assessment extracellular recordings from the CA1 revealed rhythmic field potential of 0.5 to

  15. Metric Learning for Multi-atlas based Segmentation of Hippocampus.

    PubMed

    Zhu, Hancan; Cheng, Hewei; Yang, Xuesong; Fan, Yong

    2017-01-01

    Automatic and reliable segmentation of hippocampus from MR brain images is of great importance in studies of neurological diseases, such as epilepsy and Alzheimer's disease. In this paper, we proposed a novel metric learning method to fuse segmentation labels in multi-atlas based image segmentation. Different from current label fusion methods that typically adopt a predefined distance metric model to compute a similarity measure between image patches of atlas images and the image to be segmented, we learn a distance metric model from the atlases to keep image patches of the same structure close to each other while those of different structures are separated. The learned distance metric model is then used to compute the similarity measure between image patches in the label fusion. The proposed method has been validated for segmenting hippocampus based on the EADC-ADNI dataset with manually labelled hippocampus of 100 subjects. The experiment results demonstrated that our method achieved statistically significant improvement in segmentation accuracy, compared with state-of-the-art multi-atlas image segmentation methods.

  16. Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation

    PubMed Central

    Moscovitch, Morris; Cabeza, Roberto; Winocur, Gordon; Nadel, Lynn

    2016-01-01

    The last decade has seen dramatic technological and conceptual changes in research on episodic memory and the brain. New technologies, and increased use of more naturalistic observations, have enabled investigators to delve deeply into the structures that mediate episodic memory, particularly the hippocampus, and to track functional and structural interactions among brain regions that support it. Conceptually, episodic memory is increasingly being viewed as subject to lifelong transformations that are reflected in the neural substrates that mediate it. In keeping with this dynamic perspective, research on episodic memory (and the hippocampus) has infiltrated domains, from perception to language and from empathy to problem solving, that were once considered outside its boundaries. Using the component process model as a framework, and focusing on the hippocampus, its subfields, and specialization along its longitudinal axis, along with its interaction with other brain regions, we consider these new developments and their implications for the organization of episodic memory and its contribution to functions in other domains. PMID:26726963

  17. Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus

    PubMed Central

    Labrada-Moncada, Francisco Emmanuel; Varman, Durairaj Ragu; Krüger, Janina; Morales, Teresa; Miledi, Ricardo; Martínez-Torres, Ataúlfo

    2016-01-01

    Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (−23%) and dentate gyrus (−48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression. PMID:27579183

  18. Contextually Mediated Spontaneous Retrieval Is Specific to the Hippocampus.

    PubMed

    Long, Nicole M; Sperling, Michael R; Worrell, Gregory A; Davis, Kathryn A; Gross, Robert E; Lega, Bradley C; Jobst, Barbara C; Sheth, Sameer A; Zaghloul, Kareem; Stein, Joel M; Kahana, Michael J

    2017-04-03

    Although it is now well established that the hippocampus supports memory encoding [1, 2], little is known about hippocampal activity during spontaneous memory retrieval. Recent intracranial electroencephalographic (iEEG) work has shown that hippocampal activity during encoding predicts subsequent temporal organization of memories [3], supporting a role in contextual binding. It is an open question, however, whether the hippocampus similarly supports contextually mediated processes during retrieval. Here, we analyzed iEEG recordings obtained from 215 epilepsy patients as they performed a free recall task. To identify neural activity specifically associated with contextual retrieval, we compared correct recalls, intrusions (incorrect recall of either items from prior lists or items not previously studied), and deliberations (matched periods during recall when no items came to mind). Neural signals that differentiate correct recalls from both other retrieval classes reflect contextual retrieval, as correct recalls alone arise from the correct context. We found that in the hippocampus, high-frequency activity (HFA, 44-100 Hz), a proxy for neural activation [4], was greater prior to correct recalls relative to the other retrieval classes, with no differentiation between intrusions and deliberations. This pattern was not observed in other memory-related cortical regions, including DLPFC, thus supporting a specific hippocampal contribution to contextually mediated memory retrieval.

  19. Enhanced susceptibility of CA3 hippocampus to prenatal nicotine exposure.

    PubMed

    Kalejaiye, O O; Gondré-Lewis, M C

    2017-04-01

    The brain is highly susceptible to adverse effects of drugs of abuse during early phases of life. Prenatal nicotine exposure (PNE), a preventable cause of gestational and infant mortality, can alter neuron wiring and induce sustained deficits in attention and learning. Here, a rat model of PNE (embryonic days 7-21) was used to examine the maturing hippocampus, which encodes new memories and processes emotional memory. Components of synaptic signaling were evaluated at postnatal day 14 (P14), a period of prolific synaptogenesis in rats, to determine if glutamatergic transmission-associated molecules are regulated in subregions of hippocampus as early as P14. PNE resulted in reduced expression of GluN2B, GluA2 and CaMKIIα, but elevated SNAP25 proteins specifically in the CA3 but not CA1. Only CaMKIIα was regulated in dentate gyrus at this age. These results suggest that glutamatergic and synaptic dysregulation of learning and memory may occur in hippocampus in a temporally and subregionally specific manner.

  20. A fundamental oscillatory state of isolated rodent hippocampus

    PubMed Central

    Wu, Chiping; Shen, Hui; Luk, Wah Ping; Zhang, Liang

    2002-01-01

    Population neuronal rhythms of various frequencies are observed in the rodent hippocampus during distinct behavioural states. However, the question of whether the hippocampus exhibits properties of spontaneous rhythms and population synchrony in isolation has not been definitively answered. To address this, we developed a novel preparation for studying neuronal rhythms in a relatively large hippocampal tissue in vitro. We isolated the whole hippocampus from mice up to 28 days postnatal age, removing the dentate gyrus while preserving the functional CA3-to-CA1 connections. Placing the hippocampal isolate in a perfusion chamber for electrophysiological assessment extracellular recordings from the CA1 revealed rhythmic field potential of 0.5 to ≤ 4 Hz that occurred spontaneously and propagated along the ventro-dorsal hippocampal axis. We provide convergent evidence, via measurements of extracellular pH and K+, recordings of synaptic and intracellular activities and morphological assessments, verifying that these rhythms were not the consequence of hypoxia. Data obtained via simultaneous extracellular and patch clamp recordings suggest that the spontaneous rhythms represent a summation of GABAergic IPSPs originating from pyramidal neurons, which result from synchronous discharges of GABAergic inhibitory interneurons. Similar spontaneous field rhythms were also observed in the hippocampal isolate prepared from young gerbils and rats. Based on these data, we postulate that the spontaneous rhythms represent a fundamental oscillatory state of the hippocampal circuitry isolated from extra-hippocampal inputs. PMID:11956340

  1. Cognitive Aging and the Hippocampus in Older Adults

    PubMed Central

    O’Shea, Andrew; Cohen, Ronald A.; Porges, Eric C.; Nissim, Nicole R.; Woods, Adam J.

    2016-01-01

    The hippocampus is one of the most well studied structures in the human brain. While age-related decline in hippocampal volume is well documented, most of our knowledge about hippocampal structure-function relationships was discovered in the context of neurological and neurodegenerative diseases. The relationship between cognitive aging and hippocampal structure in the absence of disease remains relatively understudied. Furthermore, the few studies that have investigated the role of the hippocampus in cognitive aging have produced contradictory results. To address these issues, we assessed 93 older adults from the general community (mean age = 71.9 ± 9.3 years) on the Montreal Cognitive Assessment (MoCA), a brief cognitive screening measure for dementia, and the NIH Toolbox-Cognitive Battery (NIHTB-CB), a computerized neurocognitive battery. High-resolution structural magnetic resonance imaging (MRI) was used to estimate hippocampal volume. Lower MoCA Total (p = 0.01) and NIHTB-CB Fluid Cognition (p < 0.001) scores were associated with decreased hippocampal volume, even while controlling for sex and years of education. Decreased hippocampal volume was significantly associated with decline in multiple NIHTB-CB subdomains, including episodic memory, working memory, processing speed and executive function. This study provides important insight into the multifaceted role of the hippocampus in cognitive aging. PMID:28008314

  2. Gonadectomy increases neurogenesis in the male adolescent rhesus macaque hippocampus.

    PubMed

    Allen, K M; Fung, S J; Rothmond, D A; Noble, P L; Weickert, C Shannon

    2014-02-01

    New neurons are continuously produced in the subgranular zone of the adult hippocampus and can modulate hippocampal plasticity across life. Adolescence is characterized by dramatic changes in sex hormone levels, and social and emotional behaviors. It is also an age for increased risk of psychiatric disorders, including schizophrenia, which may involve altered hippocampal neurogenesis. The extent to which testosterone and other testicular hormones modulate hippocampal neurogenesis and adolescent behavioral development is unclear. This study aimed to determine if removal of testicular hormones during adolescence alters neurogenesis in the male rhesus macaque hippocampus. We used stereology to examine levels of cell proliferation, cell survival and neuronal differentiation in late adolescent male rhesus macaques (4.6-yrs old) that had previously been gonadectomized or sham operated prior to puberty (2.4-yrs old). While the absence of adolescent testicular hormones had no effect on cell proliferation, cell survival was increased by 65% and indices of immature neuronal differentiation were increased by 56% in gonadectomized monkeys compared to intact monkeys. We show for the first time that presence of circulating testicular hormones, including testosterone, may decrease neuronal survival in the primate hippocampus during adolescence. Our findings are in contrast to existing studies in adults where testosterone tends to be a pro-survival factor and demonstrate that testicular hormones may reduce hippocampal neurogenesis during the age typical of schizophrenia onset.

  3. Hippocampus-dependent learning in SKAP-HOM deficient mice.

    PubMed

    Fiedler, Anna; Grecksch, Gisela; Reinhold, Annegret; Schraven, Burkhart; Becker, Axel

    2014-08-15

    SKAP-HOM is an adapter protein which regulates the cross-talk between immunoreceptors and integrins and is involved in signal transduction. It is present in murine brain structures such as the hippocampus, frontal cortex, and cerebellum. In the present study we investigated types of hippocampus-dependent learning (fear conditioning, social memory, and the Morris Water Maze) and locomotor sensitization to amphetamine in transgenic SKAP-HOM deficient mice (-/-) in comparison with respective controls (+/+). Animals from both groups showed comparable fear conditioning, and the extinction of conditioned fear was accelerated in -/-. In terms of sociability, there were no differences between the animals, but in -/- mice social memory was impaired. There was no difference between the two groups of mice in spatial learning and memory measured in the Morris Water Maze. Wild-type and deficient animals exhibited similar sensitization to amphetamine. In reaction to amphetamine challenge, the response in +/+ was enhanced. It was hypothesized that SKAP-HOM deficiency does not affect hippocampus-dependent learning in general, but that its effects on cognitive tasks seem to be dependent on the nature of the cognitive task, i.e. spatial vs. non-spatial.

  4. Neonatal amygdala or hippocampus lesions influence responsiveness to objects.

    PubMed

    Bliss-Moreau, Eliza; Toscano, Jessica E; Bauman, Melissa D; Mason, William A; Amaral, David G

    2010-07-01

    Medial temporal lobe brain structures, such as the amygdala, play an important role in the normal perception and generation of emotional behavior. Little research, however, has assessed the role of such structures across the neurodevelopmental trajectory. We assessed emotional behavioral responses of rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at 2 weeks of age and sham-operated controls. At 9 and 18 months of age, animals interacted with novel objects that varied in visual complexity as a means of varying emotional salience. All animals behaved differently in the presence of visually simple, as compared to complex, objects, suggesting that they were sensitive to variation in emotional salience. Across both experiments, amygdala-lesioned animals appeared to be less behaviorally inhibited insofar as they explored all objects most readily. Interestingly, hippocampus-lesioned animals' propensity for exploration mirrored that of control animals in some contexts but that of amygdala-lesioned animals in other contexts. At 18 months of age, both amygdala-lesioned and hippocampus-lesioned animals were judged to be less fe