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Sample records for rat hippocampus increases

  1. Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

    PubMed

    Chen, Qian; Xiao, De-Sheng

    2014-01-30

    Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO.

  2. Increasing TNF Levels Solely in the Rat Hippocampus Produces Persistent Pain-like Symptoms

    PubMed Central

    Martuscello, Regina T.; Spengler, Robert N.; Bonoiu, Adela C.; Davidson, Bruce A.; Helinski, Jadwiga; Ding, Hong; Mahajan, Supriya; Kumar, Rajiv; Bergey, Earl J.; Knight, Paul R.; Prasad, Paras N.; Ignatowski, Tracey A.

    2012-01-01

    The manifestation of chronic, neuropathic pain includes elevated levels of the cytokine tumor necrosis factor-alpha (TNF). Previously, we have shown that the hippocampus, an area of the brain most notable for its role in learning and memory formation, plays a fundamental role in pain sensation. Using an animal model of peripheral neuropathic pain, we have demonstrated that intracerebroventricular (icv) infusion of a TNF antibody adjacent to the hippocampus completely alleviated pain. Furthermore, icv infusion of rTNF adjacent to the hippocampus induced pain behavior in naïve animals similar to that expressed during a model of neuropathic pain. These data support our premise that enhanced production of hippocampal-TNF is integral in pain sensation. In the present study, TNF gene expression was induced exclusively in the hippocampus eliciting increased local bioactive TNF levels, and animals were assessed for pain behaviors. Male, Sprague-Dawley rats received stereotaxic injection of gold nanorod (GNR)-complexed cDNA (control or TNF) plasmids (nanoplasmidexes), and pain responses (i.e., thermal hyperalgesia and mechanical allodynia) were measured. Animals receiving hippocampal microinjection of TNF nanoplasmidexes developed thermal hyperalgesia bilaterally. Sensitivity to mechanical stimulation also developed bilaterally in the rat hind paws. In support of these behavioral findings, immunoreactive staining for TNF, bioactive levels of TNF, and levels of TNF mRNA as per PCR analysis were assessed in several brain regions and found to be increased only in the hippocampus. These findings indicate that the specific elevation of TNF in the hippocampus is not a consequence of pain, but in fact induces these behaviors/symptoms. PMID:22770843

  3. Increasing TNF levels solely in the rat hippocampus produces persistent pain-like symptoms.

    PubMed

    Martuscello, Regina T; Spengler, Robert N; Bonoiu, Adela C; Davidson, Bruce A; Helinski, Jadwiga; Ding, Hong; Mahajan, Supriya; Kumar, Rajiv; Bergey, Earl J; Knight, Paul R; Prasad, Paras N; Ignatowski, Tracey A

    2012-09-01

    The manifestation of chronic, neuropathic pain includes elevated levels of the cytokine tumor necrosis factor-alpha (TNF). Previously, we have shown that the hippocampus, an area of the brain most notable for its role in learning and memory formation, plays a fundamental role in pain sensation. Using an animal model of peripheral neuropathic pain, we have demonstrated that intracerebroventricular infusion of a TNF antibody adjacent to the hippocampus completely alleviated pain. Furthermore, intracerebroventricular infusion of rTNF adjacent to the hippocampus induced pain behavior in naïve animals similar to that expressed during a model of neuropathic pain. These data support our premise that enhanced production of hippocampal-TNF is integral in pain sensation. In the present study, TNF gene expression was induced exclusively in the hippocampus, eliciting increased local bioactive TNF levels, and animals were assessed for pain behaviors. Male Sprague-Dawley rats received stereotaxic injection of gold nanorod (GNR)-complexed cDNA (control or TNF) plasmids (nanoplasmidexes), and pain responses (i.e., thermal hyperalgesia and mechanical allodynia) were measured. Animals receiving hippocampal microinjection of TNF nanoplasmidexes developed thermal hyperalgesia bilaterally. Sensitivity to mechanical stimulation also developed bilaterally in the rat hind paws. In support of these behavioral findings, immunoreactive staining for TNF, bioactive levels of TNF, and levels of TNF mRNA per polymerase chain reaction analysis were assessed in several brain regions and found to be increased only in the hippocampus. These findings indicate that the specific elevation of TNF in the hippocampus is not a consequence of pain, but in fact induces these behaviors/symptoms. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  4. Iodine deficiency increases apoptosis and decreases synaptotagmin-1 and PSD-95 in rat hippocampus.

    PubMed

    Dong, Jing; Wang, Yuan; Wang, Yi; Wei, Wei; Min, Hui; Song, Binbin; Xi, Qi; Teng, Weiping; Chen, Jie

    2013-05-01

    Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs the development of the central nervous system with an unclear mechanism. Here, we show that hippocampal apoptosis, synaptotagmin-1, and PSD-95 are involved in the synaptic impairment following developmental ID. Two developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 15 ppm)-added drinking water from gestational day 6 till postnatal day (PND) 28. Then, the apoptosis in the hippocampus was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and the levels of synaptotagmin-1 and PSD-95 were detected with western blot on PND14, PND21, and PND28. The results showed that apoptosis cells and activity of caspase3 were increased in the iodine-deficient and PTU-treatment rats (P < 0.05, respectively). The iodine-deficient and PTU-treatment pups showed significantly lower level of synaptotagmin-1 and PSD-95 in hippocampus than that of controls (P < 0.05, respectively). Developmental ID resulted in the increase and delay of cell apoptosis and the decrease of synaptotagmin-1 and PSD-95 in the hippocampus, which were implicated in the impairment of brain development.

  5. 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.

  6. Repeated stress increases catalytic TrkB mRNA in rat hippocampus.

    PubMed

    Nibuya, M; Takahashi, M; Russell, D S; Duman, R S

    1999-05-28

    Northern blot analysis was utilized to distinguish between catalytic and truncated TrkB mRNA on the basis of transcript size. Repeated (10 days), but not acute, immobilization stress significantly increased levels of catalytic TrkB mRNA, but did not influence expression of truncated TrkB transcripts in rat hippocampus. Exposure to another paradigm, a combination of different, unpredictable stressors, also increased levels of catalytic, but not truncated, TrkB mRNA. In situ hybridization analysis demonstrated that chronic stress up-regulated TrkB mRNA in CA1 and CA3 pyramidal and dentate gyrus granule cells layers of hippocampus. As previously reported, both acute and chronic immobilization stress decreased expression of BDNF mRNA, suggesting that up-regulation of catalytic TrkB mRNA may be a compensatory adaptation to repeated stress.

  7. Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat.

    PubMed

    Roosevelt, Rodney W; Smith, Douglas C; Clough, Richard W; Jensen, Robert A; Browning, Ronald A

    2006-11-13

    The vagus nerve is an important source of afferent information about visceral states and it provides input to the locus coeruleus (LC), the major source of norepinephrine (NE) in the brain. It has been suggested that the effects of electrical stimulation of the vagus nerve on learning and memory, mood, seizure suppression, and recovery of function following brain damage are mediated, in part, by the release of brain NE. The hypothesis that left vagus nerve stimulation (VNS) at the cervical level results in increased extracellular NE concentrations in the cortex and hippocampus was tested at four stimulus intensities: 0.0, 0.25, 0.5, and 1.0 mA. Stimulation at 0.0 and 0.25 mA had no effect on NE concentrations, while the 0.5 mA stimulation increased NE concentrations significantly in the hippocampus (23%), but not the cortex. However, 1.0 mA stimulation significantly increased NE concentrations in both the cortex (39%) and hippocampus (28%) bilaterally. The increases in NE were transient and confined to the stimulation periods. VNS did not alter NE concentrations in either structure during the inter-stimulation baseline periods. No differences were observed between NE levels in the initial baseline and the post-stimulation baselines. These findings support the hypothesis that VNS increases extracellular NE concentrations in both the hippocampus and cortex.

  8. Increased Extracellular Concentrations of Norepinephrine in Cortex and Hippocampus Following Vagus Nerve Stimulation in the Rat.

    PubMed Central

    Roosevelt, Rodney W.; Smith, Douglas C.; Clough, Richard W.; Jensen, Robert A.; Browning, Ronald A.

    2006-01-01

    The vagus nerve is an important source of afferent information about visceral states and it provides input to the locus coeruleus (LC), the major source of norepinephrine (NE) in the brain. It has been suggested that the effects of electrical stimulation of the vagus nerve on learning and memory, mood, seizure suppression, and recovery of function following brain damage are mediated, in part, by the release of brain NE. The hypothesis that left vagus nerve stimulation (VNS) at the cervical level results in increased extracellular NE concentrations in the cortex and hippocampus was tested at four stimulus intensities 0.0, 0.25, 0.5, and 1.0 mA. Stimulation at 0.0 and 0.25 mA had no effect on NE concentrations, while the 0.5 mA stimulation increased NE concentrations significantly in the hippocampus (23%), but not the cortex. However, 1.0 mA stimulation significantly increased NE concentrations in both the cortex (39%) and hippocampus (28%) bilaterally. The increases in NE were transient and confined to the stimulation periods. VNS did not alter NE concentrations in either structure during the inter-stimulation baseline periods. No differences were observed between NE levels in the initial baseline and the post-stimulation baselines. These findings support the hypothesis that VNS increases extracellular NE concentrations in both the hippocampus and cortex. PMID:16962076

  9. Exercise increases leptin levels correlated with IGF-1 in hippocampus and prefrontal cortex of adolescent male and female rats.

    PubMed

    Uysal, Nazan; Agilkaya, Sinem; Sisman, Ali Riza; Camsari, Ulas Mehmet; Gencoglu, Celal; Dayi, Ayfer; Aksu, Ilkay; Baykara, Basak; Cingoz, Sultan; Kiray, Muge

    2017-04-01

    It is known that regular aerobic exercise has positive effects on hippocampus and prefrontal cortex. We have previously have been able to demonstrate that aerobic exercise increased IGF-1 in hippocampus. Leptin, which is associated with cognitive functions, is also involved in fat metabolism and stimulates energy consumption. While it is known that leptin stimulates IGF-1 production in hepatocytes, little known is on the link between IGF-1 and leptin in brain during aerobic exercise. In this study, we investigated the effects of regular aerobic exercise on leptin, leptin receptor expression levels in hippocampus and prefrontal cortex. Additionally, we investigated the correlation of IGF-1 levels with leptin and leptin receptor expression. During the experiment, exercise group was run on a treadmill for 30min per session at a speed of 8m/min and 0° slope, five times a week for 6 weeks. Leptin, leptin expression, IGF-1 levels and cell numbers increased in prefrontal cortex and hippocampus of exercise groups. Blood leptin levels increased in female rats in exercise group; whereas it did not change in male rats; blood IGF-1 levels were found to be increased in exercised male rats. There was a strong positive correlation between hippocampal leptin levels and hippocampal IGF-1 levels; also a strong positive correlation between hippocampal leptin receptor expression and hippocampal IGF-1. These results indicate that, increased leptin and leptin receptor expression are correlated with IGF-1 in regular aerobic exercised rats. Blood leptin and IGF-1 levels were also found to be associated with gender. Females had high blood leptin levels and males had high blood IGF-1 levels in the exercise groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Hydroxysafflor yellow A increases BDNF and NMDARs in the hippocampus in a vascular dementia rat model.

    PubMed

    Xing, Mengya; Sun, Qingna; Wang, Yiyi; Cheng, Yan; Zhang, Nan

    2016-07-01

    Hydroxysafflor yellow A (HSYA) is a drug that exerts angiogenesis regulatory and neuroprotective effects and has become an effective therapy for brain and heart ischemic disorders. There is no definite evidence supporting a therapeutic effect of HSYA in vascular dementia (VaD). We used HSYA in a rat model of chronic cerebral ischemia to determine its potential therapeutic effects in VaD. The Morris water maze (MWM) was used to evaluate spatial cognitive function, and long-term potentiation (LTP) was tested as a marker of synaptic plasticity. The expression levels of brain-derived neurotrophic factor (BDNF) and two subunits of N-methyl-d-aspartate receptor (NMDAR; GluN2A and GluN2B) in the hippocampus were measured via western blotting. The MWM results showed that the experimental VaD group had longer escape latencies than the sham group, whereas the HSYA group had a decreased escape latency compared with the VaD group (P<0.05). The LTP at CA3-CA1 synapses in the hippocampus was also enhanced in the HSYA compared with the VaD group (P<0.05). The western blotting results revealed lower hippocampal BDNF and GluN2B expression in the VaD group compared with the sham group and significantly higher hippocampal expression in the HSYA group compared with the VaD group. No significant change in GluN2A expression was detected. The results indicate that HSYA may enhance the endogenous expression of BDNF and GluN2B, which are associated with the synaptic plasticity of the hippocampus, and may improve spatial learning and memory abilities in a rat model of VaD.

  11. Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats.

    PubMed

    Alvandi, Mina Sadighi; Bourmpoula, Maria; Homberg, Judith R; Fathollahi, Yaghoub

    2017-09-22

    Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10 mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine-induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse. © 2017 Society for the Study of Addiction.

  12. Early enriched environment induces an increased conversion of proBDNF to BDNF in the adult rat's hippocampus.

    PubMed

    Cao, Wenyu; Duan, Juan; Wang, Xueqin; Zhong, Xiaolin; Hu, Zhaolan; Huang, Fulian; Wang, Hongtao; Zhang, Juan; Li, Fang; Zhang, Jianyi; Luo, Xuegang; Li, Chang-Qi

    2014-05-15

    An enriched environment has been shown to influence brain plasticity and function by involving the action of brain-derived neurotrophic factor (BDNF). BDNF, which is synthesized as a precursor molecule (proBDNF) that undergoes proteolytic cleavage, plays an important role in synaptic plasticity and contributes to several brain functions such as memory, learning, and behavior. The neurotrophins and proneurotrophins often play opposite roles in the brain, suggesting that proteolytic cleavage of proneurotrophins controls the action of neurotrophins. However, few studies have focused on the expression and cleavage of proBDNF after exposure to an enriched environment. Our study aimed to explore the effects of an early-enriched environment on the conversion of proBDNF to BDNF in the adult rats' hippocampus. We found that there was no difference in the expression of proBDNF in the hippocampus between the SE (standard environment) and EE (enriched environment) rats, but a significantly increased BDNF protein level was found in the EE rats. Thus, a remarkably enhanced ratio of BDNF to proBDNF (BDNF/proBDNF) was observed in the EE rats. In addition, the EE resulted in a remarkably up-regulated matrix metalloproteinase-9 (MMP-9) in the hippocampus, which played a key role in converting proBDNF to BDNF in the extracellular space. Furthermore, the expression of synapse-related proteins (NR1 and NR2A) was analyzed, and the results indicated that EE could significantly increase the expression of NR1 and NR2A in the hippocampus. In addition, the behavioral results showed that EE reduced anxiety-like behavior in the elevated-plus maze test and reduced immobility time in the forced swimming test. Moreover, the EE resulted in an increased preference for sucrose compared to the SE. These results suggested that the EE up-regulated MMP-9 levels within the hippocampus, which might facilitate the conversion of proBDNF to BDNF, thereby contributing to the long lasting alterations of

  13. Prenatal choline supplementation increases NGF levels in the hippocampus and frontal cortex of young and adult rats.

    PubMed

    Sandstrom, Noah J; Loy, Rebekah; Williams, Christina L

    2002-08-23

    Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.

  14. Testosterone depletion in adult male rats increases mossy fiber transmission, LTP, and sprouting in area CA3 of hippocampus

    PubMed Central

    Skucas, Vanessa A.; Duffy, Aine M.; Harte-Hargrove, Lauren; Magagna-Poveda, Alejandra; Radman, Thomas; Chakraborty, Goutam; Schroeder, Charles E.; MacLusky, Neil J.; Scharfman, H.E.

    2013-01-01

    Androgens have dramatic effects on neuronal structure and function in hippocampus. However, androgen depletion does not always lead to hippocampal impairment. To address this apparent paradox, we evaluated the hippocampus of adult male rats after gonadectomy (Gdx) or sham surgery. Surprisingly, Gdx rats showed increased synaptic transmission and long-term potentiation (LTP) of the mossy fiber (MF) pathway. Gdx rats also exhibited increased excitability and MF sprouting. We then addressed the possible underlying mechanisms, and found that Gdx induced a long-lasting upregulation of MF brain-derived neurotrophic factor (BDNF) immunoreactivity. Antagonism of Trk receptors, which bind neurotrophins such as BDNF, reversed the increase in MF transmission, excitability and LTP in Gdx rats, but there were no effects of Trk antagonism in sham controls. To determine which androgens were responsible, the effects of testosterone metabolites dihydrotestosterone (DHT) and 5α-androstane-3α,17β-diol were examined. Exposure of slices to 50 nM DHT decreased the effects of Gdx on MF transmission but 50 nM 5α-androstane-3α,17β-diol had no effect. Remarkably, there was no effect of DHT in control males. The data suggest that a Trk- and androgen receptor-sensitive form of MF transmission and synaptic plasticity emerges after Gdx. We suggest that androgens may normally be important in area CA3 to prevent hyperexcitability and aberrant axon outgrowth, but limit MF synaptic transmission and some forms of plasticity. The results also suggest a potential explanation for the maintenance of hippocampal-dependent cognitive function after androgen depletion: a reduction in androgens may lead to compensatory upregulation of MF transmission and plasticity. PMID:23392664

  15. 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.

  16. 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.

  17. Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E mediated cholesterol trafficking in neuroblastoma cell lines

    PubMed Central

    Spagnuolo, Maria Stefania; Maresca, Bernardetta; Mollica, Maria Pina; Cavaliere, Gina; Cefaliello, Carolina; Trinchese, Giovanna; Esposito, Maria Grazia; Scudiero, Rosaria; Crispino, Marianna; Abrescia, Paolo; Cigliano, Luisa

    2014-01-01

    Alteration in cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative disorders. Apolipoprotein E (ApoE) is the major component of brain lipoproteins supporting cholesterol transport. We previously reported that the acute-phase protein Haptoglobin (Hpt) binds ApoE, and influences its function in blood cholesterol homeostasis. Major aim of this study was to investigate whether Hpt influences the mechanisms by which cholesterol is shuttled from astrocytes to neurons. In detail it was studied Hpt effect on ApoE-dependent cholesterol efflux from astrocytes and ApoE-mediated cholesterol incorporation in neurons. We report here that Hpt impairs ApoE-mediated cholesterol uptake in human neuroblastoma cell line SH-SY5Y, and limits the toxicity of a massive concentration of cholesterol for these cells, while it does not affect cholesterol efflux from the human glioblastoma-astrocytoma cell line U-87 MG. As aging is the most important non-genetic risk factor for various neurodegenerative disorders, and our results suggest that Hpt modulates ApoE functions, we evaluated the Hpt and ApoE expression profiles in cerebral cortex and hippocampus of adolescent (2 months), adult (5 and 8 months), and middle-aged (16 months) rats. Hpt mRNA level was higher in hippocampus of 8 and 16 month-old than in 2-month old rats (p < 0.05), and Hpt concentration increased with the age from adolescence to middle-age (p < 0.001). ApoE concentration, in hippocampus, was higher (p < 0.001) in 5 month-old rats compared to 2 month but did not further change with aging. No age-related changes of Hpt (protein and mRNA) were found in the cortex. Our results suggest that aging is associated with changes, particularly in the hippocampus, in the Hpt/ApoE ratio. Age-related changes in the concentration of Hpt were also found in human cerebrospinal fluids. The age-related changes might affect neuronal function and survival in brain, and have important implications in brain

  18. Adult onset-hypothyroidism increases response latency and long-term potentiation (LTP) in rat hippocampus

    EPA Science Inventory

    Thyroid hormones (TH) influence central nervous system (CNS) function during both development and in adulthood. The hippocampus is critical for some types of learning and memory and is particularly sensitive to thyroid hormone deficiency. Hypothyroidism in adulthood has been ass...

  19. Adult onset-hypothyroidism increases response latency and long-term potentiation (LTP) in rat hippocampus

    EPA Science Inventory

    Thyroid hormones (TH) influence central nervous system (CNS) function during both development and in adulthood. The hippocampus is critical for some types of learning and memory and is particularly sensitive to thyroid hormone deficiency. Hypothyroidism in adulthood has been ass...

  20. Chronic neonatal nicotine exposure increases excitation in the young adult rat hippocampus in a sex-dependent manner

    PubMed Central

    Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

    2012-01-01

    Smoking during pregnancy exposes the fetus to nicotine, resulting in nicotine-stimulated neurotransmitter release. Recent evidence suggests that the hippocampus develops differently in males and females with delayed maturation in males. We show that chronic nicotine exposure during the first postnatal week has sex-specific long-term effects. Neonatal rat pups were chronically treated with nicotine (6 mg/kg/day) (CNN) from postnatal day 1 to 7 or milk only (Controls), and hippocampal slices were prepared from Control- and CNN-treated young adults. Field excitatory postsynaptic potentials (fEPSPs) or population spikes (PSs) were recorded from the CA1 hippocampus following CA1 s. radiatum stimulation. Input/Output curves constructed from fEPSP data indicated that CNN-males, but not females, had significantly increased excitatory responses compared to Controls (p<0.05, n=10 Con, n=11 CNN). Long-term potentiation (LTP) was not significantly changed by CNN. In the presence of bicuculline, which blocks inhibitory GABAA receptors, an epileptiform burst consisting of a series of PSs was evoked. The amplitude of the first PS was significantly larger in CNN-males and females compared to Controls (males: p<0.01, n=8 Con, n=8 CNN; females: p<0.05, n=9 Con, n=7 CNN). Only CNN-males also had significantly larger second PSs (p<0.05, n=8 con, n=8 CNN). Epileptiform activity evoked by zero Mg2+ incubation did not differ in amplitude or duration of bursts in CNN-males or females compared to Controls. These data indicate that neonatal nicotine exposure has long lasting effects and results in increased excitation within the CA1 hippocampus in adulthood, with males showing increased sensitivity to nicotine's effects. PMID:22119395

  1. 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.

  2. Zaprinast impairs spatial memory by increasing PDE5 expression in the rat hippocampus.

    PubMed

    Giorgi, Mauro; Pompili, Assunta; Cardarelli, Silvia; Castelli, Valentina; Biagioni, Stefano; Sancesario, Giuseppe; Gasbarri, Antonella

    2015-02-01

    In this work, we report the effect of post-training intraperitoneal administration of zaprinast on rat memory retention in the Morris water maze task that revealed a significant memory impairment at the intermediate dose of 10mg/kg. Zaprinast is capable of inhibiting both striatal and hippocampal PDE activity but to a different extent which is probably due to the different PDE isoforms expressed in these areas. To assess the possible involvement of cyclic nucleotides in rat memory impairment, we compared the effects obtained 30 min after the zaprinast injection with respect to 24h after injection by measuring both cyclic nucleotide levels and PDE activity. As expected, 30 min after the zaprinast administration, we observed an increase of cyclic nucleotides, which returned to a basal level within 24h, with the exception of the hippocampal cGMP which was significantly decreased at the dose of 10mg/kg of zaprinast. This increase in the hippocampal region is the result of a cGMP-specific PDE5 induction, confirmed by sildenafil inhibition, in agreement with literature data that demonstrate transcriptional regulation of PDE5 by cAMP/cGMP intracellular levels. Our results highlight the possible rebound effect of PDE inhibitors.

  3. 5-hydroxyindole causes convulsions and increases transmitter release in the CA1 region of the rat hippocampus

    PubMed Central

    Mannaioni, Guido; Carpenedo, Raffaella; Moroni, Flavio

    2003-01-01

    5-hydroxyindole (5-OHi) is a proposed tryptophan metabolite able to cause convulsions when systemically injected into rodents. We studied its effects using microdialysis in vivo and electrophysiological approaches in vitro. Local administration of 5-OHi into the CA1 region of the rat hippocampus, via a microdialysis probe, significantly increased glutamate concentrations in the dialysates. In rat hippocampal slices, using extracellular recordings in the CA1 region, 5-OHi (30–300 μM) increased the amplitude of population spikes and fEPSPs. In the same preparation, using intracellular recordings in CA1 pyramidal neurons, 5-OHi reduced the latency of firing induced by direct depolarization and increased both evoked excitatory and slow inhibitory postsynaptic potential amplitudes, without affecting the resting membrane potential, the after-hyperpolarization or the neuronal input resistance. It also altered GABAA-mediated neurotransmission by increasing the frequency and the amplitude of pharmacologically isolated spontaneous inhibitory postsynaptic currents (sIPSC). In separate experiments, performed by measuring AMPA or NMDA-induced depolarization in cortical wedges, 5-OHi did not modify glutamate receptor agonist responses. Our results show that 5-OHi causes convulsions, modifies the properties and the function of the hippocampal circuitry, and facilitates the output of both excitatory and inhibitory transmitters. PMID:12522096

  4. Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development.

    PubMed

    Rizzi, Massimo; Perego, Carlo; Aliprandi, Marisa; Richichi, Cristina; Ravizza, Teresa; Colella, Daniele; Velískŏvá, Jana; Moshé, Solomon L; De Simoni, M Grazia; Vezzani, Annamaria

    2003-12-01

    In adult rats, status epilepticus (SE) induces cytokine production by glia especially when seizures are associated with neuronal injury. This suggests that cytokines may play a role in seizure-induced neuronal damage. As SE-induced injury is age-specific, we used rats of different ages (with distinct susceptibilities to seizure-induced neuronal injury) to elucidate the role of cytokines in this process. Thus, we investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal injury 4 and 24 h following kainic acid-induced SE in postnatal day (PN) 9, 15, and 21 rats. At PN9, there was little activation of microglia and astrocytes at any time point studied. Interleukin-1beta (IL), tumor necrosis factor-alpha (TNF), and IL-6 or the naturally occurring IL-1 receptor antagonist (Ra) mRNA expression did not increase. No evidence of cell injury has been detected. At PN15, immunostaining of microglia and astrocytes was enhanced, but only IL-1beta mRNA expression was increased. These changes were observed 4 h after SE. Scattered injured neurons in CA3 and subiculum, but not in any other region, were present 24 h following SE. At PN21, immunostaining of microglia and astrocytes and the mRNA expression of all cytokines studied was significantly increased already 4 h after SE. At 24 h, many injured neurons were present in CA1 and CA3 regions and in 40% of rats in other forebrain areas. These data show that (i) the pattern of glia activation and cytokine gene transcription induced by SE is age-dependent and (ii) neuronal injury in the hippocampus occurs only when cytokines are induced and their synthesis precedes the appearance of neuronal damage. Thus, cytokine expression in immature brain is associated specifically with cell injury rather than with seizures per se, suggesting that proinflammatory cytokines may contribute to the occurence of SE-induced hippocampal damage.

  5. Early-life environmental intervention may increase the number of neurons, astrocytes, and cellular proliferation in the hippocampus of rats.

    PubMed

    Winkelmann-Duarte, Elisa C; Padilha-Hoffmann, Camila B; Martins, Daniel F; Schuh, Artur F S; Fernandes, Marilda C; Santin, Ricardo; Merlo, Suelen; Sanvitto, Gilberto L; Lucion, Aldo B

    2011-11-01

    Neonatal handling reduces the stress response in adulthood due to a feedback mechanism. The present study analyzed the effects of repeated neonatal environmental intervention (daily handling during the first 10 days after birth) on neuron-, astroglial cell density, and cellular proliferation of the hippocampal (CA1, CA2, and CA3) pyramidal cell layers in female rats. Pups were divided into two groups, nonhandled and handled, which were submitted to repeated handling sessions between postnatal days 1 and 10. Histological and immunohistochemical procedures were used to determine changes in neuron density, astroglial cell density, and cellular proliferation. We found an increase in neuron density in each pyramidal cell layer of the hippocampus (CA1, CA2, and CA3) in female rats (11 and 90 day old) that were handled during the neonatal period. Furthermore, we found an increase in astroglial cell density in both hemispheres of the brain in the handled group. Finally, we observed an increase in cellular proliferation in both hippocampi (CA1, CA2, and CA3) of the brain in female pups (11 days old) handled during the neonatal period. This study demonstrates that an early-life environmental intervention may induce morphological changes in a structure involved with several functions, including the stress response. The results of the current study suggest that neonatal handling may influence the animals' responses to environmental adversities later in life.

  6. Adolescent exposure to cocaine increases anxiety-like behavior and induces morphologic and neurochemical changes in the hippocampus of adult rats.

    PubMed

    Zhu, W; Mao, Z; Zhu, C; Li, M; Cao, C; Guan, Y; Yuan, J; Xie, G; Guan, X

    2016-01-28

    Repeated exposure to cocaine during adolescence may affect both physical and psychological conditions in the brain, and increase the risk of psychiatric disorders and addiction behaviors in adulthood. Adolescence represents a critical development period for the hippocampus. Moreover, different regions of the hippocampus are involved in different functions. Dorsal hippocampus (dHP) has been implicated in learning and memory, whereas ventral hippocampus (vHP) plays an important role in emotional processing. In this study, the rats that were exposed to cocaine during adolescence (postnatal days, P28-P42) showed higher anxiety-like behavior in the elevated plus maze test in adulthood (P80), but displayed normal spatial learning and memory in the Morris water maze test. Furthermore, repeated exposure to cocaine during adolescence lead to alterations in morphology of pyramidal neurons, activities of astrocytes, and levels of proteins that involved in synaptic transmission, apoptosis, inflammation and addiction in both dHP and vHP of adult rats. These findings suggest that repeated exposure to cocaine during adolescence in rats may elicit morphologic and neurochemical changes in the hippocampus when the animals reach adulthood. These changes may contribute to the increased susceptibility for psychiatric disorders and addiction seen in adults. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. MDMA increases glutamate release and reduces parvalbumin-positive GABAergic cells in the dorsal hippocampus of the rat: role of cyclooxygenase.

    PubMed

    Anneken, John H; Cunningham, Jacobi I; Collins, Stuart A; Yamamoto, Bryan K; Gudelsky, Gary A

    2013-03-01

    3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a popular drug of abuse with well-documented acute effects on serotonergic, dopaminergic, and cholinergic transmitter systems, as well as evidence of long-term disruption of serotoninergic systems in the rat brain. Recently, it was demonstrated that MDMA evokes a delayed and sustained increase in glutamate release in the hippocampus. The purpose of the present study was to determine the role of inflammatory mediators in the MDMA-induced increase in glutamate release, as well as the contribution of inflammatory pathways in the persistent neurochemical toxicity associated with repeated MDMA treatment. Treatment with the non-selective cyclooxygenase (COX) inhibitor ketoprofen and the COX-2 selective inhibitor nimesulide attenuated the increase in extracellular glutamate in the hippocampus evoked by repeated MDMA exposure (10 mg/kg, i.p., every 2 h); no attenuation was observed in rats treated with the COX-1 selective inhibitor piroxicam. Reverse dialysis of a major product of COX activity, prostaglandin E2, also resulted in a significant increase in extracellular glutamate in the hippocampus . Repeated exposure to MDMA diminished the number of parvalbumin-positive GABA interneurons in the dentate gyrus of the hippocampus, an effect that was attenuated by ketoprofen treatment. However, COX inhibition with ketoprofen did not prevent the long-term depletion of 5-HT in the hippocampus evoked by MDMA treatment. These data are supportive of the view that cyclooxygenase activity contributes to the mechanism underlying both the increased release of glutamate and decreased number of GABA interneurons in the rat hippocampus produced by repeated MDMA exposure.

  8. Corticosterone rapidly increases thorns of CA3 neurons via synaptic/extranuclear glucocorticoid receptor in rat hippocampus

    PubMed Central

    Yoshiya, Miyuki; Komatsuzaki, Yoshimasa; Hojo, Yasushi; Ikeda, Muneki; Mukai, Hideo; Hatanaka, Yusuke; Murakami, Gen; Kawata, Mitsuhiro; Kimoto, Tetsuya; Kawato, Suguru

    2013-01-01

    Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes. We demonstrated rapid effects (~1 h) of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500, and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA, or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100–1000 nM) might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded. PMID:24348341

  9. Short-term steroid treatment increases δ GABAA receptor subunit expression in rat CA1 hippocampus: Pharmacological and behavioral effects

    PubMed Central

    Shen, Hui; Gong, Qi Hua; Yuan, Maoli; Smith, Sheryl S.

    2010-01-01

    In this study, 48 h administration of 3α-OH-5β-pregnan-20-one (3α,5β-THP) or 17β-estradiol (E2)+progesterone (P) to female rats increased expression of the δ subunit of the GABAA receptor (GABAR) in CA1 hippocampus. Coexpression of α4 and δ subunits was suggested by an increased response of isolated pyramidal cells to the GABA agonist 4,5,6,7- tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), following 48 h steroid treatment, and nearly complete blockade by 300 μM lanthanum (La3+). Because α4βδ GABAR are extrasynaptic, we also recorded pharmacologically isolated GABAergic holding current from CA1 hippocampal pyramidal cells in the slice. The La3+-sensitive THIP current, representative of current gated by α4βδ GABAR, was measurable only following 48 h steroid treatment. In contrast, the bicuculline-sensitive current was not altered by steroid treatment, assessed with or without 200 nM gabazine to block synaptic current. However, 48 h steroid treatment resulted in a tonic current insensitive to the benzodiazepine agonists lorazepam (10 μM) and zolpidem (100 nM). These results suggest that 48 h steroid treatment increases expression of α4βδ GABAR which replace the ambient receptor population. Increased anxiolytic effects of THIP were also observed following 48 h steroid treatment. The findings from the present study may be relevant for alterations in mood and benzodiazepine sensitivity reported across the menstrual cycle. PMID:15950994

  10. Neonatal Nicotine Exposure Increases Excitatory Synaptic Transmission and Attenuates Nicotine-stimulated GABA release in the Adult Rat Hippocampus

    PubMed Central

    Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

    2014-01-01

    Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1–7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking. PMID:24950455

  11. Neonatal nicotine exposure increases excitatory synaptic transmission and attenuates nicotine-stimulated GABA release in the adult rat hippocampus.

    PubMed

    Damborsky, Joanne C; Griffith, William H; Winzer-Serhan, Ursula H

    2015-01-01

    Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1-7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking.

  12. Akt pathway activation and increased neuropeptide Y mRNA expression in the rat hippocampus: implications for seizure blockade.

    PubMed

    Goto, Eduardo M; Silva, Marcelo de Paula; Perosa, Sandra R; Argañaraz, Gustavo A; Pesquero, João B; Cavalheiro, Esper A; Naffah-Mazzacoratti, Maria G; Teixeira, Vicente P C; Silva, José A

    2010-04-01

    The aim of this study was to analyze the expression of survival-related molecules such Akt and integrin-linked kinase (ILK) to evaluate Akt pathway activation in epileptogenesis process. Furthermore, was also investigated the mRNA expression of neuropeptide Y, a considered antiepileptic neuropeptide, in the pilocarpine-induced epilepsy. Male Wistar rats were submitted to the pilocarpine model of epilepsy. Hippocampi were removed 6h (acute phase), 12h (late acute), 5d (silent) and 60d (chronic) after status epilepticus (SE) onset, and from animals that received pilocarpine but did not develop SE (partial group). Hippocampi collected were used to specify mRNA expression using Real-Time PCR. Immunohistochemistry assay was employed to place ILK distribution in the hippocampus and Western blot technique was used to determine Akt activation level. A decrease in ILK mRNA content was found during acute (0.39+/-0.03) and chronic (0.48+/-0.06) periods when compared to control group (0.87+/-0.10). Protein levels of ILK were also diminished during both periods. Partial group showed increased ILK mRNA expression (0.80+/-0.06) when compared with animals in the acute stage. Silent group had ILK mRNA and immunoreactivity similar to control group. Western blot assay showed an augmentation in Akt activation in silent period (0.52+/-0.03) in comparison with control group (0.44+/-0.01). Neuropeptide Y mRNA expression increased in the partial group (1.67+/-0.22) and in the silent phase (1.45+/-0.29) when compared to control group (0.36+/-0.12). Results suggest that neuropeptide Y (as anticonvulsant) might act in protective mechanisms occurred during epileptic phenomena. Together with ILK expression and Akt activation, these molecules could be involved in hippocampal neuroprotection in epilepsy. Copyright 2009 Elsevier Ltd. All rights reserved.

  13. 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.

  14. Maternal separation increases GABA(A) receptor-mediated modulation of norepinephrine release in the hippocampus of a rat model of ADHD, the spontaneously hypertensive rat.

    PubMed

    Sterley, Toni-Lee; Howells, Fleur M; Russell, Vivienne A

    2013-02-25

    Experiencing early life stress increases the risk of developing a psychiatric disorder later in life, possibly by altering neural networks, such as the locus-coeruleus norepinephrine (LC-NE) system. Whether early life stress affects the LC-NE system directly, or whether the effects are via changes in glutamate and GABA modulation of the LC-NE system, is unclear. Early life stress has been shown to alter glutamate and GABA transmission, and in particular, to alter GABA(A) receptor expression. The LC-NE system has been implicated in attention-deficit/hyperactivity disorder (ADHD), amongst other disorders, and is over-responsive to glutamate stimulation in a validated rat model of ADHD, the spontaneously hypertensive rat (SHR). It is plausible that the LC-NE system, or glutamate and GABA modulation thereof, in an individual already genetically predisposed to develop ADHD, or in SHR, may respond in a unique way to early life stress. To investigate this we applied a mild developmental stressor, maternal separation, onto SHR, and onto their control strain, Wistar-Kyoto rats (WKY), from post-natal day (P)2-14. On P50-52, in early adulthood, we assayed glutamate and potassium stimulated release of radio-actively labelled NE ((3)[H]NE) from hippocampal slices using an in vitro superfusion technique, in the presence or absence of a GABA(A) receptor antagonist, bicuculline. Our results show that maternal separation altered GABA(A) receptor-mediated modulation of NE release in the hippocampus of the two strains in opposite directions, increasing it in SHR and decreasing it in WKY. Our findings indicate that effects of early life stress are highly dependent on genetic predisposition, since opposite changes in GABA(A) receptor-mediated modulation of NE release were observed in the rat model of ADHD, SHR, and their control strain, WKY.

  15. PBDE-209 exposure damages learning and memory ability in rats potentially through increased autophagy and apoptosis in the hippocampus neuron.

    PubMed

    Sun, Wen; Du, Lili; Tang, Wenting; Kuang, Liyun; Du, Peili; Chen, Jingsi; Chen, Dunjin

    2017-03-01

    This study is to investigate the neurotoxicity of PBDE-209 during pregnancy through autophagy and apoptosis in the fetal hippocampus neuron. The autophagy protein levels of LC3-II and Beclin-1 were significantly higher in hippocampus tissue and neuron, while P62 protein were lower. Apoptosis protein Cleaved Caspase-3 and Cleaved PARP was significantly higher in PBDE dose groups and BCL-2 levels in high PBDE dose groups were significantly lower. During the Morris water maze task, the escape latency times of high PBDE dose groups were significantly longer. PBDE-209-induced autophagy leads to neurons death and inhibition of autophagy reduce PBDE-209-induced apoptotic cell death. These results suggest that exposure of the PBDE-209 during pregnancy increases hippocampal autophagy, decrease neuron viability, and it partly effect apoptosis induced by PBDE-209. All that may contribute to the decline of learning and memory ability in the offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Antidepressant dose of taurine increases mRNA expression of GABAA receptor α2 subunit and BDNF in the hippocampus of diabetic rats.

    PubMed

    Caletti, Greice; Almeida, Felipe Borges; Agnes, Grasiela; Nin, Maurício Schüler; Barros, Helena Maria Tannhauser; Gomez, Rosane

    2015-04-15

    Diabetes mellitus is a metabolic disorder associated with higher risk for depression. Diabetic rats present depressive-like behaviors and taurine, one of the most abundant free amino acids in the brain, reverses this depressive behaviors. Because taurine is a GABAA agonist modulator, we hypothesize that its antidepressant effect results from the interaction on this system by changing α2 GABAA receptor subunit expression, beside changes on BDNF mRNA, and memory in diabetic rats. Streptozotocin-diabetic and non-diabetic Wistar rats were daily injected with 100mg/kg of taurine or saline, intraperitoneally, for 30 days. At the end of the experiment, rats were exposed to the novel object recognition memory. Later they were euthanized, the brains were weighed, and the hippocampus was dissected for α2 GABAA subunit and BDNF mRNA expression. Real-time quantitative PCR (qPCR) showed that diabetic rats presented lower α2 GABAA subunit and BDNF mRNA expression than non-diabetic rats and taurine increased both parameters in these sick rats. Taurine also reversed the lower brain weight and improved the short-term memory in diabetic rats. Thus, the taurine antidepressant effect may be explained by interference with the GABA system, in line to its neuroprotective effect showed here by preventing brain weight loss and improving memory in diabetic rats.

  17. The role of 5-HT₁A receptors in fish oil-mediated increased BDNF expression in the rat hippocampus and cortex: a possible antidepressant mechanism.

    PubMed

    Vines, Aparecida; Delattre, Ana Marcia; Lima, Marcelo M S; Rodrigues, Laís Soares; Suchecki, Deborah; Machado, Ricardo B; Tufik, Sergio; Pereira, Sofia I R; Zanata, Sílvio M; Ferraz, Anete Curte

    2012-01-01

    Epidemiological and dietary studies show that nutritional deficit of omega-3 polyunsaturated fatty acids (ω-3 PUFA) is directly related to the prevalence and severity of depression. Supplementation with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) during critical periods of development (pregnancy and lactation) is essential for cortical maturation, synaptogenesis and myelination, and may also mitigate the risk for cognitive deficits and psychopathologies in young adults. The present study was performed to evaluate the involvement of serotonin (5-HT) receptors, particularly of 5-HT(1A), and hippocampal brain-derived neurotrophic factor (BDNF) expression in the antidepressant effect of ω-3 PUFA supplementation. In Experiment 1, the antidepressant effects of fish oil were assessed by the modified forced swim test in adult rats. The data indicated a robust antidepressant effect produced by this supplementation and that treatment of the rats with WAY 100135 reversed this effect. In Experiment 2, cortical and hippocampal contents of BDNF, 5-HT, dopamine (DA) and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), and 3,4-dihydroxyphenylacetic acid (DOPAC), were determined in animals subjected to the same protocol. Increased BDNF expression in the cortex and hippocampus of both age groups was detected. In 90 day-old rats, 5-HT content in the hippocampus was increased, whereas 5-HIAA formation was diminished in the fish oil group. We suggest the occurrence of a reciprocal involvement of 5-HT(1A) receptors activation and the hippocampal BDNF-increased expression mediated by fish oil supplementation. These data corroborate and expand the notion that supplementation with ω-3 PUFA produces antidepressant effects mediated by an increase in serotonergic neurotransmission, particularly in the hippocampus. This article is part of a Special Issue entitled 'Anxiety and Depression'.

  18. Endogenous BDNF protein is increased in adult rat hippocampus after a kainic acid induced excitotoxic insult but exogenous BDNF is not neuroprotective.

    PubMed

    Rudge, J S; Mather, P E; Pasnikowski, E M; Cai, N; Corcoran, T; Acheson, A; Anderson, K; Lindsay, R M; Wiegand, S J

    1998-02-01

    Systemic administration of the excitotoxin kainic acid to adult rats results in a well defined pattern of loss of the CA1 and CA3 pyramidal neurons of the hippocampus. Prior to this neuronal loss, brain-derived neurotrophic factor (BDNF) mRNA is substantially increased. We show here that BDNF protein is increased after excitotoxic insult in specific areas of the hippocampus, reaching maximal levels 24 h after the insult. BDNF protein levels in the hippocampus increase in direct relation to the severity of seizure. Up to 7 days after injection of kainic acid, levels of full-length TrkB protein were unchanged, whereas levels of truncated TrkB protein were significantly increased by 12 h. To determine whether elevations in BDNF protein levels are potentially beneficial to hippocampal neurons exposed to an excitotoxic stress, we infused exogenous BDNF prior to and during the period of neuronal death caused by kainic acid. We find that administration of high levels of exogenous BDNF does not affect severity of seizure, but does in fact, exacerbate the injury caused by kainic acid, specifically to CA3 pyramidal neurons. Although there was a trend toward sparing of CA1 pyramidal neurons on the side infused with BDNF, this was not significant. In the same paradigm, infusion of exogenous NT-3 had no effect.

  19. GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat.

    PubMed

    Cercato, Magali C; Vázquez, Cecilia A; Kornisiuk, Edgar; Aguirre, Alejandra I; Colettis, Natalia; Snitcofsky, Marina; Jerusalinsky, Diana A; Baez, María V

    2016-01-01

    It is widely accepted that NMDA receptors (NMDAR) are required for learning and memory formation, and for synaptic plasticity induction. We have previously shown that hippocampal GluN1 and GluN2A NMDAR subunits significantly increased following habituation of rats to an open field (OF), while GluN2B remained unchanged. Similar results were obtained after CA1-long-term potentiation (LTP) induction in rat hippocampal slices. Other studies have also shown NMDAR up regulation at earlier and later time points after LTP induction or learning acquisition. In this work, we have studied NMDAR subunits levels in the hippocampus and prefrontal cortex (PFC) after OF habituation and after object recognition (OR), to find out whether rising of NMDAR subunits is a general and structure-specific feature during memory formation. In 1, 2 and 3 month old rats there was an increase in hippocampal GluN1 and GluN2A, but not in GluN2B levels 70 min after OF habituation. This rise overlaps with early phase of memory consolidation, suggesting a putative relationship between them. The increases fell down to control levels 90 min after training. Similar results were obtained in the hippocampus of adult rats 70 min after OR training, without changes in PFC. Following OF test or OR discrimination phase, NMDAR subunits remained unchanged. Hence, rising of hippocampal GluN1 and GluN2A appears to be a general feature after novel "spatial/discrimination" memory acquisition. To start investigating the dynamics and possible mechanisms of these changes, we have studied hippocampal neuron cultures stimulated by KCl to induce plasticity. GluN1 and GluN2A increased both in dendrites and neuronal bodies, reaching a maximum 75 min later and returning to control levels at 90 min. Translation and/or transcription and mobilization differentially contribute to this rise in subunits in bodies and dendrites. Our results showed that the NMDAR subunits increase follows a similar time course both in vitro and in

  20. GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat

    PubMed Central

    Cercato, Magali C.; Vázquez, Cecilia A.; Kornisiuk, Edgar; Aguirre, Alejandra I.; Colettis, Natalia; Snitcofsky, Marina; Jerusalinsky, Diana A.; Baez, María V.

    2017-01-01

    It is widely accepted that NMDA receptors (NMDAR) are required for learning and memory formation, and for synaptic plasticity induction. We have previously shown that hippocampal GluN1 and GluN2A NMDAR subunits significantly increased following habituation of rats to an open field (OF), while GluN2B remained unchanged. Similar results were obtained after CA1-long-term potentiation (LTP) induction in rat hippocampal slices. Other studies have also shown NMDAR up regulation at earlier and later time points after LTP induction or learning acquisition. In this work, we have studied NMDAR subunits levels in the hippocampus and prefrontal cortex (PFC) after OF habituation and after object recognition (OR), to find out whether rising of NMDAR subunits is a general and structure-specific feature during memory formation. In 1, 2 and 3 month old rats there was an increase in hippocampal GluN1 and GluN2A, but not in GluN2B levels 70 min after OF habituation. This rise overlaps with early phase of memory consolidation, suggesting a putative relationship between them. The increases fell down to control levels 90 min after training. Similar results were obtained in the hippocampus of adult rats 70 min after OR training, without changes in PFC. Following OF test or OR discrimination phase, NMDAR subunits remained unchanged. Hence, rising of hippocampal GluN1 and GluN2A appears to be a general feature after novel “spatial/discrimination” memory acquisition. To start investigating the dynamics and possible mechanisms of these changes, we have studied hippocampal neuron cultures stimulated by KCl to induce plasticity. GluN1 and GluN2A increased both in dendrites and neuronal bodies, reaching a maximum 75 min later and returning to control levels at 90 min. Translation and/or transcription and mobilization differentially contribute to this rise in subunits in bodies and dendrites. Our results showed that the NMDAR subunits increase follows a similar time course both in vitro and

  1. IUGR increases chromatin-remodeling factor Brg1 expression and binding to GR exon 1.7 promoter in newborn male rat hippocampus.

    PubMed

    Ke, Xingrao; McKnight, Robert A; Gracey Maniar, Lia E; Sun, Ying; Callaway, Christopher W; Majnik, Amber; Lane, Robert H; Cohen, Susan S

    2015-07-15

    Intrauterine growth restriction (IUGR) increases the risk for neurodevelopment delay and neuroendocrine reprogramming in both humans and rats. Neuroendocrine reprogramming involves the glucocorticoid receptor (GR) gene that is epigenetically regulated in the hippocampus. Using a well-characterized rodent model, we have previously shown that IUGR increases GR exon 1.7 mRNA variant and total GR expressions in male rat pup hippocampus. Epigenetic regulation of GR transcription may involve chromatin remodeling of the GR gene. A key chromatin remodeler is Brahma-related gene-1(Brg1), a member of the ATP-dependent SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. Brg1 regulates gene expression by affecting nucleosome repositioning and recruiting transcriptional components to target promoters. We hypothesized that IUGR would increase hippocampal Brg1 expression and binding to GR exon 1.7 promoter, as well as alter nucleosome positioning over GR promoters in newborn male pups. Further, we hypothesized that IUGR would lead to accumulation of specificity protein 1 (Sp1) and RNA pol II at GR exon 1.7 promoter. Indeed, we found that IUGR increased Brg1 expression and binding to GR exon 1.7 promoter. We also found that increased Brg1 binding to GR exon 1.7 promoter was associated with accumulation of Sp1 and RNA pol II carboxy terminal domain pSer-5 (a marker of active transcription). Furthermore, the transcription start site of GR exon 1.7 was located within a nucleosome-depleted region. We speculate that changes in hippocampal Brg1 expression mediate GR expression and subsequently trigger neuroendocrine reprogramming in male IUGR rats.

  2. Prenatal valproate treatment produces autistic-like behavior and increases metabotropic glutamate receptor 1A-immunoreactivity in the hippocampus of juvenile rats.

    PubMed

    Peralta, Francisco; Fuentealba, Constanza; Fiedler, Jenny; Aliaga, Esteban

    2016-09-01

    Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by deficits in social communication and social interaction, and repetitive and stereotypical patterns of behavior. Previously, a common physiopathological pathway, involving the control of synaptic protein synthesis, was proposed as a convergence point in ASD. In particular, a role for local mRNA translation activated by class I metabotropic glutamate receptor type 5 (mGluR5) was suggested in genetic syndromes with autistic signs and in the prenatal exposition to the valproate model of autism. However, the role of the other members of class I metabotropic glutamate receptors, including mGluR1, has been poorly studied. The present study analyzed the immunoreactivity for mGluR1a in the hippocampus of rats prenatally treated with valproate. Pregnant dams (embryonic day 12.5) were injected with valproate (450 mg/kg) and subsequently, the behavior and mGluR1a were evaluated at postnatal day 30. Experimental rats exhibited social deficit, repetitive conduct and anxious behaviors compared with that of the control animals. Additionally, the present study observed an increased level of mGluR1a-immunoreactivity in the hilus of dentate gyrus and in the CA1 alveus region of the hippocampus. These results suggested an over‑functioning of mGluR1a signaling in the hippocampus, induced in the valproate model of autism, which may serve a role in cognitive and behavioral signs of ASD.

  3. Increased DNA double-strand break was associated with downregulation of repair and upregulation of apoptotic factors in rat hippocampus after alcohol exposure.

    PubMed

    Suman, Shubhankar; Kumar, Santosh; N'Gouemo, Prosper; Datta, Kamal

    2016-08-01

    Binge drinking is known to cause damage in critical areas of the brain, including the hippocampus, which is important for relational memory and is reported to be sensitive to alcohol toxicity. However, the roles of DNA double-strand break (DSB) and its repair pathways, homologous recombination (HR), and non-homologous end joining (NHEJ) in alcohol-induced hippocampal injury remain to be elucidated. The purpose of this first study was to assess alcohol-induced DNA DSB and the mechanism by which alcohol affects DSB repair pathways in rat hippocampus. Male Sprague-Dawley rats (8-10 weeks old) were put on a 4-day binge ethanol treatment regimen. Control animals were maintained under similar conditions but were given the vehicle without ethanol. All animals were humanely euthanized 24 h after the last dose of ethanol administration and the hippocampi were dissected for immunoblot and immunohistochemistry analysis. Ethanol exposure caused increased 4-hydroxynonenal (4-HNE) staining as well as elevated γH2AX and 53BP1 foci in hippocampal cells. Immunoblot analysis showed decreased Mre11, Rad51, Rad50, and Ku86 as well as increased Bax and p21 in samples from ethanol-treated rats. Additionally, we also observed increased activated caspase3 staining in hippocampal cells 24 h after ethanol withdrawal. Taken together, our data demonstrated that ethanol concurrently induced DNA DSB, downregulated DSB repair pathway proteins, and increased apoptotic factors in hippocampal cells. We believe these findings will provide the impetus for further research on DNA DSB and its repair pathways in relation to alcohol toxicity in brain.

  4. Adolescence fluoxetine increases serotonergic activity in the raphe-hippocampus axis and improves depression-like behaviors in female rats that experienced neonatal maternal separation.

    PubMed

    Yoo, Sang Bae; Kim, Bom-Taeck; Kim, Jin Young; Ryu, Vitaly; Kang, Dong-Won; Lee, Jong-Ho; Jahng, Jeong Won

    2013-06-01

    This study was conducted to examine if fluoxetine, a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor, would reverse adverse behavioral effects of neonatal maternal separation in female rats. Sprague-Dawley pups were separated from dam daily for 3h during postnatal day (PND) 1-14 (maternal separation; MS) or left undisturbed (non-handled; NH). Female NH and MS pups received intraperitoneal injection of fluoxetine (10mg/kg) or vehicle daily from PND 35 until the end of the whole experimental period. Rats were either subjected to behavioral tests during PND 44-54, or sacrificed for neurochemical analyses during PND 43-45. Daily food intake and weight gain of both NH and MS pups were suppressed by fluoxetine, with greater effects in MS pups. MS experience increased immobility and decrease swimming in forced swim test. Swimming was increased, although immobility was not significantly decreased, in MS females by adolescence fluoxetine. However, adolescence fluoxetine increased immobility during forced swim test and decreased time spent in open arms during elevated plus maze test in NH females. Fluoxetine normalized MS-induced decrease of the raphe 5-HT levels and increased 5-HT metabolism in the hippocampus in MS females, and increased the hypothalamic 5-HT both in NH and MS. Fluoxetine decreased the raphe 5-HT and increased the plasma corticosterone in NH females. Results suggest that decreased 5-HTergic activity in the raphe nucleus is implicated in the pathophysiology of depression-like behaviors, and increased 5-HTergic activities in the raphe-hippocampus axis may be a part of anti-depressant efficacy of fluoxetine, in MS females. Also, an extra-hypothalamic 5-HTergic activity may contribute to the increased anorectic efficacy of fluoxetine in MS females. Additionally, decreased 5-HT in the raphe and elevated plasma corticosterone may be related with fluoxetine-induced depression- and/or anxiety-like behaviors in NH females.

  5. Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the α7 nicotinic acetylcholine receptor.

    PubMed

    Li, Xiaolan; Han, Xinjia; Bao, Junjie; Liu, Yuanyuan; Ye, Aihua; Thakur, Mukesh; Liu, Huishu

    2016-07-01

    A considerable number of studies have demonstrated that nicotine, a α7-nicotinic acetylcholine receptor (α7-nAChR) agonist, can dampen immune response through the cholinergic anti-inflammatory pathway. Evidence suggests that inflammation plays a critical role in eclampsia, which contributes to maternal and fetal morbidity and mortality. In the present study, possible anti-inflammation and neuro-protective effects of nicotine via α7-nAChRs have been investigated after inducing eclampsia-like seizures in rats. Rat eclampsia-like models were established by administering lipopolysaccharide (LPS) plus pentylenetetrazol (PTZ) in pregnant rats. Rats were given nicotine from gestation day (GD) 14-19. Then, clinical symptoms were detected. Seizure severity was recorded by behavioral tests, serum levels of inflammatory cytokines were measured by Luminex assays, microglia and astrocyte expressions were detected by immunofluorescence, and changes in neuronal number in the hippocampal CA1 region among different groups were detected by Nissl staining. Our results revealed that nicotine effectively improved fetal outcomes. Furthermore, it significantly decreased systolic blood pressure, and maternal serum levels of Th1 cytokines (TNF-α, IL-1β, IL-6 and IL-12P70) and an IL-17 cytokine (IL-17A), and dramatically increased eclampsia-like seizure threshold. Moreover, this attenuated neuronal loss and decreased the expression of microglial activation markers of the hippocampal CA1 region in the eclampsia-like group. Additionally, pretreatment with α-bungarotoxin, a selective α7-nAChR antagonist could prevent the protective effects of nicotine in eclampsia-like model rats. Our findings indicate that the administration of nicotine may attenuate microglial activity and increase eclampsia-like seizure threshold in rat hippocampus through the α7 nicotinic receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Perinatal hypoxia induces a long-lasting increase in unstimulated gaba release in rat brain cortex and hippocampus. The protective effect of pyruvate.

    PubMed

    Pozdnyakova, N; Yatsenko, L; Parkhomenko, N; Himmelreich, N

    2011-01-01

    Hypoxia and seizures early in life can cause multiple neurological deficits and even chronic epilepsy. Here, we report the data obtained in rats exposed to hypoxia and seizures at age 10-12 postnatal days and taken in experiments 8-9 weeks after hypoxia treatment. A level of the extracellular GABA and the initial velocity of GABA uptake were measured in the brain cortex, hippocampus and thalamus using isolated nerve terminals (synaptosomes). It has been revealed that the extracellular [(3)H]GABA level maintained by cortical and hippocampal synaptosomes in standard conditions (with glucose as an energy substrate) was significantly higher in adult rats exposed to hypoxia/seizures at P10-12 than in the control ones, and, moreover, became unstable with tendency to increase. Pyruvate as a single energy substrate was shown to be a highly effective for lowering and stabilizing the extracellular [(3)H]GABA level. This effect of pyruvate was tightly correlated with increase in GABA uptake and GATs affinity to GABA. Thalamus was insensible to the action of perinatal hypoxia/seizures, and thalamic GATs, in contrast to cortical and hippocampal ones, had a lower affinity to GABA (the apparent Km is 39.2±3.1 μM GABA vs 8.9±1.8 μM GABA in the hippocampus). A selective vulnerability of brain regions to hypoxia is suggested to be attributed to distinct terms of their maturation at the postnatal period. Thus, perinatal hypoxia/seizures evoke a long-lasting increase in the extracellular GABA level that could be attenuated by pyruvate treatment. This effect of pyruvate is likely due to a significant increase in GATs-mediated GABA uptake and modulation of GATs kinetic properties. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats.

    PubMed

    Sivanathan, Shathveekan; Thavartnam, Kabriya; Arif, Shahneen; Elegino, Trisha; McGowan, Patrick O

    2015-06-01

    The consumption of diets high in saturated fats and obesity have been associated with impaired physical and mental health. Previous studies indicate that chronic high fat diet consumption leads to systemic inflammation in humans and non-human animal models. Studies in non-human animals suggest that altered physiological responses to stress are also a consequence of high fat diet consumption. Glucocorticoid signalling mechanisms may link immune and stress-related pathways in the brain, and were shown to be significantly altered in the brains of female rat offspring of mothers exposed to chronic high fat diet during pregnancy and lactation. For adult females, the consequence of chronic high fat diet consumption on these signalling pathways and their relationship to stress-related behaviour is not known. In this study, we examined the effects of chronic consumption of a high fat diet compared to a low fat control diet among adult female Long Evans rats. We found significant differences in weight gain, caloric intake, anxiety-related behaviours, and glucocorticoid-related gene expression over a 10-week exposure period. As expected, rats in the high fat diet group gained the most weight and consumed the greatest number of calories. Rats in the high fat diet group showed significantly greater levels of anxiety-related behaviour in the Light Dark and Open Field tasks compared to rats in the low fat diet group. Rats consuming high fat diet also exhibited reduced transcript abundance in the hippocampus of stress-related mineralocorticoid receptor and glucocorticoid receptor genes, as well as nuclear factor kappa beta gene expression, implicated in inflammatory processes. Together, these data indicate that chronic high fat diet consumption may increase anxiety-like behaviour at least in part via alterations in glucocorticoid signalling mechanisms in limbic brain regions.

  8. Protein kinase C activation increases noradrenaline release from the rat hippocampus and modifies the inhibitory effect of alpha 2-adrenoceptor and adenosine A1-receptor agonists.

    PubMed

    Fredholm, B B; Lindgren, E

    1988-05-01

    We have studied the effect of stimulating protein kinase C with phorbol esters on the release of [3H]-noradrenaline (NA) in the absence or presence of presynaptic alpha 2-adrenoceptor blocking agents and compared that to the elevation of cyclic AMP levels more than 10-fold by a combination of rolipram and forskolin. 4-beta-Phorbol 12,13-dibutyrate (PDiBu) increased stimulated (3 Hz) [3H]-NA release markedly and in a concentration dependent manner. 4-alpha-Phorbol-12,13-didecanoate was ineffective. The effect of PDiBu was not significantly reduced by nifedipine (1 microM), but was proportionally less in the presence of an alpha 2-adrenoceptor antagonist, yohimbine. PDiBu inhibited the presynaptic effect of alpha 2-adrenoceptor agonists clonidine and UK 14304. By contrast, the presynaptic effect of the adenosine analogue R-PIA was not reduced by PDiBu. PDiBu caused an increase in cyclic AMP that depended on adenosine receptor stimulation. Elevation of cyclic AMP had a limited effect on NA release from rat hippocampus, and did not significantly decrease the presynaptic inhibitory effect of UK 14304 (0.1 microM), of morphine (1 microM) or of the adenosine A1-receptor agonist CHA (1 microM). The effect of phorbol esters and several presynaptic inhibitors of NA-release in the rat hippocampus cannot be explained by changes in cyclic AMP levels in the tissue. Phorbol esters that stimulate protein kinase C appear to interact with a target that is the site of action alpha 2-adrenoceptors in this tissue. This site is not a dihydropyridine sensitive Ca-channel and is also different from the target of presynaptic adenosine receptors. Thus, activation of protein kinase C discriminates between apparently similar presynaptic mechanisms.

  9. The Increased Activity of TRPV4 Channel in the Astrocytes of the Adult Rat Hippocampus after Cerebral Hypoxia/Ischemia

    PubMed Central

    Butenko, Olena; Dzamba, David; Benesova, Jana; Honsa, Pavel; Benfenati, Valentina; Rusnakova, Vendula; Ferroni, Stefano; Anderova, Miroslava

    2012-01-01

    The polymodal transient receptor potential vanilloid 4 (TRPV4) channel, a member of the TRP channel family, is a calcium-permeable cationic channel that is gated by various stimuli such as cell swelling, low pH and high temperature. Therefore, TRPV4-mediated calcium entry may be involved in neuronal and glia pathophysiology associated with various disorders of the central nervous system, such as ischemia. The TRPV4 channel has been recently found in adult rat cortical and hippocampal astrocytes; however, its role in astrocyte pathophysiology is still not defined. In the present study, we examined the impact of cerebral hypoxia/ischemia (H/I) on the functional expression of astrocytic TRPV4 channels in the adult rat hippocampal CA1 region employing immunohistochemical analyses, the patch-clamp technique and microfluorimetric intracellular calcium imaging on astrocytes in slices as well as on those isolated from sham-operated or ischemic hippocampi. Hypoxia/ischemia was induced by a bilateral 15-minute occlusion of the common carotids combined with hypoxic conditions. Our immunohistochemical analyses revealed that 7 days after H/I, the expression of TRPV4 is markedly enhanced in hippocampal astrocytes of the CA1 region and that the increasing TRPV4 expression coincides with the development of astrogliosis. Additionally, adult hippocampal astrocytes in slices or cultured hippocampal astrocytes respond to the TRPV4 activator 4-alpha-phorbol-12,-13-didecanoate (4αPDD) by an increase in intracellular calcium and the activation of a cationic current, both of which are abolished by the removal of extracellular calcium or exposure to TRP antagonists, such as Ruthenium Red or RN1734. Following hypoxic/ischemic injury, the responses of astrocytes to 4αPDD are significantly augmented. Collectively, we show that TRPV4 channels are involved in ischemia-induced calcium entry in reactive astrocytes and thus, might participate in the pathogenic mechanisms of astroglial reactivity

  10. The hippocampus in spontaneously hypertensive rats: a quantitative microanatomical study.

    PubMed

    Sabbatini, M; Strocchi, P; Vitaioli, L; Amenta, F

    2000-01-01

    The influence of hypertension on the morphology of hippocampus was assessed in spontaneously hypertensive rats of two, four and six months and in age-matched normotensive Wistar-Kyoto rats. Values of systolic pressure were slightly increased in two-month-old spontaneously hypertensive rats in comparison with age-matched Wistar-Kyoto rats and augmented progressively with age in spontaneously hypertensive rats. No microanatomical changes were observed in the hippocampus of spontaneously hypertensive rats of two months in comparison with age-matched Wistar-Kyoto rats, whereas a decrease of white matter volume was observed in the CA(1) subfield and in the dentate gyrus of four-month-old spontaneously hypertensive rats. In the hippocampus of six-month-old spontaneously hypertensive rats a reduction of grey matter volume both in the CA(1) subfield and in the dentate gyrus, a loss of neurons affecting to a greater extent the CA(1) subfield and an increase of glial fibrillary acid protein-immunoreactive astrocytes was found. The occurrence of apoptosis and/or necrosis identified using the terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick end labelling technique was also observed in the CA(1) subfield and to a lesser extent in the dentate gyrus. The only change noticeable in the CA(3) subfield of six-month-old spontaneously hypertensive rats was a slight increase in the number of glial fibrillary acid protein-immunoreactive astrocytes. These findings indicate the occurrence of neuronal loss and of astrocyte changes in the hippocampus of spontaneously hypertensive rats of six months, being the CA(1) subfield the area most affected. The relevance of these neurodegenerative changes in hypertension and the possible occurrence of apoptosis and/or necrosis as expression of hypertensive brain damage is discussed.

  11. 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.

  12. IL-1β increases necrotic neuronal cell death in the developing rat hippocampus after status epilepticus by activating type I IL-1 receptor (IL-1RI).

    PubMed

    Medel-Matus, Jesús-Servando; Álvarez-Croda, Dulce-Mariely; Martínez-Quiroz, Joel; Beltrán-Parrazal, Luis; Morgado-Valle, Consuelo; López-Meraz, María-Leonor

    2014-11-01

    Interleukin-1β (IL-1β) is associated with seizure-induced neuronal cell death in the adult brain. The contribution of IL-1β to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. In the present study, we investigated the effects of IL-1β administration on hippocampal neuronal cell death associated with SE in the immature brain, and the role of the type I receptor of IL-1β (IL-1RI). SE was induced with lithium-pilocarpine in 14-days-old (P14) rat pups. Six hours after SE onset, pups were i.c.v. injected in the right ventricle with IL-1β (0, 0.3, 3, 30, or 300 ng), 30 ng of IL-1RI antagonist (IL-1Ra) alone, or 30 ng of IL-1Ra plus 3ng of IL-1β. As control groups, pups without seizures were injected with 3 ng of IL-1β or vehicle. Twenty-four hours after SE onset, neuronal cell death in the CA1 field of dorsal hippocampus was assessed by hematoxylin-eosin, Fluoro-Jade B and in vivo propidium iodide (PI) staining; expression of active caspase-3 (aCas-3) was also determined, using immunohistochemistry. The concentration-response curve of IL-1β showed a bell-shape. Only pups injected with 3 ng of IL-1β after SE showed a significant increase in the number of cells with eosinophilic cytoplasm and pyknotic nuclei, as well as F-JB positive cells with respect to the vehicle group. This effect was prevented when IL-1β was injected with IL-1Ra. Injection of 3 ng of IL-1β increased the number of PI-positive cells in CA1 area after SE. Injection of 3 ng of IL-1β did not produce hippocampal cell death in rats without seizures. Active caspase-3 expression was not observed after treatments in hippocampus. The activation of the IL-1β/IL-1RI system increases necrotic neuronal cell death caused by SE in rat pups.

  13. Antipsychotics increase microtubule-associated protein 2 mRNA but not spinophilin mRNA in rat hippocampus and cortex.

    PubMed

    Law, Amanda J; Hutchinson, Louise J; Burnet, Philip W J; Harrison, Paul J

    2004-05-01

    Antipsychotic (neuroleptic) drugs induce structural alterations in synaptic terminals and changes in the expression of presynaptic protein genes. Whether there are also changes in corresponding postsynaptic (dendritic) markers has not been determined. We describe the effect of 14-day treatment with typical (haloperidol, chlorpromazine) or atypical (clozapine, olanzapine, risperidone) antipsychotics on the expression of two dendritic protein genes, microtubule-associated protein 2 (MAP2) and spinophilin, using in situ hybridization, in the rat hippocampus, retrosplenial, and occipitoparietal cortices. MAP2 mRNA was increased modestly in the dentate gyrus and retrosplenial cortex by chlorpromazine, risperidone, and olanzapine and in the occipitoparietal cortex by chlorpromazine, haloperidol, and risperidone. None of the antipsychotics affected spinophilin mRNA in any area. Overall, these results show a modulation of MAP2 gene expression, likely reflecting functional or structural changes in the dendritic tree in response to some typical and atypical antipsychotics. The lack of change in spinophilin mRNA suggests that dendritic spines are not affected selectively by the drugs. The data provide further evidence that antipsychotics regulate genes involved in synaptic structure and function. Such actions may underlie their long-term effects on neural plasticity in areas of the brain implicated in the pathology of schizophrenia. Copyright 2004 Wiley-Liss, Inc.

  14. [Effect of Heroin on DLG4 Expression in Hippocampus, Amygdala and Frontal Cortex of Rats].

    PubMed

    Luo, Liang-ming; Gong, Qun; Liu, Jian-feng; Zhao, Ming-quan; Chen, Dong-dong; Xie, Yao-yao; Zhu, Hua

    2015-06-01

    To observe the expression of discs large homolog 4 (DLG4) protein in hippocampus, amygdala and frontal cortex of rats and evaluate postsynaptic density in heroin dependence. The rat heroin dependent model was established by increasing intraperitoneal injection of heroin. DLG4 proteins in hippocampus, amygdala and frontal cortex of heroin dependent 9, 18, 36 days rats were detected with immunohistochemical staining and compared with that in the control group. DLG4 proteins in hippocampus, amygdala and frontal cortex were gradually reduced with extension of heroin dependent time. Heroin dependence can affect postsynaptic density of hippocampus, amygdala and frontal cortex. The changes become more apparent with extension of heroin dependence time.

  15. Lipopolysaccharide-induced neuroinflammation leads to the accumulation of ubiquitinated proteins and increases susceptibility to neurodegeneration induced by proteasome inhibition in rat hippocampus

    PubMed Central

    2012-01-01

    Background Neuroinflammation and protein accumulation are characteristic hallmarks of both normal aging and age-related neurodegenerative diseases. However, the relationship between these factors in neurodegenerative processes is poorly understood. We have previously shown that proteasome inhibition produced higher neurodegeneration in aged than in young rats, suggesting that other additional age-related events could be involved in neurodegeneration. We evaluated the role of lipopolysaccharide (LPS)-induced neuroinflammation as a potential synergic risk factor for hippocampal neurodegeneration induced by proteasome inhibition. Methods Young male Wistar rats were injected with 1 μL of saline or LPS (5 mg/mL) into the hippocampus to evaluate the effect of LPS-induced neuroinflammation on protein homeostasis. The synergic effect of LPS and proteasome inhibition was analyzed in young rats that first received 1 μL of LPS and 24 h later 1 μL (5 mg/mL) of the proteasome inhibitor lactacystin. Animals were sacrificed at different times post-injection and hippocampi isolated and processed for gene expression analysis by real-time polymerase chain reaction; protein expression analysis by western blots; proteasome activity by fluorescence spectroscopy; immunofluorescence analysis by confocal microscopy; and degeneration assay by Fluoro-Jade B staining. Results LPS injection produced the accumulation of ubiquitinated proteins in hippocampal neurons, increased expression of the E2 ubiquitin-conjugating enzyme UB2L6, decreased proteasome activity and increased immunoproteasome content. However, LPS injection was not sufficient to produce neurodegeneration. The combination of neuroinflammation and proteasome inhibition leads to higher neuronal accumulation of ubiquitinated proteins, predominant expression of pro-apoptotic markers and increased neurodegeneration, when compared with LPS or lactacystin (LT) injection alone. Conclusions Our results identify neuroinflammation

  16. Increased seizure susceptibility and up-regulation of nNOS expression in hippocampus following recurrent early-life seizures in rats.

    PubMed

    Kim, Doo-Kwun

    2010-06-01

    This study aimed to determine the long-term change of seizure susceptibility and the role of nNOS on brain development following recurrent early-life seizures in rats. Video-EEG recordings were conducted between postnatal days 50 and 60. Alterations in seizure susceptibility were assayed on day 22 or 50 using the flurothyl method. Changes in nNOS expression were determined by quantitative immunoblotting on day 50. On average, rats had 8.4+/-2.7 seizures during 10 daily 1 hr behavioral monitoring sessions. As adults (days 50-60), all rats displayed interictal spikes in the hippocampus and/or overlying cortex. Brief electrographic seizures were recorded in only one of five animals. Rats appeared to progress from a period of marked seizure susceptibility (day 22) to one of lessened seizure susceptibility (day 50). Up-regulation of nNOS expression following early-life recurrent seizures was observed on day 50. In conclusion, these data suggested that recurrent early-life seizures had the long-term effects on seizure susceptibility late in life and up-regulatory nNOS expression on the hippocampus during brain development, and nNOS appeared to contribute to the persistent changes in seizure susceptibility, and epileptogenesis.

  17. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

    PubMed

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-06-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits.

  18. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups

    PubMed Central

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-01-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2′-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits. PMID:27419108

  19. 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.

  20. Grape juice increases the BDNF levels but not alter the S100B levels in hippocampus and frontal cortex from male Wistar Rats.

    PubMed

    Dani, Caroline; Andreazza, Ana Cristina; Gonçalves, Carlos Alberto; Kapizinski, Flávio; Henriques, João A P; Salvador, Mirian

    2017-03-02

    Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.

  1. Dopamine Transporter Blockade Increases LTP in the CA1 Region of the Rat Hippocampus via Activation of the D3 Dopamine Receptor

    ERIC Educational Resources Information Center

    Swant, Jarod; Wagner, John J.

    2006-01-01

    Dopamine has been demonstrated to be involved in the modulation of long-term potentiation (LTP) in the CA1 region of the hippocampus. As monoamine transporter blockade will increase the actions of endogenous monoamine neurotransmitters, the effect of a dopamine transporter (DAT) antagonist on LTP was assessed using field excitatory postsynaptic…

  2. Dopamine Transporter Blockade Increases LTP in the CA1 Region of the Rat Hippocampus via Activation of the D3 Dopamine Receptor

    ERIC Educational Resources Information Center

    Swant, Jarod; Wagner, John J.

    2006-01-01

    Dopamine has been demonstrated to be involved in the modulation of long-term potentiation (LTP) in the CA1 region of the hippocampus. As monoamine transporter blockade will increase the actions of endogenous monoamine neurotransmitters, the effect of a dopamine transporter (DAT) antagonist on LTP was assessed using field excitatory postsynaptic…

  3. Infusions of 3alpha,5alpha-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3alpha,5alpha-THP in midbrain, hippocampus, diencephalon, and cortex of female rats.

    PubMed

    Frye, Cheryl A; Rhodes, Madeline E

    2008-02-11

    17beta-Estradiol (E2) and progesterone (P4) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P4 metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), modulates lordosis of E2-primed rodents; 3alpha,5alpha-THP can also influence anxiety and social behaviors. To examine if 3alpha,5alpha-THP in the VTA mediates socio-sexual behaviors, we infused 3alpha,5alpha-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E2, P4, dihydroprogesterone (DHP), and 3alpha,5alpha-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3alpha,5alpha-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3alpha,5alpha-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3alpha,5alpha-THP, but neither E2 nor P4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3alpha,5alpha-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

  4. Microinfusion of the non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of wistar rats does not affect latent inhibition and prepulse inhibition, but increases startle reaction and locomotor activity.

    PubMed

    Zhang, W N; Bast, T; Feldon, J

    2000-01-01

    Latent inhibition (the retarded conditioning to a stimulus following its repeated non-reinforced pre-exposure) and prepulse inhibition (the reduction in the startle response to an intense acoustic stimulus when this stimulus is immediately preceded by a prepulse) reflect cognitive and sensorimotor gating processes, respectively, and are deficient in schizophrenic patients. The disruption of latent inhibition and prepulse inhibition in the rat is used as an animal model for the attentional deficits associated with schizophrenia. The present study tested the extent to which latent inhibition and prepulse inhibition, startle reaction and locomotor activity in the open field were affected by infusing the non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of Wistar rats. We used the same dose of MK-801 (6.25microg/0.5microl per side) previously found to be effective in the disruption of prepulse inhibition when infused into the dorsal hippocampus of Sprague-Dawley rats [Bakshi V. P. and Geyer M. A. (1998) J. Neurosci. 18, 8394-8401; Bakshi V. P. and Geyer M. A. (1999) Neuroscience 92, 113-121]. Bilateral infusion of MK-801 into the dorsal hippocampus did not disrupt latent inhibition. Furthermore, in contrast to previous studies, we failed to find a significant disruption of prepulse inhibition after MK-801 infusion into the dorsal hippocampus, although MK-801 infusion was effective in increasing the startle amplitude as well as locomotor activity in an open field. From our results, we suggest that N-methyl-D-aspartate receptor-mediated processes within the dorsal hippocampus are not necessary for the normal maintenance of the attentional processes reflected by latent inhibition and prepulse inhibition.

  5. Increased CRE-binding activity and tryptophan hydroxylase mRNA expression induced by 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in the rat frontal cortex but not in the hippocampus.

    PubMed

    García-Osta, Ana; Del Río, Joaquín; Frechilla, Diana

    2004-07-26

    A single administration of either 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") or p-chloroamphetamine (PCA) produced a rapid and marked reduction of serotonin (5-HT) content in rat frontal cortex and hippocampus. In the cortex of MDMA-treated rats, 5-HT levels returned to control values 48 h after drug administration. This recovery was correlated with an induction of CRE-binding activity and an enhanced expression of tryptophan hydroxylase (TPH) mRNA, the rate-limiting enzyme in 5-HT biosynthesis, suggesting that MDMA may up-regulate the TPH gene through a CREB-dependent mechanism. In the cortex of PCA-treated rats, neither a recovery of 5-HT levels nor changes in DNA-binding or TPH mRNA were found at the same time point. In the hippocampus of rats receiving either PCA or MDMA a decrease in TPH mRNA levels was found at all times, along with a reduced CRE-binding at the 8-h time point. The results show region-specific effects of MDMA. In the frontal cortex, the increased TPH expression suggests a compensatory response to MDMA-induced loss of serotonergic function.

  6. Acoustic hypersensitivity in adult rats after neonatal ventral hippocampus lesions.

    PubMed

    Macedo, Carlos Eduardo; Angst, Marie-Josée; Guiberteau, Thierry; Brasse, David; O'Brien, Terence John; Sandner, Guy

    2010-02-11

    Rats with a bilateral neonatal ventral hippocampus lesion (NVHL) are used as models of neurobiological aspects of schizophrenia. In view of their decreased number of GABAergic interneurons, we hypothesized that they would show increased reactivity to acoustic stimuli. We systematically characterized the acoustic reactivity of NVHL rats and sham operated controls. They were behaviourally observed during a loud white noise. A first cohort of 7 months' old rats was studied. Then the observations were reproduced in a second cohort of the same age after characterizing the reactivity of the same rats to dopaminergic drugs. A third cohort of rats was studied at 2, 3, 4, 5 and 6 months. In subsets of lesioned and control rats, inferior colliculus auditory evoked potentials were recorded. A significant proportion of rats (50-62%) showed aberrant audiogenic responses with explosive wild running resembling the initial phase of audiogenic seizures. This was not correlated with their well-known enhanced reactivity to dopaminergic drugs. The proportion of rats showing this strong reaction increased with rats' age. After the cessation of the noise, NVHL rats showed a long freezing period that did neither depend on the size of the lesion nor on the rats' age. The initial negative deflection of the auditory evoked potential was enhanced in the inferior colliculus of only NVHL rats that displayed wild running. Complementary anatomical investigations using X-ray scans in the living animal, and alizarin red staining of brain slices, revealed a thin layer of calcium deposit close to the medial geniculate nuclei in post-NVHL rats, raising the possibility that this may contribute to the hyper-reactivity to sounds seen in these animals. The findings of this study provide complementary information with potential relevance for the hyper-reactivity noted in patients with schizophrenia, and therefore a tool to investigate the underlying biology of this endophenotype.

  7. Neonatal handling and environmental enrichment increase the expression of GAP-43 in the hippocampus and promote cognitive abilities in prenatally stressed rat offspring.

    PubMed

    Zhang, Zhengyu; Zhang, Hua; Du, Baoling; Chen, Zhiqiang

    2012-07-26

    Neonatal handling and environmental enrichment have been used to aid the treatment and recovery of a diverse variety of brain dysfunctions. However, the underlying mechanism and the effects on cognitive function following neonatal handling and environmental enrichment are still unclear. In this study, we investigated GAP-43 protein levels in the hippocampus of prenatally stressed rat pups by Western blot on postnatal day (P) 10, P20 and P45. The cognitive ability of prenatally stressed rat pups was tested by using the Morris water maze on P45. GAP-43 protein levels were upregulated on P10 in the prenatal restraint stress (RS) group and the prenatal restraint stress plus neonatal handling and environmental enrichment (RE) group compared to the negative control (NC) group. However, the expression of GAP-43 in RS pups was lower on P20 and P45 than that in NC and RE pups. Exposure to prenatal stress prolonged average latency and total swim distance, but neonatal handling and environmental enrichment could reverse the change. Differences were also observed in the selection of search strategies. These results indicate that neonatal handling and environmental enrichment can improve the spatial learning and memory ability of prenatally stressed offspring, and the possible mechanism is the upregulation of GAP-43. Copyright © 2012. Published by Elsevier Ireland Ltd.

  8. 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.

  9. 17β-Estradiol, but not estrone, increases the survival and activation of new neurons in the hippocampus in response to spatial memory in adult female rats.

    PubMed

    McClure, Robyn E S; Barha, Cindy K; Galea, Liisa A M

    2013-01-01

    Estrogens fluctuate across the lifespan in women, with circulating 17β-estradiol levels higher pre-menopause than estrone and circulating estrone levels higher postmenopause than 17β-estradiol. Estrone is a common component of hormone replacement therapies, but research shows that 17β-estradiol may have a greater positive impact on cognition. Previous studies show that acute estrone and 17β-estradiol impact hippocampus-dependent learning and cell proliferation in the dentate gyrus in a dose-dependent manner in adult female rats. The current study explores how chronic treatment with estrone and 17β-estradiol differentially influences spatial learning, hippocampal neurogenesis and activation of new neurons in response to spatial memory. Adult female rats received daily injections of vehicle (sesame oil), or a 10 μg dose of either 17β-estradiol or estrone for 20 days. One day following the first hormone injection all rats were injected with the DNA synthesis marker, bromodeoxyuridine. On days 11-15 after BrdU injection rats were trained on a spatial reference version of the Morris water maze, and five days later (day 20 of estrogens treatment) were given a probe trial to assess memory retention. Cell proliferation was assessed by the endogenous cell cycle marker, Ki67, cell survival was assessed by counting the number and density of BrdU-ir cells in the dentate gyrus and cell activation was assessed by the percentage of BrdU-ir cells that were co-labelled with the immediate early gene product zif268. There were no significant differences between groups in acquisition or retention of Morris water maze. However, the 17β-estradiol group had significantly higher, while the estrone group had significantly lower, levels of cell survival (BrdU-ir cells) in the dentate gyrus compared to controls. Furthermore, rats injected with 17β-estradiol showed significantly higher levels of activation of new neurons in response to spatial memory compared to controls. These

  10. Changes in acetylcholine content, release and muscarinic receptors in rat hippocampus under cold stress

    SciTech Connect

    Fatranska, M.; Budai, D.; Gulya, K; Kvetnansky, R.

    1989-01-01

    The aim was to study the mechanism of the previously established decrease in acetylcholine (ACh) concentration in the rat hippocampus under cold stress. Male rats were exposed for 14 days to cold (5/degree/C) or kept (controls) at room temperature (24/degree/C). Acetylcholine content, release and muscarinic receptor binding were investigated in the hippocampus. Cold exposure resulted in a decrease of ACh concentration in the dorsal hippocampus. Moreover, the potassium-evoked release of ACh from hippocampal slices was increased and an increase of maximal binding capacity of (/sup 3/H)(-) quinuclidinyl benzilate in the dorsal hippocampus of cold exposed animals was also observed. Thus the decrease of hippocampal ACh concentration under cold exposure is probably due to its increased release. On balance then, our results demonstrate that cold stress in the rat induces significant activation of the hippocampal cholinergic system.

  11. Effects of a 4 month enriched environment on the hippocampus and the myelinated fibers in the hippocampus of middle-aged rats.

    PubMed

    Qiu, Xuan; Huang, Chun-Xia; Lu, Wei; Yang, Shu; Li, Chen; Shi, Xiao-Yan; Chen, Lin; Xiu, Yun; Yang, Jun-Qing; Tang, Yong

    2012-07-17

    An enriched environment has been shown to enhance learning and memory and to induce morphological changes in the hippocampus. In the present study, 14-month (middle-aged) female and male Sprague-Dawley rats were randomly divided into enriched environment (EE) rats and standard environment (SE) rats. EE rats were reared in an enriched environment and SE rats were reared in a standard environment for 4 months. The spatial learning capacity was assessed with Morris water maze. The hippocampus and the myelinated fibers in the rat hippocampus were quantitatively investigated with a transmission electronic microscope technique and stereological methods. The female rats housed in an enriched environment showed improved performance in the Morris water maze. There was no significant difference in the total volume of hippocampus between SE rats and EE rats. The total length and total volume of the myelinated fibers in the hippocampus of the female and male EE rats were significantly increased, respectively, when compared to the female and male SE rats. The increase of the total length of the myelinated nerve fibers in the hippocampus was mainly due to the increase of the myelinated fibers with diameters from 0.5 to 0.9 μm. Our results showed that a 4 month enriched environment had significant effects on the spatial learning capacity and the myelinated fibers in the hippocampus of middle-aged rats. The present study might provide an important theoretical basis for searching for an ethological strategy to delay the progress of brain aging in the future.

  12. Anxiety and hippocampus volume in the rat.

    PubMed

    Kalisch, Raffael; Schubert, Mirjam; Jacob, Wolfgang; Kessler, Melanie S; Hemauer, Rosa; Wigger, Alexandra; Landgraf, Rainer; Auer, Dorothee P

    2006-05-01

    In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior.

  13. 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.

  14. Vitex Agnus Castus Extract Improves Learning and Memory and Increases the Transcription of Estrogen Receptor α in Hippocampus of Ovariectomized Rats.

    PubMed

    Allahtavakoli, Mohammad; Honari, Najmeh; Pourabolli, Iran; Kazemi Arababadi, Mohammad; Ghafarian, Hossein; Roohbakhsh, Ali; Esmaeili Nadimi, Ali; Shamsizadeh, Ali

    2015-07-01

    Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormone-dependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. 24 female Wistar rats weighing 180-220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus (VAC) ethanolic extract orally. The last groups were treated with 40 μg/kg of estradiol valerat. Step-through passive avoidance (STPA) test was used for the evaluation of learning and memory. The hippocampal estrogen receptor α (ERα) expression was measured using Real-Time PCR. The results demonstrated that VAC extract or estradiol had better performance on step-through passive avoidance test than control group (all P<0.05). Moreover, administration of either estradiol or VAC extract increased the hippocampal mRNA level of ERα and prevented the decrease in uterine weight of ovariectomized rats. Based on our data, VAC extract improves learning and memory in ovariectomized rats. The positive effect of VAC extract on learning and memory is possibly associated with an increase in ERα gene expression in the hippocampal formation.

  15. Vitex Agnus Castus Extract Improves Learning and Memory and Increases the Transcription of Estrogen Receptor α in Hippocampus of Ovariectomized Rats

    PubMed Central

    Allahtavakoli, Mohammad; Honari, Najmeh; Pourabolli, Iran; Kazemi Arababadi, Mohammad; Ghafarian, Hossein; Roohbakhsh, Ali; Esmaeili Nadimi, Ali; Shamsizadeh, Ali

    2015-01-01

    Introduction: Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormone-dependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. Methods: 24 female Wistar rats weighing 180–220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus (VAC) ethanolic extract orally. The last groups were treated with 40 μg/kg of estradiol valerat. Step-through passive avoidance (STPA) test was used for the evaluation of learning and memory. The hippocampal estrogen receptor α (ERα) expression was measured using Real-Time PCR. Results: The results demonstrated that VAC extract or estradiol had better performance on step-through passive avoidance test than control group (all P<0.05). Moreover, administration of either estradiol or VAC extract increased the hippocampal mRNA level of ERα and prevented the decrease in uterine weight of ovariectomized rats. Discussion: Based on our data, VAC extract improves learning and memory in ovariectomized rats. The positive effect of VAC extract on learning and memory is possibly associated with an increase in ERα gene expression in the hippocampal formation. PMID:26904176

  16. [The study on the relationship between hippocampus neuronal apoptosis and hippocampus synaptic plasticity in rats exposed to aluminum].

    PubMed

    Nie, Xiaohan; Qin, Xiujun; Zhang, Huifang; Kang, Pan; Li, Zhaoyang; Niu, Qiao

    2015-07-01

    To investigate the effect of aluminum exposure on neuronal apoptosis of rats hippocampus and the correlation of and synaptic plasticity. There were 40 SPF grade SD rats which were randomly divided into four groups: the control group, the low dose group, the medium dose group and the high dose group, 10 rats in each group. The rats were daily gavaged with aluminum lactate for 30 days. The hippocampal fEPSPs in rat was measured by electrophysiological grapher and the neuronal apoptosis in hippocampus was detected by Flow cytometer. In addition, the relative expression of gene which includes caspase-3, 8, 9 was measured by Real-time PCR. Compared to the control group, the average of fEPSPs which after HFS 10, 20, 30, 40, 50, 60 min was decreased at different time point in the low dose group, the medium dose group and the high dose group (P < 0.05). Compared with the control group, the rate of apoptosis was significantly increased in the medium dose group and the high dose group (P < 0.05). Compared to the control group, the relative expression of caspase-3 in the medium dose group and the high dose group was significantly increased in Real-time PCR (P < 0.05), and the relative expression of caspase-8 in the high dose group was significantly increased (P < 0.05). Aluminum exposure may induced neuronal apoptosis in rats, and then affect hippocampal synaptic plasticity.

  17. Increased expression of Slit2 and its receptors Robo1 and Robo4 in reactive astrocytes of the rat hippocampus after transient forebrain ischemia.

    PubMed

    Park, Joo-Hee; Pak, Ha-Jin; Riew, Tae-Ryong; Shin, Yoo-Jin; Lee, Mun-Yong

    2016-03-01

    Slit2 is a secreted glycoprotein that was originally identified as a chemorepulsive factor in the developing brain; however, it was recently reported that Slit2 is associated with adult neuronal function including a variety of pathophysiological processes. To elucidate whether Slit2 is implicated in the pathophysiology of ischemic injury, we investigated the temporal changes and cellular localization of Slit2 and its predominant receptors, Robo1 and Robo4, for 28 days after transient forebrain ischemia. Slit2 and its receptors had similar overall expression patterns in the control and ischemic hippocampi. The ligand and receptors were constitutively expressed in hippocampal neurons in control animals; however, in animals with ischemic injury, their upregulation was detected in reactive astrocytes, but not in neurons or activated microglia, in the CA1 region. Astroglial induction of Slit2 and its receptors occurred by day 3 after reperfusion, and appeared to increase progressively until the final time point on day 28. Their temporal expression patterns overlapped with the time period in which reactive astrocytes undergo dynamic structural changes and appear hypertrophic in the ischemic hippocampus. The immunohistochemical data were consistent with the results of the immunoblot analyses, indicating that the expression of Slit2 and Robo increased progressively over the relatively long period of 28 days examined here. Collectively, these results suggest that Slit2/Robo signaling may be involved in regulating the astroglial reaction via autocrine or paracrine mechanisms in post-ischemic processes. Moreover, this may contribute to the dynamic morphological changes that occur in astrocytes in response to ischemic injury.

  18. rhEPO affects apoptosis in hippocampus of aging rats by upregulating SIRT1

    PubMed Central

    Wu, Haiqin; Wang, Huqing; Zhang, Wenting; Wei, Xuanhui; Zhao, Jiaxin; Yan, Pu; Liu, Chao

    2015-01-01

    The aim of this study was to elucidate the signaling pathway involved in the anti-aging effect of erythropoietin (EPO) and to clarify whether recombinant human EPO (rhEPO) affects apoptosis in the aging rat hippocampus by upregulating Sirtuin 1 (SIRT1). In this study, a rat model of aging was established using D-galactose. Behavioral changes were monitored by the Morris water maze test. Using immunohistochemistry, we studied the expression of SIRT1, B-cell lymphoma/leukemia-2 gene (Bcl-2), and Bcl-2 associated X protein (Bax) expression, and apoptotic cells in the hippocampus of a rat model of aging in which rhEPO was intraperitoneally injected. The escape latency in rats from the EPO group shortened significantly; however, the number of platform passes increased significantly from that in the D-gal group (P < 0.05). Compared to the D-gal group, in the EPO group, the number of SIRT1 and Bcl-2-positive cells increased (P < 0.05), but the number of Bax-positive cells and apoptotic cells decreased in the hippocampus of aging rats (P < 0.05). These results suggest that rhEPO regulates apoptosis-related genes and affects apoptosis in the hippocampus of aging rats by upregulating SIRT. This may be one of the important pathways underlying the anti-aging property of EPO. PMID:26261574

  19. Enhanced dopamine D1 and D2 receptor gene expression in the hippocampus of hypoglycaemic and diabetic rats.

    PubMed

    Robinson, Remya; Krishnakumar, Amee; Paulose, C S

    2009-05-01

    Hypoglycaemic coma and brain injury are potential complications of insulin therapy. Hippocampal neurons are particularly vulnerable to hypoglycaemic stress leading to memory impairment. In the present article, we have investigated the dopamine (DA) content, homovanillic acid (HVA)/DA turnover ratio, DA D(1) and DA D(2) receptors in the hippocampus of insulin-induced hypoglycaemic (IIH) and streptozotocin induced diabetic rats where brain functions are impaired. The DA content decreased significantly in hippocampus of diabetic, diabetic +IIH and control +IIH rats compared to control. The HVA/DA turnover ratio also increased significantly in diabetic, diabetic +IIH and control +IIH rats compared to control. Scatchard analysis using [(3)H] DA in the hippocampus showed a significant increase in DA receptors of diabetic, diabetic +IIH and control +IIH rats with decreased affinity. Gene expression studies using Real-time PCR showed an increased expression of DA D(1) and DA D(2) receptors in the hippocampus of hypoglycaemic and diabetic rats. Our results indicate that the dopaminergic system is impaired in the hippocampus of hypoglycaemic and hyperglycaemic rats impairing DA related functions of hippocampus. We observed a prominent dopaminergic functional disturbance in the hypoglycaemic condition than in hyperglycaemia compared to control. This dopaminergic dysfunction in hippocampus during hypoglycaemia and hyperglycaemia is suggested to contribute to cognitive and memory deficits. This will have clinical significance in the treatment of diabetes.

  20. 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.

  1. The amyloid-beta25-35 injection into the CA1 region of the neonatal rat hippocampus impairs the long-term memory because of an increase of nitric oxide.

    PubMed

    Díaz, Alfonso; De Jesús, Luis; Mendieta, Liliana; Calvillo, Minerva; Espinosa, Blanca; Zenteno, Edgar; Guevara, Jorge; Limón, Ilhuicamina Daniel

    2010-01-04

    Alzheimer's disease (AD) is characterized by the amyloid-beta (Abeta) aggregation but it is unclear when this process begins. Previously, we showed that amyloid-beta(25-35) (Abeta(25-35)) increases the nitric oxide (NO) pathways and causes neurodegenerative effects in rats. The excessive increase of NO during brain development can promote a persistent oxidative stress, but the role of the Abeta(25-35) in the neonatal age and its effects over the long term is unclear. Our aim was to evaluate if the Abeta(25-35) injection on postnatal day 7 causes loss in spatial memory by NO pathways in adult rats. Our results showed that neonatal-Abeta(25-35) injection into the hippocampus (Hp) causes significant impairments in the spatial memory after 90 days. The NO levels were found increased and argynophilic in the Hp. Other evidence of neuronal damage was an increase of the immunoreactivity for 3-nitrotyrosine (3-NT) and the glial-fibrilar acid protein (GFAP) in the Hp of the Abeta(25-35) group. In contrast, these effects were blocked by the administration of L-NAME (inhibitor of nitric oxide synthase) before the injection of Abeta(25-35). The L-NAME plus Abeta(25-35) group showed a better performance in the spatial memory compared to the Abeta(25-35) group. In addition in this group we found a decrease of NO, 3-NT and neurodegeneration in the Hp compared to the Abeta(25-35) group. This finding is a novel result about the role of Abeta(25-35) during the neonatal stage that enhances the NO production, which appears to impair the spatial memory in adult rats.

  2. Effects of cadmium on Bcl-2/ Bax expression ratio in rat cortex brain and hippocampus.

    PubMed

    Mahdavi, S; Khodarahmi, P; Roodbari, N H

    2017-01-01

    To investigate the underlying mechanism of neurotoxicity of cadmium, we examined the effects of intraperitoneal injection of cadmium on messenger RNA (mRNA) expression of Bcl-2 (B-cell lymphoma 2) and Bax (Bcl2-associated x) genes and caspase-3/7 activation in rat hippocampus and frontal cortex. Twenty-eight male Wistar rats weighing 200-250 g were randomly divided into four groups. Control group received saline and three other groups received cadmium at doses of 1, 2 and 4 mg/kg (body weight) for 15 successive days. One day after the last injection, the hippocampus and frontal cortex were dissected and removed and then the expression of Bcl-2 and Bax genes was evaluated using real-time polymerase chain reaction and apoptotic studies was done using caspase-3/7 activation assay. Cadmium reduced the mRNA level of Bcl-2 in the control group at doses of 1 ( p < 0.01), 2 and 4 mg/kg ( p < 0.001) in rat hippocampus and cortex cells. The mRNA level of Bax increased significantly compared to the control group at the doses of 1 ( p < 0.05), 2 and 4 mg/kg ( p < 0.001) in rat hippocampus. The mRNA level of Bax was increased significantly compared to the control group at the doses of 2 and 4 mg/kg ( p < 0.001) in rat cortex cells. Cadmium increased caspase-3/7 activity at doses of 1, 2 and 4 mg/kg in rat hippocampus. Caspase-3/7 activity was increased significantly at dose of 4 mg/kg in rat cortex. This decreased Bcl-2/Bax mRNA ratio induces cell apoptosis. Apoptotic effect of cadmium may be through the mitochondrial pathway by the activation of caspase-3/7.

  3. Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment.

    PubMed

    Bianchi, Enrica; Di Cesare Mannelli, Lorenzo; Micheli, Laura; Farzad, Mersedez; Aglianò, Margherita; Ghelardini, Carla

    2017-01-01

    Aspects of memory involved in cognitive mechanisms were investigated in rat after oxaliplatin (OX) chemotherapy using animal behavioural assessment of passive avoidance and social learning paradigms, which are both hippocampus-sensitive. Rodents, previously subjected to 2-week OX treatment, showed passive avoidance and social learning impairment and apoptotic processes in the hippocampus. Apoptosis rate significantly increased in cultured hippocampal cells exposed to OX at increasing doses, and this effect was dose-dependent. Ex vivo experiments showed that cell damage and apoptosis were blocked in the hippocampus from OX rats cotreated with copper sulphate (CS) which precludes OX transport inside the cell. In vivo, passive avoidance and social learning impairment could not be observed in OX rats co-administered with CS. Thus, a site of action of OX treatment on memory impairment appears to be located at the hippocampus. These findings strongly support that cellular damage induced by OX in rodent hippocampus underlies the weakening of some memory functions. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  4. Maternal caffeine intake affects acetylcholinesterase in hippocampus of neonate rats.

    PubMed

    da Silva, Rosane Souza; Richetti, Stefânia Konrad; da Silveira, Vanessa Gass; Battastini, Ana Maria Oliveira; Bogo, Mauricio Reis; Lara, Diogo R; Bonan, Carla Denise

    2008-01-01

    Transcriptional factors and signalling molecules from intracellular metabolism modulate a complex set of events during brain development. Neurotransmitter and neuromodulator synthesis and their receptor expressions vary according to different stages of brain development. The dynamics of signalling systems is often accompanied by alterations in enzyme expression and activity. Adenosine is a neuromodulator that controls the release of several neurotransmitters, including acetylcholine, which is an important neurotransmitter during brain development. Caffeine is a non-specific antagonist of adenosine receptors and can reach the immature brain. We evaluated the effects of rat maternal caffeine intake (1g/L) on acetylcholine degradation and acetylcholinesterase expression from hippocampus of 7-, 14- and 21-day-old neonates in caffeine-treated and control groups. Caffeine was not able to change the age-dependent increase of acetylcholinesterase activity or the age-dependent decrease of acetylcholinesterase expression. However, caffeine promoted an increase of acetylcholinesterase activity (42%) without modifications on the level of acetylcholinesterase mRNA transcripts in 21-day-old rats. Considering the high score of phosphorylatable residues on acetylcholinesterase, this profile can be associated with a possible regulation by specific phosphorylation sites. These results highlight the ability of maternal caffeine intake to interfere on cholinergic neurotransmission during brain development.

  5. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25317156

  7. Development of Clock Genes Expression in Rat Hippocampus.

    PubMed

    Pramong, Ratchadaporn; Wongchitrat, Prapimpun; Govitrapong, Piyarat; Phansuwan-Pujito, Pansiri

    2015-10-01

    The circadian rhythms in the suprachiasmatic nucleus (SCN), a central clock, are generated by autoregulatory network composed ofclock genes that encode transcriptionalfactors. There is a gradual development ofclock gene expression in the SCN during ontogenesis. Moreover clock genes are expressed in the adult hippocampus with circadian fashion. It is of interest to examine daily profiles ofthe clock gene mRNA and protein expressions in rat hippocampus during development. Daily profiles ofthree clock genes (Per1, Per2, and Bmal1) mRNA, and their protein expressions were analyzed in the rat hippocampus ofpups at postnatal (P) day 4 and 8 (P4 and P8), pre-weaning stage (P16), early pubertal stage (P32), and adult (P60) by real-time PCR and immunohistochemistry. The entire studied clock gene mRNAs and proteins did not exhibit circadian rhythm in early postnatal P4-P16. Rhythmic expression of Per1 and Per2 mRNA started at P32, whereas Bmal1 began at adult. However, their proteins showed circadian expression together at adult. The present study suggests that rat hippocampal molecular clock works gradually develop after birth and slower than that in the central clock SCN. It was possible that ontogenetic development of clock gene in hippocampus was waitingfor central clocksynchronization.

  8. Extracellular acidic sulfur-containing amino acids and gamma-glutamyl peptides in global ischemia: postischemic recovery of neuronal activity is paralleled by a tetrodotoxin-sensitive increase in cysteine sulfinate in the CA1 of the rat hippocampus.

    PubMed

    Andiné, P; Orwar, O; Jacobson, I; Sandberg, M; Hagberg, H

    1991-07-01

    An excessive activation of the excitatory amino acid system has been proposed as one possible mediator of the ischemia-induced delayed death of CA1 pyramidal cells in the hippocampus. Using dialytrodes in the CA1 of the rat, we have investigated multiple-unit activity and extracellular changes in acidic sulfur-containing amino acids and gamma-glutamyl peptides during ischemia (20-min, four-vessel occlusion) and during 8 h of reflow. Multiple-unit activity was abolished during ischemia and for the following 1 h, but then recovered, gradually reaching preischemic levels after 8 h of reflow. Extracellular cysteate, cysteine sulfinate, and gamma-glutamyltaurine increased (1.5- to threefold) during ischemia, and extracellular glutathione and gamma-glutamylaspartate plus gamma-glutamylglutamine increased during early reflow (two- to threefold). The recovery of neuronal activity at 4-8 h was paralleled by an increase in extracellular cysteine sulfinate (2.5-fold at 8 h of reflow). Perfusion with 10 microM tetrodotoxin at 8 h of reflow abolished the multiple-unit activity and reduced extracellular cysteine sulfinate. Considering the glutamate-like properties of cysteine sulfinate, the observed postischemic increase may be involved in the development of the delayed neuronal death.

  9. Impairment of synaptic development in the hippocampus of diabetic Goto-Kakizaki rats.

    PubMed

    Matsunaga, Yuki; Negishi, Takayuki; Hatakeyama, Akinori; Kawagoe, Yuta; Sawano, Erika; Tashiro, Tomoko

    2016-10-01

    Insulin receptor signaling has been shown to regulate essential aspects of CNS function such as synaptic plasticity and neuronal survival. To elucidate its roles during CNS development in vivo, we examined the synaptic and cognitive development of the spontaneously diabetic Goto-Kakizaki (GK) rats in the present study. GK rats are non-obese models of type 2 diabetes established by selective inbreeding of Wistar rats based on impaired glucose tolerance. Though they start exhibiting only moderate hyperglycemia without changes in plasma insulin levels from 3 weeks postnatally, behavioral alterations in the open-field as well as significant impairments in memory retention compared with Wistar rats were observed at 10 weeks and were worsened at 20 weeks. Alterations in insulin receptor signaling and signs of insulin resistance were detected in the GK rat hippocampus at 3 weeks, as early as in other insulin-responsive peripheral tissues. Significant reduction of an excitatory postsynaptic scaffold protein, PSD95, was found at 5w and later in the hippocampus of GK rats due to the absence of a two-fold developmental increase of this protein observed in Wistar control rats between 3 and 20w. In the GK rat hippocampus, NR2A which is a NMDA receptor subunit selectively anchored to PSD95 was also reduced. In contrast, both NR2B and its anchoring protein, SAP102, showed similar developmental profiles in Wistar and GK rats with expression peaks at 2 and 3w. The results suggest that early alterations in insulin receptor signaling in the GK rat hippocampus may affect cognitive performance by suppressing synaptic maturation.

  10. Structural layers of ex vivo rat hippocampus at 7T MRI.

    PubMed

    Kamsu, Jeanine Manuella; Constans, Jean-Marc; Lamberton, Franck; Courtheoux, Patrick; Denise, Pierre; Philoxene, Bruno; Coquemont, Maelle; Besnard, Stephane

    2013-01-01

    Magnetic resonance imaging (MRI) applied to the hippocampus is challenging in studies of the neurophysiology of memory and the physiopathology of numerous diseases such as epilepsy, Alzheimer's disease, ischemia, and depression. The hippocampus is a well-delineated cerebral structure with a multi-layered organization. Imaging of hippocampus layers is limited to a few studies and requires high magnetic field and gradient strength. We performed one conventional MRI sequence on a 7T MRI in order to visualize and to delineate the multi-layered hippocampal structure ex vivo in rat brains. We optimized a volumic three-dimensional T2 Rapid Acquisition Relaxation Enhancement (RARE) sequence and quantified the volume of the hippocampus and one of its thinnest layers, the stratum granulare of the dentate gyrus. Additionally, we tested passive staining by gadolinium with the aim of decreasing the acquisition time and increasing image contrast. Using appropriated settings, six discrete layers were differentiated within the hippocampus in rats. In the hippocampus proper or Ammon's Horn (AH): the stratum oriens, the stratum pyramidale of, the stratum radiatum, and the stratum lacunosum moleculare of the CA1 were differentiated. In the dentate gyrus: the stratum moleculare and the stratum granulare layer were seen distinctly. Passive staining of one brain with gadolinium decreased the acquisition time by four and improved the differentiation between the layers. A conventional sequence optimized on a 7T MRI with a standard receiver surface coil will allow us to study structural layers (signal and volume) of hippocampus in various rat models of neuropathology (anxiety, epilepsia, neurodegeneration).

  11. 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.

  12. 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

  13. Systemic angiotensin II and exercise-induced neurogenesis in adult rat hippocampus.

    PubMed

    Mukuda, Takao; Koyama, Yuka; Hamasaki, Sawako; Kaidoh, Toshiyuki; Furukawa, Yasuo

    2014-11-07

    Physical exercise is a robust stimulus that enhances hippocampal neurogenesis via cell proliferation in rodents. We examined the role of systemic angiotensin (Ang) peptides in exercise-dependent enhancement of neurogenesis in the adult rat hippocampus. Plasma angiotensin peptide concentration increased rapidly in response to 30 min of treadmill exercise. After undertaking this exercise once daily for a week, the number of proliferating cells in the hippocampus, identified by 5-bromo-2'-deoxyuridine (BrdU) incorporation, had increased compared with controls. To mimic the increase in plasma Ang peptide concentrations brought about by exercise, rats were injected with 10(-5)M Ang II once daily for a week. The number of BrdU-incorporating cells and of doublecortin (DCX)-expressing immature neurons in the hippocampus rose approximately 1.5 and 1.9-fold compared with controls, respectively. The effects were completely abolished by an Ang II receptor subtype 1 antagonist losartan. These findings, taken together, suggest that an increased concentrations of Ang peptides in the systemic circulation during exercise may promote neurogenesis in the adult rat hippocampus. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Inflammation and increased IDO in hippocampus contribute to depression-like behavior induced by estrogen deficiency.

    PubMed

    Xu, Yongjun; Sheng, Hui; Tang, Zhiping; Lu, Jianqiang; Ni, Xin

    2015-07-15

    Estrogen deficiency is involved in the development of depression. However, the mechanism underlying estrogen modulates depression-like behavior remains largely unknown. Inflammation and indoleamine-2,3-dioxygenase (IDO) have been shown to play pivotal roles in various depression models. The objective of the present study was to investigate whether estrogen deficiency-induced depression-like behavior is associated with inflammation and IDO activation in brain. The results showed that ovariectomy resulted in depression-like behavior in female rats and caused a decrease in 5-HT content and an increase in levels of IDO, IFN-γ, IL-6, toll like receptor (TLR)-4 and phosphorylated NF-κB (p65 subunit) in hippocampus but not in prefrontal cortex (PFC). 17β-Estradiol (E2) treatment ameliorated depression-like behavior and restored above neurochemical alternations in hippocampus in ovariectomized rats. Partial correlation analysis showed that the levels of phosphorylated p65, IFN-γ and IL-6 in hippocampus correlated to serum E2 level. Our study suggests that estrogen inhibits inflammation and activates of IDO and maintains 5-HT level in hippocampus, thereby ameliorating depression-like behavior.

  15. [Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression].

    PubMed

    Wang, Tao; Qin, Feng

    2010-11-01

    To investigate the effects of Xiaoyao Powder, a compound traditional Chinese herbal medicine for treatment of depression, on monoamine neurotransmitters in hippocampus of rats with postpartum depression (PPD). Ovariectomized Sprague-Dawley rats were randomly divided into 4 groups: control group, untreated group, fluoxetine hydrochloride group and Xiaoyao Powder group. Except for the control group, the rats in the other 3 groups were injected subcutaneously with estrogen for 23 successive days to induce the "pregnancy" state. In the next 30 successive days, rats were given test drugs respectively and the concentrations of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). PPD was induced in rats of untreated group, and compared with rats of control group, the concentrations of NE, DA and 5-HT in the hippocampus significantly reduced (P<0.01), while the concentration of 5-HIAA significantly increased (P<0.01). Xiaoyao Powder treatment significantly improved the behavior indexes and levels of monoamine neurotransmitters in hippocampus (P<0.01). Xiaoyao Powder and fluoxetine hydrochloride produced similar effects in rats with PPD. Xiaoyao Powder produces an antidepression effect in rats by regulating the levels of monoamine neurotransmitters in hippocampus.

  16. Modulation of 5-HT release in the hippocampus of 30-day-old rats exposed in utero to protein malnutrition.

    PubMed

    Mokler, David J; Galler, Janina R; Morgane, Peter J

    2003-05-14

    Previous in vivo microdialysis studies have shown increased spontaneous release of 5-HT in the hippocampus of adult behaving rats exposed to prenatal protein malnutrition. Furthermore, behavioral studies have shown that adolescent rats (PD30) that have been prenatally protein malnourished demonstrate an increased sensitivity to the benzodiazepine chlordiazepoxide (CDP). Given this altered sensitivity to benzodiazepines in adolescent malnourished rats, the present study was designed to test the hypothesis that the increased release of 5-HT in the hippocampus is present in adolescent rats and that this release is modulated by CDP. An altered release of 5-HT at PD30 would suggest an early developmental change associated with prenatal malnutrition. PD30 rats were implanted with microdialysis probes into the dorsal hippocampus and 5-HT release was monitored before and after administration of CDP. As previously reported in adult rats, release of 5-HT was significantly elevated in the dorsal hippocampus of PD30 rats as compared to well-nourished 30-day-old controls. Administration of CDP did not affect the release of 5-HT from the hippocampal formation of well-nourished rats but significantly decreased the elevated release of 5-HT in the malnourished rats. Following CDP, 5-HT release in the malnourished rats was at the same levels as release in well-nourished animals. Benzodiazepines have been reported to decrease extracellular 5-HT in stressed rats but not in unstressed rats. Thus, the elevated 5-HT release in the hippocampus in rats exposed to prenatal protein malnutrition may be associated with an increased response to stress. These data support other data that prenatal protein malnutrition alters the response to stressful stimuli possibly through changes in the GABAergic and/or serotonergic systems.

  17. Localization and regulation of GLUTx1 glucose transporter in the hippocampus of streptozotocin diabetic rats

    PubMed Central

    Reagan, Lawrence P.; Gorovits, Naira; Hoskin, Elena K.; Alves, Stephen E.; Katz, Ellen B.; Grillo, Claudia A.; Piroli, Gerardo G.; McEwen, Bruce S.; Charron, Maureen J.

    2001-01-01

    We describe the localization of the recently identified glucose transporter GLUTx1 and the regulation of GLUTx1 in the hippocampus of diabetic and control rats. GLUTx1 mRNA and protein exhibit a unique distribution when compared with other glucose transporter isoforms expressed in the rat hippocampus. In particular, GLUTx1 mRNA was detected in hippocampal pyramidal neurons and granule neurons of the dentate gyrus as well as in nonprincipal neurons. With immunohistochemistry, GLUTx1 protein expression is limited to neuronal cell bodies and the most proximal dendrites, unlike GLUT3 expression that is observed throughout the neuropil. Immunoblot analysis of hippocampal membrane fractions revealed that GLUTx1 protein expression is primarily localized to the intracellular compartment and exhibits limited association with the plasma membrane. In streptozotocin diabetic rats compared with vehicle-treated controls, quantitative autoradiography showed increased GLUTx1 mRNA levels in pyramidal neurons and granule neurons; up-regulation of GLUTx1 mRNA also was found in nonprincipal cells, as shown by single-cell emulsion autoradiography. In contrast, diabetic and control rats expressed similar levels of hippocampal GLUTx1 protein. These results indicate that GLUTx1 mRNA and protein have a unique expression pattern in rat hippocampus and suggest that streptozotocin diabetes increases steady-state mRNA levels in the absence of concomitant increases in GLUTx1 protein expression. PMID:11226324

  18. Single sevoflurane exposure decreases neuronal nitric oxide synthase levels in the hippocampus of developing rats

    PubMed Central

    Feng, X.; Liu, J. J.; Zhou, X.; Song, F. H.; Yang, X. Y.; Chen, X. S.; Huang, W. Q.; Zhou, L. H.; Ye, J. H.

    2012-01-01

    Background The use of general anaesthetics in young children and infants has raised concerns regarding the adverse effects of these drugs on brain development. Sevoflurane might have harmful effects on the developing brain; however, these effects have not been well investigated. Methods Postnatal day 7 (P7) Sprague–Dawley rats were continuously exposed to 2.3% sevoflurane for 6 h. We used the Fox battery test and Morris water maze (MWM) to examine subsequent neurobehavioural performance. Cleaved caspase-3 and neuronal nitric oxide synthase (nNOS) were quantified by immunoblotting, and the Nissl staining was used to observe the histopathological changes in the hippocampus. Results A single 6 h sevoflurane exposure at P7 rats resulted in increased cleaved caspase-3 expression and decreased nNOS levels in the hippocampus, and induced the loss of pyramidal neurones in the CA1 and CA3 subfields of the hippocampus at P7–8. These changes were accompanied by temporal retardation of sensorimotor reflexes. However, neither the Fox battery test at P1–21 nor the MWM test at P28–32 showed differences between the air- and sevoflurane-treated groups. Conclusions Although early exposure to sevoflurane increases activated caspase-3 expression and neuronal loss and decreases nNOS in the neonatal hippocampus, it does not affect subsequent neurobehavioural performances in juvenile rats. PMID:22535834

  19. The hippocampus in spontaneously hypertensive rats: an animal model of vascular dementia?

    PubMed

    Sabbatini, Maurizio; Catalani, Assia; Consoli, Claudia; Marletta, Nunzio; Tomassoni, Daniele; Avola, Roberto

    2002-03-15

    Hypertension is a main risk factor for cerebrovascular disease, including vascular dementia. The present study was designed to evaluate if hypertension-dependent changes of the hippocampus of spontaneously hypertensive rats (SHR) of different ages were related with those occurring in vascular dementia. The hippocampus was chosen as the brain area involved in learning and memory. Systolic pressure was slightly increased in 2-month-old SHR in comparison with age-matched normotensive Wistar-Kyoto (WKY) rats and augmented progressively with age in SHR. No microanatomical changes were observed in the hippocampus of SHR of 2 months in comparison with age-matched WKY rats. A limited decrease of white matter volume was observed in 4-month-old SHR. In SHR of 6 months, a reduction of grey matter volume both in the CA1 subfield and in the dentate gyrus occurred. Evaluation of phosphorylated 200-kDa neurofilament immunoreactivity revealed a decreased immune reaction area in the CA1 subfield of 6-month-old SHR compared to age-matched WKY rats and no changes in the expression and localization of the dendritic marker microtubule associated protein (MAP)-2. In 6-month-old SHR, an increase of glial fibrillary acidic protein (GFAP)-expression was found by Western blot analysis. Immunohistochemistry revealed an increase in number (hyperplasia), but not in size of astrocytes. These findings indicate the occurrence of cytoskeletal breakdown and astroglial changes primarily in the CA1 subfield of the hippocampus of SHR of 6 months. The occurrence in the hippocampus of SHR of regressive changes and astroglial reaction similar to those occurring in neurodegenerative disorders with cognitive impairment suggests that they represent an animal model of vascular dementia.

  20. Acute administration of l-tyrosine alters energetic metabolism of hippocampus and striatum of infant rats.

    PubMed

    Ramos, Andrea C; Ferreira, Gabriela K; Carvalho-Silva, Milena; Furlanetto, Camila B; Gonçalves, Cinara L; Ferreira, Gustavo C; Schuck, Patrícia F; Streck, Emilio L

    2013-08-01

    Tyrosinemia type II is an inborn error of metabolism caused by mutations in the gene that encodes tyrosine aminotransferase, which leads to increased blood tyrosine levels. Considering that tyrosine levels are highly elevated in fluids of patients with tyrosinemia type II, and that previous studies demonstrated significant alterations in brain energy metabolism of young rats caused by l-tyrosine, the present study aimed to evaluate the effect of acute administration of l-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase, and mitochondrial respiratory chain complexes I, II, II-III, and IV in posterior cortex, hippocampus, and striatum of infant rats. Wistar rats (10 days old) were killed 1h after a single intraperitoneal injection of tyrosine (500 mg/kg) or saline. The activities of energy metabolism enzymes were evaluated in brain of rats. Our results demonstrated that acute administration of l-tyrosine inhibited the activity of citrate synthase activity in striatum and increased the activities of malate dehydrogenase and succinate dehydrogenase in hippocampus. On the other hand, these enzymes were not affected in posterior cortex. The activities of complex I and complex II were inhibited by acute administration of l-tyrosine in striatum. On the other hand, the acute administration of l-tyrosine increased the activity of activity of complex II-III in hippocampus. Complex IV was not affected by acute administration of l-tyrosine in infant rats. Our results indicate an alteration in the energy metabolism in hippocampus and striatum of infant rats after acute administration of l-tyrosine. If the same effects occur in the brain of the patients, it is possible that energy metabolism impairment may be contribute to possible damage in memory and cognitive processes in patients with tyrosinemia type II. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  1. 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.

  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. Berberine ameliorate oxidative stress and astrogliosis in the hippocampus of STZ-induced diabetic rats.

    PubMed

    Moghaddam, Hamid Kalalian; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Khaksari, Mehdi; Norouzi, Pirasteh; Ahooie, Malihea; Mahboobi, Fatemeh

    2014-04-01

    Diabetes mellitus increases the risk of central nervous system (CNS) disorders such as stroke, seizures, dementia, and cognitive impairment. Berberine, a natural isoquinoline alkaloid, is reported to exhibit beneficial effect in various neurodegenerative and neuropsychiatric disorders. Moreover, astrocytes are proving critical for normal CNS function, and alterations in their activity and impaired oxidative stress could contribute to diabetes-related cognitive dysfunction. Metabolic and oxidative insults often cause rapid changes in glial cells. Key indicators of this response are increased synthesis of glial fibrillary acidic protein (GFAP) as an astrocytic marker. Therefore, we examined the effects of berberine on glial reactivity of hippocampus in streptozotocin (STZ)-induced diabetic rats, using GFAP immunohistochemistry. Lipid peroxidation, superoxide dismutase (SOD) activity, and nitrite levels were assessed as the parameters of oxidative stress. Eight weeks after diabetes induction, we observed increased numbers of GFAP(+) astrocytes immunostaining associated with increased lipid peroxidation, decreased superoxide dismutase activity, and elevated nitrite levels in the hippocampus of STZ-diabetic rats. In contrast, chronic treatment with berberine (50 and 100 mg/kg p.o. once daily) lowered hyperglycemia, reduced oxidative stress, and prevented the upregulation of GFAP in the brain of diabetic rats. In conclusion, the present study demonstrated that the treatment with berberine resulted in an obvious reduction of oxidative stress and GFAP-immunoreactive astrocytes in the hippocampus of STZ-induced diabetic rats.

  4. Effects of vasopressin and related peptides on neurons of the rat lateral septum and ventral hippocampus.

    PubMed

    Urban, I J

    1998-01-01

    The effects of vasopressin (VP), VP fragments and propressophysin glycopeptide on neuronal activities in the septum-hippocampus complex of rats were studied in vitro and in vivo. The frequency of the hippocampus theta rhythm in Brattleboro rats homozygous for diabetes insipidus was significantly slower than that of heterozygous litter mates and normal rats. Intracerebroventricular micro-injection of des-glycine-amide vasopressin corrected for several hours the frequency deficit of the theta rhythm in the homozygous Brattleboro rats and the centrally administered VP slowed down theta rhythm in normal rats. Microinotophoretically administered VP excited single neurons in the lateral septum of ventral hippocampus, and/or facilitated the responses of these neurons to glutamate and to stimulation of the glutamatergic afferent fibers in the fimbria bundle. The excitatory effects of VP vanished within seconds after termination of the peptide administration, however, the peptide-induced enhancement of glutamate and syntatically induced excitations were sustained for up to 60 min after the peptide administration. In vitro, pM concentrations of VP, VP 4-8 and C-terminus glycopeptide of propresophysin facilitated for 30-60 min the glutamate-mediated EPSPs in neurons of the lateral septum or the ventral hippocampus. The EPSPs increase in the lateral septum neurons was not prevented by pretreatment with antagonist of the V1a type of the vasopressin receptor. The resting membrane potential and input resistance were not affected by the peptides. A low-frequency electrical stimulation in the diagonal Band of Broca or in the Bed nucleus of the stria terminals, sources of the vasopressinergic innervation of the septum, facilitated the negative wave of the filed potentials responses evoked in the lateral septum by stimulating the fimbria bundle fibers in control Long-Evans and Brattleboro rats heterozygous for diabetes insipidus. The field potential increase was sustained for several

  5. The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus

    PubMed Central

    Bagheri-abassi, Farzaneh; Alavi, Hassan; Mohammadipour, Abbas; Motejaded, Fatemeh; Ebrahimzadeh-bideskan, Alireza

    2015-01-01

    Objective(s): Silver nanoparticles (Ag-NPs) are used widely in bedding, water purification, tooth paste and toys. These nanoparticles can enter into the body and move into the hippocampus. The aim of this study was to investigate the neurotoxicity of silver nanoparticles in the adult rat hippocampus. Materials and Methods: 12 male Wistar rats were randomly divided into two experimental and control groups (6 rats in each group). Animals in the experimental group received Ag-NPs (30 mg/kg) orally (gavage) for 28 consecutive days. Control group in the same period was treated with distilled water via gavage. At the end of experiment, animals were deeply anesthetized, sacrificed, and their brains were collected from each group. Finally the brain sections were stained using toluidine blue and TUNEL. Then to compare the groups, dark neurons (DNs) and apoptotic neurons were counted by morphometric method. Results: Results showed that the numbers of DNs and apoptotic cells in the CA1, CA2, CA3, and dentate gyrus (DG) of hippocampus significantly increased in the Ag-NPs group in comparison to the control group (P<0.05). Conclusion: Exposure to Ag-NPs can induce dark neuron and apoptotic cells in the hippocampus. PMID:26351553

  6. Proteomic Analysis of Rat Hippocampus under Simulated Microgravity

    NASA Astrophysics Data System (ADS)

    Wang, Yun; Li, Yujuan; Zhang, Yongqian; Liu, Yahui; Deng, Yulin

    It has been found that microgravity may lead to impairments in cognitive functions performed by CNS. However, the exact mechanism of effects of microgravity on the learning and memory function in animal nervous system is not elucidated yet. Brain function is mainly mediated by membrane proteins and their dysfunction causes degeneration of the learning and memory. To induce simulated microgravity, the rat tail suspension model was established. Comparative O (18) labeling quantitative proteomic strategy was applied to detect the differentially expressed proteins in rat brain hippocampus. The proteins in membrane fraction from rat hippocampus were digested by trypsin and then the peptides were separated by off-gel for the first dimension with 24 wells device encompassing the pH range of 3 - 10. An off-gel fraction was subjected into LC-ESI-QTOF in triplicate. Preliminary results showed that nearly 77% of the peptides identified were specific to one fraction. 676 proteins were identified among which 108 proteins were found differentially expressed under simulated microgravity. Using the KOBAS server, many enriched pathways, such as metabolic pathway, synaptic vesicle cycle, endocytosis, calcium signaling pathway, and SNAREs pathway were identified. Furthermore, it has been found that neurotransmitter released by Ca (2+) -triggered synaptic vesicles fusion may play key role in neural function. Rab 3A might inhibit the membrane fusion and neurotransmitter release. The protein alteration of the synaptic vesicle cycle may further explain the effects of microgravity on learning and memory function in rats. Key words: Microgravity; proteomics; synaptic vesicle; O (18) ({}) -labeling

  7. Changes in labeling of soluble and solubilized hippocampus proteins after a learning experiment in rats.

    PubMed

    Popov, N; Schulzeck, S; Matthies, H

    1976-01-01

    At various intervals after acquisition of a brightness discrimination in rats labeled leucine was intraventricularly applied. Hippocampus tissue was fractionated in soluble and solubilized insoluble protein fractions. Protein content and labeling of several electrophoretically resolved bands showed a biphasic time course: a first increase was observed 20 minutes after training including preferably soluble proteins, whereas a second increase (about eight hours after training) was mainly related to solubilized insoluble proteins.

  8. Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus

    PubMed Central

    Dale, Elena; Zhang, Hong; Leiser, Steven C; Xiao, Yixin; Lu, Dunguo; Yang, Charles R; Plath, Niels; Sanchez, Connie

    2014-01-01

    Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5-HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor. Vortioxetine has been shown to improve cognitive performance in several preclinical rat models and in patients with major depressive disorder. Here we investigated the mechanistic basis for these effects by studying the effect of vortioxetine on synaptic transmission, long-term potentiation (LTP), a cellular correlate of learning and memory, and theta oscillations in the rat hippocampus and frontal cortex. Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post-synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism. Vortioxetine also enhanced LTP in the CA1 region of the hippocampus. Finally, vortioxetine increased fronto-cortical theta power during active wake in whole animal electroencephalographic recordings. In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures. Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus. Given the central role of the hippocampus in cognition, these findings may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortioxetine. PMID:25122043

  9. Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus.

    PubMed

    Dale, Elena; Zhang, Hong; Leiser, Steven C; Xiao, Yixin; Lu, Dunguo; Yang, Charles R; Plath, Niels; Sanchez, Connie

    2014-10-01

    Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5-HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor. Vortioxetine has been shown to improve cognitive performance in several preclinical rat models and in patients with major depressive disorder. Here we investigated the mechanistic basis for these effects by studying the effect of vortioxetine on synaptic transmission, long-term potentiation (LTP), a cellular correlate of learning and memory, and theta oscillations in the rat hippocampus and frontal cortex. Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post-synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism. Vortioxetine also enhanced LTP in the CA1 region of the hippocampus. Finally, vortioxetine increased fronto-cortical theta power during active wake in whole animal electroencephalographic recordings. In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures. Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus. Given the central role of the hippocampus in cognition, these findings may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortioxetine. © The Author(s) 2014.

  10. Protective role of quercetin on PCBs-induced oxidative stress and apoptosis in hippocampus of adult rats.

    PubMed

    Selvakumar, Kandaswamy; Bavithra, Senthamilselvan; Suganthi, Muralidharan; Benson, Chellakan Selvanesan; Elumalai, Perumal; Arunkumar, Ramachandran; Krishnamoorthy, Gunasekaran; Venkataraman, Prabhu; Arunakaran, Jagadeesan

    2012-04-01

    Polychlorinated biphenyls (PCBs) exposure produces neurodegeneration and induces oxidative stress. Neuroprotective role of quercetin, on PCBs induced apoptosis in hippocampus has not yet been studied. The present study is focused to see whether quercetin supplementation precludes against PCBs induced oxidative stress and hippocampal apoptosis. The results have shown that quercetin at 50 mg/kg bwt/30 days has protected oxidative stress in hippocampus of adult male rats. Quercetin, a free radical scavenger decreased the levels of oxidative stress markers in the hippocampus of simultaneous PCB+quercetin treated rats. The pro-apoptotic and anti-apoptotic molecules such as Bad, Bid, Bax and Bcl2 were altered in the hippocampus of experimental animals. PCBs increased the DNA damage and induced neurodegeneration were assessed by histological studies. PCB induced ROS may be linked to increased hippocampal neuronal apoptosis. Quercetin supplementation decreased the neuronal damage and scavenged the free radicals induced by PCBs and protects PCBs induced apoptosis and oxidative stress.

  11. Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats.

    PubMed

    Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

    2016-04-21

    Methylphenidate (MPH) is a central stimulant, prescribed for the treatment of attention deficit/hyperactivity disorder. The long-term behavioral consequences of MPH treatment are unknown. In this study, the oxidative stress and neuroinflammation induced by various doses of MPH were investigated. Forty adult male rats were divided into 5 groups; and treated with different doses of MPH for 21 days. Twenty four hours after drug treatment, Open Field Test (OFT) was performed in all animals. At the end of the study, blood cortisol level (BCL) was measured and hippocampus was isolated and oxidative stress and inflammation parameters and histological changes were analyzed. Chronic MPH at all doses decreased central square entries, number of rearing, ambulation distance and time spent in central square in OFT. BCL increased in doses 10 and 20mg/kg of MPH. Furthermore, MPH in all doses markedly increased lipid peroxidation, mitochondrial oxidized glutathione (GSSG) level, Interleukin 1β (IL-1β) and Tumor Necrosis Factor α (TNF-α) in isolated hippocampus. MPH (10 and 20mg/kg) treated groups had decreased mitochondrial reduced glutathione (GSH) content, and reduced superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) activities. 10 and 20mg/kg of MPH change cell density and morphology of cells in Dentate Gyrus (DG) and CA1 areas of hippocampus. Chronic treatment with high doses of MPH can cause oxidative stress, neuroinflammation and neurodegeneration in hippocampus of adult rats.

  12. Upregulation of 5-HT2C receptors in hippocampus of pilocarpine-induced epileptic rats: antagonism by Bacopa monnieri.

    PubMed

    Krishnakumar, Amee; Nandhu, M S; Paulose, C S

    2009-10-01

    Emotional disturbances, depressive mood, anxiety, aggressive behavior, and memory impairment are the common psychiatric features associated with temporal lobe epilepsy (TLE). The present study was carried out to investigate the role of Bacopa monnieri extract in hippocampus of pilocarpine-induced temporal lobe epileptic rats through the 5-HT(2C) receptor in relation to depression. Our results showed upregulation of 5-HT(2C) receptors with a decreased affinity in hippocampus of pilocarpine-induced epileptic rats. Also, there was an increase in 5-HT(2C) gene expression and inositol triphosphate content in epileptic hippocampus. Carbamazepine and B. monnieri treatments reversed the alterations in 5-HT(2C) receptor binding, gene expression, and inositol triphosphate content in treated epileptic rats as compared to untreated epileptic rats. The forced swim test confirmed the depressive behavior pattern during epilepsy that was nearly completely reversed by B. monnieri treatment.

  13. The hippocampus and flexible spatial knowledge in rats.

    PubMed

    Ramos, J M; Vaquero, J M

    2000-12-01

    Lesions to the hippocampal system in rats result in a profound impairment of place or locale spatial learning although other learning strategies remain unaltered. The main objective of the present study was to investigate whether the spatial knowledge preserved in the hippocampal animals can be expressed flexibly under conditions different from those of the acquisition period. Rats with neurotoxic lesions to the dorsal hippocampus and sham-operated subjects were trained to reach the goal arm in a four-arm plus-shaped maze using a constant starting arm. During the training a transparent plexiglas barrier divided the maze in two equal halves in such a way that the animals could only travel from the starting arm to the goal arm, not having access to the remaining 50% of the maze. After seven days of training, a transfer test was used in which the starting arms were the two arms from which the animals had not started during the training phase. Results indicated that the lesioned rats made significantly more errors than the control subjects. But the most interesting results revealed that the kind of error made by the lesioned animals was congruent with the turn that they had to make during the acquisition phase in order to access the goal arm (reinforced). These results suggest that when the hippocampus is damaged a preserved highly inflexible egocentric strategy is employed to solve the spatial problem.

  14. COGNITIVE IMPAIRMENT AND MORPHOLOGICAL CHANGES IN THE DORSAL HIPPOCAMPUS OF VERY OLD FEMALE RATS

    PubMed Central

    Morel, Gustavo R.; Andersen, Tomás; Pardo, Joaquín; Zuccolilli, Gustavo O.; Cambiaggi, Vanina L.; Hereñú, Claudia B.; Goya, Rodolfo G.

    2015-01-01

    The hippocampus, a medial temporal lobe structure necessary for the formation of spatial memory, is particularly affected by both normal and pathologic aging. In previous studies, we observed a significant age-related increase in dopaminergic neuron loss in the hypothalamus and the substantia nigra of female rats, which becomes more conspicuous at extreme ages. Here, we extend our studies by assessing spatial memory 4–6 months old (young), 26 months old (old) and 29–32 months old (senile) Sprague–Dawley female rats as well as the age-related histopathological changes in their dorsal hippocampus. Age changes in spatial memory performance were assessed with a modified version of the Barnes maze test. We employed two probe trials (PT), one and five days after training, respectively, in order to evaluate learning ability as well as short-term and longer-term spatial memory retention. A set of relevant hippocampal cell markers was also quantitated in the animals by means of an unbiased stereological approach. The results revealed that old rats perform better than senile rats in acquisition trials and young rats perform better than both aging groups. However, during short-term PT both aging groups showed a preserved spatial memory while in longer-term PT, spatial memory showed deterioration in both aged groups. Morphological analysis showed a marked decrease (94–97%) in doublecortin neuron number in the dentate gyrus in both aged groups and a reduction in glial fibrillary acidic protein-positive cell number in the stratum radiatum of aging rats. Astroglial process length and branching complexity decreased in the aged rats. We conclude that while target-seeking activity and learning ability decrease in aged females, spatial memory only declines in the longer-term tests. The reduction in neuroblast number and astroglial arborescence complexity in the dorsal hippocampus are likely to play a role in the cognitive deficits of aging rats. PMID:26141841

  15. Exercise training increases size of hippocampus and improves memory.

    PubMed

    Erickson, Kirk I; Voss, Michelle W; Prakash, Ruchika Shaurya; Basak, Chandramallika; Szabo, Amanda; Chaddock, Laura; Kim, Jennifer S; Heo, Susie; Alves, Heloisa; White, Siobhan M; Wojcicki, Thomas R; Mailey, Emily; Vieira, Victoria J; Martin, Stephen A; Pence, Brandt D; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F

    2011-02-15

    The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.

  16. Influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats.

    PubMed

    Kim, Hong; Lee, Myoung-Hwa; Chang, Hyun-Kyung; Lee, Taeck-Hyun; Lee, Hee-Hyuk; Shin, Min-Chul; Shin, Mal-Soon; Won, Ran; Shin, Hye-Sook; Kim, Chang-Ju

    2006-03-01

    During the prenatal period, the development of individual is influenced by the environmental factors. In the present study, the influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats was investigated. The exposure to the noise during pregnancy caused growth retardation, decreased neurogenesis in the hippocampus, and impaired spatial learning ability in pups. The exposure to music during pregnancy, on the other hand, caused increased neurogenesis in the hippocampus and enhanced spatial learning ability in pups. The present study has shown the importance of the prenatal environmental conditions for the cognition and brain development.

  17. 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

  18. 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.

  19. 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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia.

    PubMed

    Wu, Lin; Feng, Xiao-Tao; Hu, Yue-Qiang; Tang, Nong; Zhao, Qing-Shan; Li, Tian-Wei; Li, Hai-Yuan; Wang, Qing-Bi; Bi, Xin-Ya; Cai, Xin-Kun

    2015-09-01

    Vascular dementia (VD) has been one of the most serious public health problems worldwide. It is well known that cerebral hypoperfusion is the key pathophysiological basis of VD, but it remains unclear how global genes in hippocampus respond to cerebral ischemia-reperfusion. In this study, we aimed to reveal the global gene expression profile in the hippocampus of VD using a rat model. VD was induced by repeated occlusion of common carotid arteries followed by reperfusion. The rats with VD were characterized by deficit of memory and cognitive function and by the histopathological changes in the hippocampus, such as a reduction in the number and the size of neurons accompanied by an increase in intercellular space. Microarray analysis of global genes displayed up-regulation of 7 probesets with genes with fold change more than 1.5 (P < 0.05) and down-regulation of 13 probesets with genes with fold change less than 0.667 (P < 0.05) in the hippocampus. Gene Ontology (GO) and pathway analysis showed that the up-regulated genes are mainly involved in oxygen binding and transport, autoimmune response and inflammation, and that the down-regulated genes are related to glucose metabolism, autoimmune response and inflammation, and other biological process, related to memory and cognitive function. Thus, the abnormally expressed genes are closely related to oxygen transport, glucose metabolism, and autoimmune response. The current findings display global gene expression profile of the hippocampus in a rat model of VD, providing new insights into the molecular pathogenesis of VD.

  1. Antidepressants modulate glycine action in rat hippocampus

    PubMed Central

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju

    2015-01-01

    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, were studied. In the present results, fluoxetine, tianeptine, and milnacipran reduced glycine-induced ion current in the hippocampal CA1 neurons in nystatin-perforated patch clamp method. These drugs enhanced the amplitude of the field potential in the hippocampal CA1 region in MED64 system. These results suggest that antidepressants may increase neuronal activity by enhancing field potential through inhibition on glycine-induced ion current. PMID:26730381

  2. Antidepressants modulate glycine action in rat hippocampus.

    PubMed

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju

    2015-12-01

    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, were studied. In the present results, fluoxetine, tianeptine, and milnacipran reduced glycine-induced ion current in the hippocampal CA1 neurons in nystatin-perforated patch clamp method. These drugs enhanced the amplitude of the field potential in the hippocampal CA1 region in MED64 system. These results suggest that antidepressants may increase neuronal activity by enhancing field potential through inhibition on glycine-induced ion current.

  3. The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats.

    PubMed

    Abbasnezhad, Abbasali; Hayatdavoudi, Parichehr; Niazmand, Saeed; Mahmoudabady, Maryam

    2015-01-01

    Oxidative stress plays an important role in the etiology of diabetic complications. Diabetes impairs hippocampus neurogenesis, synaptic plasticity, and learning. The aim of this study was to investigate the effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in STZ-induced diabetic rats' hippocampus. Diabetes induced by 60 mg/kg STZ, i.p, and the rats were divided into five experimental groups (n=8-10 in each group) including control (received 0.5 ml normal saline), untreated STZ-diabetic (received 0.5 ml normal saline), and treated rats received Nigella sativa extract (200 and 400 mg/kg) or metformin (300 mg/kg) by gavage for 42 days. Serum glucose concentration and body weight as well as hippocampus tissue malondialdehyde and thiol levels were determined by calorimetric assay. Serum glucose level in the diabetic rats treated with 200 mg/kg Nigella sativa extract at the days 24 and 45 decreased in comparison to untreated diabetic group (p<0.05, p<0.01, respectively). Weight loss was significantly different between metformin and Nigella sativa extract at the dose of 200 and 400 mg/kg (p<0.05). Thiol content of hippocampus increased by 200 mg/kg Nigella sativa extract in comparison to untreated diabetic group (p<0.05). Malondialdehyde content of hippocampus reduced by Nigella sativa extract, 200 mg/kg (p<0.001), 400 mg/kg (p<0.05), and metformin (p<0.05) in comparison to the untreated diabetic group. The results of the present study showed that hydroalcoholic extract of the Nigella sativa decreased oxidative stress in hippocampus of the STZ-induced diabetic rats. Nigella sativa at the dose of 200 mg/kg was more effective to reduce oxidative stress in hippocampus of rats.

  4. The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats

    PubMed Central

    Abbasnezhad, Abbasali; Hayatdavoudi, Parichehr; Niazmand, Saeed; Mahmoudabady, Maryam

    2015-01-01

    Objective: Oxidative stress plays an important role in the etiology of diabetic complications. Diabetes impairs hippocampus neurogenesis, synaptic plasticity, and learning. The aim of this study was to investigate the effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in STZ-induced diabetic rats' hippocampus. Materials and Methods: Diabetes induced by 60 mg/kg STZ, i.p, and the rats were divided into five experimental groups (n=8-10 in each group) including control (received 0.5 ml normal saline), untreated STZ-diabetic (received 0.5 ml normal saline), and treated rats received Nigella sativa extract (200 and 400 mg/kg) or metformin (300 mg/kg) by gavage for 42 days. Serum glucose concentration and body weight as well as hippocampus tissue malondialdehyde and thiol levels were determined by calorimetric assay. Results: Serum glucose level in the diabetic rats treated with 200 mg/kg Nigella sativa extract at the days 24 and 45 decreased in comparison to untreated diabetic group (p<0.05, p<0.01, respectively). Weight loss was significantly different between metformin and Nigella sativa extract at the dose of 200 and 400 mg/kg (p<0.05). Thiol content of hippocampus increased by 200 mg/kg Nigella sativa extract in comparison to untreated diabetic group (p<0.05). Malondialdehyde content of hippocampus reduced by Nigella sativa extract, 200 mg/kg (p<0.001), 400 mg/kg (p<0.05), and metformin (p<0.05) in comparison to the untreated diabetic group. Conclusion: The results of the present study showed that hydroalcoholic extract of the Nigella sativa decreased oxidative stress in hippocampus of the STZ-induced diabetic rats. Nigella sativa at the dose of 200 mg/kg was more effective to reduce oxidative stress in hippocampus of rats. PMID:26445713

  5. Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats.

    PubMed

    Duarte, João M N; Carvalho, Rui A; Cunha, Rodrigo A; Gruetter, Rolf

    2009-10-01

    Type 1 diabetes can affect hippocampal function triggering cognitive impairment through unknown mechanisms. Caffeine consumption prevents hippocampal degeneration and memory dysfunction upon different insults and is also known to affect peripheral glucose metabolism. Thus we now characterized glucose transport and the neurochemical profile in the hippocampus of streptozotocin-induced diabetic rats using in vivo(1)H NMR spectroscopy and tested the effect of caffeine consumption thereupon. We found that hippocampal glucose content and transport were unaltered in diabetic rats, irrespective of caffeine consumption. However diabetic rats displayed alterations in their hippocampal neurochemical profile, which were normalized upon restoration of normoglycaemia, with the exception of myo-inositol that remained increased (36 +/- 5%, p < 0.01 compared to controls) likely reflecting osmolarity deregulation. Compared to controls, caffeine-consuming diabetic rats displayed increased hippocampal levels of myo-inositol (15 +/- 5%, p < 0.05) and taurine (23 +/- 4%, p < 0.01), supporting the ability of caffeine to control osmoregulation. Compared to controls, the hippocampus of diabetic rats displayed a reduced density of synaptic proteins syntaxin, synaptophysin and synaptosome-associated protein of 25 kDa (in average 18 +/- 1%, p < 0.05) as well increased glial fibrillary acidic protein (20 +/- 5%, p < 0.05), suggesting synaptic degeneration and astrogliosis, which were prevented by caffeine consumption. In conclusion, neurochemical alterations in the hippocampus of diabetic rats are not related to defects of glucose transport but likely reflect osmoregulatory adaptations caused by hyperglycemia. Furthermore, caffeine consumption affected this neurochemical adaptation to high glucose levels, which may contribute to its potential neuroprotective effects, namely preventing synaptic degeneration and astrogliosis.

  6. Effects of Methyl Mercury Chloride on Rat Hippocampus Structure.

    PubMed

    Wu, Jingwei; Cheng, Guangyuan; Lu, Zhiyan; Wang, Mingyue; Tian, Jianying; Bi, Yongyi

    2016-05-01

    The objective of this study is to investigate the impacts of Methyl Mercury Chloride (MMC) on cognitive functions and ultrastructural changes of hippocampus in Sprague Dawley (SD) rats. Thirty healthy 20-day-old male SD rats weighing 30-40 g were randomly divided into three groups to receive daily injections. Two different dose levels were used: 4 mg/kg as high dose (H-MMC) and 2 mg/kg as low dose (L-MMC).The control group received 4 mg/kg saline solution (N-NaCl). After daily subcutaneous injection for 50 days, 6-day Morris water maze tests were used to assess the learning and memory functions of the rats. After a 5-day continuous training, spatial probe tests were conducted of times and paths crossing to the target quadrant on the 6th day. After the rats were euthanized, their hippocampus sections were stained with hematoxylin and eosin and analyzed under bothoptical microscope and electron microscope. The time H-MMC group spent in finding platform was significantly longer as compared toN-NaCl group on day 2 to day 5 and L-MMC group on day 4 to day 5. The number of crossing times of H-MMC group to the target quadrant was 0.63 ± 0.74, which is much lower than C-NaCl group (3.13 ± 1.56) with P value <0.05. No statistically significant difference in crossing times was found between L-MMC and C-NaCl groups. For H-MMC group, decreasing number of neurons and disorganized nerve cells were examined under light microscope. Swelling and dissolution of Golgi complex were examined under electron microscope, along with endoplasmic reticulum expansion and cytoplasmic edema. Mild cytoplasmic edema was found in L-MMC group. MMC can cause cognitive impairment in terms of learning and memory in SD rats. Additionally, it can also cause changes in the ultrastructure of neurons and morphological changes in the hippocampus, causing significant damage.

  7. [Pharmacological characterization of alpha 2-adrenoceptor regulated 5-HT release in the rat hippocampus].

    PubMed

    Numazawa, R

    1994-07-01

    The purpose of the present study is to confirm the functional regulation of alpha 2-adrenoceptor on the release of serotonin (5-HT) from the rat hippocampus in vivo. Under several pharmacological conditions, extracellular levels of 5-HT were estimated by assaying its concentrations in the perfusion fluid through the use of high-performance liquid chromatography with electrochemical detection. Extracellular 5-HT in the hippocampus was reduced by tetrodotoxin, 10 microM co-perfusion and was increased by perfusion with a selective 5-HT reuptake inhibitor, fluoxetine, 10 microM. Addition of potassium (K+; 120 mM) to the perfusion fluid evoked an approximately 3-fold increase in 5-HT release, and a calcium free medium completely prevented this K(+)-evoked 5-HT release. Potassium-evoked 5-HT release from the hippocampus of freely moving rats was significantly and concentration-dependently inhibited when alpha 2-adrenoceptor agonist, UK14,304, 0.1 microM to 10 microM was added to the perfusion solution, while the output of a 5-HT major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), remained unchanged. This action of UK14,304 was prevented by pretreatment with idazoxan, 5 mg/kg, i. p., an alpha 2-adrenoceptor antagonist. In rats that were catecholaminergically denervated with 6-hydroxydopamine, UK14,304, 10 microM also inhibited the potassium-evoked 5-HT release, but had no effect on the 5-HIAA output. The UK14,304-induced inhibition of 5-HT release was prevented by pretreatment with pertussis toxin (PTX). These findings suggest that 5-HT release is functionally modulated via alpha 2-adrenoceptors located on the serotonergic nerve terminals in the rat hippocampus. They also indicate the possibility that the inhibition of 5-HT release via alpha 2-adrenoceptors is linked to G-proteins which are substrates of PTX.

  8. Neonatal hypoxia triggers transient apoptosis followed by neurogenesis in the rat CA1 hippocampus.

    PubMed

    Daval, Jean-Luc; Pourié, Grégory; Grojean, Stéphanie; Lièvre, Valerie; Strazielle, Catherine; Blaise, Sébastien; Vert, Paul

    2004-04-01

    Continuous generation of new neurons has been demonstrated in the adult mammalian brain, and this process was shown to be stimulated by various pathologic conditions, including cerebral ischemia. Because brain oxygen deprivation is particularly frequent in neonates and represents the primary event of asphyxia, we analyzed long-term consequences of transient hypoxia in the newborn rat. Within 24 h after birth, animals were exposed to 100% N(2) for 20 min at 36 degrees C, and temporal changes in the vulnerable CA1 hippocampus were monitored. Cell density measurements revealed delayed cell death in the pyramidal cell layer reflecting apoptosis, as shown by characteristic nuclear morphology and expression levels of Bcl-2, Bax, and caspase-3. Neuronal loss was confirmed by reduced density of neuron-specific enolase (NSE)-labeled cells, and peaked by 1 wk post insult, to reach 27% of total cells. A gradual recovery then occurred, and no significant difference in cell density could be detected between controls and hypoxic rats at postnatal d 21. Repeated injections of bromodeoxyuridine (50 mg/kg) showed that newly divided cells expressing neuronal markers increased by 225% in the germinative subventricular zone, and they tended to migrate along the posterior periventricle toward the hippocampus. Therefore, transient hypoxia in the newborn rat triggered apoptosis in the CA1 hippocampus followed by increased neurogenesis and apparent anatomical recovery, suggesting that the developing brain may have a high capacity for self-repair.

  9. Dopamine depresses cholinergic oscillatory network activity in rat hippocampus.

    PubMed

    Weiss, Torsten; Veh, Rüdiger W; Heinemann, Uwe

    2003-11-01

    The dopaminergic neuronal system is implicated in cognitive processes in a variety of brain regions including the mesolimbic system. We have investigated whether dopamine also affects synchronized network activity in the hippocampus, which has been ascribed to play a pivotal role in memory formation. Gamma frequency (20-80 Hz) oscillations were induced by the cholinergic agonist carbachol. Oscillatory activity was examined in area CA3 of Wistar rat hippocampal slices, employing field potential and intracellular recordings. Application of carbachol initiated synchronized population activity in the gamma band at 40 Hz. Induced gamma activity persisted over hours and required GABAA receptors. Dopamine reversibly decreased the integrated gamma band power of the carbachol rhythm by 62%, while its frequency was not changed. By contrast, individual pyramidal cells recorded during carbachol-induced field gamma activity exhibited theta frequency (5-15 Hz) membrane potential oscillations that were not altered by dopamine. The dopamine effect on the field gamma activity was mimicked by the D1 receptor agonist SKF-383393 and partially antagonized by the D1 antagonist SCH-23390. Conversely, the D2 receptor agonist quinpirole failed to depress the oscillations, and the D2 antagonist sulpiride did not prevent the suppressive dopamine effect. The data indicate that dopamine strongly depresses cholinergic gamma oscillations in area CA3 of rat hippocampus by activation of D1-like dopamine receptors and that this effect is most likely mediated via impairment of interneurons involved in generation and maintenance of the carbachol-induced network rhythm.

  10. Proteomic identification of carbonylated proteins in F344 rat hippocampus after 1-bromopropane exposure

    SciTech Connect

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik; Ichihara, Gaku

    2012-08-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and humans. Previous proteomic analysis of rat hippocampus implicated alteration of protein expression in oxidative stress, suggesting that oxidative stress plays a role in 1-BP-induced neurotoxicity. To understand this role at the protein level, we exposed male F344 rats to 1-BP at 0, 400, or 1000 ppm for 8 h/day for 1 week or 4 weeks by inhalation and quantitated changes in hippocampal protein carbonyl using a protein carbonyl assay, two-dimensional gel electrophoresis (2-DE), immunoblotting, and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF/MS). Hippocampal reactive oxygen species and protein carbonyl were significantly increased, demonstrating 1-BP-associated induction of oxidative stress and protein damage. MALDI-TOF-TOF/MS identified 10 individual proteins with increased carbonyl modification (p < 0.05; fold-change ≥ 1.5). The identified proteins were involved in diverse biological processes including glycolysis, ATP production, tyrosine catabolism, GTP binding, guanine degradation, and neuronal metabolism of dopamine. Hippocampal triosephosphate isomerase (TPI) activity was significantly reduced and negatively correlated with TPI carbonylation (p < 0.001; r = 0.83). Advanced glycation end-product (AGE) levels were significantly elevated both in the hippocampus and plasma, and hippocampal AGEs correlated negatively with TPI activity (p < 0.001; r = 0.71). In conclusion, 1-BP-induced neurotoxicity in the rat hippocampus seems to involve oxidative damage of cellular proteins, decreased TPI activity, and elevated AGEs. -- Highlights: ► 1-BP increases hippocampal ROS levels and hippocampal and plasma protein carbonyls. ► 1-BP increases TPI carbonylation and decreases TPI activity in the hippocampus. ► 1-BP increases hippocampal and plasma AGE levels.

  11. 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.

  12. Formaldehyde impairs learning and memory involving the disturbance of hydrogen sulfide generation in the hippocampus of rats.

    PubMed

    Tang, Xiao-Qing; Zhuang, Yuan-Yuan; Zhang, Ping; Fang, Heng-Rong; Zhou, Cheng-Fang; Gu, Hong-Feng; Zhang, Hui; Wang, Chun-Yan

    2013-01-01

    Formaldehyde (FA), a well-known indoor and outdoor pollutant, has been implicated as the responsible agent in the development of neurocognitive disorders. Hydrogen sulfide (H(2)S), the third gasotransimitter, is an endogenous neuromodulator, which facilitates the induction of hippocampal long-term potentiation, involving the functions of learning and memory. In the present study, we analyzed the effects of intracerebroventricular injection of FA on the formation of learning and memory and the generation of endogenous H(2)S in the hippocampus of rats. We found that the intracerebroventricular injection of FA in rats impairs the function of learning and memory in the Morris water maze and novel object recognition test and increases the formation of apoptosis and lipid peroxidation in the hippocampus. We also showed that FA exposure inhibits the expression of cystathionine β-synthase, the major enzyme responsible for endogenous H(2)S generation in hippocampus and decreases the production of endogenous H(2)S in hippocampus in rats. These results suggested that FA-disturbed generation of endogenous H(2)S in hippocampus leads to the oxidative stress-mediated neuron damage, ultimately impairing the function of learning and memory. Our findings imply that the disturbance of endogenous H(2)S generation in hippocampus is a potential contributing mechanism underling FA-caused learning and memory impairment.

  13. Mild exercise increases dihydrotestosterone in hippocampus providing evidence for androgenic mediation of neurogenesis.

    PubMed

    Okamoto, Masahiro; Hojo, Yasushi; Inoue, Koshiro; Matsui, Takashi; Kawato, Suguru; McEwen, Bruce S; Soya, Hideaki

    2012-08-07

    Mild exercise activates hippocampal neurons through the glutamatergic pathway and also promotes adult hippocampal neurogenesis (AHN). We hypothesized that such exercise could enhance local androgen synthesis and cause AHN because hippocampal steroid synthesis is facilitated by activated neurons via N-methyl-D-aspartate receptors. Here we addressed this question using a mild-intense treadmill running model that has been shown to be a potent AHN stimulator. A mass-spectrometric analysis demonstrated that hippocampal dihydrotestosterone increased significantly, whereas testosterone levels did not increase significantly after 2 wk of treadmill running in both orchidectomized (ORX) and sham castrated (Sham) male rats. Furthermore, analysis of mRNA expression for the two isoforms of 5α-reductases (srd5a1, srd5a2) and for androgen receptor (AR) revealed that both increased in the hippocampus after exercise, even in ORX rats. All rats were injected twice with 5'-bromo-2'deoxyuridine (50 mg/kg body weight, i.p.) on the day before training. Mild exercise significantly increased AHN in both ORX and Sham rats. Moreover, the increase of doublecortin or 5'-bromo-2'deoxyuridine/NeuN-positive cells in ORX rats was blocked by s.c. flutamide, an AR antagonist. It was also found that application of an estrogen receptor antagonist, tamoxifen, did not suppress exercise-induced AHN. These results support the hypothesis that, in male animals, mild exercise enhances hippocampal synthesis of dihydrotestosterone and increases AHN via androgenenic mediation.

  14. 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.

  15. 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.

  16. 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.

  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. Up-regulation of GABA transporters and GABA(A) receptor α1 subunit in tremor rat hippocampus.

    PubMed

    Mao, Xiaoyuan; Guo, Feng; Yu, Junling; Min, Dongyu; Wang, Zhanyou; Xie, Ni; Chen, Tianbao; Shaw, Chris; Cai, Jiqun

    2010-12-17

    The loss of GABAergic neurotransmission has been closely linked with epileptogenesis. The modulation of the synaptic activity occurs both via the removal of GABA from the synaptic cleft and by GABA transporters (GATs) and by modulation of GABA receptors. The tremor rat (TRM; tm/tm) is the parent strain of the spontaneously epileptic rat (SER; zi/zi, tm/tm), which exhibits absence-like seizure after 8 weeks of age. However, there are no reports that can elucidate the effects of GATs and GABA(A) receptors (GABARs) on TRMs. The present study was conducted to detect GATs and GABAR α1 subunit in TRMs hippocampus at mRNA and protein levels. In this study, total synaptosomal GABA content was significantly decreased in TRMs hippocampus compared with control Wistar rats by high performance liquid chromatography (HPLC); mRNA and protein expressions of GAT-1, GAT-3 and GABAR α1 subunit were all significantly increased in TRMs hippocampus by real time PCR and Western blot, respectively; GAT-1 and GABAR α1 subunit proteins were localized widely in TRMs and control rats hippocampus including CA1, CA3 and dentate gyrus (DG) regions whereas only a wide distribution of GAT-3 was observed in CA1 region by immunohistochemistry. These data demonstrate that excessive expressions of GAT-1 as well as GAT-3 and GABAR α1 subunit in TRMs hippocampus may provide the potential therapeutic targets for genetic epilepsy. Copyright © 2010. Published by Elsevier Ireland Ltd.

  19. Prenatal Protein Malnutrition Affects the Density of GABAergic Interneurons During Hippocampus Development in Rats.

    PubMed

    González-Maciel, Angélica; Romero-Velázquez, Rosa María; Reynoso-Robles, Rafael; Uribe-Escamilla, Rebeca; Vargas-Sánchez, Javier; de la Garza-Montaño, Paloma; Alfaro-Rodríguez, Alfonso

    2015-01-01

    Prenatal protein malnutrition disrupts the pattern of maturation and development of the hippocampus and its neuroanatomy and increases inhibition of the granular cell layer of the fascia dentata. If local gamma-aminobutyric acid inter-neurons are partly responsible for inhibition of the hippocampus, it is reasonable to assume that there may be an increase in the gamma-aminobutyric acid cell population of prenatal protein malnutrition rats. This experimental study was conducted to ascertain the effects of prenatal protein malnutrition on the density of GABAergic interneurons at the cornus ammonis and fascia dentata in rats. Animals were investigated under two nutritional conditions: (i) prenatal protein malnutrition group fed 6% protein, and (ii) well-nourished control group fed 25% protein. Using an antibody for gamma-aminobutyric acid, immunoreactive cells (GABAergic) were assessed in the rostral-caudal direction of the dorsal hippocampus at four levels. (i) In 30-day-old rats with prenatal malnutrition, the fascia dentata had an average of 27% more GABAergic cells than the control group; this higher amount was not detectable at 90 days. (ii) There was a significant 18% increase in GABAergic neurons at level 1 of the cornus ammonis at 90 days of age. There was an increase in the population of interneurons in the fascia dentata and cornus ammonis in prenatal protein malnutrition rats. We conclude that prenatal hypoprotein malnutrition produces changes at 30 days in the fascia dentata. Results suggest that prenatal malnutrition also produces a delay in the programmed chronology of gamma-aminobutyric acid interneurons. Finally, in cornus ammonis, at 90 days of age, prenatal protein malnutrition showed an increase only at level 1; this effect may be evidenced in the long term, despite postnatal rehabilitation.

  20. Long-term intermittent feeding restores impaired GR signaling in the hippocampus of aged rat.

    PubMed

    Tesic, Vesna; Perovic, Milka; Lazic, Divna; Kojic, Snezana; Smiljanic, Kosara; Ruzdijic, Sabera; Rakic, Ljubisav; Kanazir, Selma

    2015-05-01

    Diminished glucocorticoid signaling is associated with an age-related decline in hippocampal functioning. In this study we demonstrate the effect of intermittent, every other day (EOD) feeding on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the hippocampus of middle-aged (18-month-old) and aged (24-month-old) Wistar rats. In aged ad libitum-fed rats, a decrease in the level of total GR and GR phosphorylated at Ser(232) (pGR) was detected. Conversely, aged rats subjected to EOD feeding, starting from 6 months of age, showed an increase in GR and pGR levels and a higher content of hippocampal corticosterone. Furthermore, prominent nuclear staining of pGR was observed in CA1 pyramidal and DG granule neurons of aged EOD-fed rats. These changes were accompanied by increased Sgk-1 and decreased GFAP transcription, pointing to upregulated transcriptional activity of GR. EOD feeding also induced an increase in the expression of the mineralocorticoid receptor. Our results reveal that intermittent feeding restores impaired GR signaling in the hippocampus of aged animals by inducing rather than by stabilizing GR signaling during aging.

  1. Chronic sleep restriction disrupts interendothelial junctions in the hippocampus and increases blood-brain barrier permeability.

    PubMed

    Hurtado-Alvarado, G; Velázquez-Moctezuma, J; Gómez-González, B

    2017-10-01

    Chronic sleep loss in the rat increases blood-brain barrier permeability to Evans blue and FITC-dextrans in almost the whole brain and sleep recovery during short periods restores normal blood-brain barrier permeability. Sleep loss increases vesicle density in hippocampal endothelial cells and decreases tight junction protein expression. However, at the ultrastructural level the effect of chronic sleep loss on interendothelial junctions is unknown. In this study we characterised the ultrastructure of interendothelial junctions in the hippocampus, the expression of tight junction proteins, and quantified blood-brain barrier permeability to fluorescein-sodium after chronic sleep restriction. Male Wistar rats were sleep restricted using the modified multiple platform method during 10 days, with a daily schedule of 20-h sleep deprivation plus 4-h sleep recovery at their home-cages. At the 10th day hippocampal samples were obtained immediately at the end of the 20-h sleep deprivation period, and after 40 and 120 min of sleep recovery. Samples were processed for transmission electron microscopy and western blot. Chronic sleep restriction increased blood-brain barrier permeability to fluorescein-sodium, and decreased interendothelial junction complexity by increasing the frequency of less mature end-to-end and simply overlap junctions, even after sleep recovery, as compared to intact controls. Chronic sleep loss also induced the formation of clefts between narrow zones of adjacent endothelial cell membranes in the hippocampus. The expression of claudin-5 and actin decreased after chronic sleep loss as compared to intact animals. Therefore, it seems that chronic sleep loss disrupts interendothelial junctions that leads to blood-brain barrier hyperpermeability in the hippocampus. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

  2. Influence of Chronic Amphetamine Treatment and Acute Withdrawal on Serotonin Synthesis and Clearance Mechanisms in the Rat Ventral Hippocampus

    PubMed Central

    Barr, Jeffrey L.; Scholl, Jamie L.; Solanki, Rajeshwari R.; Watt, Michael J.; Lowry, Christopher A.; Renner, Kenneth J.; Forster, Gina L.

    2012-01-01

    Amphetamine withdrawal in both humans and rats is associated with increased anxiety states, which are thought to contribute to drug relapse. Serotonin in the ventral hippocampus mediates affective behaviors, and reduced serotonin levels in this region are observed in rat models of high anxiety, including during withdrawal from chronic amphetamine. This goal of this study was to understand the mechanisms by which reduced ventral hippocampus serotonergic neurotransmission occurs during amphetamine withdrawal. Serotonin synthesis (assessed by accumulation of serotonin precursor as a measure of the capacity of in vivo tryptophan hydroxylase activity), expression of serotonergic transporters, and in vivo serotonergic clearance using in vivo microdialysis, were assessed in the ventral hippocampus in adult male Sprague Dawley rats at 24 hours withdrawal from chronic amphetamine. Overall, results showed that diminished extracellular serotonin at 24 hours withdrawal from chronic amphetamine was not accompanied by a change in capacity for serotonin synthesis (in vivo tryptophan hydroxylase activity), nor serotonin transporter expression or function in the ventral hippocampus, but instead was associated with increased expression and function of organic cation transporters (low affinity, high capacity serotonin transporters). These findings suggest that 24 hours withdrawal from chronic amphetamine reduces the availability of extracellular serotonin in the ventral hippocampus by increasing organic cation transporter-mediated serotonin clearance, which may represent at future pharmacological target for reversing anxiety states during drug withdrawal. PMID:23157166

  3. Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

    PubMed

    Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

    2015-02-01

    Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI.

  4. The effect of Chinese Jinzhida recipe on the hippocampus in a rat model of diabetes-associated cognitive decline

    PubMed Central

    2013-01-01

    Background To investigate the effects of treatment with Multi component Chinese Medicine Jinzhida (JZD) on behavioral deficits in diabetes-associated cognitive decline (DACD) rats and verify our hypothesis that JZD treatment improves cognitive function by suppressing the endoplasmic reticulum stress (ERS) and improving insulin signaling transduction in the rats’ hippocampus. Methods A rat model of type 2 diabetes mellitus (T2DM) was established using high fat diet and streptozotocin (30 mg/kg, ip). Insulin sensitivity was evaluated by the oral glucose tolerance test and the insulin tolerance test. After 7 weeks, the T2DM rats were treated with JZD. The step-down test and Morris water maze were used to evaluate behavior in T2DM rats after 5 weeks of treatment with JZD. Levels of phosphorylated proteins involved in the ERS and in insulin signaling transduction pathways were assessed by Western blot for T2DM rats’ hippocampus. Results Compared to healthy control rats, T2DM rats initially showed insulin resistance and had declines in acquisition and retrieval processes in the step-down test and in spatial memory in the Morris water maze after 12 weeks. Performance on both the step-down test and Morris water maze tasks improved after JZD treatment. In T2DM rats, the ERS was activated, and then inhibited the insulin signal transduction pathways through the Jun NH2-terminal kinases (JNK) mediated. JZD treatment suppressed the ERS, increased insulin signal transduction, and improved insulin resistance in the rats’ hippocampus. Conclusions Treatment with JZD improved cognitive function in the T2DM rat model. The possible mechanism for DACD was related with ERS inducing the insulin signal transduction dysfunction in T2DM rats’ hippocampus. The JZD could reduce ERS and improve insulin signal transduction and insulin resistance in T2DM rats’ hippocampus and as a result improved the cognitive function. PMID:23829668

  5. Bayesian decoding using unsorted spikes in the rat hippocampus

    PubMed Central

    Layton, Stuart P.; Chen, Zhe; Wilson, Matthew A.

    2013-01-01

    A fundamental task in neuroscience is to understand how neural ensembles represent information. Population decoding is a useful tool to extract information from neuronal populations based on the ensemble spiking activity. We propose a novel Bayesian decoding paradigm to decode unsorted spikes in the rat hippocampus. Our approach uses a direct mapping between spike waveform features and covariates of interest and avoids accumulation of spike sorting errors. Our decoding paradigm is nonparametric, encoding model-free for representing stimuli, and extracts information from all available spikes and their waveform features. We apply the proposed Bayesian decoding algorithm to a position reconstruction task for freely behaving rats based on tetrode recordings of rat hippocampal neuronal activity. Our detailed decoding analyses demonstrate that our approach is efficient and better utilizes the available information in the nonsortable hash than the standard sorting-based decoding algorithm. Our approach can be adapted to an online encoding/decoding framework for applications that require real-time decoding, such as brain-machine interfaces. PMID:24089403

  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. [Effect of electromagnetic radiation on discharge activity of neurons in the hippocampus CA1 in rats].

    PubMed

    Tong, Jun; Chen, Su; Liu, Xiang-Ming; Hao, Dong-Mei

    2013-09-01

    In order to explore effect of electromagnetic radiation on learning and memory ability of hippocampus neuron in rats, the changes in discharge patterns and overall electrical activity of hippocampus neuron after electromagnetic radiation were observed. Rat neurons discharge was recorded with glass electrode extracellular recording technology and a polygraph respectively. Radiation frequency of electromagnetic wave was 900 MHZ and the power was 10 W/m2. In glass electrode extracellular recording, the rats were separately irradiated for 10, 20, 30, 40, 50 and 60 min, every points repeated 10 times and updated interval of 1h, observing the changes in neuron discharge and spontaneous discharge patterns after electromagnetic radiation. In polygraph recording experiments, irradiation group rats for five days a week, 6 hours per day, repeatedly for 10 weeks, memory electrical changes in control group and irradiation group rats when they were feeding were repeatedly monitored by the implanted electrodes, observing the changes in peak electric digits and the largest amplitude in hippocampal CA1 area, and taking some electromagnetic radiation sampling sequence for correlation analysis. (1) Electromagnetic radiation had an inhibitory role on discharge frequency of the hippocampus CA1 region neurons. After electromagnetic radiation, discharge frequency of the hippocampus CA1 region neurons was reduced, but the changes in scale was not obvious. (2) Electromagnetic radiation might change the spontaneous discharge patterns of hippocampus CA1 region neurons, which made the explosive discharge pattern increased obviously. (3) Peak potential total number within 5 min in irradiation group was significantly reduced, the largest amplitude was less than that of control group. (4) Using mathematical method to make the correlation analysis of the electromagnetic radiation sampling sequence, that of irradiation group was less than that of control group, indicating that there was a tending

  8. Functional relationships between the hippocampus and dorsomedial striatum in learning a visual scene-based memory task in rats.

    PubMed

    Delcasso, Sébastien; Huh, Namjung; Byeon, Jung Seop; Lee, Jihyun; Jung, Min Whan; Lee, Inah

    2014-11-19

    The hippocampus is important for contextual behavior, and the striatum plays key roles in decision making. When studying the functional relationships with the hippocampus, prior studies have focused mostly on the dorsolateral striatum (DLS), emphasizing the antagonistic relationships between the hippocampus and DLS in spatial versus response learning. By contrast, the functional relationships between the dorsomedial striatum (DMS) and hippocampus are relatively unknown. The current study reports that lesions to both the hippocampus and DMS profoundly impaired performance of rats in a visual scene-based memory task in which the animals were required to make a choice response by using visual scenes displayed in the background. Analysis of simultaneous recordings of local field potentials revealed that the gamma oscillatory power was higher in the DMS, but not in CA1, when the rat performed the task using familiar scenes than novel ones. In addition, the CA1-DMS networks increased coherence at γ, but not at θ, rhythm as the rat mastered the task. At the single-unit level, the neuronal populations in CA1 and DMS showed differential firing patterns when responses were made using familiar visual scenes than novel ones. Such learning-dependent firing patterns were observed earlier in the DMS than in CA1 before the rat made choice responses. The present findings suggest that both the hippocampus and DMS process memory representations for visual scenes in parallel with different time courses and that flexible choice action using background visual scenes requires coordinated operations of the hippocampus and DMS at γ frequencies. Copyright © 2014 the authors 0270-6474/14/3415534-14$15.00/0.

  9. Functional Relationships between the Hippocampus and Dorsomedial Striatum in Learning a Visual Scene-Based Memory Task in Rats

    PubMed Central

    Delcasso, Sébastien; Huh, Namjung; Byeon, Jung Seop; Lee, Jihyun; Jung, Min Whan

    2014-01-01

    The hippocampus is important for contextual behavior, and the striatum plays key roles in decision making. When studying the functional relationships with the hippocampus, prior studies have focused mostly on the dorsolateral striatum (DLS), emphasizing the antagonistic relationships between the hippocampus and DLS in spatial versus response learning. By contrast, the functional relationships between the dorsomedial striatum (DMS) and hippocampus are relatively unknown. The current study reports that lesions to both the hippocampus and DMS profoundly impaired performance of rats in a visual scene-based memory task in which the animals were required to make a choice response by using visual scenes displayed in the background. Analysis of simultaneous recordings of local field potentials revealed that the gamma oscillatory power was higher in the DMS, but not in CA1, when the rat performed the task using familiar scenes than novel ones. In addition, the CA1-DMS networks increased coherence at γ, but not at θ, rhythm as the rat mastered the task. At the single-unit level, the neuronal populations in CA1 and DMS showed differential firing patterns when responses were made using familiar visual scenes than novel ones. Such learning-dependent firing patterns were observed earlier in the DMS than in CA1 before the rat made choice responses. The present findings suggest that both the hippocampus and DMS process memory representations for visual scenes in parallel with different time courses and that flexible choice action using background visual scenes requires coordinated operations of the hippocampus and DMS at γ frequencies. PMID:25411483

  10. 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.

  11. Disruption of Energy Transfer and Redox Status by Sulfite in Hippocampus, Striatum, and Cerebellum of Developing Rats.

    PubMed

    de Moura Alvorcem, Leonardo; da Rosa, Mateus Struecker; Glänzel, Nícolas Manzke; Parmeggiani, Belisa; Grings, Mateus; Schmitz, Felipe; Wyse, Angela T S; Wajner, Moacir; Leipnitz, Guilhian

    2017-08-01

    Patients with sulfite oxidase (SO) deficiency present severe brain abnormalities, whose pathophysiology is not yet elucidated. We evaluated the effects of sulfite and thiosulfate, metabolites accumulated in SO deficiency, on creatine kinase (CK) activity, mitochondrial respiration and redox status in hippocampus, striatum and cerebellum of developing rats. Our in vitro results showed that sulfite and thiosulfate decreased CK activity, whereas sulfite also increased malondialdehyde (MDA) levels in all brain structures evaluated. Sulfite further diminished mitochondrial respiration and increased DCFH oxidation and hydrogen peroxide production in hippocampus. Sulfite-induced CK activity decrease was prevented by melatonin (MEL), resveratrol (RSV), and dithiothreitol while increase of MDA levels was prevented by MEL and RSV. Regarding the antioxidant system, sulfite increased glutathione concentrations in hippocampus and striatum. In addition, sulfite decreased the activities of glutathione peroxidase in all brain structures, of glutathione S-transferase in hippocampus and cerebellum, and of glutathione reductase in cerebellum. In vivo experiments performed with intrahippocampal administration of sulfite demonstrated that this metabolite increased superoxide dismutase activity without altering other biochemical parameters in rat hippocampus. Our data suggest that impairment of energy metabolism and redox status may be important pathomechanisms involved in brain damage observed in individuals with SO deficiency.

  12. 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.

  13. [Anxiety level during morphine abstinence correlates with the status of nitrergic system in the rat hippocampus].

    PubMed

    Peregud, D I; Vorontsova, O N; Iakovlev, A A; Panchenko, L F; Guliaeva, N V

    2007-04-01

    Opiate addiction is accompanied by long-term structural and functional changes in brain regions persisting during abstinence, this status being an experimental model of the aberrant neuroplasticity. Nitric oxide is known to be involved in mechanisms of psychopathological events during opiate abstinence. In this study, indices of a nitregic system (nitric synthase activity--NOS, nitrites and nitrates concentration--NOx-) were measured in the rat brain region during morphine abstinence. Prior to this, the rats were tested for anxiety in an elevated plus maze. NOS activity increased in hippocampus 3 days after morphine withdrawal, while NOx--6 days after withdrawal. No changes of the nitrergic system could be revealed in other brain regions under study. Six days (but not 3 days) after morphine withdrawal, rats visited the open arms of the plus maze more frequently and spent more time in these arms as compared with respective controls. The data suggest that nitrergic system changes in the hippocampus may be involved in molecular mechanisms of behavioural alteration during morphine abstinence in rats.

  14. Neurogenesis in the dentate gyrus of the rat hippocampus enhanced by tickling stimulation with positive emotion.

    PubMed

    Yamamuro, Takuya; Senzaki, Kouji; Iwamoto, Satomi; Nakagawa, Yoshimi; Hayashi, Takashi; Hori, Miyo; Sakamoto, Shigeko; Murakami, Kazuo; Shiga, Takashi; Urayama, Osamu

    2010-12-01

    Hippocampal neurogenesis is influenced by many factors. In this study, we examined the effect of tactile stimulation (tickling), which induced positive emotion, on neurogenesis in the dentate gyrus (DG) of the hippocampus. Four week-old rats were tickled for 5 min/day on 5 consecutive days and received 5-bromo-2'-deoxyuridine (BrdU) administration for 4 days from the second tickling day. Then they were allowed to survive for 18 h or 3 weeks after the end of BrdU treatment. Neurogenesis in the DG was compared between the tickled and untickled rats by using immunohistochemistry with anti-BrdU antibody. The result showed that the number of BrdU- and NeuN (neural cell marker)-double positive neurons on 18h as well as 3 weeks of the survival periods was significantly increased in the tickled group as compared with the untickled group. The expression of mRNA of brain-derived neurotrophic factor (BDNF) in the hippocampus of the tickled rats was not altered when compared with the control rats. In conclusion, tickling stimulation which induces positive emotion may affect the generation and survival of new neurons of the DG through the BDNF-independent pathway.

  15. Memory and the Hippocampus: A Synthesis from Findings with Rats, Monkeys, and Humans.

    ERIC Educational Resources Information Center

    Squire, Larry R.

    1991-01-01

    The role of the hippocampus in memory function is discussed. Work with rats, monkeys, and humans largely agrees concerning its function and structure. The hippocampus is essential for a type of memory designated "declarative," the ability to remember that a visual object was presented in a particular context. (SLD)

  16. Effect of Sodium Valproate on Cognitive Function and Hippocampus of Rats After Convulsive Status Epilepticus

    PubMed Central

    Wu, Peng; Hong, Siqi; Zhong, Min; Guo, Yi; Chen, Hengsheng; Jiang, Li

    2016-01-01

    Background The aim of this study was to explore the effect and possible mechanism of sodium valproate (VPA) on the cognitive function and the hippocampus of rats after convulsive status epilepticus (CES). Material/Methods A rat model of CES was established and the Morris water maze was used to observe changes in the cognitive function of the rats after the administration of VPA. Acute hippocampal slices were made to detect field excitatory postsynaptic potential. Western blot analysis was used to test for the expression of CaMKII and p-CaMKII. Results (1) CSE caused no spatial reference memory (SFM) or spatial working memory (SWM) damage to 15-day-old (P15) rats, but caused significant SRM and SWM damage to 35-day-old (P35) rats. VPA damaged the SRM and SWM of P15 rats in both the CSE and control groups. However, VPA improved the memory damage caused by CSE in P35 rats. (2) VPA treatment in vivo increased the induced success rate and the sustainable time of long-term potentiation (LTP) in P35 rats, and also inhibited the expression of CaMKII and p-CaMKII in both P15 and P35 rats. Conclusions VPA significantly improved spatial cognitive dysfunction in a CSE model of P35 rats, and damaged the spatial memory of normal P15 and P35 rats. Improvements after administration of VPA were closely related to the increase of induced success rate and the prolongation of the sustainable time of LTP. VPA treatment in vivo, which inhibited expression and phosphorylation of CaMKII, showed no obvious inhibition on LTP, which may be related to the elution effect of VPA. PMID:28033307

  17. Selective Estrogen Receptor Modulators Regulate Dendritic Spine Plasticity in the Hippocampus of Male Rats

    PubMed Central

    González-Burgos, Ignacio; Rivera-Cervantes, Martha C.; Velázquez-Zamora, Dulce A.; Feria-Velasco, Alfredo; Garcia-Segura, Luis Miguel

    2012-01-01

    Some selective estrogen receptor modulators, such as raloxifene and tamoxifen, are neuroprotective and reduce brain inflammation in several experimental models of neurodegeneration. In addition, raloxifene and tamoxifen counteract cognitive deficits caused by gonadal hormone deprivation in male rats. In this study, we have explored whether raloxifene and tamoxifen may regulate the number and geometry of dendritic spines in CA1 pyramidal neurons of the rat hippocampus. Young adult male rats were injected with raloxifene (1 mg/kg), tamoxifen (1 mg/kg), or vehicle and killed 24 h after the injection. Animals treated with raloxifene or tamoxifen showed an increased numerical density of dendritic spines in CA1 pyramidal neurons compared to animals treated with vehicle. Raloxifene and tamoxifen had also specific effects in the morphology of spines. These findings suggest that raloxifene and tamoxifen may influence the processing of information by hippocampal pyramidal neurons by affecting the number and shape of dendritic spines. PMID:22164341

  18. The rat's resistance to superstition: role of the hippocampus.

    PubMed

    Devenport, L D; Holloway, F A

    1980-08-01

    Superstitious operant behavior, in all possible respects similar to that described for pigeons, was found to characterize the behavior of male rats with bilateral hippocampal lesions (hippocampals). Robust superfluous activitiess accompanied noncontingent (random time) and shifts from contingent (random interval) to noncontingent pellet delivery. These activities were minimized but not eliminated by an operant contingency. In contrast, sham-operate performance was distinguished by a stripping away of superfluities in all contingency conditions. Although a variety of responses were emitted superstitiously, the topography of behavior in hippocampal rats was not different from that of sham operates. Unlike sham operates, which varied their behavior spontaneously and in response to experimental changes, hippocampals did not cease their repetitive, high frequency sequences until reinforcers were withheld. As the detection of a free operant contingency seems to depend upon response-cued discrimination learning, and in view of the hippocampal failure to generate these cues, a link between superstitious response output and response rigidity is hypothesized. It is proposed that the hippocampus permits the control of behavior by contingency and that without the structure, operant behavior is guided by simple response-reinforcer contiguity.

  19. [Effects of polydatin on learning and memory and Cdk5 kinase activity in the hippocampus of rats with chronic alcoholism].

    PubMed

    Li, Xin-juan; Zhang, Yan; Xu, Chun-yang; Li, Shuang; Du, Ai-lin; Zhang, Li-bin; Zhang, Rui-ling

    2015-03-01

    To observe the effects of polydatin on learning and memory and cyclin-dependent kinase 5 (Cdk5) kinase activity in the hippocampus of rats with chronic alcoholism. Forty rats were randomly divided into 4 groups: control group, chronic alcoholism group, low and high polydatin group. The rat chronic alcoholism model was established by ethanol 3.0 g/(kg · d) (intragastric administration). The abstinence scoring was used to evaluate the rats withdrawal symptoms; cognitive function was measured by Morris water maze experiment; Cdk5 protein expression in the hippocampus was detected by immunofluorescence; Cdk5 kinase activity in the hippocampus was detected by liquid scintillation counting method. The abstinence score, escape latency, Cdk5 kinase activity in chronic alcoholism group rats were significantly higher than those of control group (P < 0.05). The abstinence score, escape latency in high polydatin group rats were significantly lower than those of chronic alcoholism group (P < 0.05); Cdk5 kinase activity in high and low polydatin group rats was significantly lower than that of chronic alcoholism group( P < 0.05); immunofluorescence showed that the Cdk5 positive cells of chronic alcoholism group were significantly increased compared with control group (P < 0.05), and the Cdk5 positive cells of polydatin groups were significantly decreased compared with chronic alcoholism group ( P < 0.05). Polydatin-reduced the chronic alcoholism damage may interrelate with regulation of Cdk5 kinase activity.

  20. Feeding with powdered diet after weaning affects sex difference in acetylcholine release in the hippocampus in rats.

    PubMed

    Takase, K; Mitsushima, D; Masuda, J; Mogi, K; Funabashi, T; Endo, Y; Kimura, F

    2005-01-01

    We have reported in the past that female rats fed a powdered diet showed better spatial learning and memory functions than female rats a fed pelleted diet. In the present study, we examined the effects of feeding with powdered diet on acetylcholine release in the hippocampus in both sexes of rats. After weaning (3 weeks of age), rats were fed either standard pelleted diet or powdered diet, and after maturation (9-12 weeks of age), they were used in an in vivo microdialysis study, in which no eserine (a cholinesterase inhibitor) was added to the perfusate. The dialysate was collected from the dorsal hippocampus at 20-min intervals under freely moving conditions for more than 24 h. Acetylcholine in the dialysate was measured by high performance liquid chromatography. As we reported previously, the acetylcholine release showed a clear daily rhythm in both sexes, and males showed significantly greater acetylcholine release in the hippocampus than females in rats fed pelleted diet. Conversely, in rats fed powdered diet, no sex difference in the acetylcholine release was observed, since feeding with powdered diet significantly increased the acetylcholine release only in females. To further examine the number of cholinergic neurons in the medial septum and horizontal limb of the diagonal band of Broca, immunocytochemistry for choline acetyltransferase was performed in both sexes of rats fed either standard pelleted diet or powdered diet. However, neither sex nor feeding conditions affect the number of choline acetyltransferase immunoreactive cells in the areas. These results suggest that powdered diet after weaning enhances spontaneous acetylcholine release in the hippocampus in female rats without changes in the number of cholinergic neurons in the areas. It is possible that this effect of feeding contributes to improve the performance in spatial learning and memory functions in female rats fed powdered diet.

  1. Methylphenidate Causes Behavioral Impairments and Neuron and Astrocyte Loss in the Hippocampus of Juvenile Rats.

    PubMed

    Schmitz, Felipe; Pierozan, Paula; Rodrigues, André F; Biasibetti, Helena; Grunevald, Matheus; Pettenuzzo, Letícia F; Scaini, Giselli; Streck, Emilio L; Netto, Carlos A; Wyse, Angela T S

    2017-08-01

    Although the use, and misuse, of methylphenidate is increasing in childhood and adolescence, there is little information about the consequences of this psychostimulant chronic use on brain and behavior during development. The aim of the present study was to investigate hippocampus biochemical, histochemical, and behavioral effects of chronic methylphenidate treatment to juvenile rats. Wistar rats received intraperitoneal injections of methylphenidate (2.0 mg/kg) or an equivalent volume of 0.9 % saline solution (controls), once a day, from the 15th to the 45th day of age. Results showed that chronic methylphenidate administration caused loss of astrocytes and neurons in the hippocampus of juvenile rats. BDNF and pTrkB immunocontents and NGF levels were decreased, while TNF-α and IL-6 levels, Iba-1 and caspase 3 cleaved immunocontents (microglia marker and active apoptosis marker, respectively) were increased. ERK and PKCaMII signaling pathways, but not Akt and GSK-3β, were decreased. SNAP-25 was decreased after methylphenidate treatment, while GAP-43 and synaptophysin were not altered. Both exploratory activity and object recognition memory were impaired by methylphenidate. These findings provide additional evidence that early-life exposure to methylphenidate can have complex effects, as well as provide new basis for understanding of the biochemical and behavioral consequences associated with chronic use of methylphenidate during central nervous system development.

  2. Sleep deprivation induces spatial memory impairment by altered hippocampus neuroinflammatory responses and glial cells activation in rats.

    PubMed

    Wadhwa, Meetu; Kumari, Punita; Chauhan, Garima; Roy, Koustav; Alam, Shahnawaz; Kishore, Krishna; Ray, Koushik; Panjwani, Usha

    2017-11-15

    We aimed to investigate the glial cells activation as a potential mechanism involved in the sleep deprivation (SD) induced cognitive impairment through changes in inflammatory cytokines. We analyzed the spatial memory, inflammatory cytokine levels, and gliosis during SD. SD induced spatial memory impairment, imbalance of inflammatory (increased pro- and decreased anti-) cytokines in both hippocampus and plasma in association with glial cells activation in the hippocampus of sleep-deprived rats were observed. Further analysis of the data presented a correlation between spatial memory impairment and activated microglia induced increased pro-inflammatory cytokines after 48h of SD. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Dynamic Change in Cells Expressing IL-1β in Rat Hippocampus after Status Epilepticus

    PubMed Central

    Sakuma, Satoru; Tokuhara, Daisuke; Otsubo, Hiroshi; Yamano, Tsunekazu; Shintaku, Haruo

    2014-01-01

    BACKGROUND The time course of cytokine dynamics after seizure remains controversial. Here we evaluated the changes in the levels and sites of interleukin (IL)-1β expression over time in the hippocampus after seizure. METHODS Status epilepticus (SE) was induced in adult Wistar rats by means of intraperitoneal injection of kainic acid (KA). Subsequently, the time courses of cellular localization and IL-1β concentration in the hippocampus were evaluated by means of immunohistochemical and quantitative assays. RESULTS On day 1 after SE, CA3 pyramidal cells showed degeneration and increased IL-1β expression. In the chronic phase (>7 days after SE), glial fibrillary acidic protein (GFAP)—positive reactive astrocytes—appeared in CA1 and became IL-1β immunoreactive. Their IL-1β immunoreactivity increased in proportion to the progressive hypertrophy of astrocytes that led to gliosis. Quantitative analysis showed that hippocampal IL-1β concentration progressively increased during the acute and chronic phases. CONCLUSION IL-1β affects the hippocampus after SE. In the acute phase, the main cells expressing IL-1β were CA3 pyramidal cells. In the chronic phase, the main cells expressing IL-1β were reactive astrocytes in CA1. PMID:25210490

  4. Ketogenic diet does not change NKCC1 and KCC2 expression in rat hippocampus.

    PubMed

    Gómez-Lira, Gisela; Mendoza-Torreblanca, Julieta Griselda; Granados-Rojas, Leticia

    2011-09-01

    In control rats, we examined the effects of ketogenic diet on NKCC1 and KCC2 expression levels in hippocampus. Neither the number of NKCC1 immunoreactive cells nor the intensity of labeling of KCC2 was found to modify in hippocampus of the rats after ketogenic diet treatment. These results indicate that ketogenic diet by itself does not modify the expression of these cation chloride cotransporters.

  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. 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.

  7. Impact of sex and hormones on new cells in the developing rat hippocampus: a novel source of sex dimorphism?

    PubMed Central

    Zhang, Jian-Min; Konkle, Anne T. M.; Zup, Susan L.; McCarthy, Margaret M.

    2009-01-01

    The hippocampus is a key brain region regulating complex cognitive and emotional responses, and is implicated in the etiology of depressive and anxiety disorders, many of which exhibit some degree of sex difference. The male rat hippocampus is consistently reported to be slightly but significantly larger than the female. The majority of studies on the development of volumetric sex differences have focused on the effects of estradiol (E2), with relatively few focusing on androgens. We examined the impact of both E2 and androgens on newly born cells in the developing rat hippocampus, and report that neonatal males have significantly more 5-bromo-2′-deoxyuridine-5′-monophosphate (BrdU)+ cells than females. Both testosterone (T) and dihydrotestosterone treatment of females significantly increased the number of BrdU+ cells, an effect blocked by the androgen receptor antagonist, flutamide. However, only T significantly increased the number of neuronal nuclear antigen+ neurons in the female rat hippocampus. Interestingly, E2 treatment also increased BrdU+ cells in females, but had no effect on neuron number. Instead, E2 and T significantly increased the number of newly born glial fibrillary acidic protein or glutamine synthetase+ glial cells in females, indicating that androgens and E2 may act independently to achieve distinct endpoints. Quantification of pyknotic cells at two different developmental time points indicates no sex difference in the number of cells dying, suggesting, but not proving, that gonadal steroids are promoting cell genesis. PMID:18333959

  8. Effects of dorsal hippocampus catecholamine depletion on paired-associates learning and place learning in rats.

    PubMed

    Roschlau, Corinna; Hauber, Wolfgang

    2017-04-14

    Growing evidence suggests that the catecholamine (CA) neurotransmitters dopamine and noradrenaline support hippocampus-mediated learning and memory. However, little is known to date about which forms of hippocampus-mediated spatial learning are modulated by CA signaling in the hippocampus. Therefore, in the current study we examined the effects of 6-hydroxydopamine-induced CA depletion in the dorsal hippocampus on two prominent forms of hippocampus-based spatial learning, that is learning of object-location associations (paired-associates learning) as well as learning and choosing actions based on a representation of the context (place learning). Results show that rats with CA depletion of the dorsal hippocampus were able to learn object-location associations in an automated touch screen paired-associates learning (PAL) task. One possibility to explain this negative result is that object-location learning as tested in the touchscreen PAL task seems to require relatively little hippocampal processing. Results further show that in rats with CA depletion of the dorsal hippocampus the use of a response strategy was facilitated in a T-maze spatial learning task. We suspect that impaired hippocampus CA signaling may attenuate hippocampus-based place learning and favor dorsolateral striatum-based response learning.

  9. Treadmill exercise alters ecstasy- induced long- term potentiation disruption in the hippocampus of male rats.

    PubMed

    Sajadi, Azam; Amiri, Iraj; Gharebaghi, Alireza; Komaki, Alireza; Asadbeigi, Masoumeh; Shahidi, Siamak; Mehdizadeh, Mehdi; Soleimani Asl, Sara

    2017-06-13

    3, 4-methylenedioxymethamphetamine (MDMA) or ecstasy is a derivative of amphetamine that leads to long term potentiation (LTP) disruption in the hippocampal dentate gyrus (DG). Exercise has been accepted as a treatment for the improvement of neurodegenerative disease. Herein, the effects of exercise on the MDMA- induced neurotoxicity were assessed. Male Wistar rats received intraperitoneal injection of MDMA (10 mg/kg) and exercised for one month on a treadmill (Simultaneously or asynchronously with MDMA). LTP and expression of BDNF were assessed using electrophysiology and western blotting methods, respectively. MDMA attenuated the field excitatory post-synaptic potential (fEPSP) slope in comparison with the control group, whereas treadmill exercise increased this parameter when compared to MDMA group. Furthermore, BDNF expression significantly decreased in MDMA group and treadmill exercise could increase that. In conclusion, results of this study suggest that synchronous exercise is able to improve MDMA-induced LTP changes through increase of BDNF expression in the hippocampus of rats.

  10. Pharmacological characterization of alpha 2-adrenoceptor regulated serotonin release in the rat hippocampus.

    PubMed

    Numazawa, R; Yoshioka, M; Matsumoto, M; Togashi, H; Kemmotsu, O; Saito, H

    1995-06-16

    The purpose of the present study was to confirm the functional regulation by alpha 2-adrenoceptors of the release of serotonin (5-HT) from the rat hippocampus in vivo. Under several pharmacological conditions, extracellular levels of 5-HT were estimated by assaying its concentrations in the perfusate by high performance liquid chromatography with electrochemical detection. Extracellular 5-HT in the hippocampus was reduced by tetrodotoxin (10 microM) co-perfusion, but increased by perfusion of a selective 5-HT re-uptake inhibitor, fluoxetine (10 microM). Addition of potassium (K+, 120 mM) to the perfusion fluid evoked an approximately 3-fold increase in 5-HT release. When the alpha 2-adrenoceptor agonist UK14,304 (0.1-10 microM) was added to the perfusion solution, the K(+)-evoked 5-HT release was significantly inhibited in a concentration-dependent manner. This inhibitory action of UK14,304 was reversed by pretreatment with an alpha 2-adrenoceptor antagonist, idazoxan (5 mg/kg, i.p.). In rats which were catecholaminergically denervated with 6-hydroxydopamine, UK14,304 (10 microM) still inhibited the K(+)-evoked 5-HT release. Treatment with pertussis toxin (PTX) did not alter the K(+)-evoked release of 5-HT but abolished the inhibitory effect of UK14,304. These findings suggest that 5-HT release is functionally modulated via alpha 2-adrenoceptors located on the serotonergic nerve terminals in the rat hippocampus and furthermore, the possibility that the inhibitory of alpha 2-adrenoceptors is linked to G-proteins which are substrates of PTX.

  11. Mild exercise increases dihydrotestosterone in hippocampus providing evidence for androgenic mediation of neurogenesis

    PubMed Central

    Okamoto, Masahiro; Hojo, Yasushi; Inoue, Koshiro; Matsui, Takashi; Kawato, Suguru; McEwen, Bruce S.; Soya, Hideaki

    2012-01-01

    Mild exercise activates hippocampal neurons through the glutamatergic pathway and also promotes adult hippocampal neurogenesis (AHN). We hypothesized that such exercise could enhance local androgen synthesis and cause AHN because hippocampal steroid synthesis is facilitated by activated neurons via N-methyl-D-aspartate receptors. Here we addressed this question using a mild-intense treadmill running model that has been shown to be a potent AHN stimulator. A mass-spectrometric analysis demonstrated that hippocampal dihydrotestosterone increased significantly, whereas testosterone levels did not increase significantly after 2 wk of treadmill running in both orchidectomized (ORX) and sham castrated (Sham) male rats. Furthermore, analysis of mRNA expression for the two isoforms of 5α-reductases (srd5a1, srd5a2) and for androgen receptor (AR) revealed that both increased in the hippocampus after exercise, even in ORX rats. All rats were injected twice with 5′-bromo-2′deoxyuridine (50 mg/kg body weight, i.p.) on the day before training. Mild exercise significantly increased AHN in both ORX and Sham rats. Moreover, the increase of doublecortin or 5′-bromo-2′deoxyuridine/NeuN-positive cells in ORX rats was blocked by s.c. flutamide, an AR antagonist. It was also found that application of an estrogen receptor antagonist, tamoxifen, did not suppress exercise-induced AHN. These results support the hypothesis that, in male animals, mild exercise enhances hippocampal synthesis of dihydrotestosterone and increases AHN via androgenenic mediation. PMID:22807478

  12. 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.

  13. Lithium Treatment Prevents Apoptosis in Neonatal Rat Hippocampus Resulting from Sevoflurane Exposure.

    PubMed

    Zhou, Xue; da Li, Wen-; Yuan, Bao-Long; Niu, Li-Jun; Yang, Xiao-Yu; Zhou, Zhi-Bin; Chen, Xiao-Hui; Feng, Xia

    2016-08-01

    We aimed to observe the therapeutic effects of lithium on inhalational anesthetic sevoflurane-induced apoptosis in immature brain hippocampus. From postnatal day 5 (P5) to P28, male Sprague-Dawley pups were intraperitoneally injected with lithium chloride or 0.9 % sodium chloride. On P7 after the injection, pups were exposed to 2.3 % sevoflurane or air for 6 h. Brain tissues were harvested 12 h and 3 weeks after exposure. Cleaved caspase-3, nNOS protein, GSK-3β,p-GSK-3β were assessed by Western blot, and histopathological changes were assessed using Nissl stain and TUNEL stain. From P28, we used the eight-arm radial maze test and step-through test to evaluate the influence of sevoflurane exposure on the learning and memory of juvenile rats. The results showed that neonatal sevoflurane exposure induced caspase-3 activation and histopathological changes in hippocampus can be attenuated by lithium chloride. Sevoflurane increased GSK-3β activity while pretreatment of lithium decreased GSK-3β activity. Moreover, sevoflurane showed possibly slight but temporal influence on the spatial learning and the memory of juvenile rats, and chronic use of lithium chloride might have the therapeutic effect. Our current study suggests that lithium attenuates sevoflurane induced neonatal hippocampual damage by GSK-3β pathway and might improve learning and memory deficits in rats after neonatal exposure.

  14. Dietary tryptophan restriction in rats triggers astrocyte cytoskeletal hypertrophy in hippocampus and amygdala.

    PubMed

    Zhang, Limei; Corona-Morales, Aleph A; Vega-González, Arturo; García-Estrada, Joaquín; Escobar, Alfonso

    2009-02-06

    We have previously reported that dietary tryptophan (TRP) restriction in a rat crucial postnatal developmental stage induces depression-like behavior and alters dendritic spine density in CA1 pyramidal neurons and granule cells of the hippocampus. Due to astrocyte involvement in critical brain mechanisms, it seems worth to investigate possible adaptive changes in the glial population with TRP restriction. Experimental rats were fed with low TRP diet (20% of TRP level of the laboratory rat chow) from postnatal days 30-60. Antibody against glial fibrillary acidic protein (GFAP), a principal intermediate filament in astrocytes, was used to evaluate cytoskeletal hypertrophy and glial proliferation. Our results showed an increase in size and branching of GFAP-immunoreactive (IR) cells in the dorsal hippocampus and amygdala, characteristics of an astrocytic activation. No significant differences were found regarding the number of GFAP-IR cells in both regions. These results indicate that dietary TRP restriction can induce astrocytic activation, hence, provide further evidences supporting the hypothesis that serotonin may also modulate glial morphology.

  15. Genistein inhibits aggregation of exogenous amyloid-beta₁₋₄₀ and alleviates astrogliosis in the hippocampus of rats.

    PubMed

    Bagheri, Maryam; Roghani, Mehrdad; Joghataei, Mohammad-Taghi; Mohseni, Simin

    2012-01-06

    We addressed the question of whether injection of Amyloid beta (Aβ)(1-40) in the rat brain is associated with pathology in the hippocampus, and if genistein has any protective effect against the neuronal damage caused by Aβ(1-40). Genistein is a plant-derived compound with a structure similar to that of the female sex hormone estrogen and it was recently shown that pretreatment with a single dose of genistein ameliorated learning and memory deficits in an (Aβ)(1-40) rat model of Alzheimer's disease. Here, we report that injection of the amyloid peptide into the hippocampus of rats led to formation of Aβ(1-40) positive aggregates close to the lateral blade of the dentate gyrus (DGlb). We also observed the following in the hippocampus: extensive cell death in the DGlb (P<0.0001), CA1 (P=0.03), and CA3 (P=0.002); an increased number of iNOS-expressing cells (P=0.01) and gliosis. Genistein given to rats by gavage 1h before injection of Aβ(1-40) inhibited the formation of Aβ(1-40) positive aggregates in the brain tissue and led to increased number of nNOS(+) (P=0.0001) cells in the hippocampus compared to sham-operated genistein-treated controls. Treatment with genistein also alleviated the extensive astrogliosis that occurred in Aβ(1-40)-injected hippocampus to a level similar to that observed in sham-operated rats. We conclude that the neurons in the DGlb are most sensitive to Aβ(1-40), and a single dose of genistein can ameliorate Aβ(1-40) induced pathology. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Effects of Administered Ethanol and Methamphetamine on Glial Glutamate Transporters in Rat Striatum and Hippocampus.

    PubMed

    Alshehri, Fahad S; Althobaiti, Yusuf S; Sari, Youssef

    2017-03-01

    Exposure to ethanol (EtOH) or methamphetamine (MA) can lead to increase in extracellular glutamate concentration in the brain. Although studies from ours showed the effects of EtOH exposure on key glial glutamate transporters, little is known about the effects of sequential exposure to EtOH and MA or MA alone on certain glial glutamate transporters. In this study, we investigated the effects of sequential exposure to EtOH and MA on the expression of the major glutamate transporters, glutamate transporter 1 (GLT-1), as well as cystine/glutamate antiporter (xCT) and glutamate aspartate transporter (GLAST) in striatum and hippocampus. We also tested the effects of ceftriaxone (CEF), known to upregulate GLT-1, in animals administered EtOH and MA. Wistar rats were orally gavaged with EtOH (6 g/kg) or water for 7 days. On the following day (day 8), the rats received four intraperitoneal (i.p.) injections of MA (10 mg/kg) or saline (vehicle) occurring every 2 h. The rats were then treated with CEF (200 mg/kg/day, i.p.) or saline on days 8, 9, and 10. EtOH or MA exposure caused a significant downregulation of GLT-1 expression as compared to control groups in striatum and hippocampus. Furthermore, sequential exposure of EtOH and MA caused a significant downregulation of GLT-1 expression as compared to either drug administered alone in both brain regions. Importantly, GLT-1 expression was restored following CEF treatment. There were no significant differences on xCT and GLAST expression in striatum and hippocampus between all groups. These findings demonstrated that sequential exposure to EtOH and MA has additive effect in downregulation of GLT-1 and this effect can be attenuated by CEF treatment.

  17. (R)-roscovitine, a cyclin-dependent kinase inhibitor, enhances tonic GABA inhibition in rat hippocampus.

    PubMed

    Ivanov, A; Tyzio, R; Zilberter, Y; Ben-Ari, Yehezkel

    2008-10-02

    Pharmacological agents that mediate a persistent GABAergic conductance are of considerable interest for treatment of epilepsy. (R)-roscovitine is a membrane permeable cyclin-dependent kinase inhibitor, designed to block cell division. It is currently undergoing a phase II clinical trial as an anticancer drug. We show that (R)-roscovitine increases a tonic GABA-mediated current in rat hippocampal neurons. This enhanced tonic current appears independent of synaptic GABA release and requires functional transmembrane GABA transport. The effect of (R)-roscovitine is associated with neither modification of GABAA receptors nor protein kinase activity, but is associated with a significant increase in intracellular GABA concentration in hippocampal GABAergic neurons. (R)-roscovitine-induced tonic inhibition significantly suppresses spontaneous spiking activity of hippocampal pyramidal cells. Therefore, (R)-roscovitine is a potent modulator of neuronal activity in rat hippocampus and may provide a tool for preventing paroxysmal activity.

  18. Cortical spreading depolarization increases adult neurogenesis, and alters behavior and hippocampus-dependent memory in mice.

    PubMed

    Urbach, Anja; Baum, Eileen; Braun, Falko; Witte, Otto W

    2017-05-01

    Cortical spreading depolarizations are an epiphenomenon of human brain pathologies and associated with extensive but transient changes in ion homeostasis, metabolism, and blood flow. Previously, we have shown that cortical spreading depolarization have long-lasting consequences on the brains transcriptome and structure. In particular, we found that cortical spreading depolarization stimulate hippocampal cell proliferation resulting in a sustained increase in adult neurogenesis. Since the hippocampus is responsible for explicit memory and adult-born dentate granule neurons contribute to this function, cortical spreading depolarization might influence hippocampus-dependent cognition. To address this question, we induced cortical spreading depolarization in C57Bl/6 J mice by epidural application of 1.5 mol/L KCl and evaluated neurogenesis and behavior at two, four, or six weeks thereafter. Congruent with our previous findings in rats, we found that cortical spreading depolarization increases numbers of newborn dentate granule neurons. Moreover, exploratory behavior and object location memory were consistently enhanced. Reference memory in the water maze was virtually unaffected, whereas memory formation in the Barnes maze was impaired with a delay of two weeks and facilitated after four weeks. These data show that cortical spreading depolarization produces lasting changes in psychomotor behavior and complex, delay- and task-dependent changes in spatial memory, and suggest that cortical spreading depolarization-like events affect the emotional and cognitive outcomes of associated brain pathologies.

  19. Endogenous opioid peptides as neurotransmitters in the rat hippocampus

    SciTech Connect

    Neumaier, J.F.

    1989-01-01

    The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced ({sup 3}H)-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of ({sup 3}H)-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand ({sup 3}H)-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity.

  20. Capsaicin reduces Alzheimer-associated tau changes in the hippocampus of type 2 diabetes rats

    PubMed Central

    Xu, Weijie; Liu, Juanhong; Ma, Delin; Yuan, Gang; Lu, Yan

    2017-01-01

    Type 2 diabetes (T2D) is a high-risk factor for Alzheimer’s disease (AD) due to impaired insulin signaling pathway in brain. Capsaicin is a specific transient receptor potential vanilloid 1 (TRPV1) agonist which was proved to ameliorate insulin resistance. In this study, we investigated whether dietary capsaicin could reduce the risk of AD in T2D. T2D rats were fed with capsaicin-containing high fat (HF) diet for 10 consecutive days (T2D+CAP). Pair-fed T2D rats (T2D+PF) fed with the HF-diet of average dose of T2D+CAP group were included to control for the effects of reduced food intake and body weight. Capsaicin-containing standard chow was also introduced to non-diabetic rats (NC+CAP). Blood glucose and insulin were monitored. The phosphorylation level of tau at individual sites, the activities of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) and glycogen synthase kinase-3β (GSK-3β) were analyzed by Western blots. The results revealed that the levels of phosphorylated tau protein at sites Ser199, Ser202 and Ser396 in hippocampus of T2D+CAP group were decreased significantly, but these phospho-sites in T2D+PF group didn’t show such improvements compared with T2D group. There were almost no changes in non-diabetic rats on capsaicin diet (NC+CAP) compared with the non-diabetic rats with normal chow (NC). Increased activity of PI3K/AKT and decreased activity of GSK-3β were detected in hippocampus of T2D+CAP group compared with T2D group, and these changes did not show in T2D+PF group either. These results demonstrated that dietary capsaicin appears to prevent the hyperphosphorylation of AD-associated tau protein by increasing the activity of PI3K/AKT and inhibiting GSK-3β in hippocampus of T2D rats, which supported that dietary capsaicin might have a potential use for the prevention of AD in T2D. PMID:28225806

  1. Capsaicin reduces Alzheimer-associated tau changes in the hippocampus of type 2 diabetes rats.

    PubMed

    Xu, Weijie; Liu, Juanhong; Ma, Delin; Yuan, Gang; Lu, Yan; Yang, Yan

    2017-01-01

    Type 2 diabetes (T2D) is a high-risk factor for Alzheimer's disease (AD) due to impaired insulin signaling pathway in brain. Capsaicin is a specific transient receptor potential vanilloid 1 (TRPV1) agonist which was proved to ameliorate insulin resistance. In this study, we investigated whether dietary capsaicin could reduce the risk of AD in T2D. T2D rats were fed with capsaicin-containing high fat (HF) diet for 10 consecutive days (T2D+CAP). Pair-fed T2D rats (T2D+PF) fed with the HF-diet of average dose of T2D+CAP group were included to control for the effects of reduced food intake and body weight. Capsaicin-containing standard chow was also introduced to non-diabetic rats (NC+CAP). Blood glucose and insulin were monitored. The phosphorylation level of tau at individual sites, the activities of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) and glycogen synthase kinase-3β (GSK-3β) were analyzed by Western blots. The results revealed that the levels of phosphorylated tau protein at sites Ser199, Ser202 and Ser396 in hippocampus of T2D+CAP group were decreased significantly, but these phospho-sites in T2D+PF group didn't show such improvements compared with T2D group. There were almost no changes in non-diabetic rats on capsaicin diet (NC+CAP) compared with the non-diabetic rats with normal chow (NC). Increased activity of PI3K/AKT and decreased activity of GSK-3β were detected in hippocampus of T2D+CAP group compared with T2D group, and these changes did not show in T2D+PF group either. These results demonstrated that dietary capsaicin appears to prevent the hyperphosphorylation of AD-associated tau protein by increasing the activity of PI3K/AKT and inhibiting GSK-3β in hippocampus of T2D rats, which supported that dietary capsaicin might have a potential use for the prevention of AD in T2D.

  2. Profiling Proteins in the Hypothalamus and Hippocampus of a Rat Model of Premenstrual Syndrome Irritability

    PubMed Central

    Wei, Sheng; Wei, Xia; Wu, Jibiao

    2017-01-01

    Premenstrual syndrome (PMS) refers to several physical and mental symptoms (such as irritability) commonly encountered in clinical gynaecology. The incidence of PMS has been increasing, attracting greater attention from medical fields. However, PMS pathogenesis remains unclear. This study employed two-dimensional gel electrophoresis (2DE) for proteomic map analysis of the hypothalamus and hippocampus of rat models of premenstrual syndrome (PMS) irritability. Matrix-assisted laser desorption/ionisation time of flight mass spectroscopy (MALDI-TOF-MS) was used to identify proteins possibly related with PMS irritability. Baixiangdan, a traditional Chinese medicine effective against PMS irritability, was used in the rat model to study putative target proteins of this medicine. The hypothalamus and hippocampus of each group modelling PMS displayed the following features: decreased expression of Ulip2, tubulin beta chain 15, α actin, and interleukin 1 receptor accessory protein; increased expression of kappa-B motif-binding phosphoprotein; decreased expression of hydrolase at the end of ubiquitin carboxy, albumin, and aldolase protein; and increased expression of M2 pyruvate kinase, panthenol-cytochrome C reductase core protein I, and calcium-binding protein. Contrasting with previous studies, the current study identified new proteins related to PMS irritability. Our findings contribute to understanding the pathogenesis of PMS irritability and could provide a reference point for further studies. PMID:28255462

  3. Profiling Proteins in the Hypothalamus and Hippocampus of a Rat Model of Premenstrual Syndrome Irritability.

    PubMed

    Qiao, Mingqi; Sun, Peng; Wang, Yang; Wei, Sheng; Wei, Xia; Song, Chunhong; Wang, Fushun; Wu, Jibiao

    2017-01-01

    Premenstrual syndrome (PMS) refers to several physical and mental symptoms (such as irritability) commonly encountered in clinical gynaecology. The incidence of PMS has been increasing, attracting greater attention from medical fields. However, PMS pathogenesis remains unclear. This study employed two-dimensional gel electrophoresis (2DE) for proteomic map analysis of the hypothalamus and hippocampus of rat models of premenstrual syndrome (PMS) irritability. Matrix-assisted laser desorption/ionisation time of flight mass spectroscopy (MALDI-TOF-MS) was used to identify proteins possibly related with PMS irritability. Baixiangdan, a traditional Chinese medicine effective against PMS irritability, was used in the rat model to study putative target proteins of this medicine. The hypothalamus and hippocampus of each group modelling PMS displayed the following features: decreased expression of Ulip2, tubulin beta chain 15, α actin, and interleukin 1 receptor accessory protein; increased expression of kappa-B motif-binding phosphoprotein; decreased expression of hydrolase at the end of ubiquitin carboxy, albumin, and aldolase protein; and increased expression of M2 pyruvate kinase, panthenol-cytochrome C reductase core protein I, and calcium-binding protein. Contrasting with previous studies, the current study identified new proteins related to PMS irritability. Our findings contribute to understanding the pathogenesis of PMS irritability and could provide a reference point for further studies.

  4. Effects of static magnetic field and cadmium on oxidative stress and DNA damage in rat cortex brain and hippocampus.

    PubMed

    Amara, Salem; Douki, Thierry; Garrel, Catherine; Favier, Alain; Ben Rhouma, Khémais; Sakly, Mohsen; Abdelmelek, Hafedh

    2011-03-01

    The present study was undertaken to determine the effect of co-exposure to static magnetic field (SMF) and cadmium (Cd) on the antioxidant enzymes activity and DNA integrity in rat brain. Sub-chronic exposure to CdCl (CdCl(2), 40 mg/L, per os) for 30 days resulted in a significant reduction in antioxidant enzyme activity such as the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in frontal cortex and hippocampus. Total GSH were decreased in the frontal cortex of the Cd-exposed group. Cd exposure induced an increase in malondialdehyde (MDA) concentration in the frontal cortex and hippocampus. Moreover, the same exposure increased 8-oxo-7,8-dihydro-2-desoxyguanosine (8-oxodGuo) level in rat brain. Interestingly, the combined effect of SMF (128 mT, 1 hour/day for 30 consecutive days) and CdCl (40 mg/L, per os) decreased the SOD activity and glutathione level in frontal cortex as compared with the Cd group. Moreover, the association between SMF and Cd increased MDA concentration in frontal cortex as compared with Cd-exposed rats. DNA analysis revealed that SMF exposure failed to alter 8-oxodGuo concentration in Cd-exposed rats. Our data showed that Cd exposure altered the antioxidant enzymes activity and induced oxidative DNA lesions in rat brain. The combined effect of SMF and Cd increased oxidative damage in rat brain as compared with Cd-exposed rats.

  5. The Effects of L-arginine on the Hippocampus of Male Rat Fetuses under Maternal Stress

    PubMed Central

    Mahmoudi, Reza; Enant, Elham; Delaviz, Hamdollah; Rad, Parastou; Roozbehi, Amrollah; Jafari Barmak, Mehrzad; Azizi, Arsalan

    2016-01-01

    Introduction: Prenatal stress has deleterious effects on the development of the brain and is associated with behavioral and psychosocial problems in childhood and adulthood. This study aimed to determine the protective effect of L-arginine on fetal brain under maternal stress. Methods: Twenty pregnant Wistar rats (weighting 200–230 g) were randomly divided into 4 groups (n=5 for each group). The first nonstress and stress groups received 2 mL of normal saline and the other nonstress and stress two groups received L-arginine (200 mg/kg, IP) from their 5th to 20th days of pregnancy. The pregnant rats were killed on 20th day and the brain fetuses removed and prefrontal cortical thickness, total neurons in the prefrontal cortex and in the areas of CA1, CA2, and CA3 of the hippocampus were measured and counted. Nitrite levels in the brain were measured as an indicator for nitric oxide (NO) level. Results: There was a significant decrease of mean number of pyramidal cells in the CA1 in prenatal stress group compared to nonstress and nonstress plus arginine groups. The NO level in brain tissue increased significantly in the stress plus arginine (3.8±0.4 nmol/mg) and in nonstress rats (2.9±0.3 nmol/mg) compared to the stress group (1.8±0.1 nmol/mg). Prefrontal cortical thickness decreased significantly in stress rats (1.2±0.09 mm) compared to the nonstress plus arginine (1.7±0.15 mm) and nonstress (1.6±0.13 mm) groups. Discussion: Results indicated that prenatal stress could lead to neurodegeneration of hippocampus and prefrontal cortex of rat fetuses. L-arginine as a precursor of NO synthesis had neuroprotective effect during prenatal stress and could be used an effective treatment for stress. PMID:27303594

  6. Surface L-type Ca2+ channel expression levels are increased in aged hippocampus

    PubMed Central

    Núñez-Santana, Félix Luis; Oh, Myongsoo Matthew; Antion, Marcia Diana; Lee, Amy; Hell, Johannes Wilhelm; Disterhoft, John Francis

    2014-01-01

    Age-related increase in L-type Ca2+ channel (LTCC) expression in hippocampal pyramidal neurons has been hypothesized to underlie the increased Ca2+ influx and subsequent reduced intrinsic neuronal excitability of these neurons that lead to age-related cognitive deficits. Here, using specific antibodies against Cav1.2 and Cav1.3 subunits of LTCCs, we systematically re-examined the expression of these proteins in the hippocampus from young (3 to 4 month old) and aged (30 to 32 month old) F344xBN rats. Western blot analysis of the total expression levels revealed significant reductions in both Cav1.2 and Cav1.3 subunits from all three major hippocampal regions of aged rats. Despite the decreases in total expression levels, surface biotinylation experiments revealed significantly higher proportion of expression on the plasma membrane of Cav1.2 in the CA1 and CA3 regions and of Cav1.3 in the CA3 region from aged rats. Furthermore, the surface biotinylation results were supported by immunohistochemical analysis that revealed significant increases in Cav1.2 immunoreactivity in the CA1 and CA3 regions of aged hippocampal pyramidal neurons. In addition, we found a significant increase in the level of phosphorylated Cav1.2 on the plasma membrane in the dentate gyrus of aged rats. Taken together, our present findings strongly suggest that age-related cognitive deficits cannot be attributed to a global change in L-type channel expression nor to the level of phosphorylation of Cav1.2 on the plasma membrane of hippocampal neurons. Rather, increased expression and density of LTCCs on the plasma membrane may underlie the age-related increase in L-type Ca2+ channel activity in CA1 pyramidal neurons. PMID:24033980

  7. [Effects of electromagnetic irradiation on glucocorticoid in serum and its receptor expression in rat hippocampus].

    PubMed

    Li, Mao-quan; Wang, Yan-yan; Zhang, Guang-bin; Yu, Zheng-ping

    2007-04-01

    To explore the role and mechanism of glucocorticoid (GC) in the harmful bio-effects of electromagnetic irradiation. Rats were exposed to 65 mW/cm(2) electromagnetic wave for 20 min. At 10 min, 30 min, 3 h, 12 h after irradiation, their learning and memory abilities were tested by Morris water maze. The levels of corticosterone (CORT) in serum were measured by radioimmunoprecipitation assay and the changes of total glucocorticoid receptor (GR) expression and GR nuclear translocation in rat hippocampus were measured by reverse transcription-polymerase chain reaction and Western blot. The rats had learning and memory deficits at 10 min, 30 min and 3 h after irradiation, but at 12 h had no difference from the normal control. The levels of corticosterone in serum increased significantly at 10 min, 30 min, decreased at 3 h and increased significantly compared with 12 h after irradiation. GR mRNA and total GR protein expression in rat hippocampus had no significant changes at 10 min, 30 min after irradiation. At 3 h, 12 h GR mRNA expression significantly decreased by 69%, 76% respectively and GR total protein decreased by 58%, 67% respectively. There were significant differences between the two groups and the corresponding controls (P<0.05). And compared with the control, the GR nuclear translocation increased significantly at 3 h and 12 h (P<0.05). GC may take part in the injury to learning and memory abilities after electromagnetic irradiation, and the non-genomic and genomic effects of GC may play a major role in the early and late stage, respectively.

  8. Primary Blast-Induced Changes in Akt and GSK3β Phosphorylation in Rat Hippocampus

    PubMed Central

    Wang, Yushan; Sawyer, Thomas W.; Tse, Yiu Chung; Fan, Changyang; Hennes, Grant; Barnes, Julia; Josey, Tyson; Weiss, Tracy; Nelson, Peggy; Wong, Tak Pan

    2017-01-01

    Traumatic brain injury (TBI) due to blast from improvised explosive devices has been a leading cause of morbidity and mortality in recent conflicts in Iraq and Afghanistan. However, the mechanisms of primary blast-induced TBI are not well understood. The Akt signal transduction pathway has been implicated in various brain pathologies including TBI. In the present study, the effects of simulated primary blast waves on the phosphorylation status of Akt and its downstream effector kinase, glycogen synthase kinase 3β (GSK3β), in rat hippocampus, were investigated. Male Sprague-Dawley (SD) rats (350–400 g) were exposed to a single pulse shock wave (25 psi; ~7 ms duration) and sacrificed 1 day, 1 week, or 6 weeks after exposure. Total and phosphorylated Akt, as well as phosphorylation of its downstream effector kinase GSK3β (at serine 9), were detected with western blot analysis and immunohistochemistry. Results showed that Akt phosphorylation at both serine 473 and threonine 308 was increased 1 day after blast on the ipsilateral side of the hippocampus, and this elevation persisted until at least 6 weeks postexposure. Similarly, phosphorylation of GSK3β at serine 9, which inhibits GSK3β activity, was also increased starting at 1 day and persisted until at least 6 weeks after primary blast on the ipsilateral side. In contrast, p-Akt was increased at 1 and 6 weeks on the contralateral side, while p-GSK3β was increased 1 day and 1 week after primary blast exposure. No significant changes in total protein levels of Akt and GSK were observed on either side of the hippocampus at any time points. Immunohistochemical results showed that increased p-Akt was mainly of neuronal origin in the CA1 region of the hippocampus and once phosphorylated, the majority was translocated to the dendritic and plasma membranes. Finally, electrophysiological data showed that evoked synaptic N-methyl-d-aspartate (NMDA) receptor activity was significantly increased

  9. The longitudinal study of rat hippocampus influenced by stress: early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats.

    PubMed

    Jin, Fengkui; Li, Lei; Shi, Mei; Li, Zhenzi; Zhou, Jinghua; Chen, Li

    2013-06-01

    Epidemiologic studies indicate that early adverse experience is related to learning disabilities in adults, but the neurobiological mechanisms have not yet been identified. We used longitudinal animal experiments to test the hypothesis that early life stress enhances hippocampal vulnerability and working memory deficit in adult rats. The expression of Synaptophysin (SYN) and apoptosis (Apo) in hippocampal CA3 and dentate gyrus (DG) regions were examined to evaluate the effects of environmental factors on the hippocampus. The working memory errors via radial 8-arm maze were studied to evaluate the long-term effect of early stress on rats' spatial learning ability. Our results indicated that chronic restraint stress in early life and forced cold water swimming stress in adulthood reduced SYN expression and increased Apo levels in rat hippocampus, but the hippocampal damage tended to recover when rats returned to a non-stress environment. In addition, when the rats were exposed to forced cold water swimming stress during adulthood, SYN expression (CA3 and DG regions) and Apo levels (CA3 region) in rat hippocampus showed statistical difference between early restraint stress group and non-early restraint stress group (rats exposed to stress in adulthood only). One month after the two groups of rats returned to non-stress environment, this difference of SYN expression (CA3 and DG regions) and working memory deficit between the two groups was still statistically significant. Our study findings suggested that early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats, and reduces structural plasticity of hippocampus.

  10. Escitalopram affects spexin expression in the rat hypothalamus, hippocampus and striatum.

    PubMed

    Pałasz, Artur; Suszka-Świtek, Aleksandra; Filipczyk, Łukasz; Bogus, Katarzyna; Rojczyk, Ewa; Worthington, John; Krzystanek, Marek; Wiaderkiewicz, Ryszard

    2016-12-01

    Spexin (SPX) is a recently discovered neuropeptide that exhibits a large spectrum of central and peripheral regulatory activity, especially when considered as a potent anorexigenic factor. It has already been proven that antidepressants, including selective serotonin reuptake inhibitors (SSRI), can modulate peptidergic signaling in various brain structures. Despite these findings, there is so far no information regarding the influence of treatment with the SSRI antidepressant escitalopram on brain SPX expression. In this current study we measured SPX mRNA and protein expression in the selected brain structures (hypothalamus, hippocampus and striatum) of rats chronically treated with a 10mg/kg dose of escitalopram using quantitative Real-Time PCR and immunohistochemistry. Strikingly, long-term (4 week) drug treatment led to the downregulation of SPX expression in the rat hypothalamus. This supports the hypothesis that SPX may be involved in the hypothalamic serotonin-dependent actions of SSRI antidepressants and possibly also in the central mechanism of body mass increase. Conversely, SPX expression increased in the hippocampus and striatum. This is the first report of the effects of a neuropsychiatric medication on SPX expression in animal brain. Our findings shed a new light on the pharmacology of antidepressants and may contribute to a better understanding of the alternative mechanisms responsible for antidepressant action. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. 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.

  12. Quantitative analysis of iron concentration and expression of ferroportin 1 in the cortex and hippocampus of rats induced by cerebral ischemia.

    PubMed

    Li, Lin; Li, Yan-wei; Zhao, Jin-ying; Liu, Yue-Ze; Holscher, Christian

    2009-11-01

    Iron overload induced by brain ischemia has been shown to be involved in neurodegenerative disease. Little is known about the relationship between brain ischemia and ferroportin 1 (FP1). The aims of this study are: (i) to determine whether iron accumulation in the brain is induced by cerebral hypoperfusion; and (ii) to test whether expression of FP1 is influenced by cerebral ischemia. The common carotid arteries (CCA) of rats were ligated bilaterally to induce cerebral ischemia, and the iron concentration of the cortex and hippocampus was measured by graphite furnace atomic absorption spectrometry. Iron was stained by Perl's method. The expression of FP1 mRNA and protein was shown by the reverse transcriptase polymerase chain reaction and immunohistochemical methods. The iron concentration in the cortex and hippocampus of ischemic rats had increased on day 7 (CCA7) and significantly on day 28 (CCA28) compared to control rats. More iron granules had been deposited in the cerebral cortex and hippocampus in rats with bilaterally ligated CCA on CCA7 and CCA28. In ischemic rats, FP1 expression in the cerebral cortex and hippocampus was decreased by CCA7 and this was more marked by CCA28 compared to control rats. We therefore concluded that iron deposition in the cerebral cortex and hippocampus of rats is induced by cerebral ischemia. Iron deposition may be attributed to the decrease in FP1 expression, and this inhibition of FP1 expression could be a major contributor to the formation of iron deposits in cerebral ischemia.

  13. Baicalin influences the dendritic morphology of newborn neurons in the hippocampus of chronically stressed rats.

    PubMed

    Jiang, Xinghua; Xu, Junmei; Zou, Dingquan; Yang, Lin; Wang, Yaping

    2013-02-25

    Chronic stress models, established in adult Sprague-Dawley rats through a 14-day subcutaneous injection of 40 mg/kg corticosterone, once per day, were given a daily oral feeding of 50 mg/kg baicalin. The study was an attempt to observe the effect of baicalin on neurogenesis in chronically stressed rats. Results showed that subcutaneous injection of corticosterone significantly decreased the total number of doublecortin-positive neurons in the hippocampus. The reduced cell number caused by corticosterone was mainly due to the decrease of class II doublecortin-positive neurons, but the class I doublecortin-positive neurons were unaffected. Baicalin treatment increased the number of both class I and class II doublecortin-positive neurons. In addition, doublecortin-positive neurons showed less complexity in dendritic morphology after corticosterone injection, and this change was totally reversed by baicalin treatment. These findings suggest that baicalin exhibits a beneficial effect on adult neurogenesis.

  14. 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

  15. Exposure to 2.45 GHz electromagnetic fields elicits an HSP-related stress response in rat hippocampus.

    PubMed

    Yang, Xue-Sen; He, Gen-Lin; Hao, Yu-Tong; Xiao, Yang; Chen, Chun-Hai; Zhang, Guang-Bin; Yu, Zheng-Ping

    2012-07-01

    The issue of possible neurobiological effects of the electromagnetic field (EMF) exposure is highly controversial. To determine whether electromagnetic field exposure could act as an environmental stimulus capable of producing stress responses, we employed the hippocampus, a sensitive target of electromagnetic radiation, to assess the changes in its stress-related gene and protein expression after EMF exposure. Adult male Sprague-Dawley rats with body restrained were exposed to a 2.45 GHz EMF at a specific absorption rate (SAR) of 6 W/kg or sham conditions. cDNA microarray was performed to examine the changes of gene expression involved in the biological effects of electromagnetic radiation. Of 2048 candidate genes, 23 upregulated and 18 downregulated genes were identified. Of these differential expression genes, two heat shock proteins (HSP), HSP27 and HSP70, are notable because expression levels of both proteins are increased in the rat hippocampus. Result from immunocytochemistry revealed that EMF caused intensive staining for HSP27 and HSP70 in the hippocampus, especially in the pyramidal neurons of cornu ammonis 3 (CA3) and granular cells of dentate gyrus (DG). The gene and protein expression profiles of HSP27 and HSP70 were further confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Our data provide direct evidence that exposure to electromagnetic fields elicits a stress response in the rat hippocampus.

  16. Effect of exercise on synaptophysin and calcium/calmodulin-dependent protein kinase levels in prefrontal cortex and hippocampus of a rat model of developmental stress

    PubMed Central

    Hescham, Sarah; Grace, Laurian; Kellaway, Lauriston A; Bugarith, Kishor; Russell, Vivienne A

    2010-01-01

    Stress affects the brain differently depending on the timing, duration and intensity of the stressor. Separation from the dam for 3 hours per day is a potent stressor for rat pups which causes activation of the hypothalamic-pituitary-adrenal (HPA) axis, evidenced by increased plasma levels of adrenocorticotropin (ACTH) and glucocorticoids. Behaviourally, animals display anxiety-like behaviour while structurally, changes occur in neuronal dendrites and spines in the hippocampus and prefrontal regions involved in emotion and behaviour control. The aim of the present study was to determine whether maternal separation alters expression of synaptic markers, synaptophysin and calcium/calmodulin-dependent protein kinase II, CaMKII, in rat hippocampus and prefrontal cortex. A second aim was to determine whether voluntary exercise had a beneficial effect on the expression of these proteins in rat brain. Maternal separation occurred from postnatal day 2 (P2) to P14 for 3 hours per day. Exercised rats were housed in cages with attached running wheels from P29 to P49. At P65, the prefrontal cortex and hippocampus were removed for protein quantification. Maternal separation did not have any effect while exercise increased synaptophysin and CaMKII in the ventral hippocampus but not in the dorsal hippocampus or prefrontal cortex. Since the ventral hippocampus is associated with anxiety-related behaviour, these findings are consistent with the fact that voluntary exercise increases anxiety-like behaviour and improves learning and memory. PMID:19821017

  17. Developmental expression of parvalbumin mRNA in the cerebral cortex and hippocampus of the rat.

    PubMed

    de Lecea, L; del Río, J A; Soriano, E

    1995-08-01

    Parvalbumin (PARV) belongs to the family of calcium-binding proteins bearing the EF hand domain. Immunocytochemical studies in the cerebral cortex have demonstrated that neurons containing PARV include two types of GABAergic interneurons, namely, basket and axo-axonic chandelier cells. The present study examines the onset and pattern of PARV mRNA expression during the development of rat neocortex and hippocampus by means of 'in situ' hybridization with an oligonucleotide probe corresponding to rat PARV cDNA. In animals aged P0-P6 no signal was detected above background in neocortex or hippocampus. At P8, a few cortical cells displayed a number of silver grains just above background levels. By P10 PARV mRNA-expressing cells in the neocortex were detected almost exclusively in layer V of somatosensory, frontal and cingulate cortices. At P12 PARV mRNA was mainly detected in layers IV, V and VIa. By P14 there was a marked overall increase in the entire neocortex, including layer II-III, both in the number of cells and in their intensity of labelling. Further maturation in the pattern of PARV mRNA concentration was observed between P16 and P21. In the hippocampus low hybridization was observed at P10-P12. In subsequent stages both the number of positive cells and the intensity of labelling increased steadily. No clear-cut radial gradients for the expression of PARV mRNA were observed in the hippocampal region. Our results show that the developmental radial gradient followed by PARV mRNA expression in the neocortex does not follow an 'inside-out' gradient, consistent with previous immunocytochemical findings. Taken together, these data indicate that the developmental sequence followed by the PARV protein directly reflects mRNA abundance and suggest that PARV mRNA expression correlates with the functional maturation of cortical interneurons.

  18. Prenatal and lactational lead exposure enhanced oxidative stress and altered apoptosis status in offspring rats' hippocampus.

    PubMed

    Lu, Xiaobo; Jin, Cuihong; Yang, Jinghua; Liu, Qiufang; Wu, Shengwen; Li, Dandan; Guan, Yangyang; Cai, Yuan

    2013-01-01

    Oxidative stress and apoptosis facilitation in the developing central nervous system (CNS) have been inferred as two mechanisms related to lead's neurotoxicity, and excessive reactive oxygen species (ROS) can promote oxidative stress and apoptosis facilitation. Few studies systematically investigated the potential relationship among oxidative stress, ROS generation, and apoptosis facilitation after lead exposure in earlier life as a whole. To better understand the adverse effect on the developing central nervous system (CNS) after lead exposure during pregnancy and lactation, the indexes of oxidative stress, apoptosis status, and Bax and Bcl-2 expression of offspring rats' hippocampus were determined. Pregnant rats were randomly divided into four groups and given free access to drinking water which contained 0 %, 0.05 %, 0.1 %, and 0.2 % Pb(AC)(2) respectively from gestation day 0 to postnatal day 21 (PND21). Results showed that ROS and malondialdehyde level of either PND7 or PND21 pups' hippocampus were significantly raised; reduced glutathione level and superoxide dismutase activity were obviously decreased following the increase of blood and brain lead level. Similar to apoptotic indexes, Bax/Bcl-2 ratio increased after 0.1 % and 0.2 % Pb(AC)(2) exposure, especially for the pups on PND7. Comparing with cortex, the hippocampus seemed much more sensitive to damage induced by lead. We concluded that the disruption of pro-oxidant and antioxidant balance and apoptosis facilitation could be associated with the mechanisms of neurotoxicity after lead exposure in earlier life.

  19. Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus

    PubMed Central

    Cohen, Ami; Soleiman, Matthew T.; Talia, Reneta; Koob, George F.; George, Olivier; Mandyam, Chitra D.

    2014-01-01

    Rationale Limited access nicotine self-administration decreases hippocampal neurogenesis, providing a mechanism for the deleterious effects of nicotine on hippocampal neuronal plasticity. However, recent studies have shown that limited access nicotine self-administration does not exhibit key features of nicotine dependence such as motivational withdrawal and increased motivation for nicotine after deprivation. Objectives The present study used extended access nicotine self-administration (0.03 mg/kg/infusion, 21h/day (d), 4d) with intermittent periods of deprivation (3d) for 14 weeks, to test the hypothesis that this model enhances nicotine seeking and produces distinct responses in hippocampal neurogenesis when compared with limited access (1h/day, 4d) intake. Animals in the extended access group were either perfused prior to or following their final deprivation period, whereas animals in the limited access group were perfused after their last session. Results Limited access nicotine self-administration and extended access nicotine self-administration with periodic deprivation did not affect proliferation and differentiation of oligodendrocyte progenitors in the medial prefrontal cortex (mPFC). Conversely, extended access nicotine self-administration with periodic deprivation enhanced proliferation and differentiation of hippocampal neural progenitors. Furthermore, in the hippocampus, the number of differentiating NeuroD-labeled cells strongly and positively correlated with enhanced nicotine seeking in rats that experienced extended access nicotine self-administration. Conclusions These findings demonstrate that extended access versus limited access to nicotine self-administration differentially affects the generation of new oligodendroglia and new neurons during adulthood. The increases in the number of differentiating cells in extended access nicotine self-administering rats may consequently contribute to aberrant hippocampal neurogenesis and may contribute to

  20. Rats use hippocampus to recognize positions of objects located in an inaccessible space.

    PubMed

    Levcik, D; Nekovarova, T; Stuchlik, A; Klement, D

    2013-02-01

    Rat hippocampus plays a crucial role in many spatial tasks, including recognition of position of objects, which can be approached and explored. Whether hippocampus is also necessary for recognizing positions of objects located in an inaccessible part of the environment remains unclear. To address this question, we conditioned rats to press a lever when an object displayed on a distant computer screen was in a particular position ("reward position") and not to press the lever when the object was in other positions ("nonreward positions"). After the rats had reached an asymptotic performance, the role of the dorsal hippocampus was assessed by blocking its activity with muscimol. The rats without functional dorsal hippocampus did not discriminate the reward position from the nonreward positions. Then the same rats were trained to discriminate light and dark conditions. The hippocampal inactivation did not disrupt the ability to discriminate these two conditions. It indicated that the inactivation itself had no major effect on the operant behavior and its control by visual stimuli. We conclude that rats use dorsal hippocampus for recognizing positions of objects located in an inaccessible part of the environment.

  1. Neonatal ventral hippocampus lesion alters the dopamine content in the limbic regions in postpubertal rats.

    PubMed

    Alquicer, Glenda; Silva-Gómez, Adriana B; Peralta, Fernando; Flores, Gonzalo

    2004-04-01

    The neonatal ventral Hippocampus (nVH) lesion in rats has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. The schizophrenic patients tend to social isolation. In addition, considerable evidence from behavioral and neurochemistry studies strongly implicate the dopamine (DA) system and the medial part of the prefrontal cortex (mPFC) in the pathophysiology of the social isolation syndrome. In order to assess effects of the postweaning social isolation (pwSI) on the DA system of the nVH lesions, we investigated the DA content and its metabolite, DOPAC in different limbic subregions in rats postpubertally at postnatal day (P) 78 following nVH lesions at P7 with and without pwSI for 8 weeks. The DA and DOPAC were measured by HPLC with electrochemical detection. The nVH lesion induces increase in the DA content in the hippocampus with no effect in the mPFC, nucleus accumbens and caudate-putamen, while the pwSI induces major increase in the DA content in limbic subregions such as the mPFC, nucleus accumbens and hipocampus with opposite effect in the caudate-putamen. These results suggest that while pwSI has an effect in the postpubertal content of DA in both sham and nVH lesions in rats, the nVH-lesioned rats appear to be affected to a greater extent than the sham animals underscoring the influence of pwSI differences in the development of behaviors in the nVH-lesioned animals.

  2. [Effects of aluminum intake on the content of aluminum, iron, zinc and lipid peroxidation in the hippocampus of rats].

    PubMed

    Jia, Y; Zhong, C; Wang, Y; Zhao, R

    2001-05-01

    Effect of long-term exposure to aluminum on the content of aluminum, iron, zinc, copper and the lipid peroxidation in hippocampus was studied. Sprague-Dawley rats were randomly divided into four groups by body weight. Aluminum chloride was added to diet at doses of Al3+ 0, 11.2, 55.9 and 111.9 mg/kg BW for successive 90 days. Neuro-behavioral tests consisted of open field and passive-avoidance conditioning were performed. SOD and GSH-Px activities and MDA levels were detected by spectrophotometry. The values of aluminum, iron, zinc and copper were measured by atomic absorption spectroscopy. The spontaneous motor ability in the open field and the latency of passive avoidance were decreased as compared with the controls. The concentration of aluminum was increased and iron and zinc were decreased copper was not changed significantly; the activities of SOD and GSH-Px were reduced, while the value of MDA was increased in hippocampus. The results suggested that long-term aluminum-exposure could lead to high accumulation of aluminum in hippocampus, which could disturb the normal distribution of iron and zinc, decrease the activities of antioxidase and increase the level of lipid peroxidation. Accumulation of aluminum and accompany with reduction of iron, zinc in hippocampus and oxidative damage to hippocampus might interpret the neurotoxicity of aluminum.

  3. Effects of vitamin A deficiency and opioids on parvalbumin + interneurons in the hippocampus of the HIV-1 transgenic rat.

    PubMed

    Guo, Ming; Bryant, Joseph; Sultana, Shireen; Jones, Odell; Royal, Walter

    2012-07-01

    Opioid use in HIV infection has been associated with an increased frequency of neurological disease and cognitive impairment and vitamin A deficiency has been linked to progressive HIV disease in drug users. In this report the potential effects of these factors, alone and in combination, on gamma amino butyric acid (GABA)-expression interneurons in hippocampus in the HIV-1 transgenic rat (TG) model were studied. TG and wild-type (WT) F344 Fisher rats deficient in vitamin A from birth were implanted either with a 37.5 mg morphine tablet or with a matching placebo and total numbers of neurons and of parvalbumin+ neurons were quantitated and parvalbumin expression was quantitated in the CA1 hippocampal region of the rats. These studies showed that total neuronal numbers were decreased in the TG versus WT Fisher rats and that this decrease was enhanced by the vitamin A deficient diet and by treatment with morphine. In contrast, there was no significant change noted in numbers of parvalbumin+ neurons. However, levels of parvalbumin expression were decreased for vitamin A deficient and morphine-treated WT rats as compared to WT rats on the normal diet and placebo-treated WT rats. For TG rats, parvalbumin expression was higher for vitamin A deficient TG rats treated with either placebo or morphine than for WT vitamin A deficient rats treated with placebo, and placebo treated vitamin A deficient TG rats showed higher expression than morphine treated vitamin A deficient rats. Expression was also higher for vitamin A deficient morphine-treated rats than for the corresponding WT rat groups and for vitamin A deficient TG rats treated with placebo. For the remaining groups, parvalbumin was similar for the TG and WT rats. These findings suggest that in hippocampus vitamin A deficiency and morphine can increase parvalbumin expression, perhaps as a manifestation of a stress response. Parvalbumin-expressing GABA-ergic interneurons regulate the primary neuronal output from

  4. Socialization alleviates burden of oxidative-stress in hippocampus and prefrontal cortex in morphine addiction period in male rats .

    PubMed

    Famitafreshi, Hamidreza; Karimian, Morteza

    2017-09-19

    Addiction is a compulsive drug-seeking and drug-taking behavior. Reduction of high-risk behaviors can reduce the burden of addiction in society and can improve the overall prognosis of drug addiction. The aim of this study is to show that reduction of oxidative stress with socialization will reduce occurrence of high-risk behavior during addiction period. Fifty-four male Sprague-Dawley rats were randomly divided into four groups: socialized, isolated, addicted socialized and addicted isolated. For inducing morphine dependence, rats received morphine (5 mg/rat/kg/day) for 14 days. Socialization was induced by putting two rats in a large cage for 14 days. On the other hand, isolation was induced by putting rats in separate small cages covered with black plastic for the same period. At the end of study, rats were experimented with shuttle box for assessing avoidance memory and also tested with social interaction test to measure novelty-seeking behavior and anxiety level. Then animals were sacrificed for neurochemical analysis. Brain was isolated to assess oxidative-stress (OS) indices such as malondialdehyde (MDA), glutathione and nitrite/nitrate in prefrontal cortex and hippocampus. After 14 days of morphine injection, rats in socialized group had improved avoidance memory, increased anxiety levels and reduced novelty-seeking behavior. Furthermore, isolated rats had reduced glutathione and nitrite/nitrate, and higher MDA levels in prefrontal cortex and hippocampus as compared to socialized rats. Pair state had positive effect on OS indices in prefrontal cortex and hippocampus and results in reduction of relapse and poor prognosis. Thus, OS has an important role for alleviation of severity of addiction period. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Evidence That the Rat Hippocampus Has Contrasting Roles in Object Recognition Memory and Object Recency Memory

    PubMed Central

    Albasser, Mathieu M.; Amin, Eman; Lin, Tzu-Ching E.; Iordanova, Mihaela D.; Aggleton, John P.

    2012-01-01

    Adult rats with extensive, bilateral neurotoxic lesions of the hippocampus showed normal forgetting curves for object recognition memory, yet were impaired on closely related tests of object recency memory. The present findings point to specific mechanisms for temporal order information (recency) that are dependent on the hippocampus and do not involve object recognition memory. The object recognition tests measured rats exploring simultaneously presented objects, one novel and the other familiar. Task difficulty was varied by altering the retention delays after presentation of the familiar object, so creating a forgetting curve. Hippocampal lesions had no apparent effect, despite using an apparatus (bow-tie maze) where it was possible to give lists of objects that might be expected to increase stimulus interference. In contrast, the same hippocampal lesions impaired the normal preference for an older (less recent) familiar object over a more recent, familiar object. A correlation was found between the loss of septal hippocampal tissue and this impairment in recency memory. The dissociation in the present study between recognition memory (spared) and recency memory (impaired) was unusually compelling, because it was possible to test the same objects for both forms of memory within the same session and within the same apparatus. The object recency deficit is of additional interest as it provides an example of a nonspatial memory deficit following hippocampal damage. PMID:23025831

  6. Evidence that the rat hippocampus has contrasting roles in object recognition memory and object recency memory.

    PubMed

    Albasser, Mathieu M; Amin, Eman; Lin, Tzu-Ching E; Iordanova, Mihaela D; Aggleton, John P

    2012-10-01

    Adult rats with extensive, bilateral neurotoxic lesions of the hippocampus showed normal forgetting curves for object recognition memory, yet were impaired on closely related tests of object recency memory. The present findings point to specific mechanisms for temporal order information (recency) that are dependent on the hippocampus and do not involve object recognition memory. The object recognition tests measured rats exploring simultaneously presented objects, one novel and the other familiar. Task difficulty was varied by altering the retention delays after presentation of the familiar object, so creating a forgetting curve. Hippocampal lesions had no apparent effect, despite using an apparatus (bow-tie maze) where it was possible to give lists of objects that might be expected to increase stimulus interference. In contrast, the same hippocampal lesions impaired the normal preference for an older (less recent) familiar object over a more recent, familiar object. A correlation was found between the loss of septal hippocampal tissue and this impairment in recency memory. The dissociation in the present study between recognition memory (spared) and recency memory (impaired) was unusually compelling, because it was possible to test the same objects for both forms of memory within the same session and within the same apparatus. The object recency deficit is of additional interest as it provides an example of a nonspatial memory deficit following hippocampal damage. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  7. [Effects of electromagnetic radiation on RAF/MEK/ERK signaling pathway in rats hippocampus].

    PubMed

    Zuo, Hong-yan; Wang, De-wen; Peng, Rui-yun; Wang, Shui-ming; Gao, Ya-bing; Xu, Xin-ping; Ma, Jun-Jie

    2009-05-01

    To study the development of changes for signaling molecules related to Raf/MEK/ERK pathway in hippocampus of rats after electromagnetic radiation, and investigate the mechanisms of radiation injury. Rats were exposed to X-HPM, S-HPM and EMP radiation source respectively, and animal model of electromagnetic radiation was established. Western blot was used to detect the expression of Raf-1, phosphorylated Raf-1 and phospholylated ERK. The expression of Raf-1 down-regulated during 6 h-14 d after radiation, most significantly at 7 d, and recovered at 28 d. There was no significant difference between the radiation groups. The expression of phosphorylated Raf-1 and phosphorylated ERK both up-regulated at 6 h and 7 d after radiation, more significantly at 6 h, and the two microwave groups were more serious for phosphorylated ERK. During 6 h-14 d after S-HPM radiation, the expression of phosphorylated Raf-1 increased continuously, but phosphorylated ERK changed wavily, 6 h and 7 d were expression peak. Raf/MEK/ERK signaling pathway participates in the hippocampus injury induced by electromagnetic radiation. The excessive activation of ERK pathway may result in the apoptosis and death of neurons, which is the important mechanism of recognition disfunction caused by electromagnetic radiation.

  8. The MRI Contrast Agent Gadoteridol Enhances Distribution of rAAV1 in the Rat Hippocampus

    PubMed Central

    Hullinger, Rikki; Ugalde, Jeanet; Purón-Sierra, Liliana; Osting, Sue; Burger, Corinna

    2013-01-01

    Contrast agents are commonly used in combination with magnetic resonance imaging (MRI) to monitor the distribution of molecules in the brain. Recent experiments conducted in our laboratory have shown that co-infusion of recombinant Adeno-associated virus serotype 5 (rAAV5) and the MRI contrast agent gadoteridol (Gd) enhances vector transduction of in the rat striatum. The goal of this study was to determine whether gadoteridol may also be used as a tool to enhance transduction efficiency of rAAV1 and rAAV5 within the rat hippocampus. We show that Gd/rAAV1-GFP but not Gd/rAAV5-GFP co-infusion results in significantly higher distribution of the transgene both in the injected hemisphere as well as in the contralateral side and adjacent areas of cortex along the injection track. We also show that Gd/rAAV1-GFP co-infusion has no deleterious effect on hippocampal function as assessed by two tests of spatial memory formation. This work indicates that gadoteridol can be exploited as a method to increase transduction efficiency of AAV1 in the hippocampus for animal studies. PMID:24048419

  9. Induction of autophagy in rat hippocampus and cultured neurons by iron.

    PubMed

    He, Y; Hua, Y; Song, S; Liu, W; Keep, R F; Xi, G

    2008-01-01

    Autophagy occurs in the brain after intracerebral hemorrhage (ICH). Iron is an important factor causing neuronal death and brain atrophy after ICH. In this study, we examined whether iron can induce autophagy in the hippocampus and in cultured neurons. For in vivo studies, rats received an infusion of either saline or ferrous iron into the right hippocampus and were killed 1, 3, or 7 days later for Western blot analysis of microtubule-associated protein light chain-3 (LC3). For in vitro studies, primary cultured cortex neurons from rat embryos were exposed to ferrous iron. Cells were used for Western blot analysis of LC3 and monodansylcadaverine (MDC) staining 24h later. Intrahippocampal injection of ferrous iron resulted in an increased conversion of LC3-I to LC3-II. Exposure of primary cultured neurons to ferrous iron also induced an enhanced conversion of LC3-I to LC3-II. MDC labeling showed an accumulation of MDC in cultured neurons exposed to ferrous iron. These results indicate that autophagy is induced by iron in neurons and that iron-induced autophagy may contribute to brain injury after ICH.

  10. The MRI contrast agent gadoteridol enhances distribution of rAAV1 in the rat hippocampus.

    PubMed

    Hullinger, R; Ugalde, J; Purón-Sierra, L; Osting, S; Burger, C

    2013-12-01

    Contrast agents are commonly used in combination with magnetic resonance imaging (MRI) to monitor the distribution of molecules in the brain. Recent experiments conducted in our laboratory have shown that co-infusion of recombinant Adeno-associated virus serotype 5 (rAAV5) and the MRI contrast agent gadoteridol (Gd) enhances vector transduction in the rat striatum. The goal of this study was to determine whether gadoteridol may also be used as a tool to enhance transduction efficiency of rAAV1 and rAAV5 within the rat hippocampus. We show that Gd/rAAV1-GFP but not Gd/rAAV5-GFP co-infusion results in significantly higher distribution of the transgene both in the injected hemisphere as well as in the contralateral side and adjacent areas of cortex along the injection track. We also show that Gd/rAAV1-GFP co-infusion has no deleterious effect on hippocampal function as assessed by two tests of spatial memory formation. This work indicates that Gd can be exploited as a method to increase transduction efficiency of AAV1 in the hippocampus for animal studies.

  11. Morphine Withdrawal Modifies Prion Protein Expression in Rat Hippocampus

    PubMed Central

    Mattei, Vincenzo; Martellucci, Stefano; Santilli, Francesca; Manganelli, Valeria; Garofalo, Tina; Candelise, Niccolò; Caruso, Alessandra; Sorice, Maurizio; Scaccianoce, Sergio

    2017-01-01

    The hippocampus is a vulnerable brain structure susceptible to damage during aging and chronic stress. Repeated exposure to opioids may alter the brain so that it functions normally when the drugs are present, thus, a prolonged withdrawal might lead to homeostatic changes headed for the restoration of the physiological state. Abuse of morphine may lead to Reacting Oxygen Species-induced neurodegeneration and apoptosis. It has been proposed that during morphine withdrawal, stress responses might be responsible, at least in part, for long-term changes of hippocampal plasticity. Since prion protein is involved in both, Reacting Oxygen Species mediated stress responses and synaptic plasticity, in this work we investigate the effect of opiate withdrawal in rats after morphine treatment. We hypothesize that stressful stimuli induced by opiate withdrawal, and the subsequent long-term homeostatic changes in hippocampal plasticity, might modulate the Prion protein expression. Our results indicate that abstinence from the opiate induced a time-dependent and region-specific modification in Prion protein content, indeed during morphine withdrawal a selective unbalance of hippocampal Prion Protein is observable. Moreover, Prion protein overexpression in hippocampal tissue seems to generate a dimeric structure of Prion protein and α-cleavage at the hydrophobic domain. Stress factors or toxic insults can induce cytosolic dimerization of Prion Protein through the hydrophobic domain, which in turn, it stimulates the α-cleavage and the production of neuroprotective Prion protein fragments. We speculate that this might be the mechanism by which stressful stimuli induced by opiate withdrawal and the subsequent long-term homeostatic changes in hippocampal plasticity, modulate the expression and the dynamics of Prion protein. PMID:28081197

  12. Chronaxie Measurements in Patterned Neuronal Cultures from Rat Hippocampus

    PubMed Central

    Rotem, Assaf; Moses, Elisha; Neef, Andreas

    2015-01-01

    Excitation of neurons by an externally induced electric field is a long standing question that has recently attracted attention due to its relevance in novel clinical intervention systems for the brain. Here we use patterned quasi one-dimensional neuronal cultures from rat hippocampus, exploiting the alignment of axons along the linear patterned culture to separate the contribution of dendrites to the excitation of the neuron from that of axons. Network disconnection by channel blockers, along with rotation of the electric field direction, allows the derivation of strength-duration (SD) curves that characterize the statistical ensemble of a population of cells. SD curves with the electric field aligned either parallel or perpendicular to the axons yield the chronaxie and rheobase of axons and dendrites respectively, and these differ considerably. Dendritic chronaxie is measured to be about 1 ms, while that of axons is on the order of 0.1 ms. Axons are thus more excitable at short time scales, but at longer time scales dendrites are more easily excited. We complement these studies with experiments on fully connected cultures. An explanation for the chronaxie of dendrites is found in the numerical simulations of passive, realistically structured dendritic trees under external stimulation. The much shorter chronaxie of axons is not captured in the passive model and may be related to active processes. The lower rheobase of dendrites at longer durations can improve brain stimulation protocols, since in the brain dendrites are less specifically oriented than axonal bundles, and the requirement for precise directional stimulation may be circumvented by using longer duration fields. PMID:26186201

  13. Cranial irradiation modulates hypothalamic-pituitary-adrenal axis activity and corticosteroid receptor expression in the hippocampus of juvenile rat.

    PubMed

    Velickovic, Natasa; Djordjevic, Ana; Drakulic, Dunja; Stanojevic, Ivana; Secerov, Bojana; Horvat, Anica

    2009-01-01

    Glucocorticoids, essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity, exert their action on the hippocampus through two types of corticosteroid receptors: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Recent studies report that exposure of juvenile rats to cranial irradiation adversely affects HPA axis stability leading to its activation along with radiation- induced inflammation. This study was aimed to examine the acute effects of radiation on HPA axis activity and hippocampal corticosteroid receptor expression in 18-day-old rats. Since immobilization was part of irradiation procedure, both irradiated and sham-irradiated animals were exposed to this unavoidable stress. Our results demonstrate that the irradiated rats exhibited different pattern of corticosteroid receptor expression and hormone levels compared to respective controls. These differences included upregulation of GR protein in the hippocampus with a concomitant elevation of GR mRNA and an increase in circulating level of corticosterone. In addition, the expression of MR, both at the level of protein and gene expression, was not altered. Taken together, this study demonstrates that cranial irradiation in juvenile rats leads to enhanced HPA axis activity and increased relative GR/MR ratio in hippocampus. The present paper intends to show that neuroendocrine response of normal brain tissue to localized irradiation comprise both activation of HPA axis and altered corticosteroid receptor balance, probably as consequence of innate immune activation.

  14. Endogenous homovanillic acid levels differ between rat and rabbit caudate, hippocampus, and cortical regions.

    PubMed

    Reader, T A; Dewar, K M

    1989-11-01

    Endogenous dopamine (DA) levels and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3MT) and homovanillic acid (HVA) were measured by high-performance liquid chromatography in the entorhinal-piriform (EnPi), cingulate (CIN), sensorimotor (SSM) and visual (VIS) cortices as well as is the caudate (CAU) and hippocampus (HIP) of Sprague-Dawley (SD) rats and New Zealand (NZ) rabbits. The DA, DOPAC and 3MT contents were similar in both species. The HVA levels however, although they followed DA distribution, were several-fold higher in NZ rabbits than in SD rats for all cortices, HIP and CAU. In addition, total metabolite contents and DA turnover (estimated from 'DA metabolite/DA' ratios) were significantly higher in NZ rabbits than in SD rats, suggesting an increased release and/or metabolism in the former species. The HVA/DA ratios were much higher for NZ rabbit regions than for SD rats, indicating an increased DA release in the former species since the DOPAC/DA ratios (index of intraneuronal degradation) were similar.

  15. Anti-inflammatory Function of Phyllostachys Edulis Extract in the Hippocampus of HIV-1 Transgenic Rats

    PubMed Central

    Pang, Xiaosha; Panee, Jun

    2016-01-01

    HIV induces neuroinflammation. We evaluated the anti-inflammatory effect of an extract from bamboo Phyllostachys edulis in the hippocampus of HIV-1 transgenic (TG) rats. Five (5) one-month-old TG rats and 5 Fisher 344 (F344) rats were fed a control diet, another 5 TG rats were fed the control diet supplemented with bamboo extract (BEX, 11 grams dry mass per 4057 Kcal). After 9 months of dietary treatment, the gene and protein expression of interleukin 1 beta (IL-1β), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1), and the protein expression p65 and c-Jun were analyzed in the hippocampus. Compared to the F344 rats, the TG rats fed control diet showed significantly higher protein expression of GFAP and c-Jun, and mRNA and protein levels of IL-1β. BEX supplement to the TG rats significantly lowered protein expressions of GFAP, p65, and c-Jun, and showed a trend to decrease the protein expression of IL-1β. Compared to the TG rats, TG+BEX rats also downregulated the mRNA levels of IL-1β and TNFα. In summary, neuroinflammation mediated by the NFκB and AP-1 pathways in the hippocampus of the TG rats was effectively abolished by dietary supplement of BEX. PMID:27398410

  16. 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.

  17. Diabetic ketoacidosis in juvenile rats is associated with reactive gliosis and activation of microglia in the hippocampus.

    PubMed

    Lo, Weei; O'Donnell, Martha; Tancredi, Daniel; Orgain, Myra; Glaser, Nicole

    2016-03-01

    Type 1 diabetes may be associated with structural and functional alterations in the brain. The role of diabetic ketoacidosis (DKA) in causing these alterations has not been well explored. We used immunohistochemical staining to investigate cellular alterations in brain specimens from juvenile rats with DKA before, during, and after treatment with insulin and saline, and compared these to samples from diabetic rats and normal controls. Glial fibrillary acidic protein (GFAP) staining intensity was increased in the hippocampus during DKA and increased further during insulin/saline treatment. Twenty-four and 72 h after treatment, hippocampal GFAP intensity declined but remained above control levels. There were no significant changes in GFAP intensity in the cortex or striatum. OX42 staining intensity was increased during untreated DKA and increased further during insulin/saline treatment in the hippocampus and cortex. NeuN staining intensity was decreased after DKA treatment in the striatum but not in other regions. DKA causes inflammatory changes in the brain including reactive gliosis and activation of microglia. These findings are present during untreated DKA, but intensify during insulin/saline treatment. The hippocampus was disproportionately affected, consistent with previous studies showing deficits in hippocampal functions in rats after DKA recovery and decreased memory capacity in children with a history of DKA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. 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.

  19. Effects of Infantile Repeated Hyperglycemia on Neuronal Density of Hippocampus and Pentylentetrazol Induced Convulsions in Male Wistar Rats

    PubMed Central

    Moghadami, Malihe; Moghimi, Ali; Jalal, Razieh; Behnam-Rasouli, Morteza; Mahdavi-Shahri, Naser

    2012-01-01

    Objective(s):High blood glucose induces molecular, cellular, morphological and behavioral changes in the brain. Metabolic disturbances, contribute to the hippocampus injury and development of partial focal seizures. The aim of this study was to investigate the effects of infantile repeated hyperglycemia on neuronal density of hippocampal CA3 region in newborn Wistar male rats and its effect on chemoconvulsant pentylentetrazol (PTZ) induced generalized seizures in adults. Materials and Methods:Ten days old male Wistar rats were randomly divided into 2 groups (n=20 for each): hyperglycemic and control. Hyperglycemia was induced by intraperitoneal injections of 2 g/kg dextrose solution, twice a day, for 2 weeks. Control animals received saline solution in the same manner. Blood glucose was regularly measured. After that, the brains of rats from each group (n=10) were removed for histological analysis of the CA3 region of hippocampus by stereological method. Other animals (n=10) were kept to grow older. Afterwards, seizure was induced in hyperglycemic and control adult rats, by an intraperitoneal injection of 45 mg/kg PTZ solution and then latency of convulsions onset and severity of seizures for each group were recorded. Results:Results showed that hippocampal neuronal density decreased significantly and susceptibility to PTZ induced convulsions increased in experimental animals. Conclusion:The result determined that repeated increments in daily blood sugar levels in infantile period may damage neuronal structures of hippocampus and also make adults more susceptible to PTZ induced convulsions in adulthood period. PMID:23493812

  20. Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury.

    PubMed

    Cope, Elise C; Morris, Deborah R; Gower-Winter, Shannon D; Brownstein, Naomi C; Levenson, Cathy W

    2016-05-01

    There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (p<0.05), and supplemental zinc significantly increased this by an additional 2-fold (p<0.0001). While the survival of these proliferating cells decreased at the same rate in ZA and in ZS rats after injury, the total density of newly born cells was approximately 60% higher in supplemented rats 1wk after TBI. Furthermore, chronic zinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (p<0.01). While the effect of zinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI.

  1. Neuroprotective effects of Withania coagulans root extract on CA1 hippocampus following cerebral ischemia in rats

    PubMed Central

    Sarbishegi, Maryam; Heidari, Zahra; Mahmoudzadeh- Sagheb, Hamidreza; Valizadeh, Moharram; Doostkami, Mahboobeh

    2016-01-01

    Objective: Oxygen free radicals may be implicated in the pathogenesis of ischemia reperfusion damage. The beneficial effects of antioxidant nutrients, as well as complex plant extracts, on cerebral ischemia-reperfusion injuries are well known. This study was conducted to determine the effects of the hydro-alcoholic root extract of Withania coagulans on CA1 hippocampus oxidative damages following global cerebral ischemia/reperfusion in rat. Materials and Methods: Male Wistar rats were randomly divided in five groups: control, sham operated, Ischemia/ Reperfiusion (IR), and Withania Coagulans Extract (WCE) 500 and 1000mg/kg + I/R groups. Ischemia was induced by ligation of bilateral common carotid arteries for 30 min after 30 days of WCE administration. Three days after, the animals were sacrificed, their brains were fixed for histological analysis (NISSL and TUNEL staining) and some samples were prepared for measurement of malondialdehyde (MDA) level and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity in hippocampus. Results: WCE showed neuroprotective activity by significant decrease in MDA level and increase in the SOD, CAT and GPx activity in pretreated groups as compared to I/R groups (p<0.001). The number of intact neurons was increased while the number of TUNEL positive neurons in CA1 hippocampal region in pretreated groups were decreased as compared to I/R group (p<0.001). Conclusion: WCE showed potent neuroprotective activity against oxidative stress-induced injuries caused by global cerebral ischemia/ reperfusion in rats probably by radical scavenging and antioxidant activities. PMID:27516980

  2. 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

  3. The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress.

    PubMed

    Jiang, Wenbo; Li, Bai; Chen, Yingying; Gao, Shuying

    2017-08-26

    Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1β and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

  4. Chronic intermittent ethanol (CIE) administration in rats decreases levels of neurosteroids in hippocampus, accompanied by altered behavioral responses to neurosteroids and memory function.

    PubMed

    Cagetti, Elisabetta; Pinna, Graziano; Guidotti, Alessandro; Baicy, Kate; Olsen, Richard W

    2004-03-01

    The administration of ethanol on a chronic intermittent regimen (CIE) involving multiple withdrawal episodes is a model for ethanol dependence. After CIE, rats exhibited reduced seizure threshold, increased anxiety, tolerance to GABAergic sedative-hypnotic drugs, and changes in GABA(A) receptor function and subunit composition in hippocampus. Previous studies have shown that acute and chronic ethanol may induce changes in the levels of the neurosteroid 3alpha-hydroxysteroid-5alpha-pregnan-20-one (3alpha, 5alpha-THP) in the brain. Therefore, the current study analyses the correlation between chronic intermittent ethanol effects on the level of 3alpha, 5alpha-THP in hippocampus of CIE rats and the behavioral changes in sensitivity to neurosteroids. After CIE, the levels for 3alpha, 5alpha-THP were significantly reduced in hippocampus of rats. The mRNA levels for the enzymes 5alpha-reductase and 3alpha-HSD in hippocampus were also reduced. In vivo, (in contrast to a tolerance to the hypnotic effect of steroids), CIE rats showed increased sensitivity to the anticonvulsant and to the anxiolytic effect of the steroid alphaxalone. Perhaps, this is a response to lowered levels of endogenous neuroactive steroids. CIE rats also showed impairment of hippocampus-dependent memory function. These results suggest that changes in neurosteroids level and in vivo sensitivity to these compounds are involved in the development of ethanol dependence in the CIE model.

  5. Context-driven cocaine-seeking in abstinent rats increases activity-regulated gene expression in the basolateral amygdala and dorsal hippocampus differentially following short and long periods of abstinence.

    PubMed

    Hearing, M C; Schochet, T L; See, R E; McGinty, J F

    2010-10-13

    In this study, the expression patterns of zif268 and activity-regulated cytoskeleton-associated gene (arc) were investigated in the basolateral amygdala (BLA) and dorsal hippocampal (dHPC) subregions during context-induced drug-seeking following 22 h or 15 d abstinence from cocaine self-administration. Arc and zif/268 mRNA in BLA and dHPC increased after re-exposure to the cocaine-paired chamber at both timepoints; however, only the BLA increases (with one exception-see below) were differentially affected by the presence or absence of the cocaine-paired lever in the chamber. Following 22 h of abstinence, arc mRNA was significantly increased in the BLA of cocaine-treated rats re-exposed to the chamber only with levers extended, whereas following 15 d of abstinence, arc mRNA in the BLA was increased in cocaine-treated rats returned to the chamber with or without levers extended. In contrast, zif268 mRNA in the BLA was greater in cocaine-treated rats returned to the chamber with levers extended vs. levers retracted only after 15 d of abstinence. In the dentate gyrus (DG) following 22 h of abstinence, zif268 mRNA was greater in rats returned to the chamber where levers were absent regardless of drug treatment whereas arc mRNA was increased in CA1 (cell bodies and dendrites) and CA3 only in cocaine-treated groups. Following 15 d of abstinence, arc mRNA was significantly greater in CA1 and CA3 of both cocaine-treated groups returned to the chamber than in those placed into a familiar, non-salient alternate environment; however, only in CA1 cell bodies the cocaine context-induced increases significantly greater than in yoked-saline controls. In contrast, zif/268 mRNA in all dHPC regions was significantly greater in both cocaine-treated groups returned to the cocaine context than in the cocaine-treated group returned to an alternative environment or saline-treated groups. These data suggest that the temporal dynamics of arc and zif268 gene expression in the BLA and d

  6. Effects of benzo(a)pyrene exposure on the ATPase activity and calcium concentration in the hippocampus of neonatal rats.

    PubMed

    Yang, Kai; Chen, Chengzhi; Cheng, Shuqun; Cao, Xianqing; Tu, Baijie

    2017-03-30

    To investigate whether postnatal benzo(a)pyrene (B(a)P) exposure caused the impairments on the process of neurodevelopment and the alteration in the calcium medium in the neonatal rats. Eighty neonatal Sprague Dawley (SD) rats were randomly divided into 5 groups (untreated control group, vehicle group, 0.02 mg/kg, 0.2 mg/kg and 2 mg/kg B(a)P-exposed group). Rats were treated with B(a)P by the intragastric administration from postnatal day (PND) 4 to 25. Morris water maze (MWM) was employed to observe the spatial memory of rats. The activity of calcium adenosine triphosphatase (Ca2+-ATPase), sodium-potassium adenosine triphosphatase (Na+-K+-ATPase) and calcium-magnesium adenosine triphosphatase (Ca2+-Mg2+-ATPase) in the hippocampus were detected by commercial kits. Fura-2 pentakis(acetoxymethyl) (Fura-2/AM) probe and reactive oxygen species (ROS) reagent kit were used for measuring the concentration of Ca2+ and ROS in the hippocampus synapse, respectively. Rats exposed to B(a)P resulted in the deficits in the spatial memory manifested by the increased escape latency and decreased number of crossing platform and time spent in target quadrant in comparison with the control groups. Benzo(a)pyrene exposure caused the significant decrease in the ATPase activity in the hippocampus and caused Ca2+ overload in the synaptic, besides, the ROS concentration increased significantly which may further induce neurobehavioral impairment of the neonatal rats. Our findings suggest that postnatal B(a)P exposure may cause the neurobehavioral impairments in the neonatal rats, which were mediated by the decreased ATPase activity and elevated Ca2+ concentration. Int J Occup Med Environ Health 2017;30(2):203-211.

  7. The small GTPase RhoA, but not Rac1, is essential for conditioned aversive memory formation through regulation of actin rearrangements in rat dorsal hippocampus.

    PubMed

    Wang, Jun; Wang, Yu-hua; Hou, Yuan-yuan; Xi, Tao; Liu, Yao; Liu, Jing-gen

    2013-06-01

    Actin rearrangements are induced in the dorsal hippocampus after conditioned morphine withdrawal, and involved in the formation of conditioned place aversion. In the present study, we investigated the mechanisms underlying the actin rearrangements in rat dorsal hippocampus induced by conditioned morphine withdrawal. The RhoA-ROCK pathway inhibitor Y27632 (8.56 μg/1 μL per side) or the Rac1 inhibitor NSC23766 (25 μg/1 μL per side) was microinjected into the dorsal hippocampus of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal was assessed. Crude synaptosomal fraction of hippocampus was prepared, and the amount of F-actin and G-actin was measured with an Actin Polymerization Assay Kit. Conditioned morphine withdrawal significantly increased actin polymerization in the dorsal hippocampus at 1 h following the naloxone injection. Preconditioning with microinjection of Y27632, but not NSC23766, attenuated CPA, and blocked the increase in actin polymerization in the dorsal hippocampus. Our results suggest that the small GTPase RhoA, but not Rac1, in the dorsal hippocampus is responsible for CPA formation, mainly through its regulation of actin rearrangements.

  8. The representation of space and the hippocampus in rats, robots and humans.

    PubMed

    Burgess, N; Donnett, J G; O'Keefe, J

    1998-01-01

    Experimental evidence suggests that the hippocampus represents locations within an allocentric representation of space. The environmental inputs that underlie the rat's representation of its own location within an environment (in the firing of place cells) are the distances to walls, and different walls are identified by their allocentric direction from the rat. We propose that the locations of goals in an environment is stored downstream of the place cells, in the subiculum. In addition to firing rate coding, place cells may use phase coding relative to the theta rhythm of the EEG. In some circumstances path integration may be used, in addition to environmental information, as an input to the hippocampal system. A detailed computational model of the hippocampus successfully guides the navigation of a mobile robot. The model's behaviour is compared to electrophysiological and behavioural data in rats, and implications for the role of the hippocampus in primates are explored.

  9. Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy.

    PubMed

    Doná, Flávia; Conceição, Isaltino Marcelo; Ulrich, Henning; Ribeiro, Eliane Beraldi; Freitas, Thalma Ariani; Nencioni, Ana Leonor Abrahao; da Silva Fernandes, Maria José

    2016-06-01

    Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5'-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy.

  10. Basic properties of somatosensory-evoked responses in the dorsal hippocampus of the rat

    PubMed Central

    Bellistri, Elisa; Aguilar, Juan; Brotons-Mas, Jorge R; Foffani, Guglielmo; de la Prida, Liset Menendez

    2013-01-01

    The hippocampus is a pivotal structure for episodic memory function. This ability relies on the possibility of integrating different features of sensory stimuli with the spatio-temporal context in which they occur. While recent studies now suggest that somatosensory information is already processed by the hippocampus, the basic mechanisms still remain unexplored. Here, we used electrical stimulation of the paws, the whisker pad or the medial lemniscus to probe the somatosensory pathway to the hippocampus in the anaesthetized rat, and multisite electrodes, in combination with tetrode and intracellular recordings, to look at the properties of somatosensory hippocampal responses. We found that peripheral and lemniscal stimulation elicited small local field potential responses in the dorsal hippocampus about 35–40 ms post-stimulus. Current source density analysis established the local nature of these responses, revealing associated synaptic sinks that were consistently confined to the molecular layer (ML) of the dentate gyrus (DG), with less regular activation of the CA1 stratum lacunosum moleculare (SLM). A delayed (40–45 ms), potentially active, current source that outlasted the SLM sink was present in about 50% cases around the CA1 pyramidal cell layer. Somatosensory stimulation resulted in multi-unit firing increases in the majority of DG responses (79%), whereas multi-unit firing suppression was observed in the majority of CA1 responses (62%). Tetrode and intracellular recordings of individual cells confirmed different firing modulation in the DG and the CA1 region, and verified the active nature of both the early ML sink and delayed somatic CA1 source. Hippocampal responses to somatosensory stimuli were dependent on fluctuations in the strength and composition of synaptic inputs due to changes of the ongoing local (hippocampal) and distant (cortical) state. We conclude that somatosensory signals reach the hippocampus mainly from layer II entorhinal cortex to

  11. Fucose incorporation into rat hippocampus structures after acquisition of a brightness discrimination. A histoautoradiographic analysis.

    PubMed

    Pohle, W; Rüthrich, H L; Popov, N; Matthies, H

    1979-01-01

    Using a brigthness discrimination model in rats, the labeling of discrete hippocampus formation structures was studied after intraventricular application of [3H]-fucose. This substance was injected 5 min before training as well as 5 min, 3, 7 and 23 h after training, the pulse period lasting 120 min in all cases. A significantly training-related enhanced labeling of CA1, CA3 and CA4 cell bodies and fibres revealed that a biphasic time course occurring when radioactive fucose was applied 5 min before training and 7 h after training, whereas the increased labeling of area dentata structures was evidenced only after application of radioactive fucose 5 min before and after training. In all structures under investigation the training-related increase in labeling was more pronounced in the fibre layers than in the pyramidal and granular cell bodies.

  12. Ethanol Affects Network Activity in Cultured Rat Hippocampus: Mediation by Potassium Channels

    PubMed Central

    Korkotian, Eduard; Bombela, Tatyana; Odegova, Tatiana; Zubov, Petr; Segal, Menahem

    2013-01-01

    The effects of ethanol on neuronal network activity were studied in dissociated cultures of rat hippocampus. Exposure to low (0.25–0.5%) ethanol concentrations caused an increase in synchronized network spikes, and a decrease in the duration of individual spikes. Ethanol also caused an increase in rate of miniature spontaneous excitatory postsynaptic currents. Higher concentrations of ethanol eliminated network spikes. These effects were reversible upon wash. The effects of the high, but not the low ethanol were blocked by the GABA antagonist bicuculline. The enhancing action of low ethanol was blocked by apamin, an SK potassium channel antagonist, and mimicked by 1-EBIO, an SK channel opener. It is proposed that in cultured hippocampal networks low concentration of ethanol is associated with SK channel activity, rather than the GABAergic receptor. PMID:24260098

  13. Dynamic expression of the polysialyltransferase in adult rat hippocampus performing an olfactory associative task.

    PubMed

    Manrique, Christine; Migliorati, Martine; Gilbert, Valérie; Brezun, Jean-Michel; Chaillan, Franck A; Truchet, Bruno; Khrestchatisky, Michel; Guiraudie-Capraz, Gaëlle; Roman, François S

    2014-08-01

    Neural cell adhesion molecule (NCAM) is associated with polysialic acid (PSA), and its function is highly dependent on the extent of polysialylation through the activity of two polysialyltransferases, sialyltransferase-X (STX) and polysialyltransferase (PST). PSA-NCAM plays an important role in synaptic plasticity in the hippocampus. The involvement of STX and PST during mnesic processes was assessed in the adult rat hippocampus. We investigated whether different levels in learning and memory using an olfactory associative task influenced STX and PST gene expression in the hippocampus using semiquantitative transcription-polymerase chain reaction. Then, NCAM polysialylation and cell proliferation were quantified in the dentate gyrus of a "Learning and Memory" group using immunohistochemistry. We found that only the expression level of PST mRNA increased with learning performance and returned to an initial level when learned associations were consolidated in long-term memory, while STX mRNA levels remained unchanged. This phenomenon was accompanied by an increase in PSA on NCAM but not by cell proliferation in the dentate gyrus. Our results suggest a different involvement for STX and PST in neural plasticity: while STX is probably involved in the proliferation of neural progenitor cells, PST could play a key role in synaptic plasticity of mature neural networks. The expression of the STX and PST genes could, therefore, be useful markers of neurobiological plasticity in the brain, allowing to follow chronological events in limbic and cortical structures related first to learning and memory processes (for PST) and, second, to adult neurogenesis processes (for STX).

  14. 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.

  15. Involvement of pregnane xenobiotic receptor in mating-induced allopregnanolone formation in the midbrain and hippocampus and brain-derived neurotrophic factor in the hippocampus among female rats.

    PubMed

    Frye, C A; Koonce, C J; Walf, A A

    2014-09-01

    Given that the pregnane neurosteroid, 5α-pregnan-3α-ol-20-one (3α,5α-THP), is increased following behavioral challenges (e.g., mating), and that there is behavioral-induced biosynthesis of 3α,5α-THP in midbrain and mesocorticolimbic structures, 3α,5α-THP likely has a role in homeostasis and motivated reproduction and reproduction-related behaviors (e.g., affect, affiliation). The role of pregnane xenobiotic receptor (PXR), involved in cholesterol metabolism, for these effects is of continued interest. We hypothesized that there would be differences in brain levels of 3α,5α-THP following varied behavioral experiences, an effect abrogated by knockdown of PXR in the midbrain. Proestrous rats were infused with PXR antisense oligonucleotides (AS-ODNs) or vehicle to the ventral tegmental area before different behavioral manipulations and assessments. Endpoints were expression levels of PXR in the midbrain, 3α,5α-THP, and ovarian steroids (estradiol, progesterone, dihydroprogesterone) in the midbrain, striatum, hippocampus, hypothalamus, prefrontal cortex, and plasma. Across experiments, knocking down PXR reduced PXR expression and 3α,5α-THP levels in the midbrain and hippocampus. There were differences in terms of the behavioral manipulations, such that paced mating had the most robust effects to increase 3α,5α-THP levels and reduce open field exploration and social interaction. An additional question that was addressed is whether brain-derived neurotrophic factor (BDNF) is a downstream factor for regulating effects of behavioral-induced 3α,5α-THP biosynthesis. Rats infused with PXR AS-ODNs had lower levels of BDNF in the hippocampus. Thus, PXR may be a regulator of mating-induced 3α,5α-THP formation and behavioral changes and neural plasticity, such as BDNF.

  16. Proteomic changes in rat hippocampus and adrenals following short-term sleep deprivation

    PubMed Central

    Poirrier, Jean-Etienne; Guillonneau, François; Renaut, Jenny; Sergeant, Kjell; Luxen, Andre; Maquet, Pierre; Leprince, Pierre

    2008-01-01

    Background To identify the biochemical changes induced by sleep deprivation at a proteomic level, we compared the hippocampal proteome of rats either after 4 hours of sleep or sleep deprivation obtained by gentle handling. Because sleep deprivation might induce some stress, we also analyzed proteomic changes in rat adrenals in the same conditions. After sleep deprivation, proteins from both tissues were extracted and subjected to 2D-DIGE analysis followed by protein identification through mass spectrometry and database search. Results In the hippocampus, 87 spots showed significant variation between sleep and sleep deprivation, with more proteins showing higher abundance in the latter case. Of these, 16 proteins were present in sufficient amount for a sequencing attempt and among the 12 identified proteins, inferred affected cellular functions include cell metabolism, energy pathways, transport and vesicle trafficking, cytoskeleton and protein processing. Although we did not observe classical, macroscopic effect of stress in sleep-deprived rats, 47 protein spots showed significant variation in adrenal tissue between sleep and sleep deprivation, with more proteins showing higher abundance following sleep. Of these, 16 proteins were also present in sufficient amount for a sequencing attempt and among the 13 identified proteins, the most relevant cellular function that was affected was cell metabolism. Conclusion At a proteomic level, short term sleep deprivation is characterized by a higher expression of some proteins in the hippocampus and a lower abundance of other proteins in the adrenals (compared to normal sleep control). Altogether, this could indicate a general activation of a number of cellular mechanisms involved in the maintenance of wakefulness and in increased energy expenditure during sleep deprivation. These findings are relevant to suggested functions of sleep like energy repletion and the restoration of molecular stocks or a more global homeostasis of

  17. Acetylcholine release in the hippocampus during the operant conditioned reflex and the footshock stimulus in rats.

    PubMed

    Dong, Yu; Mao, Jianjun; Shangguan, Dihua; Zhao, Rui; Liu, Guoquan

    2004-10-14

    The activity of the septo-hippocampal cholinergic pathway was investigated by measuring changes in the extracellular acetylcholine (ACh) levels in the hippocampus, by means of microdialysis, during the operant conditioned reflex and the repeated footshock stimulus. Microdialysis samplings were conducted in a Skinner box where lights were delivered as conditioned stimuli (CS) paired with footshocks as unconditioned stimuli (US). Two groups of rats were used. Extracellular ACh and choline (Ch) in samples collected at 6min intervals were assessed by high-performance liquid chromatography with electrochemical detection. The elevation of hippocampus ACh was observed in the two experimental groups. The increase in ACh during aversive stimulus (footshock) was significantly larger and was probably related to the number of footshocks. There might be moderate increase in the hippocampal ACh release during the retrieval of information. The concentration of choline showed no significant fluctuation in the two groups during the whole process. This experiment explored in more detail hippocampal cholinergic activity in relation to the two different procedures.

  18. Noninvasive Focused Ultrasound Stimulation Can Modulate Phase-Amplitude Coupling between Neuronal Oscillations in the Rat Hippocampus

    PubMed Central

    Yuan, Yi; Yan, Jiaqing; Ma, Zhitao; Li, Xiaoli

    2016-01-01

    Noninvasive focused ultrasound stimulation (FUS) can be used to modulate neural activity with high spatial resolution. Phase-amplitude coupling (PAC) between neuronal oscillations is tightly associated with cognitive processes, including learning, attention, and memory. In this study, we investigated the effect of FUS on PAC between neuronal oscillations and established the relationship between the PAC index and ultrasonic intensity. The rat hippocampus was stimulated using focused ultrasound at different spatial-average pulse-average ultrasonic intensities (3.9, 9.6, and 19.2 W/cm2). The local field potentials (LFPs) in the rat hippocampus were recorded before and after FUS. Then, we analyzed PAC between neuronal oscillations using a PAC calculation algorithm. Our results showed that FUS significantly modulated PAC between the theta (4–8 Hz) and gamma (30–80 Hz) bands and between the alpha (9–13 Hz) and ripple (81–200 Hz) bands in the rat hippocampus, and PAC increased with incremental increases in ultrasonic intensity. PMID:27499733

  19. Alteration of Behavioral Changes and Hippocampus Galanin Expression in Chronic Unpredictable Mild Stress-Induced Depression Rats and Effect of Electroacupuncture Treatment

    PubMed Central

    Mo, Yuping; Yao, Haijiang; Song, Hongtao; Wang, Xin; Chen, Wanshun; Abulizi, Jiawula; Xu, Anping; Tang, Yinshan; Han, Xiangbo; Li, Zhigang

    2014-01-01

    To explore new noninvasive treatment options for depression, this study investigated the effects of electric acupuncture (EA) for depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighteen male Sprague-Dawley rats were randomly assigned into three groups: control, model, and EA groups. Rats were treated by EA once daily for 21 days. The results showed that body weight and sucrose consumption were significantly increased in EA group than in the model group. The crossing numbers and rearing numbers in the open field test significantly decreased in the model group but not in the EA group. And EA treatments upregulated levels of hippocampus galanin (Gal) in UCMS rats back to relative normal levels. The present study suggested that EA had antidepressant effects on UCMS model rats. The potential antidepressant effect may be related to upregulating Gal expression in hippocampus. PMID:25530777

  20. Acute and chronic effects of nicotine on serotonin uptake in prefrontal cortex and hippocampus of rats.

    PubMed

    Awtry, Tammy L; Werling, Linda L

    2003-12-01

    We sought to investigate the effect of nicotine exposure (chronic and acute) on serotonin transporter (SERT) activity in two regions of the brain important for behavioral effects of nicotine. We first looked at the effects of chronic nicotine exposure (0.7 mg/kg nicotine, twice a day for 10 days) on [(3)H]5-HT uptake in prefrontal cortex (PFC) and hippocampus of rats. A significant increase in [(3)H]5-HT uptake was observed in synaptosomes prepared from both regions. To rule out the possibility that the increases were due to the last injection given, in a separate set of experiments a single injection of nicotine was administered the evening before sacrifice. No change in uptake occurred in either region, suggesting that the increases in uptake caused by nicotine was an effect of chronic exposure and not to an acute treatment. SERT binding studies, using prefrontocortical or hippocampal membrane preparations, revealed that chronic nicotine exposure significantly increased B(max) which correlated to an increase in SERT density. Lastly, we looked at the short-term effect of nicotine on [(3)H]5-HT uptake. Rats received a single nicotine injection 15-75 min before sacrifice. PFC synaptosomes displayed a time-dependent increase in uptake, whereas hippocampal synaptosomes showed an increase at only one time point.

  1. Postnatal treadmill exercise alleviates short-term memory impairment by enhancing cell proliferation and suppressing apoptosis in the hippocampus of rat pups born to diabetic rats.

    PubMed

    Kim, Young Hoon; Sung, Yun-Hee; Lee, Hee-Hyuk; Ko, Il-Gyu; Kim, Sung-Eun; Shin, Mal-Soon; Kim, Bo-Kyun

    2014-08-01

    During pregnancy, diabetes mellitus exerts detrimental effects on the development of the fetus, especially the central nervous system. In the current study, we evaluated the effects of postnatal treadmill exercise on short-term memory in relation with cell proliferation and apoptosis in the hippocampus of rat pups born to streptozotocin (STZ)-induced diabetic maternal rats. Adult female rats were mated with male rats for 24 h. Two weeks after mating, the pregnant female rats were divided into two groups: control group and STZ injection group. The pregnant rats in the STZ injection group were administered 40 mg/kg of STZ intraperitoneally. After birth, the rat pups were divided into the following four groups: control group, control with postnatal exercise group, maternal STZ-injection group, and maternal STZ-injection with postnatal exercise group. The rat pups in the postnatal exercise groups were made to run on a treadmill for 30 min once a day, 5 times per week for 2 weeks beginning 4 weeks after birth. The rat pups born to diabetic rats were shown to have short-term memory impairment with suppressed cell proliferation and increased apoptosis in the hippocampal dentate gyrus. Postnatal treadmill exercise alleviated short-term memory impairment by increased cell proliferation and suppressed apoptosis in the rat pups born to diabetic rats. These findings indicate that postnatal treadmill exercise may be used as a valuable strategy to ameliorate neurodevelopmental problems in children born to diabetics.

  2. 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

  3. 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.

  4. Modulation of ( sup 3 H)-glutamate binding by serotonin in the rat hippocampus: An autoradiographic study

    SciTech Connect

    Mennini, T.; Miari, A. )

    1991-01-01

    Serotonin (5-HT) added in vitro increased ({sup 3}H)-glutamate specific binding in the rat hippocampus, reaching statistical significance in layers rich in N-Methyl-D-Aspartate sensitive glutamate receptors. This effect was explained by a significant increase in the apparent affinity of ({sup 3}H)-glutamate when 5-HT is added in vitro. Two days after lesion of serotonergic afferents to the hippocampus with 5,7- Dihydroxytryptamine ({sup 3}H)-glutamate binding was significantly decreased in the CA3 region and stratum lacunosum moleculare of the hippocampus, this reduction being reversed by in vitro addition of 10 {mu}M 5-HT. The decrease observed is due to a significant reduction of quisqualate-insensitive (radiatum CA3) and kainate receptors (strata oriens, radiatum, pyramidal of CA3). Five days after lesion ({sup 3}H)-glutamate binding increased significantly in the CA3 region of the hippocampus but was not different from sham animals in the other hippocampal layers. Two weeks after lesion ({sup 3}H)-glutamate binding to quisqualate-insensitive receptors was increased in all the hippocampal layers, while kainate and quisqualate-sensitive receptors were not affected. These data are consistent with the possibility that 5-HT is a direct positive modulator of glutamate receptor subtypes.

  5. Coherence between Rat Sensorimotor System and Hippocampus Is Enhanced during Tactile Discrimination

    PubMed Central

    Zuo, Yangfang; Stella, Federico; Diamond, Mathew E.

    2016-01-01

    Rhythms with time scales of multiple cycles per second permeate the mammalian brain, yet neuroscientists are not certain of their functional roles. One leading idea is that coherent oscillation between two brain regions facilitates the exchange of information between them. In rats, the hippocampus and the vibrissal sensorimotor system both are characterized by rhythmic oscillation in the theta range, 5–12 Hz. Previous work has been divided as to whether the two rhythms are independent or coherent. To resolve this question, we acquired three measures from rats—whisker motion, hippocampal local field potential (LFP), and barrel cortex unit firing—during a whisker-mediated texture discrimination task and during control conditions (not engaged in a whisker-mediated memory task). Compared to control conditions, the theta band of hippocampal LFP showed a marked increase in power as the rats approached and then palpated the texture. Phase synchronization between whisking and hippocampal LFP increased by almost 50% during approach and texture palpation. In addition, a greater proportion of barrel cortex neurons showed firing that was phase-locked to hippocampal theta while rats were engaged in the discrimination task. Consistent with a behavioral consequence of phase synchronization, the rats identified the texture more rapidly and with lower error likelihood on trials in which there was an increase in theta-whisking coherence at the moment of texture palpation. These results suggest that coherence between the whisking rhythm, barrel cortex firing, and hippocampal LFP is augmented selectively during epochs in which the rat collects sensory information and that such coherence enhances the efficiency of integration of stimulus information into memory and decision-making centers. PMID:26890254

  6. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    PubMed

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development.

  7. Exposure to PM2.5 causes genetic changes in fetal rat cerebral cortex and hippocampus.

    PubMed

    Chao, Ming-Wei; Yang, Chin-Hua; Lin, Po-Ting; Yang, Yu-Hsiu; Chuang, Yu-Chen; Chung, Meng-Chi; Tseng, Chia-Yi

    2016-08-19

    PM2.5 travels along the respiratory tract and enters systemic blood circulation. Studies have shown that PM2.5 increases the incidence of various diseases not only in adults but also in newborn infants. It causes chronic inflammation in pregnant women and retards fetal development. In this study, pregnant rats were exposed to PM2.5 for extended periods of time and it was found that PM2.5 exposure increased immune cells in mother rats. In addition, cytokines and free radicals rapidly accumulated in the amniotic fluid and indirectly affected the fetuses. The authors collected cerebral cortex and hippocampus samples at E18 and analyzed changes of miRNA levels. Expression levels of cortical miR-6315, miR-3588, and miR-466b-5p were upregulated, and positively correlated with the genes Pkn2 (astrocyte migration), Gorab (neuritogenesis), and Mobp (allergic encephalomyelitis). In contrast, PM2.5 decreased expression of miR-338-5p and let-7e-5p, both related to mental development. Further, PM2.5 exposure increased miR-3560 and let-7b-5p in the hippocampus, two proteins that regulate genes Oxct1 and Lin28b that control ketogenesis and glycosylation, and neural cell differentiation, respectively. miR-99b-5p, miR-92b-5p, and miR-99a-5p were decreased, leading to reduced expression of Kbtbd8 and Adam11 which reduced cell mitosis, migration, and differentiation, and inhibited learning abilities and motor coordination of the fetus. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.

  8. Aberrant NMDA-dependent LTD after perinatal ethanol exposure in young adult rat hippocampus.

    PubMed

    Kervern, Myriam; Silvestre de Ferron, Benoît; Alaux-Cantin, Stéphanie; Fedorenko, Olena; Antol, Johann; Naassila, Mickael; Pierrefiche, Olivier

    2015-08-01

    Irreversible cognitive deficits induced by ethanol exposure during fetal life have been ascribed to a lower NMDA-dependent synaptic long-term potentiation (LTP) in the hippocampus. Whether NMDA-dependent long-term depression (LTD) may also play a critical role in those deficits remains unknown. Here, we show that in vitro LTD induced with paired-pulse low frequency stimulation is enhanced in CA1 hippocampus field of young adult rats exposed to ethanol during brain development. Furthermore, single pulse low frequency stimulation, ineffective at this age (LFS600), induced LTD after ethanol exposure accompanied with a stronger response than controls during LFS600, thus revealing an aberrant form of activity-dependent plasticity at this age. Blocking NMDA receptor or GluN2B containing NMDA receptor prevented both the stronger response during LFS600 and LTD whereas Zinc, an antagonist of GluN2A containing NMDA receptor, was ineffective on both responses. In addition, LFS600-induced LTD was revealed in controls only with a reduced-Mg(2+) medium. In whole dissected hippocampus CA1 field, perinatal ethanol exposure increased GluN2B subunit expression in the synaptic compartment whereas GluN2A was unaltered. Using pharmacological tools, we suggest that LFS600 LTD was of synaptic origin. Altogether, we describe a new mechanism by which ethanol exposure during fetal life induces a long-term alteration of synaptic plasticity involving NMDA receptors, leading to an aberrant LTD. We suggest this effect of ethanol may reflect a delayed maturation of the synapse and that aberrant LTD may also participates to long-lasting cognitive deficits in fetal alcohol spectrum disorder. © 2015 Wiley Periodicals, Inc.

  9. The cation-chloride cotransporter NKCC1 promotes sharp waves in the neonatal rat hippocampus

    PubMed Central

    Sipilä, Sampsa T; Schuchmann, Sebastian; Voipio, Juha; Yamada, Junko; Kaila, Kai

    2006-01-01

    Earlier studies indicate a crucial role for the interconnected network of intrinsically bursting CA3 pyramidal neurons in the generation of in vivo hippocampal sharp waves (SPWs) and their proposed neonatal in vitro counterparts, the giant depolarizing potentials (GDPs). While mechanisms involving ligand- and voltage-gated channels have received lots of attention in the generation of CA3 network events in the immature hippocampus, the contribution of ion-transport mechanisms has not been extensively studied. Here, we show that bumetanide, a selective inhibitor of neuronal Cl− uptake mediated by the Na+–K+–2Cl− cotransporter isoform 1 (NKCC1), completely and reversibly blocks SPWs in the neonate (postnatal days 7–9) rat hippocampus in vivo, an action also seen on GDPs in slices (postnatal days 1–8). These findings strengthen the view that GDPs and early SPWs are homologous events. Gramicidin-perforated patch recordings indicated that NKCC1 accounts for a large (∼10 mV) depolarizing driving force for the GABAA current in the immature CA3 pyramids. Consistent with a reduction in the depolarization mediated by endogenous GABAA-receptor activation, bumetanide inhibited the spontaneous bursts of individual neonatal CA3 pyramids, but it slightly increased the interneuronal activity as seen in the frequency of spontaneous GABAergic currents. An inhibitory effect of bumetanide was seen on the in vitro population events in the absence of synaptic GABAA receptor-mediated transmission, provided that a tonic GABAA receptor-mediated current was present. Our work indicates that NKCC1 expressed in CA3 pyramidal neurons promotes network activity in the developing hippocampus. PMID:16644806

  10. Epileptiform activity triggers long-term plasticity of GABAB receptor signalling in the developing rat hippocampus

    PubMed Central

    Tosetti, P; Ferrand, N; Brun, I Colin-Le; Gaïarsa, JL

    2005-01-01

    GABAB receptor (GABABR)-mediated presynaptic inhibition regulates neurotransmitter release from synaptic terminals. In the neonatal hippocampus, GABABR activation reduces GABA release and terminates spontaneous network discharges called giant depolarizing potentials (GDPs). Blocking GABABRs transforms GDPs into longer epileptiform discharges. Thus, GABABR-mediated presynaptic inhibition of GABA release (GABA auto-inhibition) controls both spontaneous network activity and excitability in the developing hippocampus. Here we show that extensive release of endogenous GABA during epileptiform activity impairs GABA auto-inhibition, but not GABABR-mediated inhibition of glutamate release, leading to hyperexcitability of the neonatal hippocampal network. Paired-pulse depression of GABA release (PPD) and heterosynaptic depression of glutamate release were used to monitor the efficacy of presynaptic GABABR-mediated inhibition in slices. PPD, but not heterosynaptic depression, was dramatically reduced after potassium (K+)-induced ictal-like discharges (ILDs), suggesting a selective impairment of GABABR-dependent presynaptic inhibition of GABAergic terminals. Impairing GABA auto-inhibition induced a 44% increase in GDP width and the appearance of pathological network discharges. Preventing GABA-induced activation of GABABRs during ILDs avoided PPD loss and most modifications of the network activity. In contrast, a partial block of GABABRs induced network discharges strikingly similar to those observed after K+-driven ILDs. Finally, neither loss of GABA auto-inhibition nor network hyperexcitability could be observed following synchronous release of endogenous GABA in physiological conditions (during GDPs at 1 Hz). Thus, epileptiform activity was instrumental to impair GABABR-dependent presynaptic inhibition of GABAergic terminals. In conclusion, our results indicate that endogenous GABA released during epileptiform activity can reduce GABA auto-inhibition and trigger

  11. The cation-chloride cotransporter NKCC1 promotes sharp waves in the neonatal rat hippocampus.

    PubMed

    Sipilä, Sampsa T; Schuchmann, Sebastian; Voipio, Juha; Yamada, Junko; Kaila, Kai

    2006-06-15

    Earlier studies indicate a crucial role for the interconnected network of intrinsically bursting CA3 pyramidal neurons in the generation of in vivo hippocampal sharp waves (SPWs) and their proposed neonatal in vitro counterparts, the giant depolarizing potentials (GDPs). While mechanisms involving ligand- and voltage-gated channels have received lots of attention in the generation of CA3 network events in the immature hippocampus, the contribution of ion-transport mechanisms has not been extensively studied. Here, we show that bumetanide, a selective inhibitor of neuronal Cl- uptake mediated by the Na+-K+-2Cl- cotransporter isoform 1 (NKCC1), completely and reversibly blocks SPWs in the neonate (postnatal days 7-9) rat hippocampus in vivo, an action also seen on GDPs in slices (postnatal days 1-8). These findings strengthen the view that GDPs and early SPWs are homologous events. Gramicidin-perforated patch recordings indicated that NKCC1 accounts for a large ( approximately 10 mV) depolarizing driving force for the GABAA current in the immature CA3 pyramids. Consistent with a reduction in the depolarization mediated by endogenous GABAA-receptor activation, bumetanide inhibited the spontaneous bursts of individual neonatal CA3 pyramids, but it slightly increased the interneuronal activity as seen in the frequency of spontaneous GABAergic currents. An inhibitory effect of bumetanide was seen on the in vitro population events in the absence of synaptic GABAA receptor-mediated transmission, provided that a tonic GABAA receptor-mediated current was present. Our work indicates that NKCC1 expressed in CA3 pyramidal neurons promotes network activity in the developing hippocampus.

  12. Dexmedetomidine Oral Mucosa Patch for Sedation Suppresses Apoptosis in Hippocampus of Normal Rats

    PubMed Central

    2017-01-01

    Purpose Dexmedetomidine, an α2-adrenergic agonist, provides sedative and analgesic effects without significant respiratory depression. Dexmedetomidine has been suggested to have an antiapoptotic effect in response to various brain insults. We developed an oral mucosa patch using dexmedetomidine for sedation. The effects of the dexmedetomidine oral mucosa patch on cell proliferation and apoptosis in the hippocampus were evaluated. Methods A hydrogel oral mucosa patch was adhered onto the oral cavity of physiologically normal rats, and was attached for 2 hours, 6 hours, 12 hours, or 24 hours. Plasma dexmedetomidine concentrations were determined by liquid chromatography– electrospray ionization–tandem mass spectrometry–multiple-ion reaction monitoring (LC-ESI-MS/MS-MRM). Cell proliferation in the hippocampus was detected by Ki-67 immunohistochemistry. Caspase-3 immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, and Western blotting for Bax and Bcl-2 were performed to detect hippocampal apoptosis. The levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) in the hippocampus were also measured by Western blotting. Results Plasma dexmedetomidine concentration increased according to the attachment time of the dexmedetomidine oral mucosa patch. Hippocampal cell proliferation did not change due to the dexmedetomidine oral mucosa patch, and the dexmedetomidine oral mucosa patch exerted no significant effect on BDNF or TrkB expression. In contrast, the dexmedetomidine oral mucosa patch exerted an antiapoptotic effect depending on the attachment time of the dexmedetomidine oral mucosa patch. Conclusions A dexmedetomidine oral mucosa patch can be used as a convenient tool for sedation, and is of therapeutic value due to its antiapoptotic effects under normal conditions. PMID:28446017

  13. The study of learning in networks of purified-cultured rat hippocampus neurons

    NASA Astrophysics Data System (ADS)

    Li, Xiangning; Zhou, Wei; Sun, Ni; Luo, Qingming

    2003-12-01

    Learning is crucial for brain functioning, especially for hippocampus. To understand the basis of physiological information processing of hippocampus, we developed the networks of purified-cultured rat hippocampus neurons on a planar 60-microelectrode array MEA. We describe how these networks are prepared, their structure, and the forms of spontaneous activity they exhibit. We stimulate the network at a low frequency until a desired predefined response is observed 50- 10 msec after a stimulus, at which point the stimulus is stopped for 5 min. Repeated cycles of this procedure ultimately lead to the desired response being directly elicited by the stimulus. These results demonstrate that there is learning in networks composed of purified-cultured hippocampus neurons.

  14. Crossing fiber arrays in the rat hippocampus as demonstrated by three-dimensional reconstruction.

    PubMed

    Tamamaki, N; Nojyo, Y

    1991-01-15

    The hippocampus is a neural substrate playing a key role in short-term memory. In order to achieve a better understanding of how the hippocampus functions in "learning and memory," we conducted an intracellular horseradish peroxidase (HRP) study of the CA3 pyramidal neurons and the granule cells of the fascia dentata. The axon of the CA3 pyramidal neurons has two components, the longitudinal association system and the Schaffer collateral system. The latter component is organized in a lamellar fashion and follows the alvear fiber stream. An electron microscopic analysis of myelinated fibers suggested that most myelinated fibers in the hippocampus are organized parallel to the alvear fibers. The mossy fibers of the granule cells, however, do not follow the alvear fiber stream. We propose a new model of the organization of the intrinsic excitatory circuitry of the rat hippocampus in which the distinct lamellar organization of the pyramidal and granule cells creates a crossing neural network.

  15. Salvia miltiorrhiza extract protects white matter and the hippocampus from damage induced by chronic cerebral hypoperfusion in rats.

    PubMed

    Kim, Min-Soo; Bang, Ji Hye; Lee, Jun; Kim, Hyeon Woo; Sung, Sang Hyun; Han, Jung-Soo; Jeon, Won Kyung

    2015-11-23

    Salvia miltiorrhiza (SM), an herbal plant, is traditionally used in the treatment of cardiovascular and cerebrovascular diseases in Asian countries. SM has multiple biological effects including anti-inflammatory activity. The present study is aimed at investigating the effects of SM extract in rats with chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion was induced in male Wistar rats by permanent bilateral common carotid artery occlusion (BCCAo). The rats were divided into 3 groups: sham-control, BCCAo treated with vehicle, and BCCAo treated with SM extract. Vehicle or SM extract (200 mg/kg) were administered daily by oral gavage beginning on day 21 after BCCAo and continuing to day 42. Immunohistochemical analyses were used to measure Iba-1-positive microglia and myelin basic protein (MBP) in white matter and hippocampal tissue. In addition, the expression levels of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, and the toll-like receptor (TLR) pathway in the hippocampus, were analyzed by western blot. Administration of SM extract attenuated the activation of microglial cells in the white matter and hippocampus after BCCAo. SM extract also prevented neuroinflammation after BCCAo by reducing hippocampal levels of TNF-α, IL-1β, and IL-6, and increasing the reduced levels of MBP in the white matter and hippocampus. Further, the administration of SM extract alleviated the up-regulation of hippocampal TLR4 and myeloid differentiation primary response gene 88 (MyD88) in rats with chronic BCCAo. Our findings suggest that SM may be a promising therapeutic candidate in vascular dementia because of its protective effects against damage to the white matter and hippocampus after BCCAo.

  16. Behavior‐dependent activity patterns of GABAergic long‐range projecting neurons in the rat hippocampus

    PubMed Central

    Micklem, Ben; Borhegyi, Zsolt; Swiejkowski, Daniel A.; Valenti, Ornella; Viney, Tim J.; Kotzadimitriou, Dimitrios; Klausberger, Thomas

    2017-01-01

    ABSTRACT Long‐range glutamatergic and GABAergic projections participate in temporal coordination of neuronal activity in distributed cortical areas. In the hippocampus, GABAergic neurons project to the medial septum and retrohippocampal areas. Many GABAergic projection cells express somatostatin (SOM+) and, together with locally terminating SOM+ bistratified and O‐LM cells, contribute to dendritic inhibition of pyramidal cells. We tested the hypothesis that diversity in SOM+ cells reflects temporal specialization during behavior using extracellular single cell recording and juxtacellular neurobiotin‐labeling in freely moving rats. We have demonstrated that rare GABAergic projection neurons discharge rhythmically and are remarkably diverse. During sharp wave‐ripples, most projection cells, including a novel SOM+ GABAergic back‐projecting cell, increased their activity similar to bistratified cells, but unlike O‐LM cells. During movement, most projection cells discharged along the descending slope of theta cycles, but some fired at the trough jointly with bistratified and O‐LM cells. The specialization of hippocampal SOM+ projection neurons complements the action of local interneurons in differentially phasing inputs from the CA3 area to CA1 pyramidal cell dendrites during sleep and wakefulness. Our observations suggest that GABAergic projection cells mediate the behavior‐ and network state‐dependent binding of neuronal assemblies amongst functionally‐related brain regions by transmitting local rhythmic entrainment of neurons in CA1 to neuronal populations in other areas. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27997999

  17. Thrombin modulates persistent sodium current in CA1 pyramidal neurons of young and adult rat hippocampus.

    PubMed

    Lunko, O O; Isaev, D S; Krishtal, O O; Isaeva, E V

    2015-01-01

    Serine protease thrombin, a key factor of blood coagulation, participates in many neuronal processes important for normal brain functioning and during pathological conditions involving abnormal neuronal synchronization, neurodegeneration and inflammation. Our previous study on CA3 pyramidal neurons showed that application ofthrombin through the activation of specific protease-activated receptor 1 (PAR1) produces a significant hyperpolarizing shift of the activation of the TTX-sensitive persistent voltage-gated Na+ current (I(Nap)) thereby affecting membrane potential and seizure threshold at the network level. It was shown that PAR1 is also expressed in CA1 area of hippocampus and can be implicated in neuronal damage in this area after status epilepticus. The aim of the present study was to evaluate the effect of thrombin on I(NaP) in CA1 pyramidal neurons from adult and young rats. Using whole cell patch-clamp technique we demonstrate that thrombin application results in the hyperpolarization shift of I(NaP) activation as well as increase in the I(NaP) amplitude in both age groups. We have found that I(NaP) in pyramidal neurons of hippocampal CA 1 region is more vulnerable to the thrombin action than I(NaP) in pyramidal neurons of hippocampal CA3 region. We have also found that the immature hippocampus is more sensitive to thrombin action which emphasizes the contribution of thrombin-dependent pathway to the regulation of neuronal activity in immature brain.

  18. Activation of the insulin-signaling pathway in sciatic nerve and hippocampus of type 1 diabetic rats

    PubMed Central

    King, MR.; Anderson, NJ.; Liu, C.; Law, E.; Cundiff, M.; Mixcoatl-Zecuatl, TM.; Jolivalt, CG

    2015-01-01

    Peripheral neuropathy is a major complication associated with diabetes and central neuropathy characterized by Alzheimer’s disease-like features in the brain is associated with increased dementia risk for patients with diabetes. Although glucose uptake into the cells of the nervous system is insulin-independent, contribution of impaired insulin support is clearly recognized to play a role, however not yet fully understood, in the development of neuropathy. In this study, we assessed the direct role of insulin on the PNS and CNS of insulin-dependent type 1 diabetic rats. Fresh sciatic nerve and hippocampus from control and diabetic rats were incubated with varied ex vivo concentrations of insulin and phosphorylation levels of insulin receptor and GSK3β were assessed by Western blot analysis. Both sciatic nerve and hippocampus from type 1 diabetic rats were highly responsive to exogenous insulin with a significantly increased phosphorylation of insulin receptor and GSK3 compared to tissues from control rats. Further, sustained in vivo insulin delivery, not sufficient to restore normal blood glucose, normalized the activation of both insulin receptor and GSK3 in both PNS and CNS tissues. These results suggest that the insulin-signaling pathway is responsive to exogenous insulin in the nervous system of insulin-deficient type 1 diabetic rats and that constant insulin delivery restore normal nerve function and may protect peripheral and central nervous system from damage. PMID:26149351

  19. NMDA receptor subunit and CaMKII changes in rat hippocampus by congenital HCMV infection: a mechanism for learning and memory impairment.

    PubMed

    Wu, De; Yang, Li; Bu, Xiaosong; Tang, Jiulai; Fan, Xiaocheng

    2017-03-22

    The aim of this study was to investigate the effects of congenital human cytomegalovirus infection on the expression levels of N-methyl-D-aspartate receptors (NRs) and Ca/calmodulin-dependent protein kinase II (CaMKII) in the hippocampal neurons of neonatal Sprague-Dawley (SD) rats. Pregnant SD rats were divided into an experimental group and a control group (n=10 in each group). Spatial learning and memory of the offspring of SD rats were evaluated using the Morris water-maze test. Pathological studies of hippocampus sections were carried out. The concentration of [Ca] was measured using a dual-wavelength spectrophotometer method. The expression levels of NRs were detected by an immunohistochemical study. Western blot was performed to detect the expression level of CaMKII. In the Morris water-maze test, the rats in the experimental group showed significantly increased escape latency and distance traveled than the control group. Damaged and structural disorders of the dentate granule in the hippocampus were found in the experimental rats. Immunohistochemistry results showed that the expression levels of NR subunits in the hippocampus of the experimental group were significantly decreased. The concentration of [Ca] in the experimental group was significantly increased. In contrast, the level of CaMKII in the experimental group was significantly decreased. The expressions of the NR subunit and CaMKII were decreased in rat hippocampus by human cytomegalovirus congenital infection, which may be associated with the mechanism underlying the impairment of learning and memory function.

  20. Correlation between oxytocin neuronal sensitivity and oxytocin receptor binding: An electrophysiological and autoradiographical study comparing rat and guinea pig hippocampus

    SciTech Connect

    Raggenbass, M.; Tribollet, E.; Dubois-Dauphin, M.; Dreifuss, J.J. )

    1989-01-01

    In transverse hippocampal slices from rat and guinea pig brains, the authors obtained unitary extracellular recordings from nonpyramidal neurones located in or near the stratum pyramidale in the CA1 field and in the transition region between the CA1 and the subiculum. In rats, these neurones responded to oxytocin at 50-1,000 nM by a reversible increase in firing rate. The oxytocin-induced excitation was suppressed by a synthetic structural analogue that acts as a potent, selective antioxytocic on peripheral receptors. Nonpyramidal neurones were also excited by carbachol at 0.5-10 {mu}M. The effect of this compound was postsynaptic and was blocked by the muscarinic antagonist atropine. In guinea pigs, by contrast, nonpyramidal neurones were unaffected by oxytocin, although they were excited by carbachol. Light microscopic autoradiography, carried out using a radioiodinated selective antioxytocic as a ligand, revealed labeling in the subiculum and in the CA1 area of the hippocampus of rats, whereas no oxytocin-binding sites were detected in the hippocampus of guinea pigs. The results indicate (i) that a hippocampal action of oxytocin is species-dependent and (ii) that a positive correlation exists between neuronal responsiveness to oxytocin and the presence in the hippocampus of high-affinity binding sites for this peptide.

  1. Increased dentate neurogenesis after grafting of glial restricted progenitors or neural stem cells in the aging hippocampus.

    PubMed

    Hattiangady, Bharathi; Shuai, Bing; Cai, Jingli; Coksaygan, Turhan; Rao, Mahendra S; Shetty, Ashok K

    2007-08-01

    Neurogenesis in the dentate gyrus (DG) declines severely by middle age, potentially because of age-related changes in the DG microenvironment. We hypothesize that providing fresh glial restricted progenitors (GRPs) or neural stem cells (NSCs) to the aging hippocampus via grafting enriches the DG microenvironment and thereby stimulates the production of new granule cells from endogenous NSCs. The GRPs isolated from the spinal cords of embryonic day 13.5 transgenic F344 rats expressing human alkaline phosphatase gene and NSCs isolated from embryonic day 9 caudal neural tubes of Sox-2:EGFP transgenic mice were expanded in vitro and grafted into the hippocampi of middle-aged (12 months old) F344 rats. Both types of grafts survived well, and grafted NSCs in addition migrated to all layers of the hippocampus. Phenotypic characterization revealed that both GRPs and NSCs differentiated predominantly into astrocytes and oligodendrocytic progenitors. Neuronal differentiation of graft-derived cells was mostly absent except in the dentate subgranular zone (SGZ), where some of the migrated NSCs but not GRPs differentiated into neurons. Analyses of the numbers of newly born neurons in the DG using 5'-bromodeoxyuridine and/or doublecortin assays, however, demonstrated considerably increased dentate neurogenesis in animals receiving grafts of GRPs or NSCs in comparison with both naïve controls and animals receiving sham-grafting surgery. Thus, both GRPs and NSCs survive well, differentiate predominantly into glia, and stimulate the endogenous NSCs in the SGZ to produce more new dentate granule cells following grafting into the aging hippocampus. Grafting of GRPs or NSCs therefore provides an attractive approach for improving neurogenesis in the aging hippocampus. Disclosure of potential conflicts of interest is found at the end of this article.

  2. Bisphenol-A rapidly enhanced passive avoidance memory and phosphorylation of NMDA receptor subunits in hippocampus of young rats

    SciTech Connect

    Xu Xiaohong Li Tao; Luo Qingqing; Hong Xing; Xie Lingdan; Tian Dong

    2011-09-01

    Bisphenol-A (BPA), an endocrine disruptor, is found to influence development of brain and behaviors in rodents. The previous study indicated that perinatal exposure to BPA impaired learning-memory and inhibited N-methyl-D-aspartate receptor (NMDAR) subunits expressions in hippocampus during the postnatal development in rats; and in cultured hippocampal neurons, BPA rapidly promotes dynamic changes in dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDAR subunit NR2B. In the present study, we examined the rapid effect of BPA on passive avoidance memory and NMDAR in the developing hippocampus of Sprague-Dawley rats at the age of postnatal day 18. The results showed that BPA or estradiol benzoate (EB) rapidly extended the latency to step down from the platform 1 h after footshock and increased the phosphorylation levels of NR1, NR2B, and mitogen-activated extracellular signal-regulated kinase (ERK) in hippocampus within 1 h. While 24 h after BPA or EB treatment, the improved memory and the increased phosphorylation levels of NR1, NR2B, ERK disappeared. Furthermore, pre-treatment with an estrogen receptors (ERs) antagonist, ICI182,780, or an ERK-activating kinase inhibitor, U0126, significantly attenuated EB- or BPA-induced phosphorylations of NR1, NR2B, and ERK within 1 h. These data suggest that BPA rapidly enhanced short-term passive avoidance memory in the developing rats. A non-genomic effect via ERs may mediate the modulation of the phosphorylation of NMDAR subunits NR1 and NR2B through ERK signaling pathway. - Highlights: > BPA rapidly extended the latency to step down from platform 1 h after footshock. > BPA rapidly increased pNR1, pNR2B, and pERK in hippocampus within 1 h. > ERs antagonist or MEK inhibitor attenuated BPA-induced pNR1, pNR2B, and pERK.

  3. Metabotropic glutamate receptor 5 in Down's syndrome hippocampus during development: increased expression in astrocytes.

    PubMed

    Iyer, A M; van Scheppingen, J; Milenkovic, I; Anink, J J; Lim, D; Genazzani, A A; Adle-Biassette, H; Kovacs, G G; Aronica, E

    2014-01-01

    Metabotropic glutamate receptor 5 (mGluR5) is highly expressed throughout the forebrain and hippocampus. Several lines of evidence support the role of this receptor in brain development and developmental disorders, as well as in neurodegenerative disorders like Alzheimer's disease (AD). In the present study, the expression pattern of mGluR5 was investigated by immunocytochemistry in the developing hippocampus from patients with Down's syndrome (DS) and in adults with DS and AD. mGluR5 was expressed in developing human hippocampus from the earliest stages tested (9 gestational weeks), with strong expression in the ventricular/subventricular zones. We observed a consistent similar temporal and spatial neuronal pattern of expression in DS hippocampus. However, in DS we detected increased prenatal mGluR5 expression in white matter astrocytes, which persisted postnatally. In addition, in adult DS patients with widespread ADassociated neurodegeneration (DS-AD) increased mGluR5 expression was detected in astrocytes around amyloid plaque. In vitro data confirm the existence of a modulatory crosstalk between amyloid-β and mGluR5 in human astrocytes. These findings demonstrate a developmental regulation of mGluR5 in human hippocampus and suggest a role for this receptor in astrocytes during early development in DS hippocampus, as well as a potential contribution to the pathogenesis of ADassociated pathology.

  4. Ginsenoside Rg1 Decreases Aβ1–42 Level by Upregulating PPARγ and IDE Expression in the Hippocampus of a Rat Model of Alzheimer's Disease

    PubMed Central

    Quan, QianKun; Wang, Jue; Li, Xi; Wang, Yi

    2013-01-01

    Background and Purpose The present study was designed to examine the effects of ginsenoside Rg1 on expression of peroxisome proliferator-activated receptor γ (PPARγ) and insulin-degrading enzyme (IDE) in the hippocampus of rat model of Alzheimer's disease (AD) to determine how ginsenoside Rg1 (Rg1) decreases Aβ levels in AD. Experimental Approach Experimental AD was induced in rats by a bilateral injection of 10 µg soluble beta-amyloid peptide 1–42 (Aβ1–42) into the CA1 region of the hippocampus, and the rats were treated with Rg1 (10 mg·kg−1, intraperitoneally) for 28 days. The Morris water maze was used to test spatial learning and memory performance. Hematoxylin-eosin staining was performed to analyze the hippocampal histopathological damage. Immunohistochemistry, western blotting, and real-time PCR were used to detect Aβ1–42, PPARγ, and insulin-degrading enzyme (IDE) expression in the hippocampus. Key Results Injection of soluble Aβ1–42 into the hippocampus led to significant dysfunction of learning and memory, hippocampal histopathological abnormalities and increased Aβ1–42 levels in the hippocampus. Rg1 treatment significantly improved learning and memory function, attenuated hippocampal histopathological abnormalities, reduced Aβ1–42 levels and increased PPARγ and IDE expression in the hippocampus; these effects of Rg1 could be effectively inhibited by GW9662, a PPARγ antagonist. Conclusions and Implications Given that PPARγ can upregulate IDE expression and IDE can degrade Aβ1–42, these results indicate that Rg1 can increase IDE expression in the hippocampus by upregulating PPARγ, leading to decreased Aβ levels, attenuated hippocampal histopathological abnormalities and improved learning and memory in a rat model of AD. PMID:23520555

  5. 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.

  6. 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.

  7. Effects of treadmill exercise on cyclooxygenase-2 in the hippocampus in type 2 diabetic rats: correlation with the neuroblasts.

    PubMed

    Hwang, In Koo; Yi, Sun Shin; Yoo, Ki-Yeon; Park, Ok Kyu; Yan, Bingchun; Kim, Il Yong; Kim, Yo Na; Song, Wook; Moon, Seung Myung; Won, Moo-Ho; Seong, Je Kyung; Yoon, Yeo Sung

    2010-06-23

    Cyclooxygenase (COX) is a rate-limiting enzyme in synthesis of prostaglandins from arachidonic acid. In this study, we observed the effects of a physical exercise on COX-2 immunoreactivity in the hippocampus using immunohistochemistry in rats. In addition, we examined effects of administration of a COX-2 inhibitor, celecoxib, on neuroblast differentiation. At 6weeks of age, Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats were put on a treadmill with or without running for 1h/session/day for 5weeks. The running speed was gradually increased from 16 to 22m/min with 2m/min per 2weeks. In the ZLC and ZDF rats, COX-2 immunoreaction was detected in the granule cell layer of the dentate gyrus and in the stratum pyramidale of the CA2/3 region; COX-2 immunoreaction in the CA1 region was hardly detected. In the exercised-ZLC and ZDF rats, COX-2 immunoreactivity was significantly increased compared to that in the ZLC and ZDF rats, showing that COX-2 immunoreactivity in the exercised-ZDF rats was slightly low than that in the exercised-ZDF rats. In addition, weak COX-2 immunoreactivity was shown in the CA1 region by exercise. On the other hand, the repeated oral administration of celecoxib to 4-week-old ZDF rats significantly decreased the neuroblasts in the subgranular zone of the dentate gyrus. These results suggest that COX-2 may be associated with the increase of synaptic plasticity or contacts in the hippocampus.

  8. Haloperidol and clozapine affect social behaviour in rats postnatally lesioned in the ventral hippocampus.

    PubMed

    Becker, Axel; Grecksch, Gisela

    2003-08-01

    Neonatal ibotenic acid lesion of the ventral hippocampus results in altered patterns of social behaviour. After puberty, lesioned animals spent less time in social interaction and the nonaggressive/aggressive behaviour ratio shifted towards increased aggressiveness. In this study, the effects on social behaviour of the neuroleptic drugs haloperidol (HAL) and clozapine (CLO) after acute and subchronic treatment were studied. Seven-day-old rats were lesioned and social behaviour was tested at the age of 13 weeks. Drug effects were tested after acute (HAL 0.025 mg/kg, CLO 1.0 mg/kg) and subchronic (10 injections, HAL 0.075 mg/kg, CLO 5.0 mg/kg) administration. For comparison, diazepam (DZP, 0.5 mg/kg) was used in the acute experiment. After acute administration, DZP had no effect on social behaviour in sham-lesioned rats, but nonaggressive behaviour increased significantly in lesioned animals. CLO and HAL did reduce the time sham-lesioned rats spent in social contact, and CLO also increased % nonaggressive behaviour in lesioned rats. Here, HAL had no effect. Subchronic administration did not alter social behaviour in sham-lesioned animals. However, CLO increased the time lesioned animals spent in social interaction, whereas HAL had an effect on nonaggressive behaviour. The results of this study indicate that the lesion model is sensitive to differentiated effects of classical neuroleptic drugs such as HAL and atypical neuroleptic drugs like CLO. It might be a useful tool in the search for potential neuroleptic drugs.

  9. STRESS-INDUCED CHANGES IN EXTRACELLULAR DOPAMINE AND SEROTONIN IN THE MEDIAL PREFRONTAL CORTEX AND DORSAL HIPPOCAMPUS OF PRENATALLY MALNOURISHED RATS

    PubMed Central

    Mokler, David J.; Torres, Olga I.; Galler, Janina R.; Morgane, Peter J.

    2009-01-01

    Prenatal protein malnutrition continues to be a significant problem in the world today. Exposure to prenatal protein malnutrition increases the risk of a number of neuropsychiatric disorders in adulthood including depression, schizophrenia and attentional deficit disorder. In the present experiment we have examined the effects of stress on extracellular serotonin (5-HT) and dopamine in the medial prefrontal cortex and dorsal hippocampus of rats exposed in utero to protein malnutrition. The medial prefrontal cortex and dorsal hippocampus were chosen as two limbic forebrain regions involved in learning and memory, attention and the stress response. Extracellular 5-HT and dopamine were determined in the medial prefrontal cortex and dorsal hippocampus of adult male Sprague-Dawley rats using dual probe in vivo microdialysis. Basal extracellular 5-HT did not differ between malnourished and well-nourished controls in either the medial prefrontal cortex or the dorsal hippocampus. Basal extracellular dopamine was significantly decreased in the medial prefrontal cortex of malnourished animals. Restraint stress (20 m) produced a significant rise in extracellular dopamine in the medial prefrontal cortex of well-nourished rats but did not alter release in malnourished rats. In malnourished rats, stress produced an increase in 5-HT in the hippocampus, whereas stress produced a decrease in 5-HT in the hippocampus of well-nourished rats. These data demonstrate that prenatal protein malnutrition alters dopaminergic neurotransmission in the medial prefrontal cortex as well as altering the dopaminergic and serotonergic response to stress. These changes may provide part of the bases for alterations in malnourished animals’ response to stress. PMID:17368432

  10. Stress-induced changes in extracellular dopamine and serotonin in the medial prefrontal cortex and dorsal hippocampus of prenatally malnourished rats.

    PubMed

    Mokler, David J; Torres, Olga I; Galler, Janina R; Morgane, Peter J

    2007-05-07

    Prenatal protein malnutrition continues to be a significant problem in the world today. Exposure to prenatal protein malnutrition increases the risk of a number of neuropsychiatric disorders in adulthood including depression, schizophrenia and attentional deficit disorder. In the present experiment, we have examined the effects of stress on extracellular serotonin (5-HT) and dopamine in the medial prefrontal cortex and dorsal hippocampus of rats exposed in utero to protein malnutrition. The medial prefrontal cortex and dorsal hippocampus were chosen as two limbic forebrain regions involved in learning and memory, attention and the stress response. Extracellular 5-HT and dopamine were determined in the medial prefrontal cortex and dorsal hippocampus of adult male Sprague-Dawley rats using dual probe in vivo microdialysis. Basal extracellular 5-HT did not differ between malnourished and well-nourished controls in either the medial prefrontal cortex or the dorsal hippocampus. Basal extracellular dopamine was significantly decreased in the medial prefrontal cortex of malnourished animals. Restraint stress (20 m) produced a significant rise in extracellular dopamine in the medial prefrontal cortex of well-nourished rats but did not alter release in malnourished rats. In malnourished rats, stress produced an increase in 5-HT in the hippocampus, whereas stress produced a decrease in 5-HT in the hippocampus of well-nourished rats. These data demonstrate that prenatal protein malnutrition alters dopaminergic neurotransmission in the medial prefrontal cortex as well as alters the dopaminergic and serotonergic response to stress. These changes may provide part of the bases for alterations in malnourished animals' response to stress.

  11. Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

    ERIC Educational Resources Information Center

    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

  12. Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

    ERIC Educational Resources Information Center

    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

  13. Nicotine-prevented learning and memory impairment in REM sleep-deprived rat is modulated by DREAM protein in the hippocampus.

    PubMed

    Abd Rashid, Norlinda; Hapidin, Hermizi; Abdullah, Hasmah; Ismail, Zalina; Long, Idris

    2017-06-01

    REM sleep deprivation is associated with impairment in learning and memory, and nicotine treatment has been shown to attenuate this effect. Recent studies have demonstrated the importance of DREAM protein in learning and memory processes. This study investigates the association of DREAM protein in REM sleep-deprived rats hippocampus upon nicotine treatment. Male Sprague Dawley rats were subjected to normal condition, REM sleep deprivation and control wide platform condition for 72 hr. During this procedure, saline or nicotine (1 mg/kg) was given subcutaneously twice a day. Then, Morris water maze (MWM) test was used to assess learning and memory performance of the rats. The rats were sacrificed and the brain was harvested for immunohistochemistry and Western blot analysis. MWM test found that REM sleep deprivation significantly impaired learning and memory performance without defect in locomotor function associated with a significant increase in hippocampus DREAM protein expression in CA1, CA2, CA3, and DG regions and the mean relative level of DREAM protein compared to other experimental groups. Treatment with acute nicotine significantly prevented these effects and decreased expression of DREAM protein in all the hippocampus regions but only slightly reduce the mean relative level of DREAM protein. This study suggests that changes in DREAM protein expression in CA1, CA2, CA3, and DG regions of rat's hippocampus and mean relative level of DREAM protein may involve in the mechanism of nicotine treatment-prevented REM sleep deprivation-induced learning and memory impairment in rats.

  14. Aluminium-induced electrophysiological, biochemical and cognitive modifications in the hippocampus of aging rats.

    PubMed

    Sethi, Pallavi; Jyoti, Amar; Singh, Rameshwar; Hussain, Ejaz; Sharma, Deepak

    2008-11-01

    Aluminium (Al) is the most abundant metal known for its neurotoxicity in humans. It gains easy access to the central nervous system under normal physiological conditions and accumulates in different brain regions. It has been reported to be involved in the etiology of several neurodegenerative diseases. In this study, we have investigated the effects of long-term intake of aluminium chloride (AlCl(3)) on the electrophysiological, behavioral, biochemical and histochemical functions of hippocampus. Wistar rats were fed with AlCl(3) at a dose of 50mg/(kgday) for 6 months in the drinking water. Effect of long-term intake of Al was studied on the electrical activity of hippocampal CA1 and CA3 regions in brain of young and old rats. Morris water maze and open field tests were performed to investigate the cognitive and anxiety status of aging rats intoxicated with aluminium. Our studies indicate that aluminium intake results in increased multiple unit activity and adversely affect the spatial learning and memory abilities of both young and old rats. Aluminium intake also inflicts oxidative stress-related damage to lipids, membrane associated proteins (Na-K ATPase and PKC) and endogenous antioxidant enzyme activity (SOD, GPx and GST). The compromised antioxidant system might be playing a crucial role in the observed Al-induced alterations. We have observed that the magnitude of AlCl(3)-induced alteration was considerably higher in younger group of rats compared to older group. In conclusion, the results of the present study implicates that aluminium treatment exerts its neurotoxic effects by altering the overall physiology of brain, and the induced changes were strongly correlated with each other.

  15. Effect of soy milk on circulating 17- β estradiol, number of neurons in cerebral cortex and hippocampus and determination of their ratio in neonatal ovariectomized rats

    PubMed Central

    Marzban Abbasabadi, Behrokh; Tadjalli, Mina

    2016-01-01

    This study was conducted to evaluate the effect of soy milk on serum 17- β estradiol level and number of neurons in cerebral cortex and hippocampus as well as determination of the ratio of neurons in cortical and hippocampal regions in neonatal ovariectomized rats. Thirty female rats (one day old) were divided into six groups of five. At day 7, ovariectomy surgery was performed in four groups and two other groups were assumed as sham and control groups. Three groups of ovareictomaized rats were fed with soy milk at the doses of 0.75, 1.50 and 3.00 mL kg-1 per day since they were 14. At day 60, the blood samples were collected to measure the17- β estradiol concentration, and then the brain of rats were prepared for histological studies. The serum 17- β estradiol level significantly increased in ovariectomized rats fed with soy milk compared to ovariectomized rats with no soy milk supplementation. In addition, the results showed that soy milk significantly increased the number of neurons in CA1, CA2 and dentate gyrus regions of hippocampus and granular layer of cerebral cortex in ovariectomized rats, whereas there was no significant change in number of neurons in CA3 zone of hippocampus and molecular, pyramidal and multiform layers of cerebral cortex in ovariectomized rats fed with soy milk. The ratio of cerebral cortex neurons to hippocampal neurons had no significant changes among the experimental groups. PMID:28144428

  16. Lanthanum damages learning and memory and suppresses astrocyte-neuron lactate shuttle in rat hippocampus.

    PubMed

    Jin, Cuihong; Gao, Liang; Li, Yingqi; Wu, Shengwen; Lu, Xiaobo; Yang, Jinghua; Cai, Yuan

    2017-10-09

    Rare-earth elements (REEs) are applied in various fields by virtue of their superior physical and chemical properties. Surveys have reported that REEs can impair learning and memory in children and induce neurobehavioral abnormalities in animals. However, the mechanism underlying this neurotoxicity is still unclear. Lanthanum (La) is often chosen to study the effects of REEs. Here, we investigated the role of astrocyte-neuron lactate shuttle (ANLS) in spatial learning and memory impairment induced by LaCl3 in hippocampus, an important spatial memory-related brain region. Pregnant Wistar rats were exposed to 0, 0.125, 0.25, 0.5, or 1% LaCl3 in drinking water during pregnancy and lactation. After weaning, young rats continued to receive 0, 0.125, 0.25, 0.5, and 1% LaCl3 in the drinking water for 1 month. The results showed that LaCl3 exposure impaired the spatial learning and memory of rats in Morris water maze test, significantly reduced the mRNA and protein levels of glycogen synthetase, glycogen phosphorylase, lactate dehydrogenase A, monocarboxylate transporter 4, MCT-1, and MCT-2, and decreased total LDH activity and lactate contents in rat hippocampus. These results indicate that LaCl3 impairs spatial learning and memory in rats probably by suppressing ANLS in rat hippocampus. The study provides a novel clue of energy supply for neurons to clarify the neurotoxicity of REEs.

  17. Blunted inflammation mediated by NF-κB activation in hippocampus alleviates chronic normobaric hypoxia-induced anxiety-like behavior in rats.

    PubMed

    Fan, Junming; Fan, Xiaofang; Li, Yang; Guo, Jinbin; Xia, Dongmei; Ding, Lu; Zheng, Qingqing; Wang, Wei; Xue, Feng; Chen, Ran; Liu, Shouting; Hu, Lianggang; Gong, Yongsheng

    2016-04-01

    This study aims to investigate whether inflammation mediated by NF-κB activation is involved in the induction of anxiety-like behavior in chronic normobaric hypoxia (CNH) exposed rats and to investigate the underlying mechanism. To this end, rats were exposed in a normobaric hypoxic chamber with a fraction of inspired oxygen (FIO2) of ∼ 10%, 23 h/d, continues for 2 weeks. Anxiety-like behavior was tested by elevated plus maze and open field, inflammatory response, nucleus translocation of NF-κB, and signaling pathway in hippocampus were examined. CNH induced a significant increase of anxiety- like behavior and inflammation responses, which were ameliorated by NF-κB inhibitor, PDTC pretreatment, suggesting that the anxiogenic effect induced by inflammation is through NF-κB activation. CNH treatment significantly increased nucleus translocation of p65 and p105 in hippocampus, which was suppressed by PDTC pretreatment. In addition, CNH treatment significantly increased Iba-1, iNOS, COX-2, and p-PKA in hippocampus, which were blocked by PDTC pretreatment, suggesting CNH may activate microglia cells in hippocampus through NF-κB pathway. In conclusion, our results illustrate a mechanism that, activation of NF-κB in hippocampus may trigger the proinflammatory response of microglia cells, and iNOS-PKA pathway may involve in anxiogenic effect in CNH exposed rats.

  18. Changes in aminoacidergic and monoaminergic neurotransmission in the hippocampus and amygdala of rats after ayahuasca ingestion

    PubMed Central

    de Castro-Neto, Eduardo Ferreira; da Cunha, Rafael Henrique; da Silveira, Dartiu Xavier; Yonamine, Mauricio; Gouveia, Telma Luciana Furtado; Cavalheiro, Esper Abrão; Amado, Débora; Naffah-Mazzacoratti, Maria da Graça

    2013-01-01

    AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography (HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion (gavage). Animals were killed 40 min after drug ingestion and the structures stored at -80 °C until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. RESULTS: The results showed decreased concentrations of glycine (GLY) (0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid (GABA) (1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level (0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA (0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg (1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg (2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg (1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg (noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg (noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg (noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs 2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION

  19. Changes in aminoacidergic and monoaminergic neurotransmission in the hippocampus and amygdala of rats after ayahuasca ingestion.

    PubMed

    de Castro-Neto, Eduardo Ferreira; da Cunha, Rafael Henrique; da Silveira, Dartiu Xavier; Yonamine, Mauricio; Gouveia, Telma Luciana Furtado; Cavalheiro, Esper Abrão; Amado, Débora; Naffah-Mazzacoratti, Maria da Graça

    2013-11-26

    To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography (HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion (gavage). Animals were killed 40 min after drug ingestion and the structures stored at -80 °C until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. The results showed decreased concentrations of glycine (GLY) (0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid (GABA) (1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level (0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA (0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg (1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg (2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg (1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg (noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg (noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg (noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs 2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). Our data suggest increased

  20. Long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus.

    PubMed

    Caillard, O; Ben-Ari, Y; Gaiarsa, J L

    1999-07-01

    1. The plasticity of GABAergic synapses was investigated in neonatal rat hippocampal slices obtained between postnatal days 3 and 6 using intracellular recording techniques. Ionotropic glutamate receptor antagonists were present throughout the experiments to isolate GABAA receptor-mediated postsynaptic potentials (GABAA PSPs) or currents (GABAA PSCs). 2. Repetitive depolarizing pulses (20 pulses, 0.5 s duration, at 0.1 Hz, each pulse generating 4-6 action potentials) induced a long-term potentiation in the slope and amplitude of the evoked GABAA PSPs and GABAA PSCs. 3. Long-term potentiation was prevented by intracellular injection of the calcium chelator BAPTA (50 mM), or when the voltage-dependent calcium channels blockers Ni2+ (50 microM) and nimodipine (10 microM) were bath applied. 4. Repetitive depolarizing pulses induced a persistent (over 1 h) increase in the frequency of spontaneous GABAA PSCs. 5. Repetitive depolarizing pulses induced a long-lasting increase in the frequency of miniature GABAA PSCs, without altering their amplitude or decay-time constant. 6. It is concluded that the postsynaptic activation of voltage-dependent calcium channels leads to a long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus. This form of plasticity is expressed as an increase in the probability of GABA release or in the number of functional synapses, rather than as an upregulation of postsynaptic GABAA receptor numbers or conductance at functional synapses.

  1. Neuroprotective effects of silymarin on ischemia-induced delayed neuronal cell death in rat hippocampus.

    PubMed

    Hirayama, Koki; Oshima, Hideki; Yamashita, Akiko; Sakatani, Kaoru; Yoshino, Atsuo; Katayama, Yoichi

    2016-09-01

    We examined the effects of silymarin, which was extracted from Silybum marianum, on delayed neuronal cell death in the rat hippocampus. Rats were divided into four groups: sham-operated rats (sham group), rats which underwent ischemic surgery (control group), rats which were treated with silymarin before and after ischemic surgery (pre group), and rats which were treated with silymarin after ischemic surgery only (post group). We performed the ischemic surgery by occluding the bilateral carotid arteries for 20min and sacrificed the rats one week after the surgery. Silymarin was administered orally at 200mg/kg body weight. Smaller numbers of delayed cell deaths were noted in the rat CA1 region of the pre- and post-groups, and no significant difference was observed between these groups. There were few apoptotic cell deaths in all groups. Compared to the control group, significantly fewer cell deaths by autophagy were found in the pre- and post-group. We concluded that silymarin exerts a preservation effect on delayed neuronal cell death in the rat hippocampus and this effect has nothing to do with the timing of administering of silymarin. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Expression of trkB mRNA is altered in rat hippocampus after experimental brain trauma.

    PubMed

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

    1998-08-31

    Recent investigations have shown that expression of mRNAs for the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) is differentially altered in the hippocampus following traumatic brain injury. In the present study, modulation of neurotrophin receptor expression was examined in the hippocampus in a rat model of traumatic brain injury using in situ hybridization. Messenger RNA for trkB, the high-affinity receptor for BDNF and neurotrophin-4 (NT-4), was increased between 3 and 6 h bilaterally in the dentate gyrus following a lateral fluid-percussion brain injury of moderate severity (2.0-2.1 atm). No time-dependent alterations were observed for trkB mRNA in hippocampal subfields CA1 and CA3. Levels of mRNA for trkC, the high-affinity receptor for NT-3, did not change in any region of the hippocampus. These data demonstrate that lateral fluid-percussion injury modulates expression of trkB mRNA in the hippocampus and support a role for BDNF/trkB signalling mechanisms in secondary events associated with traumatic brain injury.

  3. Treatment with dexamethasone and vitamin D3 attenuates neuroinflammatory age-related changes in rat hippocampus.

    PubMed

    Moore, Michelle; Piazza, Alessia; Nolan, Yvonne; Lynch, Marina A

    2007-10-01

    Among the changes which occur in the brain with age is an increase in hippocampal concentration of proinflammatory cytokines like interleukin-1beta (IL-1beta) and an increase in IL-1beta-induced signaling. Here we demonstrate that the increase in IL-1beta concentration is accompanied by an increase in expression of IL-1 type I receptor (IL-1RI) and an age-related increase in microglial activation, as shown by increased expression of the cell surface marker, major histocompatibility complex II (MHCII) and increased MHCII staining. The evidence indicates that these age-related changes were abrogated in hippocampus of aged rats treated with dexamethasone and vitamin D3. Similarly, the age-related increases in activation of the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), as well as caspase-3 and PARP were all attenuated in hippocampal tissue prepared from rats that received dexamethasone and vitamin D3. The data indicate that dexamethasone and vitamin D3 ameliorated the age-related increase in IFNgamma and suggest that IFNgamma may be the trigger leading to microglial activation, since it increases MHCII mRNA and IL-1beta release from cultured glia. In parallel with its ability to decrease microglial activation in vivo, we report that treatment of cultured glia with dexamethasone and vitamin D3 blocked the lipopolysaccharide increased MHCII mRNA and IL-1beta concentration, while the IL-1beta-induced increases in activation of JNK and caspase 3 in cultured neurons were also reversed by treatment with dexamethasone and vitamin D3. The data suggest that the antiinflammatory effect of dexamethasone and vitamin D3 derives from their ability to downreguate microglial activation.

  4. 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.

  5. Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

    PubMed

    Yucel, Atakan; Yucel, Nermin; Ozkanlar, Seckin; Polat, Elif; Kara, Adem; Ozcan, Halil; Gulec, Mustafa

    2016-04-01

    Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.

  6. [Mechanism for apoptosis of hippocampus neuron induced by hypothyroidism in perinatal rats].

    PubMed

    Huang, Xin-wen; Yang, Ru-lai; Zhao, Zheng-yan; Ji, Chai; Yang, Rong-wang

    2005-07-01

    To investigate the mechanism for the apoptosis of hippocampus neuron induced by hypothyroidism in perinatal rats. Hypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at 1, 5, 10 and 15d, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free triiodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by chemoluminescence. Hippocampus specimens were collected from the control and hypothyroid pups.Mitochondia was examined under transmission electron microscopy. Translocation of apoptogenic molecules (Bax, cytochrome C and AIF) and activation of caspase-3 were analyzed by Western Blotting. Significantly low circulating FT(3) and FT(4) levels confirmed the hypothyroid status of the experimental pups. Electron microscopy showed that altered morphology of mitochondria significantly increased under hypothyroid conditions. The expression of Bax in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.05),and significantly higher in mitochondria (P<0.001). The expression of cytochrome c in the cytosol of hypothyroid pups was significantly higher than that of control pups at all stages of development (1,10 and 15 d:P<0.05, 5d: P<0.001), and lower in mitochondria (P<0.05). The expression of AIF in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.001), and significantly lower in mitochondria (1, 5d: P<0.001, 10, 15 d: P<0.01). he expression of caspase-3 P20 in the cytosol of hypothyroid pups was significantly higher as compared with that of the age-matched controls (1, 15d: P<0.01, 5,1 0 d: P<0.001). The intrinsic death pathway in mitochondria may be one of the mechanisms with which hypothyroid induces apoptosis of hippocampus neuron in developing rats.

  7. Expression Pattern of Peroxisome Proliferator-Activated Receptors in Rat Hippocampus following Cerebral Ischemia and Reperfusion Injury

    PubMed Central

    Wang, Hong; Jiang, Rong; He, Qin; Zhang, Yunmei; Zhang, Yanli; Li, Yong; Zhuang, Ruichun; Luo, Ying; Li, Yu; Wan, Jinyuan; Tang, Yong; Yu, Huarong; Jiang, Qingsong; Yang, Junqing

    2012-01-01

    The present study was designed to investigate the pattern of time-dependent expression of peroxisome proliferator-activated receptors (PPARα, β, and γ) after global cerebral ischemia and reperfusion (I/R) damage in the rat hippocampus. Male Sprague Dawley (SD) rats were subjected to global cerebral I/R. The rat hippocampi were isolated to detect the expression of PPARs mRNA and protein levels at 30 min–30 d after I/R by RT-PCR and Western blot analysis, respectively. The expression levels of PPARs mRNA and protein in the rat hippocampus significantly increased and peaked at 24 h for PPARα and γ (at 48 h for PPARβ) after I/R, then gradually decreased, and finally approached control levels on d 30. The present results suggest that global cerebral I/R can cause obvious increases of hippocampal PPARs mRNA and protein expression within 15 d after I/R. These findings may help to guide the experimental and clinical therapeutic use of PPARs agonists against brain injury. PMID:23304113

  8. Chronic noise exposure causes persistence of tau hyperphosphorylation and formation of NFT tau in the rat hippocampus and prefrontal cortex.

    PubMed

    Cui, Bo; Zhu, Lixing; She, Xiaojun; Wu, Mingquan; Ma, Qiang; Wang, Tianhui; Zhang, Na; Xu, Chuanxiang; Chen, Xuewei; An, Gaihong; Liu, Hongtao

    2012-12-01

    The non-auditory effects of noise exposure on the central nervous system have been established both epidemiologically and experimentally. Chronic noise exposure (CNE) has been associated with tau hyperphosphorylation and Alzheimer's disease (AD)-like pathological changes. However, experimental evidence for these associations remains limited. The aim of the current study was to explore the effects of CNE [100 dB sound pressure level (SPL) white noise, 4 h/d×14 d] on tau phosphorylation in the rat hippocampus and the prefrontal cortex. Forty-eight male Wistar rats were randomly assigned to two groups: a noise-exposed group and a control group. The levels of radioimmunoprecipitation assay (RIPA)-soluble and RIPA-insoluble phosphorylated tau at Ser202, Ser396, Ser404, and Ser422 in the hippocampus and the prefrontal cortex were measured at different time points (days 0, 3, 7, and 14) after the end of the last noise exposure. Exposure to white noise for 14 consecutive days significantly increased the levels of tau phosphorylation at Ser202, Ser396, Ser404, and Ser422, the sites typically phosphorylated in AD brains, in the hippocampus and the prefrontal cortex. Tau hyperphosphorylation persisted for 7 to 14 d after the cessation of noise exposure. These alterations were also concomitant with the generation of pathological neurofibrillary tangle (NFT) tau 3, 7 and 14 d after the end of the stimulus. Furthermore, lasting increases in proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A), were found to occur in close correspondence with increase in tau hyperphosphorylation. The results of this study show that CNE leads to long-lasting increases in non-NFT hyperphosphorylated tau and delayed formation of misfolded NFT tau in the hippocampus and the prefrontal cortex. Our results also provide evidence for the involvement of GSK3β and PP2A in these processes.

  9. Angiotensin IV possibly acts through PKMzeta in the hippocampus to regulate cognitive memory in rats.

    PubMed

    Chow, Lok-Hi; Tao, Pao-Luh; Chen, Yuan-Hao; Lin, Yu-Hui; Huang, Eagle Yi-Kung

    2015-10-01

    Ang IV is an endogenous peptide generated from the degradation of angiotensin II. Ang IV was found to enhance learning and memory in CNS. PKMzeta was identified to be a fragment of PKCzeta (protein kinase Czeta). Its continuous activation was demonstrated to be correlated with the formation of memory in the hippocampus. Therefore, we investigated whether PKMzeta participates in the effects of Ang IV on memory. We first examined the effect of Ang IV on non-spatial memory/cognition in modified object recognition test in rats. Our data showed that Ang IV could increase the exploration time on novel object. The co-administration of ZIP (PKMzeta inhibitor) with Ang IV significantly blocked the effect by Ang IV. The effects of Ang IV on hippocampal LTP at the CA1 region were also evaluated. Ang IV significantly increased the amplitude and slope of the EPSPs, which was consistent with other reports. Surprisingly, instead of potentiating LTP, Ang IV caused a failed maintenance of LTP. Moreover, there was no quantitative change in PKMzeta induced by Ang IV and/or ZIP after behavioral experiments. Taken together, our data re-confirmed the finding of the positive effect of Ang IV to enhance memory/cognition. The increased strength of EPSPs with Ang IV could also have certain functional relevance. Since the behavioral results suggested the involvement of PKMzeta, we hypothesized that the enhancement of memory/cognition by Ang IV may rely on an increase in PKMzeta activity. Overall, the present study provided important advances in our understanding of the action of Ang IV in the hippocampus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. 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.

  11. 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.

  12. Gene Expression Profile of the Hippocampus of Rats Subjected to Chronic Immobilization Stress

    PubMed Central

    Li, Xiao-Hong; Chen, Jia-Xu; Yue, Guang-Xin; Liu, Yue-Yun; Zhao, Xin; Guo, Xiao-Ling; Liu, Qun; Jiang, You-Ming; Bai, Ming-Hua

    2013-01-01

    Objective This study systematically investigated the effect of chronic stress on the hippocampus and its damage mechanism at the whole genome level. Methods The rat whole genome expression chips (Illumina) were used to detect gene expression differences in the hippocampus of rats subjected to chronic immobilization stress (daily immobilization stress for 3 h, for 7 or 21 days). The hippocampus gene expression profile was studied through gene ontology and signal pathway analyses using bioinformatics. A differentially expressed transcription regulation network was also established. Real-time quantitative polymerase chain reaction (RT-PCR) was used to verify the microarray results and determine expression of the Gabra1, Fadd, Crhr2, and Cdk6 genes in the hippocampal tissues. Results Compared to the control group, 602 differentially expressed genes were detected in the hippocampus of rats subjected to stress for 7 days, while 566 differentially expressed genes were expressed in the animals experiencing stress for 21 days. The stress significantly inhibited the primary immune system functions of the hippocampus in animals subjected to stress for both 7 and 21 days. Immobilization activated the extracellular matrix receptor interaction pathway after 7 day exposure to stress and the cytokine-cytokine receptor interaction pathway. The enhanced collagen synthesis capacity of the hippocampal tissue was the core molecular event of the stress regulation network in the 7-day group, while the inhibition of hippocampal cell growth was the core molecular event in the 21-day group. For the Gabra1, Fadd, Crhr2, and Cdk6 genes, RT-PCR results were nearly in line with gene chip assay results. Conclusion During the 7-day and 21-day stress processes, the combined action of polygenic, multilevel, and multi-signal pathways leads to the disorder of the immunologic functions of the hippocampus, hippocampal apoptosis, and proliferation disequilibrium. PMID:23544040

  13. Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: involvement of glutamate excitotoxicity.

    PubMed

    Cattani, Daiane; de Liz Oliveira Cavalli, Vera Lúcia; Heinz Rieg, Carla Elise; Domingues, Juliana Tonietto; Dal-Cim, Tharine; Tasca, Carla Inês; Mena Barreto Silva, Fátima Regina; Zamoner, Ariane

    2014-06-05

    Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup(®) (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup(®) (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup(®) (0.00005-0.1%) during 30min and experiments were carried out to determine whether glyphosate affects (45)Ca(2+) influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, (14)C-α-methyl-amino-isobutyric acid ((14)C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup(®) (30min) increases (45)Ca(2+) influx by activating NMDA receptors and voltage-dependent Ca(2+) channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup(®)-induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup(®) increased (3)H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup(®) decreased (3)H-glutamate uptake and metabolism, while induced (45)Ca(2+) uptake and (14)C-MeAIB accumulation in immature rat hippocampus. Taken together, these results demonstrated that Roundup(®) might lead to excessive extracellular glutamate levels and consequently to glutamate excitotoxicity and oxidative stress in rat hippocampus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. [Influence of chronic lead exposure in rats during the developmental stage on expression of leptin in plasma, cerebrospinal fluid, and hippocampus].

    PubMed

    Shi, Xue-Mei; Fu, Ya-Wen; Huang, Lai-Rong; Yang, Hui

    2016-08-01

    To investigate the influence of lead exposure in rats during the developmental stage on the expression of leptin in plasma, cerebrospinal fluid, and hippocampus, as well as investigating whether leptin is associated with the mechanism of cognitive impairment induced by lead exposure. The rat model of cognitive impairment after chronic lead exposure was established by adding lead acetate into drinking water. According to the concentration of lead acetate in drinking water, the rats were divided into control (0 ppm), low-lead (50 ppm), medium-lead (200 ppm), and high-lead groups (1 000 ppm), with 16 rats in each group. Atomic absorption spectrometry was used to measure the content of lead in the plasma, cerebrospinal fluid and hippocampus. ELISA was used to measure the level of leptin in the plasma and cerebrospinal fluid. Immunohistochemistry was used to observe the distribution of leptin protein in the hippocampus. Western blot was used for relative quantification of leptin proteins in the hippocampus. Compared with the control group, the lead exposure groups showed significant increases in the content of lead in blood, cerebrospinal fluid, and hippocampus (P<0.01), as well as significant reductions in the levels of leptin in plasma and cerebrospinal fluid (P<0.05). The results of immunohistochemical staining showed that leptin was mainly distributed in the cytoplasm of pyramidal neurons in the hippocampal CA region. The results of Western blot showed that compared with the control group, the three lead exposure groups showed a slight increase in the protein expression of leptin in the hippocampus (P>0.05). Lead exposure can reduce the levels of leptin in plasma and cerebrospinal fluid in rats, which may be associated with the mechanism of cognitive impairment induced by lead exposure.

  15. The Research on the Relationship of RAGE, LRP-1, and Aβ Accumulation in the Hippocampus, Prefrontal Lobe, and Amygdala of STZ-Induced Diabetic Rats.

    PubMed

    Ma, Lou-Yan; Fei, Yu-Lang; Wang, Xiao-Ye; Wu, Song-Di; Du, Jun-Hui; Zhu, Mei; Jin, Long; Li, Ming; Li, Hai-Long; Zhai, Jia-Jia; Ji, Lu-Peng; Ma, Ran-Ran; Liu, Song-Fang; Li, Mo; Ma, Li; Ma, Xiao-Rui; Qu, Qiu-Min; Lv, Ya-Li

    2017-05-01

    Diabetes mellitus (DM) has been regarded as an important risk factor for Alzheimer's disease (AD), and diabetic patients and animals have shown cognitive dysfunction. More research has shown that the amyloid-β (Aβ), which is a hallmark of AD, was found deposited in the hippocampus of diabetic rats. This Aβ accumulation is regulated by the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein (LRP-1). However, the expression of RAGE and LRP-1 in diabetic rats is not very clear. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether the expression of RAGE and LRP-1 is related to Aβ1-42 deposition at the hippocampus, prefrontal lobe, and amygdala in DM. We found that diabetic rats had longer escape latency and less frequency of entrance into the target zone than that of the control group (P < 0.05) in the Morris water maze (MWM) test. The Aβ1-42 expression in the hippocampus and prefrontal lobe significantly increased in the DM group compared to the control group (P < 0.05). RAGE increased (P < 0.05), while LRP-1 decreased (P < 0.05) in the hippocampus tissue and prefrontal lobe tissue of DM rats. The Aβ1-42 deposition was correlated with RAGE positively (P < 0.05), but with LRP-1 negatively (P < 0.05). Further, the expression levels of Aβ1-42, RAGE, and LRP-1 were not changed in the amygdala between the diabetic rats and the control group. These findings indicated that upregulating RAGE and/or downregulating LRP-1 at the hippocampus and the prefrontal lobe contributed to the Aβ1-42 accumulation and then further promoted the cognitive impairment of diabetic rats.

  16. Effect of treatment with choline alphoscerate on hippocampus microanatomy and glial reaction in spontaneously hypertensive rats.

    PubMed

    Tomassoni, Daniele; Avola, Roberto; Mignini, Fiorenzo; Parnetti, Lucilla; Amenta, Francesco

    2006-11-20

    The influence of long term treatment with choline alphoscerate on microanatomy of hippocampus and glial reaction was assessed in spontaneously hypertensive rats (SHR) used as an animal model of cerebrovascular disease. Choline alphoscerate is a cholinergic precursor, which has shown to be effective in countering cognitive symptoms in forms of dementia disorders of degenerative, vascular or combined origin. Male spontaneously hypertensive rats (SHR) aged 6 months and age-matched normotensive Wistar-Kyoto (WKY) rats were treated for 8 weeks with an oral daily dose of 100 mg/kg of choline alphoscerate, 285 mg/kg of phosphatidylcholine (lecithin) or vehicle. On the hippocampus of different animal groups, nerve cell number and GFAP-immunoreactive astrocytes were assessed by neuroanatomical, immunochemical and immunohistochemical techniques associated with quantitative analysis. Treatment with choline alphoscerate countered nerve cell loss and glial reaction primarily in the CA1 subfields and in the dentate gyrus of the hippocampus of SHR. Phosphatidylcholine did not affect hypertension-dependent changes in hippocampal microanatomy. Both compounds did not affect blood pressure values in SHR. These data suggest that choline alphoscerate may play a role in the countering hippocampal changes induced by cerebrovascular involvement. The observation that treatment with choline alphoscerate attenuates the extent of glial reaction in the hippocampus of SHR suggests also that the compound may afford neuroprotection in this animal model of vascular brain damage.

  17. Delayed effects of spiperone on serotonin1A receptors in the dorsal hippocampus of rats.

    PubMed Central

    Dennis, T; Blier, P; de Montigny, C

    1993-01-01

    The effects of 5-HT1A antagonists spiperone, methiothepin and BMY 7378 on [3H]-8-OH-DPAT binding were determined in vitro and ex vivo in rat hippocampus CA3 membrane preparations, and ex vivo in tissue sections of CA1 and CA3 subfields using quantitative autoradiography. In CA3 membranes from rats sacrificed 1 h or 24 h after administration of 5 mg/kg i.p. spiperone or methiothepin, no decrease in [3H]-8-OH-DPAT Bmax values approached statistical significance. Autoradiograms from identically treated rats showed significant increases in Kd values in both CA1 and CA3 hippocampal subfields 24 h but not 1 h after administration of the drugs, while no changes were observed in the dorsal raphe at either time. In vitro co-incubation of membranes with spiperone (200 or 500 nM) or methiothepin (500 nM) resulted in significant decreases in both affinity and Bmax values. In contrast, co-incubation with BMY 7378 (5 nM) increased only Kd values. GTP gamma S produced a concentration-dependent inhibition of specific [3H]8-OH-DPAT binding. At 0.1 mM of GTP gamma S, Kd values were increased three-fold and Bmax values were significantly decreased. When membranes were co-incubated with GTP gamma S and spiperone or BMY 7378, Kd values increased further. Moreover, the effects of spiperone and GTP gamma S on Bmax values were additive. It is concluded that BMY 7378 acts as a competitive antagonist at hippocampal post-synaptic 5-HT1A receptors, whereas spiperone and methiothepin exert their delayed antagonistic effects at these receptors through a non-competitive mechanism of action, possibly affecting the coupling of the receptors to their Gi/o proteins. PMID:8297925

  18. PEGylated Carbon Nanotubes Impair Retrieval of Contextual Fear Memory and Alter Oxidative Stress Parameters in the Rat Hippocampus

    PubMed Central

    Dal Bosco, Lidiane; Weber, Gisele E. B.; Parfitt, Gustavo M.; Paese, Karina; Gonçalves, Carla O. F.; Serodre, Tiago M.; Furtado, Clascídia A.; Santos, Adelina P.; Monserrat, José M.; Barros, Daniela M.

    2015-01-01

    Carbon nanotubes (CNT) are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate the neurotoxicity of these nanomaterials. The present work assessed the effects of single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG) on the consolidation and retrieval of contextual fear memory in rats and on oxidative stress parameters in the hippocampus. SWCNT-PEG were dispersed in water at concentrations of 0.5, 1.0, and 2.1 mg/mL and infused into the rat hippocampus. The infusion was completed immediately after training and 30 min before testing of a contextual fear conditioning task, resulting in exposure times of 24 h and 30 min, respectively. The results showed that a short exposure to SWCNT-PEG impaired fear memory retrieval and caused lipid peroxidation in the hippocampus. This response was transient and overcome by the mobilization of antioxidant defenses at 24 h. These effects occurred at low and intermediate but not high concentration of SWCNT-PEG, suggesting that the observed biological response may be related to the concentration-dependent increase in particle size in SWCNT-PEG dispersions. PMID:25738149

  19. iTRAQ-based proteomics analysis of hippocampus in spatial memory deficiency rats induced by simulated microgravity.

    PubMed

    Wang, Tingmei; Chen, Hailong; Lv, Ke; Ji, Guohua; Zhang, Yongliang; Wang, Yanli; Li, Yinghui; Qu, Lina

    2017-03-22

    It has been demonstrated that simulated microgravity (SM) may lead to cognitive dysfunction. However, the underlying mechanism remains unclear. In present study, tail-suspension (30°) rat was employed to explore the effects of 28 days of SM on hippocampus-dependent learning and memory capability and the underlying mechanisms. We found that 28-day tail-suspension rats displayed decline of learning and memory ability in Morris water maze (MWM) test. Using iTRAQ-based proteomics analysis, a total of 4774 proteins were quantified in hippocampus. Of these identified proteins, 147 proteins were differentially expressed between tail-suspension and control group. Further analysis showed these differentially expressed proteins (DEPs) involved in different molecular function categories, and participated in many biological processes. Based on the results of PANTHER pathway analysis and further western blot verification, we observed the expression of glutamate receptor 1 (GluR1) and glutamate receptor 4 (GluR4) which involved in metabotropic glutamate receptor group III pathway and ionotropic glutamate receptor pathway were significantly induced by SM. Moreover, an increased concentration of glutamic acid (Glu) was also found in hippocampus while the concentrations of 5-hydroxytryptamine (5-HT), dopamine (DA), γ-amino acid butyric acid (GABA) and epinephrine (E) were decreased. Our finding confirms that 28-day SM exposure can cause degrading of the spatial learning and memory capability and the possible mechanisms might be related with glutamate excitotoxicity and imbalances in specific neurotransmitters.

  20. DNA methylation in the developing hippocampus and amygdala of anxiety-prone versus risk-taking rats.

    PubMed

    Simmons, Rebecca K; Howard, Jasmine L; Simpson, Danielle N; Akil, Huda; Clinton, Sarah M

    2012-01-01

    All organisms exhibit a wide range of emotional behaviors and interact with the environment in different ways. Some individuals may be more quiet and shy whereas others are more outgoing and adventurous. These temperamental and personality differences can predispose individuals to certain psychopathologies which may be influenced by genetic vulnerability and/or early life experiences. Rodent models can be used to recapitulate emotional reactivity differences, and these models can, in turn, be used to examine potential neurobiological underpinnings of these traits. The present study utilizes two strains of rats that were selectively bred for differences in novelty seeking. High Novelty-Responding (bHR) rats are very active in response to novelty, exhibit exaggerated risk-taking, aggression, impulsivity, and show increased behavioral response to cocaine. Low Novelty-Responding (bLR) rats show increased anxiety, depressive behavior and vulnerability to chronic stress. One way in which the bHR versus bLR behavioral phenotypes may differ is through epigenetic modification of DNA. DNA can be modified through processes such as acetylation or methylation to either enhance or subdue gene expression. This study examines putative differences in methylation levels in the hippocampus and amygdala of developing bHR-bLR rats. Previous research observed widespread gene expression differences in the bLR developing hippocampus, and the current study aims to begin to examine potential epigenetic factors that may contribute to those gene differences. The amygdala was chosen because it is involved in emotional processes, in part through its connections with the hippocampus. Therefore, the present study used in situ hybridization to assess the expression of DNA methyltransferase-1 (DNMT1) mRNA in the hippocampus, amygdala and several other brain areas of bHR and bLR pups at three developmental time points: postnatal days (P) 7, 14, and 21. We focused on the first 3 postnatal weeks, in

  1. Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus.

    PubMed

    Tran, Phu V; Kennedy, Bruce C; Lien, Yu-Chin; Simmons, Rebecca A; Georgieff, Michael K

    2015-02-15

    Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency. Copyright © 2015 the American Physiological Society.

  2. Increased expression of the TIAR protein in the hippocampus of Alzheimer patients.

    PubMed

    Oleana, V H; Salehi, A; Swaab, D F

    1998-05-11

    T-cell restricted intracellular antigen related protein (TIAR) is an RNA-binding protein that is supposed to be involved in the process of stress-induced apoptosis. TIAR triggers DNA fragmentation in permeabilized thymocytes and its expression diminishes in the cell nucleus and rises simultaneously in the cytoplasm during Fas-induced cell death. Using a monoclonal antibody against TIAR, we stained different areas of the hippocampus from seven controls and 14 patients with Alzheimer's disease (AD). There was a clear expression of TIAR in the hippocampus of non-demented controls. Surprisingly, a significant increase was found in the expression of TIAR in the hippocampal area in AD. The increased expression of TIAR in AD may be related to the process of neurodegeneration in the hippocampus.

  3. Chronic atypical antipsychotics, but not haloperidol, increase neurogenesis in the hippocampus of adult mouse.

    PubMed

    Chikama, Koji; Yamada, Hidetaka; Tsukamoto, Tatsuo; Kajitani, Kosuke; Nakabeppu, Yusaku; Uchimura, Naohisa

    2017-09-09

    It is suggested that altered neuroplasticity contributes to the pathophysiology of schizophrenia and antipsychotics may exhibit some of their therapeutic efficacies by improving neurogenesis and/or proliferation of neural progenitors. The aim of this study is to investigate whether chronic antipsychotics treatment affect neurogenesis in adult mouse hippocampus. Animals were administered olanzapine, quetiapine, clozapine, risperidone, aripiprazole, or haloperidol via the osmotic minipump for 21 days and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. BrdU-positive cells in the hippocampus were quantified by stereology. Aripiprazole, quetiapine, clozapine, and olanzapine significantly increased density of BrdU-positive cells in the hippocampus. Interestingly, other antipsychotic drugs had tendency to increasing BrdU-positive cells, whereas haloperidol had propensity to decrease with a marginal significance. These results suggest that differences of neurogenesis among these drugs may, at least in part, account for their pharmacological profiles. Copyright © 2017. Published by Elsevier B.V.

  4. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus

    PubMed Central

    2014-01-01

    Background Antidepressants have been shown to affect levels of brain-derived neurotrophic factor (BDNF) and VGF (non-acronymic) whose transcriptions are dependent on cAMP response element binding protein (CREB) in long term treatment. The aim of this study was to verify the subacute antidepressant effects of crocin, an active constituent of saffron (Crocus sativus L.), and its effects on CREB, BDNF, and VGF proteins, transcript levels and amount of active, phosphorylated CREB (P-CREB) protein in rat hippocampus. Methods Crocin (12.5, 25, and 50 mg/kg), imipramine (10 mg/kg; positive control) and saline (1 mL/kg; neutral control) were administered intraperitoneally (IP) to male Wistar rats for 21 days. The antidepressant effects were studied using the forced swimming test (FST) on day 21 after injection. Protein expression and transcript levels of genes in the rat hippocampus were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. Results Crocin significantly reduced the immobility time in the FST. Western blot analysis showed that 25 and 50 mg/kg of crocin increased the levels of CREB and BDNF significantly and dose dependently. All doses of crocin increased the VGF levels in a dose-dependent manner. Levels of p-CREB increased significantly by 50 mg/kg dose of crocin. Only 12.5 mg/kg crocin could significantly increase the transcript levels of BDNF. No changes in CREB and VGF transcript levels were observed in all groups. Conclusions These results suggest that crocin has antidepressant-like action by increasing CREB, BDNF and VGF levels in hippocampus. PMID:24401376

  5. [Electrical activities of bursting-firing neurons in epileptic network reestablishment of rat hippocampus].

    PubMed

    Wang, Wen-Ting; Qin, Xing-Kui; Yin, Shi-Jin; Han, Dan

    2003-12-25

    The purpose of our present work was to study the discharge of bursting-firing neurons (BFNs) in ipsilateral or contralateral hippocampus (HPC), and its relations to the reestablishment of local epileptic networks. The experiments were performed on 140 Sprague Dawley male rats (150-250 g). Acute tetanization (60 Hz, 2 s, 0.4 -0.6 mA) of the right posterior dorsal hippocampus (ATPDH) was administered to establish rat epilepsy model. The single unit discharges and the depth electrographs were simultaneously recorded from ipsilateral or contralateral HPC. In other experimental rats, acute tetanization of the right anterior dorsal HPC (ATADH) was used. Extracellular unit discharges in the CA1 region were simultaneously recorded from bilateral anterior dorsal hippocampi. Analysis of hippocampal BFN firing patterns before or after administration of the tetanization was focused on according to their location in the HPC epileptic networks in vivo. Single unit discharges of 138 hippocampal neurons were recorded from ipsilateral and/or contralateral anterior dorsal HPC. Of the 138 neurons recorded, 19 were BFNs. 13 BFNs were tetanus-evoked and the remaining 6 were spontaneous ones. The evoked reactions of the single hippocampal neuron induced by the tetanization mainly included: (1) the firing patterns of the BFNs in ipsilateral anterior dorsal HPC were obviously modulated by the ATPDH from tonic firing into rhythmic bursting. The bursting interspike intervals (BISI) decreased. (2) There were mild modulations of the firing patterns of the BFNs in contralateral anterior dorsal HPC following post-inhibition of the firing rate of single neuron induced by the ATPDH. The interspike intervals (ISI) increased obviously. (3) Post-facilitation of rhythmic bursting-firing of the BFNs in contralateral anterior dorsal HPC was induced by ATADH; both the ISI and the IBI increased. (4) Synchronous or asynchronous rhythmic bursting-firing of the BFNs and the network epileptiform events

  6. Reduction in Aβ-induced cell death in the hippocampus of 17β-estradiol-treated female rats is associated with an increase in IGF-I signaling and somatostatinergic tone.

    PubMed

    Perianes-Cachero, Aránzazu; Canelles, Sandra; Aguado-Llera, David; Frago, Laura M; Toledo-Lobo, María Val; Carrera, Iván; Cacabelos, Ramón; Chowen, Julie A; Argente, Jesús; Arilla-Ferreiro, Eduardo; Barrios, Vicente

    2015-12-01

    Several studies indicate that 17β-estradiol (E2) protects against amyloid β-peptide (Aβ)-induced cell death and activates factors associated with learning and memory, a function involving the hippocampal somatostatinergic system. As alterations in somatostatin have been demonstrated in Alzheimer's disease, we examined whether E2 prevents changes in the hippocampal somatostatinergic system induced by Aβ25-35 and cell death, as well as the possible involvement of leptin and insulin-like growth factor (IGF)-I signaling. We also measured the levels of Aβ proteases neprilysin and insulin-degrading-enzyme. Co-administration of E2 with Aβ25-35 reduced both its levels and cell death, in addition to preventing the Aβ-induced depletion of some somatostatinergic parameters. Activation of leptin and IGF-I pathways increased after E2 co-administration, and this correlated with changes in the somatostatinergic system. Changes in some components of this system were inversely related with Aβ levels and cell death. Moreover, neprilysin levels were increased only in Aβ plus E2-treated rats and E2 prevented the Aβ-induced insulin-degrading-enzyme reduction. Our results suggest that the E2-induced reduction in cell death is related to lower Aβ levels, probably because of IGF-I and somatostatin modulation of Aβ proteases. We asked how 17β-estradiol (E2) protects against β-amyloid (Aβ)-induced cell death. E2 co-administration prevents Aβ-produced depletion of hippocampal somatostatin (SRIF) by an IGF-I-mediated mechanism, being related this protective effect with an increase in Aβ proteases. Our results suggest that the E2-induced reduction in cell death is related to lower Aβ levels, probably because of SRIF modulation of Aβ proteases. CREB, cAMP response element-binding protein; IGF-I, insulin-like growth factor-I; STAT3, signal transducer and activator of transcription-3. © 2015 International Society for Neurochemistry.

  7. Superoxide dismutase and catalase activities in rat hippocampus pretreated with garcinielliptone FC from Platonia insignis.

    PubMed

    da Costa Júnior, Joaquim S; de Almeida, Antonia Amanda C; Costa, Jéssica Pereira; das Graças Lopes Citó, Antonia Maria; Saffi, Jenifer; de Freitas, Rivelilson Mendes

    2012-04-01

    Platonia insignis Mart. (Clusiaceae), commonly known as "bacuri," is a timber and fruit native species of the Brazilian Amazon. Some plants of the Clusiaceae family have their pharmacological properties associated with the presence of xanthone and polycyclic polyprenylated acylphloroglucinols derivatives, which have antioxidant and anticarcinogenic activities. The aim of this study was to assess the in vivo potential of extracts, fractions, and garcinielliptone FC isolated from of Platonia insignis seeds as a natural antioxidant. Male Wistar rats (250-280 g; 2 months old) were treated with Tween 80 0.05% dissolved in 0.9% saline (i.p, vehicle - control group), ethanol extract (EE), hexane extract (HE), dichloromethane fraction (DMF), ethyl acetate fraction (EAF), and garcinielliptone FC (GFC) isolated from P. insignis at doses 2 mg/kg (i.p.). All groups were observed for 24 h after the treatment. The antioxidant enzymatic activities [superoxide dismutase (SOD) and catalase (CAT)] were measured using spectrophotometric methods. There were no marked alterations in SOD and CAT activities in rat hippocampus after pretreatment with EE, HE, DMF, EAF, and GFC. However, the pretreatment with GFC induced a significantly increase of 13, 17, 19, and 13% in SOD activities when compared to EE, HE, DMF, or EAF groups, respectively. Our findings strongly support the hypothesis that GFC isolated from P. insignis has a significant potential to be used as a natural antioxidant agent probably due to the modulation of enzymatic activity of hippocampal SOD.

  8. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Prior Learning of Relevant Nonaversive Information Is a Boundary Condition for Avoidance Memory Reconsolidation in the Rat Hippocampus.

    PubMed

    Radiske, Andressa; Gonzalez, Maria Carolina; Conde-Ocazionez, Sergio A; Feitosa, Anatildes; Köhler, Cristiano A; Bevilaqua, Lia R; Cammarota, Martín

    2017-10-04

    Reactivated memories can be modified during reconsolidation, making this process a potential therapeutic target for posttraumatic stress disorder (PTSD), a mental illness characterized by the recurring avoidance of situations that evoke trauma-related fears. However, avoidance memory reconsolidation depends on a set of still loosely defined boundary conditions, limiting the translational value of basic research. In particular, the involvement of the hippocampus in fear-motivated avoidance memory reconsolidation remains controversial. Combining behavioral and electrophysiological analyses in male Wistar rats, we found that previous learning of relevant nonaversive information is essential to elicit the participation of the hippocampus in avoidance memory reconsolidation, which is associated with an increase in theta- and gamma-oscillation power and cross-frequency coupling in dorsal CA1 during reactivation of the avoidance response. Our results indicate that the hippocampus is involved in memory reconsolidation only when reactivation results in contradictory representations regarding the consequences of avoidance and suggest that robust nesting of hippocampal theta-gamma rhythms at the time of retrieval is a specific reconsolidation marker.SIGNIFICANCE STATEMENT Posttraumatic stress disorder (PTSD) is characterized by maladaptive avoidance responses to stimuli or behaviors that represent or bear resemblance to some aspect of a traumatic experience. Disruption of reconsolidation, the process by which reactivated memories become susceptible to modifications, is a promising approach for treating PTSD patients. However, much of what is known about fear-motivated avoidance memory reconsolidation derives from studies based on fear conditioning instead of avoidance-learning paradigms. Using a step-down inhibitory avoidance task in rats, we found that the hippocampus is involved in memory reconsolidation only when the animals acquired the avoidance response in an

  10. Sleep enhances memory consolidation in the hippocampus-dependent object-place recognition task in rats.

    PubMed

    Binder, Sonja; Baier, Paul Christian; Mölle, Matthias; Inostroza, Marion; Born, Jan; Marshall, Lisa

    2012-02-01

    The positive impact of sleep on memory consolidation has been shown for human subjects in numerous studies, but there is still sparse knowledge on this topic in rats, one of the most prominent model species in neuroscience research. Here, we examined the role of sleep in the object-place recognition task, a task closely comparable to tasks typically applied for testing human declarative memory: It is a one-trial task, hippocampus-dependent, not stressful and can be repeated within the same animal. A test session consisted of the Sample trial, followed by a 2-h retention interval and a Test trial, the latter examining the memory the rat had for the places of two objects presented at the Sample trial. In Experiment 1, each rat was tested twice, with the retention interval taking place either in the morning or evening, i.e., in the inactive or active phase, respectively. Rats showed significantly (p<0.01) better memory for object place after the Morning session. To control for confounding circadian factors, in Experiment 2 rats were tested four times, i.e., in the morning or in the evening while sleep was or was not deprived. Sleep during the retention interval was recorded polysomnographically. Rats only showed significant memory for the target object place in the Test trial after the Morning retention interval in the absence of sleep deprivation, and recognition performance in this condition was significantly superior to that in the three other conditions (p<0.05). EEG recordings during spontaneous morning sleep revealed increased slow oscillation (0.85-2.0 Hz) and upper delta (2.0-4.0 Hz), but reduced spindle band (10.5-13.5 Hz) activity, as compared to evening sleep. However, spindle band power was increased in the Morning retention interval in comparison to a Morning Baseline period (p<0.05). We conclude that consolidation of object-place memory depends on sleep, and presumably requires NonREM sleep rich in both slow wave and spindle activity.

  11. A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study.

    PubMed

    Calderón, Naima; Betancourt, Luis; Hernández, Luis; Rada, Pedro

    2017-03-06

    The ketogenic diet (KD) is acknowledged as an unconventional option in the treatment of epilepsy. Several lines of investigation point to a possible role of glutamate and gamma-aminobutyric acid (GABA) as main contributors in this protective effect. Other biomolecules could also be involved in the beneficial consequence of the KD, for example, the diamine agmatine has been suggested to block imidazole and glutamate NMDA receptor and serves as an endogenous anticonvulsant in different animal models of epilepsy. In the present report, we have used microdialysis coupled to capillary electrophoresis to monitor microdialysate levels of GABA, glutamate and agmatine in the hippocampus of rats submitted to a KD for 15days compared to rats on a normal rat chow diet. A significant increase in GABA and agmatine levels while no change in glutamate levels was observed. These results support the notion that the KD modifies different transmitters favoring inhibitory over excitatory neurotransmitters.

  12. Deep brain stimulation macroelectrodes compared to multiple microelectrodes in rat hippocampus

    PubMed Central

    Arcot Desai, Sharanya; Gutekunst, Claire-Anne; Potter, Steve M.; Gross, Robert E.

    2014-01-01

    Microelectrode arrays (wire diameter <50 μm) were compared to traditional macroelectrodes for deep brain stimulation (DBS). Understanding the neuronal activation volume may help solve some of the mysteries associated with DBS, e.g., its mechanisms of action. We used c-fos immunohistochemistry to investigate neuronal activation in the rat hippocampus caused by multi-micro- and macroelectrode stimulation. At ± 1V stimulation at 25 Hz, microelectrodes (33 μm diameter) had a radius of activation of 100 μm, which is 50% of that seen with 150 μm diameter macroelectrode stimulation. Macroelectrodes activated about 5.8 times more neurons than a single microelectrode, but displaced ~20 times more neural tissue. The sphere of influence of stimulating electrodes can be significantly increased by reducing their impedance. By ultrasonic electroplating (sonicoplating) the microelectrodes with platinum to increase their surface area and reduce their impedance by an order of magnitude, the radius of activation increased by 50 μm and more than twice the number of neurons were activated within this increased radius compared to unplated microelectrodes. We suggest that a new approach to DBS, one that uses multiple high-surface area microelectrodes, may be more therapeutically effective due to increased neuronal activation. PMID:24971060

  13. Effect of protein malnutrition on redox state of the hippocampus of rat.

    PubMed

    Bonatto, Fernanda; Polydoro, Manuela; Andrades, Michael Everton; da Frota Júnior, Mário Luís Conte; Dal-Pizzol, Felipe; Rotta, Liane Nanci; Souza, Diogo Onofre; Perry, Marcos Luiz; Moreira, José Cláudio Fonseca

    2005-04-25

    The protein malnutrition is a worldwide problem, affecting mainly newborns and children of developing countries. This deficiency reaches the brain in the most critical period of the development. Various consequences are related to this insult, such as memory disturbance, learning, and behavioral impairment. Protein content of the diet plays an important role on antioxidant mechanisms. This study observed the effects of protein malnutrition on rat hippocampus redox state. Wistar rats were separate in four groups, receiving different diets: first group with 25% casein, protein deficient group with 8% casein, and the same two groups supplemented with methionine (0.15%). Diets were isocaloric and were administered since the prenatal period up to the sacrifice. Rats were decapitated at 21 or 75 days old and hippocampus were isolated for measuring the lipoperoxidation by TBARS method, protein oxidative damage by carbonyl (DNPH) levels, and the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). There was significant alterations in the activities of the enzyme SOD, lipoperoxidation, and protein oxidation in hippocampus of 21 and 75 day-old rats fed with 25% of protein with methionine and the groups fed with low levels of protein (8%) both supplemented or not with methionine. Our data suggest that both the content of protein in the diet and the essential amino acid methionine may alter the antioxidant system and the redox state of the brain.

  14. Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury.

    PubMed

    Schober, Michelle E; Requena, Daniela F; Davis, Lizeth J; Metzger, Ryan R; Bennett, Kimberly S; Morita, Denise; Niedzwecki, Christian; Yang, Zhihui; Wang, Kevin K W

    2014-07-29

    After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 Spectrin breakdown products (SBDPs) while proteolysis by Caspase 3 produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative importance of caspase-dependent apoptosis or calpain-dependent excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat, controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting a few days, and increased 145 SBDPs within the first few days lasting up to 14 days after injury. Little is known about SBDPs in the immature brain after TBI. Since development affects susceptibility to apoptosis after TBI, we hypothesized that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to SHAM during the first 3 and 5 days, respectively. SBDPs were measured in hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both brain tissues ipsilateral to injury during the first 3 days, while changes in contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more marked and enduring in hippocampus than in cortex. Against expectations, 120 SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations occurred early after CCI, similar to previous studies in the adult rat, but resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain-dependent, but not caspase-dependent, cell death predominates in the 17 day old rat after CCI. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Alpha II Spectrin Breakdown Products in Immature Sprague Dawley Rat Hippocampus and Cortex after Traumatic Brain Injury

    PubMed Central

    Schober, Michelle E; Requena, Daniela F; Davis, Lizeth J; Metzger, Ryan; Bennett, Kim; Morita, Denise; Niedzwecki, Christian; Yang, Zhihui; Wang, Kevin K W

    2014-01-01

    After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 SBDPs (Spectrin Breakdown Products) while proteolysis by Caspase 3 produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative importance of caspase-dependent apoptosis or calpain-dependent excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat, controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting a few days, and increased 145 SBDPs within the first few days lasting up to 14 days after injury. Little is known about SBDPs in the immature brain after TBI. Since development affects susceptibility to apoptosis after TBI, we hypothesized that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to SHAM during the first 3 and 5 days, respectively. SBDPs were measured in hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both brain tissues ipsilateral to injury during the first 3 days, while changes in contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more marked and enduring in hippocampus than in cortex. Against expectations, 120 SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations occurred early after CCI, similar to previous studies in the adult rat, but resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain-dependent, but not caspase-dependent, cell death predominates in the 17 day old rat after CCI. PMID:24929209

  16. Chronic nicotine exposure inhibits estrogen-mediated synaptic functions in hippocampus of female rats.

    PubMed

    Raval, Ami P; Sick, Justin T; Gonzalez, Gabriel J; Defazio, R Anthony; Dong, Chuanhui; Sick, Thomas J

    2012-05-23

    Nicotine, the addictive agent in cigarettes, reduces circulating estradiol-17β (E₂) and inhibits E₂-mediated intracellular signaling in hippocampus of female rats. In hippocampus, E₂-signaling regulates synaptic plasticity by phosphorylation of the N-methyl-D-aspartic acid receptor subunit NR2B and cyclic-AMP response element binding protein (pCREB). Therefore, we hypothesized that chronic nicotine exposure induces synaptic dysfunction in hippocampus of female rats. Female rats were exposed to nicotine or saline for 16 days followed by electrophysiological analysis of hippocampus. Briefly, population measurements of excitatory post-synaptic field potentials (fEPSPs) were recorded from stratum radiatum of the CA1 hippocampal slice subfield. A strict software-controlled protocol was used which recorded 30 min of baseline data (stimulation rate of 1/min), a paired-pulse stimulation sequence followed by tetanic stimulation, and 1h of post-tetanus recording. EPSP amplitude and the initial EPSP slope were measured off-line. We then investigated by Western blot analysis the effects of nicotine on hippocampal estrogen receptor-beta (ER-β), NR2B and pCREB. The results demonstrated significantly decreased post-tetanic potentiation and paired-pulse facilitation at the 40, and 80 ms interval in nicotine-exposed rats compared to the saline group. Western blot analysis revealed that nicotine decreased protein levels of ER-β, NR2B, and pCREB. We also confirmed the role of E₂ in regulating NR2B and pCREB phosphorylation by performing Western blots in hippocapmal tissue obtained from E₂-treated ovariectomized rats. In conclusion, chronic nicotine exposure attenuates short-term synaptic plasticity, and the observed synaptic defects might be a consequence of loss of estradiol-17β-signaling. However, determining the exact molecular mechanisms of chronic nicotine exposure on synaptic plasticity specific to the female brain require further investigation. Copyright © 2012

  17. Pharmacological characterisation of the histamine H3 receptor in the rat hippocampus.

    PubMed

    Alves-Rodrigues, A; Timmerman, H; Willems, E; Lemstra, S; Zuiderveld, O P; Leurs, R

    1998-03-30

    The purpose of this report was to pharmacologically characterise the histamine H3 in the rat hippocampus using radioligand binding studies with the H3 receptor antagonist [125I]iodophenpropit and the H3 receptor mediated inhibition of [3H]noradrenaline release. A dissociation constant of 0.33 nM and a maximal number of binding sites of 125 fmol/mg protein were found for [125I]iodophenpropit. Competition studies showed stereoselectivity for the (R) and (S) enantiomers of alpha-methylhistamine and 10 microM of GTPgammaS shifted the curve of (R)-alpha-methylhistamine rightwards. Up to 1 microM, (R)-alpha-methylhistamine displaced only 30% whereas the tested H3-antagonists displaced 50-60% of the total [125I]iodophenpropit bound. This indicates the presence of an additional non-H3 receptor binding site(s) for [125I]iodophenpropit in the rat hippocampus. This secondary site shows low affinity for H3 agonists, but high affinity for the tested H3 antagonists. Electrically evoked [3H]acetylcholine release was shown in slices of rat hippocampus. No H3 receptor modulation of [3H]acetylcholine release from hippocampal slices was detectable. However, H3 receptor activation inhibited 42% of the electrically-evoked [3H]noradrenaline release in rat hippocampal slices. The inhibition of [3H]noradrenaline release was effectively antagonized by the H3 antagonists thioperamide and burimamide. We describe the pharmacological identification of the histamine H3 receptor in the rat hippocampus and its similarities and differences from the cortical H3 receptor. These studies enable us to investigate changes in density and functionality of the hippocampal H3 receptor under (patho)physiological conditions.

  18. Increased phase synchronization of spontaneous calcium oscillations in epileptic human versus normal rat astrocyte cultures

    NASA Astrophysics Data System (ADS)

    Balázsi, Gábor; Cornell-Bell, Ann H.; Moss, Frank

    2003-06-01

    Stochastic synchronization analysis is applied to intracellular calcium oscillations in astrocyte cultures prepared from epileptic human temporal lobe. The same methods are applied to astrocyte cultures prepared from normal rat hippocampus. Our results indicate that phase-repulsive coupling in epileptic human astrocyte cultures is stronger, leading to an increased synchronization in epileptic human compared to normal rat astrocyte cultures.

  19. Functional emergence of the hippocampus in context fear learning in infant rats

    PubMed Central

    Raineki, Charlis; Holman, Parker J.; Debiec, Jacek; Bugg, Melissa; Beasley, Allyson; Sullivan, Regina M.

    2009-01-01

    The hippocampus is a part of the limbic system and is important for the formation of associative memories, such as acquiring information about the context (e.g. the place where an experience occurred) during emotional learning (e.g. fear conditioning). Here, we assess whether the hippocampus is responsible for pups’ newly emerging context learning. In all experiments, postnatal day (PN) 21 and PN24 rat pups received 10 pairings of odor-0.5mA shock or control unpaired odor-shock, odor only and shock only. Some pups were used for context, cue or odor avoidance tests, while the remaining pups were used for c-Fos immunohistochemistry to assess hippocampal activity during acquisition. Our results show that cue and odor avoidance learning were similar at both ages, while contextual fear learning and learning-associated hippocampal (CA1, CA3 and dentate gyrus) activity (c-Fos) only occurred in PN24 paired pups. To assess a causal relationship between the hippocampus and context conditioning, we infused muscimol into the hippocampus, which blocked acquisition of context fear learning in the PN24 pups. Muscimol or vehicle infusions did not affect cue learning or aversion to the odor at PN21 or PN24. The results suggest that the newly emerging contextual learning exhibited by PN24 pups is supported by the hippocampus. PMID:19739248

  20. Functional emergence of the hippocampus in context fear learning in infant rats.

    PubMed

    Raineki, Charlis; Holman, Parker J; Debiec, Jacek; Bugg, Melissa; Beasley, Allyson; Sullivan, Regina M

    2010-09-01

    The hippocampus is a part of the limbic system and is important for the formation of associative memories, such as acquiring information about the context (e.g., the place where an experience occurred) during emotional learning (e.g., fear conditioning). Here, we assess whether the hippocampus is responsible for pups' newly emerging context learning. In all experiments, postnatal day (PN) 21 and PN24 rat pups received 10 pairings of odor-0.5 mA shock or control unpaired odor-shock, odor only, or shock only. Some pups were used for context, cue or odor avoidance tests, while the remaining pups were used for c-Fos immunohistochemistry to assess hippocampal activity during acquisition. Our results show that cue and odor avoidance learning were similar at both ages, while contextual fear learning and learning-associated hippocampal (CA1, CA3, and dentate gyrus) activity (c-Fos) only occurred in PN24 paired pups. To assess a causal relationship between the hippocampus and context conditioning, we infused muscimol into the hippocampus, which blocked acquisition of context fear learning in the PN24 pups. Muscimol or vehicle infusions did not affect cue learning or aversion to the odor at PN21 or PN24. The results suggest that the newly emerging contextual learning exhibited by PN24 pups is supported by the hippocampus.

  1. Fear of the unexpected: Hippocampus mediates novelty-induced return of extinguished fear in rats

    PubMed Central

    Maren, Stephen

    2013-01-01

    Several lines of evidence indicate an important role for the hippocampus in the recovery of fear memory after extinction. For example, hippocampal inactivation prevents the renewal of fear to an extinguished conditioned stimulus (CS) when it is presented outside the extinction context. Renewal of extinguished responding is accompanied by associative novelty (an unexpected occurrence of a familiar CS in a familiar place), the detection of which may require the hippocampus. We therefore examined whether the hippocampus also mediates the recovery of extinguished fear caused by other unexpected events, including presenting a familiar CS in a novel context or presenting a novel cue with the CS in a familiar context (e.g., external disinhibition). Rats underwent Pavlovian fear conditioning and extinction using an auditory CS and freezing behavior served as the index of conditioned fear. In Experiment 1, conditioned freezing to the extinguished CS was renewed in a novel context and this was eliminated by intra-hippocampal infusions of the GABAA agonist, muscimol, prior to the test. In Experiment 2, muscimol inactivation of the hippocampus reduced the external disinhibition of conditioned freezing that occurred when a novel white noise accompanied the extinguished tone CS. Collectively, these results suggest that the hippocampus mediates the return of fear when extinguished CSs are unexpected, or when unexpected stimuli accompany CS presentation. Ultimately, a violation of expectations about when, where, and with what other stimuli an extinguished CS will occur may form the basis of spontaneous recovery, renewal, and external disinhibition. PMID:23791555

  2. MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

    PubMed

    Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

    2016-12-01

    3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures.

  3. Astrocyte fatty acid binding protein-7 is a marker for neurogenic niches in the rat hippocampus.

    PubMed

    Young, John K; Heinbockel, Thomas; Gondré-Lewis, Marjorie C

    2013-12-01

    Recent research has determined that newborn neurons in the dentate gyrus of the hippocampus of the macaque are frequently adjacent to astrocytes immunoreactive for fatty acid binding protein-7 (FABP7). To investigate if a similar relationship between FABP7-positive (FABP7+) astrocytes and proliferating cells exists in the rodent brain, sections of brains from juvenile rats were stained by immunohistochemistry to demonstrate newborn cells (antibody to Ki67 protein) and FABP7+ astrocytes. In rat brains, FABP7+ astrocytes were particularly abundant in the dentate gyrus of the hippocampus and were frequently close to dividing cells immunoreactive for Ki67 protein. FABP7+ astrocytes were also present in the olfactory bulbs, arcuate nucleus of the hypothalamus, and in the dorsal medulla subjacent to the area postrema, sites where more modest numbers of newborn neurons can also be found. These data suggest that regional accumulations of FABP7+ astrocytes may represent reservoirs of cells having the potential for neurogenesis. Because FABP7+ astrocytes are particularly abundant in the hippocampus, and since the gene for FABP7 has been linked to Alzheimer's disease, age-related changes in FABP7+ astrocytes (mitochondrial degeneration) may be relevant to age-associated disorders of the hippocampus.

  4. The effects of 30 mT electromagnetic fields on hippocampus cells of rats

    PubMed Central

    Teimori, Farzaneh; Khaki, Amir A.; Rajabzadeh, Asghar; Roshangar, Leila

    2016-01-01

    Background: Despite the use of electromagnetic waves in the treatment of some acute and chronic diseases, application of these waves in everyday life has created several problems for humans, especially the nerve system. In this study, the effects of 30mT electromagnetic fields (EMFs) on the hippocampus is investigated. Methods: Twenty-four 5-month Wistar rats weighing 150–200 g were divided into two groups. The experimental group rats were under the influence of an EMF at an intensity of 3 mT for approximately 4 hours a day (from 8 AM to 12 PM) during 10 weeks. After the hippocampus was removed, thin slides were prepared for transmission electron microscope (TEM) to study the ultrastructural tissue. Cell death detection POD kits were used to determine the apoptosis rate. Results: The results of the TEM showed that, in the hippocampus of the experimental group, in comparison to the control group, there was a substantial shift; even intracellular organelles such as the mitochondria were morphologically abnormal and uncertain. The number of apoptotic cells in the exposed group compared to the control group showed significant changes. Conclusions: Similar to numerous studies that have reported the effects of EMFs on nerves system, it was also confirmed in this lecture. Hence, the hippocampus which is important in regulating emotions, behavior, motivation, and memory functions, may be impaired by the negative impacts of EMFs. PMID:27453795

  5. Localization of glucocorticoid receptor messenger ribonucleic acid in hippocampus of rat brain using in situ hybridization

    SciTech Connect

    Yang, G.; Matocha, M.F.; Rapoport, S.I.

    1988-08-01

    An in situ hybridization procedure was applied to quantify glucocorticoid receptor (GR) mRNAs in the hippocampus of rat brain. Hybridization was carried out using a radiolabeled antisense probe complementary to the rat liver GR gene. The specificity of the method was validated by showing: 1) a high cellular grain density in sections hybridized with an antisense but not a sense probe; 2) agreement between the experimental and theoretical temperature at which 50% of the hybrids melted, and 3) a high signal distribution of GR mRNA in the hippocampus, a region of brain known to preferentially concentrate steroid hormones. Within the hippocampus, however, subregional differences in hybridization densities were observed. Quantitative autoradiography indicated that the average neuronal silver grain number was highest in the pyramidal cell layers of CA2 and CA4 and lowest in those of CA1 and CA3. Also, there was a significant difference in the average grain number between all of the cell fields except for that between CA2 and CA4. These results show that contiguous but neuroanatomically distinct cell fields of the hippocampus express different levels of GR transcripts, and indicate that differential regulation of GR expression occurs in subpopulations of hippocampal neurons.

  6. Impact of Several Types of Stresses on Short-term Memory and Apoptosis in the Hippocampus of Rats.

    PubMed

    Kim, Bo-Kyun; Ko, Il-Gyu; Kim, Sung-Eun; Kim, Chang-Ju; Yoon, Jee-Sang; Baik, Hyung-Hwan; Jin, Byung-Kwan; Lee, Choong-Yeol; Baek, Sang-Bin; Shin, Mal-Soon

    2013-09-01

    Stress has a deteriorating effect on hippocampal function. It also contributes to symptom exacerbation in many disease states, including overactive bladder and interstitial cystitis/bladder pain syndrome. We investigated the effects of various types of stresses (restraint, noise, and cold) on short-term memory and apoptosis in relation with corticotropin-releasing factor (CRF) expression. Rats in the restraint stress group were restrained in a transparent Plexiglas cylinder for 60 minutes twice daily. Rats in the noise stress group were exposed to the 120 dB supersonic machine sound for 60 minutes twice daily. Rats in the cold stress group were placed in a cold chamber at 4℃ for 60 minutes twice daily. Each stress was applied for 10 days. A step-down avoidance test for short-term memory, immunohistochemistry for caspase-3 expression, and western blot analysis for Bax and Bcl-2 expressions were conducted. Latency time was decreased and CRF expression in the hippocampal dentate gyrus and hypothalamic paraventricular nucleus were increased in all of the stress groups. The number of caspase-3-positive cells in the hippocampal dentate gyrus was increased and the expressions of Bax and Bcl2 in the hippocampus were decreased in all of the stress groups. All of the stress groups experienced short-term memory impairment induced by apoptosis in the hippocampus. The present results suggest the possibility that these stresses affecting the impairment of short-term memory may also induce functional lower urinary tract disorders.

  7. [Change of catecholamine in serum and hippocampus of rats after electromagnetic irradiation and the selection of protective site].

    PubMed

    Yang, Xuesen; Suo, Yulan; Zhang, Guangbin; Yu, Zhengping

    2002-08-01

    To study the role of catecholamine(CA) in the mechanism of bio-effect of electromagnetic irradiation. The contents of norepinephrine (NE), epinephrine (E) and dopamine (DA) in serum and hippocampus of rats at 0, 8, 24, 48 hours after electromagnetic irradiation were measured by using high performance liquid chromatography with electrochemical detector(HPLC-ECD), and the influence of two kinds of shelter on CA was studied. The levels of CA in serum and hippocampus increased obviously in an instant, decreased at 8 h and increased significantly again at 24 h after irradiation without shielding irradiation. But at 48 h, the levels of NA, DA in hippocampus were still higher and the serum's NA, DA were not different from the control. After irradiation with whole body shielding, the levels of CA had no changes. The contents of CA increased significantly only at 24 h after irradiation by 65 W/cm2 electromagnetic wave with trunk shielding. After irradiation by 129 W/cm2 with trunk shielding, the change of CA were similar to that of no shielding. CA may take part in the injury to central nervous system and cardiovascular system after electromagnetic irradiation. And the injury to central nervous system may sustain longer than that of cardiovascular system. The protective effect of whole body shielding is the best, while trunk shielding may have some protective effect following lower and middle power electromagnetic wave. The most important protective measure is to shield the head.

  8. Glutamate binding is altered in hippocampus and cortex of Wistar rats after pilocarpine-induced Status Epilepticus.

    PubMed

    Cunha, Alexandra Olimpio Siqueira; Mortari, Márcia Renata; Carolino, Ruither Oliveira Gomes; Coutinho-Netto, Joaquim; Dos Santos, Wagner Ferreira

    2007-08-31

    Several evidences have pointed to biochemical alterations in some brain structures after experimental Status Epilepticus (SE). Thus, the effects of pilocarpine-induced SE on the glutamate binding in the hippocampus and cortex of Wistar rats were evaluated. Groups of animals were submitted to a 3h SE induced by intrahippocampal microinjection of pilocarpine, which was interrupted by the administration of sodium thiopental. Two weeks later the animals were sacrificed and had their cerebral cortices and hippocampi removed in order to perform the binding experiments. The results show that the pilocarpine-induced SE provoked an increase in 2.5-fold in the B(max) values for glutamate binding in the cortex, but not in the hippocampus. Moreover, we observed a 4-fold increase for the Kd values in the hippocampus and a 2-fold increase in the cortex. These findings might indicate that the epileptogenesis involves alterations in the glutamate receptors that are not restricted to the limbic system. Moreover, changes in these receptors are not exclusively of number, but rather involve the affinity for their ligands.

  9. Changes in the regulation of 5-hydroxytryptamine release by alpha2-adrenoceptors in the rat hippocampus after long-term desipramine treatment.

    PubMed

    Yoshioka, M; Matsumoto, M; Numazawa, R; Togashi, H; Smith, C B; Saito, H

    1995-12-29

    In vivo microdialysis was used to measure the effects of long-term treatment of rats with desipramine upon the regulation by alpha2-adrenoceptors of serotonin (5-hydroxytryptamine, 5-HT) release from the serotonergic neurons in the hippocampus. Rats were injected with saline or desipramine, 10 mg/kg, i.p., every 12 h for 14 days. When added to the perfusion solution, brimonidine, an alpha2-adrenoceptor agonist, significantly inhibited the K+-evoked release of 5-HT in the hippocampi of saline-treated, control rats. This action of brimonidine was prevented by pretreating the rats with idazoxan, an alpha2-adrenoceptor antagonist. Long-term desipramine treatment significantly reduced the inhibitory effect of brimonidine upon the K+-evoked 5-HT release. With long-term administration of desipramine, noradrenaline content in the hippocampi was significantly decreased as compared with that of the control rats, whereas the basal noradrenaline concentration in the dialysate was significantly increased. On the other hand, both the 5-HT content of the hippocampus and the basal 5-HT concentration in the dialysate were significantly increased. The present study suggests that long-term administration of desipramine causes a functional subsensitivity of the presynaptic alpha2-adrenoceptors that regulate serotonergic neuronal function in the rat hippocampus. It also supports the concept that changes in the sensitivity of alpha2-adrenoceptors that regulate neurotransmitter release play an important role in the mechanism of antidepressant drug action.

  10. Sensitization to the conditioned rewarding effects of morphine modulates gene expression in rat hippocampus.

    PubMed

    Marie-Claire, Cynthia; Courtin, Cindie; Robert, Amelie; Gidrol, Xavier; Roques, Bernard P; Noble, Florence

    2007-02-01

    Opiates addiction is characterized by its long-term persistence. In order to study the enduring changes in long-term memory in hippocampus, a pivotal region for this process, we used suppression subtractive hybridization to compare hippocampal gene expression in morphine and saline-treated rats. Animals were subjected to an extended place preference paradigm consisting of four conditioning phases. Sensitization to the reinforcing effects of the drug occurred after three conditioning phases. After 25 days of treatment rats were euthanized and the complementary DNA (cDNA) from the hippocampus of morphine-dependent and saline-treated animals were then screened for differentially expressed cDNAs. The selected 177 clones were then subjected to a microarray procedure and 20 clones were found differentially regulated. The pattern of regulated genes suggests impairments in neurotransmitter release and the activation of neuroprotective pathways.

  11. Acute antiapoptotic effects of hydrocortisone in the hippocampus of neonatal rats.

    PubMed

    Menshanov, P N; Bannova, A V; Bulygina, V V; Dygalo, N N

    2013-01-01

    Natural glucocorticoid hydrocortisone was suggested as a potent substitution for dexamethasone in the treatment of bronchopulmonary dysplasia in neonates. The aim of this study was to investigate whether hydrocortisone is able to affect the expression of apoptotic genes and the intensity of naturally occurring cell death in the developing rat hippocampus. Hormone treatment decreased procaspase-3 and active caspase-3 levels as well as DNA fragmentation intensity in the hippocampal formation of one-week-old rats in 6 h after injection. These changes were accompanied by an upregulation of antiapoptotic protein Bcl-XL, while expression of proapoptotic protein Bax remained unchanged. The action of hydrocortisone was glucocorticoid receptor-independent, as the selective glucocorticoid receptor agonist dexamethasone did not affect either apoptotic protein levels or DNA fragmentation intensity in the hippocampal region. The data are the first evidences for in vivo antiapoptotic effects of hydrocortisone in the developing hippocampus.

  12. Sensitization to the conditioned rewarding effects of morphine modulates gene expression in rat hippocampus

    PubMed Central

    Marie-Claire, Cynthia; Courtin, Cindie; Robert, Amelie; Gidrol, Xavier; Roques, Bernard P.; Noble, Florence

    2007-01-01

    SUMMARY Opiates addiction is characterized by its long term persistence. In order to study the enduring changes in long-term memory in hippocampus, a pivotal region for this process, we used Suppression Subtractive Hybridization to compare hippocampal gene expression in morphine and saline-treated rats. Animals were subjected to an extended place preference paradigm consisting of four conditioning phases. Sensitization to the reinforcing effects of the drug occurred after 3 conditioning phases. After 26 days of treatment rats were sacrificed and the complementary DNA (cDNA) from the hippocampus of morphine-dependent and saline-treated animals were then screened for differentially expressed cDNAs. The selected 177 clones were then subjected to a microarray procedure and 20 clones were found differentially regulated. The pattern of regulated genes suggest impairments in neurotransmitter release and the activation of neuroprotective pathways. PMID:17014870

  13. [Activation of autophagy pathway in hippocampus and deterioration of learning and memory ability by intermittent hypoxia in rats after cerebral ischemia].

    PubMed

    Guo, Xiangfei; Zhao, Yaning; Li, Jianmin; Liu, Wenqian; Chen, Changxiang

    2016-09-01

    Objective To investigate the effects of different duration of intermittent hypoxia on the autophagy pathway in the hippocampus and the learning and memory ability after cerebral ischemia in rats. Methods 100 male Wistar rats were randomly divided into sham operation (SO) group, ischemia/reperfusion (I/R) group, intermittent hypoxia for 7 days combined with ischemia/reperfusion (IH7-I/R) group, intermittent hypoxia for 14 days combined with ischemia/reperfusion (IH14-I/R) group, intermittent hypoxia for 21 days combined with ischemia/reperfusion (IH21-I/R) group, n =20 in each group. The rats in IH7-I/R group, IH14-I/R group and IH21-I/R group were respectively subjected to intermittent hypoxia for 7, 14 and 21 days prior to I/R modeling by improved Pulsinelli four-vessel occlusion (4-VO). The morphological changes of nerve cells in the hippocampus of rat brain were detected by HE staining; the levels of mammalian target of rapamycin (mTOR) and beclin 1 mRNA in the hippocampus were determined by quantitative real-time PCR; the distribution of mTOR and beclin 1 in the hippocampus was observed by immunohistochemistry; the learning and memory ability of rats was assessed by the Morris water maze test. Results Compared with the SO group, the never cell morphology was damaged, the number of survival neurons in the hippocampus was reduced, the expressions of mTOR and beclin 1 in the hippocampus were strengthened, and the learning and memory ability declined in the I/R group. Compared with the I/R group, the never cell morphology was damaged seriously, the number of survival neurons in the hippocampus decreased, the expressions of mTOR and beclin 1 in the hippocampus increased, and the learning and memory ability dropped in the intermittent hypoxia groups. What's more, the above changes were dependent on the duration of intermittent hypoxia. Conclusion Intermittent hypoxia aggravates the dysfunction of learning and memory after cerebral ischemia and the damages increase

  14. Disturbance of endogenous hydrogen sulfide generation and endoplasmic reticulum stress in hippocampus are involved in homocysteine-induced defect in learning and memory of rats.

    PubMed

    Li, Man-Hong; Tang, Ji-Ping; Zhang, Ping; Li, Xiang; Wang, Chun-Yan; Wei, Hai-Jun; Yang, Xue-Feng; Zou, Wei; Tang, Xiao-Qing

    2014-04-01

    Homocysteine (Hcy) is a risk factor for Alzheimer's disease (AD). Hydrogen sulfide (H2S) acts as an endogenous neuromodulator and neuroprotectant. It has been shown that endoplasmic reticulum (ER) stress is involved in the pathological mechanisms of the learning and memory dysfunctions and that H2S exerts its neuroprotective role via suppressing ER stress. In the present work, we explored the effects of intracerebroventricular injection of Hcy on the formation of learning and memory, the generation of endogenous H2S, and the expression of ER stress in the hippocampus of rats. We found that intracerebroventricular injection of Hcy in rats leads to learning and memory dysfunctions in the Morris water maze and novel of object recognition test and decreases in the expression of cystathionine-β-synthase, the major enzyme responsible for endogenous H2S generation, and the generation of endogenous H2S in the hippocampus of rats. We also showed that exposure of Hcy could up-regulate the expressions of glucose-regulated protein 78 (GRP78), CHOP, and cleaved caspase-12, which are the major mark proteins of ER stress, in the hippocampus of rats. Taken together, these results suggest that the disturbance of hippocampal endogenous H2S generation and the increase in ER stress in the hippocampus are related to Hcy-induced defect in learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. 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

  16. Dynamic release of amino acid transmitters induced by valproate in PTZ-kindled epileptic rat hippocampus.

    PubMed

    Li, Zhi-Ping; Zhang, Xu-Ying; Lu, Xiang; Zhong, Ming-Kang; Ji, Yong-Hua

    2004-03-01

    In the present communication, the dynamic release of amino acid (AA) transmitters induced by valproate (VPA) in pentylenetetrazol (PTZ)-kindled freely moving rats hippocampus has been determined. The results showed that glutamate and aspartate release were significantly increased during the seizure/interical periods, and markedly decreased after the application of 200mg/kg valproate. In contrast, gamma-aminobutyric acid and taurine release were markedly decreased during interical period, and significantly increased during the seizure period. Glycine release was similar to the case of glutamate and aspartate release. The increase of either gamma-aminobutyric acid/taurine or glycine releases during the seizure period could be inhibited by the application of valproate likewise. The results indicate that: (a) the imbalance between excitatory and inhibitory neurotransmitters is really involved in epilepsy; (b) the modulation of valproate on the major amino acid neurotransmitters certainly plays one of important roles on antiepilepsy efficacy; (c) the pentylenetetrazol-kindled epileptogenesis model is a fit one for approaching the mechanisms of valproate modulating amino acid neurotransmitters.

  17. Developmental changes in GABAergic actions and seizure susceptibility in the rat hippocampus.

    PubMed

    Khazipov, Roustem; Khalilov, Ilgam; Tyzio, Roman; Morozova, Elena; Ben-Ari, Yezekiel; Holmes, Gregory L

    2004-02-01

    The immature brain is prone to seizures but the underlying mechanisms are poorly understood. We explored the hypothesis that increased seizure susceptibility during early development is due to the excitatory action of GABA. Using noninvasive extracellular field potential and cell-attached recordings in CA3 of Sprague-Dawley rat hippocampal slices, we compared the developmental alterations in three parameters: excitatory actions of GABA, presence of the immature pattern of giant depolarizing potentials (GDPs) and severity of epileptiform activity generated by high potassium. The GABA(A) receptor agonist isoguvacine increased firing of CA3 pyramidal cells in neonatal slices while inhibiting activity in adults. A switch in the GABA(A) signalling from excitation to inhibition occurred at postnatal day (P) 13.5 +/- 0.4. Field GDPs were present in the form of spontaneous population bursts until P12.7 +/- 0.3. High potassium (8.5 mm) induced seizure-like events (SLEs) in 35% of slices at P7-16 (peak at P11.3 +/- 0.4), but only interictal activity before and after that age. The GABA(A) receptor antagonist bicuculline reduced the frequency or completely blocked SLEs and induced interictal clonic-like activity accompanied by a reduction in the frequency but an increase in the amplitude of the population spikes. In slices with interictal activity, bicuculline typically caused a large amplitude interictal clonic-like activity at all ages; in slices from P5-16 rats it was often preceded by one SLE at the beginning of bicuculline application. These results suggest that, in the immature hippocampus, GABA exerts dual (both excitatory and inhibitory) actions and that the excitatory component in the action of GABA may contribute to increased excitability during early development.

  18. Mifepristone repairs region-dependent alteration of synapsin I in hippocampus in rat model of depression.

    PubMed

    Wu, Li-Min; Han, Hui; Wang, Qu-Nan; Hou, Hai-Long; Tong, Hui; Yan, Xue-Bo; Zhou, Jiang-Ning

    2007-12-01

    Clinical investigations present much evidence that the glucocorticoid receptor (GR) antagonist mifepristone leads to a rapid amelioration of depression. The molecular mechanisms of mifepristone involved in the treatment of depression are not fully understood. Depression is associated with hippocampal plasticity, for which increased excitatory amino acid (EAA) release in CA3 induced by chronic stress is responsible, and glucocorticoids have a permissive role and act synergistically with EAAs in producing neuronal damage. Moreover, glucocorticoids increase synapsin I, which has a key role in the release of neurotransmitter, including EAAs. Hereby, we hypothesize that major depression involves synapsin I alteration and that mifepristone blocks this alteration. In the present study, we observed both the expression of hippocampal synapsin I and depression-associated behavior in a rat model of depression induced by chronic unpredictable mild stress (CUMS). The result showed that a region-dependent synapsin I alteration occurs in the rat hippocampus after 21 days of CUMS, that is, it increases in dentate gyrus (DG)/CA3 and decreases in the CA1 region. Correlation analysis indicated that the decrease of synapsin I in CA1 is highly correlated with the increase in the DG/CA3 subfield. Simultaneously, the region-dependent alteration of synapsin I is correlated with depression-associated behaviors. Both the alteration of synapsin I and the depression-associated behavior were rapidly restored after treatment with mifepristone for 1 week. The result suggests that the molecular mechanism underlying the treatment of depression with mifepristone is associated with the rapid repair of the synaptic alteration.

  19. Acamprosate blocks the increase in dopamine extracellular levels in nucleus accumbens evoked by chemical stimulation of the ventral hippocampus.

    PubMed

    Cano-Cebrián, M J; Zornoza-Sabina, T; Guerri, C; Polache, A; Granero, L

    2003-10-01

    Recently, we have shown that acamprosate is able to modulate extracellular dopamine (DA) levels in the nucleus accumbens (NAc) and may act as an antagonist of N-methyl-D-aspartate (NMDA) receptors. Neurochemical studies show that chemical stimulation (using NMDA) of the ventral subiculum (vSub) of the hippocampus produces robust and sustained increases in extracellular DA levels in the NAc, an effect mediated through ionotropic glutamate (iGlu) receptors. The present study examines whether acamprosate locally infused in the NAc of rats could block or attenuate the increase in NAc extracellular DA elicited by chemical stimulation (with 5 mM NMDA) of the ventral subiculum of the hippocampus. The stimulation of the vSub during perfusion of artificial cerebrospinal fluid in NAc induced a significant and persistent increase in NAc DA levels. Reverse dialysis of 0.05 mM acamprosate in NAc blocked the increase in DA evoked by the chemical stimulation of the vSub. These data support the possibility that the antagonism at the NMDA receptors in NAc can explain, at least in part, the mechanism of action of this drug.

  20. Growth hormone prevents neuronal loss in the aged rat hippocampus.

    PubMed

    Azcoitia, Iñigo; Perez-Martin, Margarita; Salazar, Veronica; Castillo, Carmen; Ariznavarreta, Carmen; Garcia-Segura, Luis M; Tresguerres, Jesus A F

    2005-05-01

    Decline of growth hormone (GH) with aging is associated to memory and cognitive alterations. In this study, the number of neurons in the hilus of the dentate gyrus has been assessed in male and female Wistar rats at 3, 6, 12, 14, 18, 22 and 24 months of age, using the optical fractionator method. Male rats had more neurons than females at all the ages studied. Significant neuronal loss was observed in both sexes between 22 and 24 months of age. In a second experiment, 22 month-old male and female rats were treated for 10 weeks with 2 mg/kg/day of GH or saline. At 24 months of age, animals treated with GH had more neurons in the hilus than animals treated with saline. These findings indicate that GH is neuroprotective in old animals and that its administration may ameliorate neuronal alterations associated to aging.

  1. Treadmill running prevents age-related memory deficit and alters neurotrophic factors and oxidative damage in the hippocampus of Wistar rats.

    PubMed

    Vanzella, Cláudia; Neves, Juliana Dalibor; Vizuete, Adriana Fernanda; Aristimunha, Dirceu; Kolling, Janaína; Longoni, Aline; Gonçalves, Carlos Alberto Saraiva; Wyse, Angela T S; Netto, Carlos Alexandre

    2017-09-15

    Clinical and pre-clinical studies indicate that exercise is beneficial to many aspects of brain function especially during aging. The present study investigated the effects of a treadmill running protocol in young (3month-old) and aged (22month-old) male Wistar rats, on: I) cognitive function, as assessed by spatial reference memory in the Morris water maze; II) oxidative stress parameters and the expression of neurotrophic factors BDNF, NT-3, IGF-1 and VEGF in the hippocampus. Animals of both ages were assigned to sedentary (non-exercised) and exercised (20min of daily running sessions, 3 times per week for 4weeks) groups. Cognition was assessed by a reference memory task run in the Morris water maze; twenty four hours after last session of behavioral testing hippocampi were collected for biochemical analysis. Results demonstrate that the moderate treadmill running exercise: I) prevented age-related deficits in reference memory in the Morris water maze; II) prevented the age-related increase of reactive oxygen species levels and lipid peroxidation in the hippocampus; III) caused an increase of BDNF, NT-3 and IGF-1 expression in the hippocampus of aged rats. Taken together, results suggest that both exercise molecular effects, namely the reduction of oxidative stress and the increase of neurotrophic factors expression in the hippocampus, might be related to its positive effect on memory performance in aged rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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.

  3. Proteomic changes in female rat hippocampus following exposure to a terrified sound stress.

    PubMed

    Yang, Juan; Hu, Lili; Song, Tusheng; Liu, Yong; Wu, Qiuhua; Zhao, Lingyu; Liu, Liying; Zhao, Xiaoge; Zhang, Dianzeng; Huang, Chen

    2014-06-01

    Stress plays a profound role in the onset of affective disorders, including an elevation in risk factors for depression and anxiety. Women are twice as vulnerable to stress as men because of greater sensitivity to a substance produced during times of anxiety. To better define the abnormal proteins implicated in cognitive deficits and other stress-induced dysfunction, female rats were exposed to terrified sound stress, and two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) were utilized to determine the differential protein expression in the hippocampus in sound-stressed female rats compared with controls. Quantitative differences were found in 44 protein spots which were differentially expressed between the stressed and control groups (fold change of >2; p < 0.01). Eighteen protein spots were downregulated, and 26 protein spots were upregulated in the stressed group. The seven most differentially expressed proteins were identified and validated as follows: dihydropyrimidinase-related protein 2 (DRP-2), creatine kinase B type, dynamin-1 protein, alpha-internexin, glial fibrillary acidic protein beta, gamma-enolase, and peptidyl-prolyl cis-trans isomerase A. Changes in protein levels were detected in the hippocampus of female rats subjected to terrified sound stress. The findings herein may open new opportunities for further investigations on the modulation induced in the hippocampus by stress at the molecular level, especially with respect to females stress.

  4. A histological study of toxic effects of aluminium sulfate on rat hippocampus.

    PubMed

    Çabuş, N; Oğuz, E O; Tufan, A Ç; Adıgüzel, E

    2015-02-01

    Aluminium has toxic effects on many organ systems of the human body. Aluminium toxicity also is a factor in many neurodegenerative diseases. We investigated changes in numbers of hippocampal neurons in rats exposed to aluminium using an optical fractionator and we investigated aluminium-induced apoptosis using the transferase mediated dUTP nick end labeling (TUNEL) assay. Twenty-four female rats were divided equally into control, sham and aluminium-exposed groups. The control group received no treatment. The two treatment groups were injected intraperitoneally with 1 ml 0.9% saline without (sham) and with 3 mg/ml aluminium sulfate every day for two weeks. Following the treatments, the brains were removed, the left hemisphere was used for hippocampal neuron counting using an optical fractionator and the right hemisphere was investigated using hippocampal TUNEL assay to determine the apoptotic index. The number of neurons in the stratum pyramidale of the hippocampus was significantly less in the aluminium group than in the control and sham groups; there was no significant difference between the control and sham groups. The apoptotic index also was significantly higher in the aluminium group than in the other two groups. We quantified the toxic effects of aluminium on the rat hippocampus and determined that apoptosis was the mechanism of aluminium-induced neuron death in the hippocampus.

  5. Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

    PubMed

    Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

    2016-11-09

    Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

  6. Vortioxetine promotes early changes in dendritic morphology compared to fluoxetine in rat hippocampus.

    PubMed

    Chen, Fenghua; du Jardin, Kristian Gaarn; Waller, Jessica A; Sanchez, Connie; Nyengaard, Jens R; Wegener, Gregers

    2016-02-01

    Preclinical studies reveal that the multimodal antidepressant vortioxetine enhances long-term potentiation and dendritic branching compared to a selective serotonin reuptake inhibitor (SSRI). In the present study, we investigated vortioxetine׳s effects on spines and dendritic morphology in rat hippocampus at two time points compared to the SSRI, fluoxetine. Rats were dosed for 1 and 4 weeks with vortioxetine and fluoxetine at doses relevant for antidepressant activity. Dendritic morphology of pyramidal neurons (i.e., dendritic length, dendritic branch, spine number and density, and Sholl analysis) was examined in Golgi-stained sections from hippocampal CA1. After 1 week of treatment, vortioxetine significantly increased spine number (apical and basal dendrites), spine density (only basal), dendritic length (only apical), and dendritic branch number (apical and basal), whereas fluoxetine had no effect. After 4 weeks of treatment, vortioxetine significantly increased all measures of dendritic spine morphology as did fluoxetine except for spine density of basal dendrites. The number of intersections in the apical and basal dendrites was also significantly increased for both treatments after 4 weeks compared to control. In addition, 4 weeks of vortioxetine treatment, but not fluoxetine, promoted a decrease in spine neck length. In conclusion, 1-week vortioxetine treatment induced changes in spine number and density and dendritic morphology, whereas an equivalent dose of fluoxetine had no effects. Decreased spine neck length following 4-week vortioxetine treatment suggests a transition to mature spine morphology. This implies that vortioxetine׳s effects on spine and dendritic morphology are mediated by mechanisms that go beyond serotonin reuptake inhibition.

  7. Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats.

    PubMed

    Andrews, Jessica L; Newell, Kelly A; Matosin, Natalie; Huang, Xu-Feng; Fernandez-Enright, Francesca

    2015-12-03

    Postnatal administration of phencyclidine (PCP) in rodents causes major disturbances to neurological processes resulting in severe modifications to normal behavioral traits into adulthood. It is routinely used to model psychiatric disorders such as schizophrenia, producing many of the dysfunctional processes in the brain that are present in this devastating disorder, including elevated levels of apoptosis during neurodevelopment and disruptions to myelin and plasticity processes. Lingo-1 (or Leucine-rich repeat and immunoglobulin domain-containing protein) is responsible for negatively regulating neurite outgrowth and the myelination of axons. Recent findings using a postmortem human brain cohort showed that Lingo-1 signaling partners in the Nogo receptor (NgR)/p75/TNF receptor orphan Y (TROY) signaling complex, and downstream signaling partners With No Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1), play a significant part in schizophrenia pathophysiology. Here we have examined the implication of Lingo-1 and its signaling partners in a neurodevelopmental model of schizophrenia using PCP to determine if these pathways are altered in the hippocampus throughout different stages of neurodevelopment. Male Sprague-Dawley rats were injected subcutaneously with PCP (10mg/kg) or saline solution on postnatal days (PN) 7, 9, and 11. Rats (n=6/group) were sacrificed at PN12, 5weeks, or 14weeks. Relative expression levels of Lingo-1 signaling proteins were examined in the hippocampus of the treated rats. p75 and Myt1 were decreased (0.001≤p≤0.011) in the PCP treated rats at PN12. There were no significant changes in any of the tested proteins at 5weeks (p>0.05). At 14weeks, p75, TROY, and Myt1 were increased in the PCP treated rats (0.014≤p≤0.022). This is the first report of an alteration in Lingo-1 signaling proteins in the rat hippocampus, both directly after PCP treatment in early development and in adulthood. Based on our results, we propose that

  8. Telomerase dysregulation in the hippocampus of a rat model of depression: normalization by lithium.

    PubMed

    Wei, Ya Bin; Backlund, Lena; Wegener, Gregers; Mathé, Aleksander A; Lavebratt, Catharina

    2015-01-24

    Telomeres are protective DNA-protein complexes at the ends of each chromosome, maintained primarily by the enzyme telomerase. Shortening of the blood leukocyte telomeres is associated with aging, several chronic diseases, and stress, eg, major depression. Hippocampus is pivotal in the regulation of cognition and mood and the main brain region of telomerase activity. Whether there is telomere dysfunction in the hippocampus of depressed subjects is unknown. Lithium, used in the treatment and relapse prevention of mood disorders, was found to protect against leukocyte telomere shortening in humans, but the mechanism has not been elucidated. To answer the questions whether telomeres are shortened and the telomerase activity changed in the hippocampus and whether lithium could reverse the process, we used a genetic model of depression, the Flinders Sensitive Line rat, and treated the animals with lithium. Telomere length, telomerase reverse transcriptase (Tert) expression, telomerase activity, and putative mediators of telomerase activity were investigated in the hippocampus of these animals. The naïve Flinders Sensitive Line had shorter telomere length, downregulated Tert expression, reduced brain-derived neurotrophic factor levels, and reduced telomerase activity compared with the Flinders Resistant Line controls. Lithium treatment normalized the Tert expression and telomerase activity in the Flinders Sensitive Line and upregulated β-catenin. This is the first report showing telomere dysregulation in hippocampus of a well-defined depression model and restorative effects of lithium treatment. If replicated in other models of mood disorder, the findings will contribute to understanding both the telomere function and the mechanism of lithium action in hippocampus of depressed patients. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  9. Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus.

    PubMed

    Dal Bosco, Lidiane; Weber, Gisele E; Parfitt, Gustavo M; Cordeiro, Arthur P; Sahoo, Sangram K; Fantini, Cristiano; Klosterhoff, Marta C; Romano, Luis Alberto; Furtado, Clascídia A; Santos, Adelina P; Monserrat, José M; Barros, Daniela M

    2015-01-01

    Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the

  10. Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus

    PubMed Central

    Dal Bosco, Lidiane; Weber, Gisele E.; Parfitt, Gustavo M.; Cordeiro, Arthur P.; Sahoo, Sangram K.; Fantini, Cristiano; Klosterhoff, Marta C.; Romano, Luis Alberto; Furtado, Clascídia A.; Santos, Adelina P.; Monserrat, José M.; Barros, Daniela M.

    2015-01-01

    Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the

  11. Differential induction of c-Jun and Fos-like proteins in rat hippocampus and dorsal striatum after training in two water maze tasks.

    PubMed

    Teather, Lisa A; Packard, Mark G; Smith, Diane E; Ellis-Behnke, Rutledge G; Bazan, Nicolas G

    2005-09-01

    Research examining the neuroanatomical bases of memory in mammals suggests that the hippocampus and dorsal striatum are parts of independent memory systems that mediate "cognitive" and stimulus-response "habit" memory, respectively. At the molecular level, increasing evidence indicates a role for immediate early gene (IEG) expression in memory formation. The present experiment examined whether acquisition of cognitive and habit memory result in differential patterns of IEG protein product expression in these two brain structures. Adult male Long-Evans rats were trained in either a hippocampal-dependent spatial water maze task, or a dorsal striatal-dependent cued water maze task. Ninety minutes after task acquisition, brains were removed and processed for immunocytochemical procedures, and the number of cells expressing Fos-like immunoreactivity (Fos-like-IR) and c-Jun-IR in sections from the dorsal hippocampus and the dorsal striatum were counted. In the dorsal hippocampus of rats trained in the spatial task, there were significantly more c-Jun-IR pyramidal cells in the CA1 and CA3 regions, relative to rats that had acquired the cued task, yoked controls (free-swim), or naïve (home cage) rats. Relative to rats receiving cued task training and control conditions, increases in Fos-like IR were also observed in the CA1 region of rats trained in the spatial task. In rats that had acquired the cued task, patches of c-Jun-IR were observed in the posteroventral striatum; no such patches were evident in rats trained in the spatial task, yoked-control rats, or naïve rats. The results demonstrate that IEG protein product expression is up-regulated in a task-dependent and brain structure-specific manner shortly after acquisition of cognitive and habit memory tasks.

  12. Differential effects of benzodiazepines on phospholipid methylation in hippocampus and cerebellum of rats

    SciTech Connect

    Tacconi, M.T.; Salmona, M.

    1988-01-01

    To elucidate the relationship between the occupancy of BDZ binding sites and phospholipid methylation in brain, the authors examined phosphatidylethanolamine-N-methyltransferase (PEMT) activity in synaptosomes of rat hippocampi and cerebella in the presence of BDZ ligands with different modes of action. We found that Ro 5-4864, a specific ligand for peripheral type receptors, increased PL methylation in hippocampal and cerebellar synaptosomes. This effect was directly related to receptor occupancy, since the specific antagonist PK11195 inhibited the rise in PEMT activity induced by Ro 5-4864. Clonazepam, on the other hand, tended to reduce PL production in cerebellum and hippocampus except for hiccocampal (/sup 3/H)-phosphatidyl-N-monomethylethanolamine which was elevated by 40 to 70% at doses ranging from 10/sup -9/ to 10/sup -6/M. When equimolar concentrations of the antagonist Ro 15-1788 were given in association the clonazepam-induced phosphatidyl-N-monomethylethanolamine increase was reduced by 70%. These data support the involvement of structural and functional membrane alterations in the action of BDZ. 20 references, 2 figures, 2 tables.

  13. Diphenyl diselenide modulates gene expression of antioxidant enzymes in the cerebral cortex, hippocampus and striatum of female hypothyroid rats.

    PubMed

    Roseni Mundstock Dias, Glaecir; Medeiros Golombieski, Ronaldo; de Lima Portella, Rafael; Pires do Amaral, Guilherme; Antunes Soares, Félix; Teixeira da Rocha, João Batista; Wayne Nogueira, Cristina; Vargas Barbosa, Nilda

    2014-01-01

    Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status. To investigate whether or not dietary diphenyl diselenide can modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid conditions. Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ-treated rats were either fed or not with a diet containing diphenyl diselenide (5 ppm). mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in the cerebral cortex, hippocampus and striatum. Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR-1) in brain structures. SOD-2 was increased in the cortex and striatum, while TrxR-2 increased in the cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in the cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and reactive oxygen species levels in the hippocampus and striatum, and a decrease in nonprotein thiols in the cerebral cortex. Diphenyl diselenide was effective in reducing brain oxidative stress and normalizing most of the changes observed in gene expression of antioxidant enzymes. The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, diphenyl diselenide may be considered a promising molecule to counteract these effects in a hypothyroidism state. © 2014 S. Karger AG, Basel.

  14. Downregulation of caveolin-1 contributes to the synaptic plasticity deficit in the hippocampus of aged rats

    PubMed Central

    Liu, Yang; Liang, Zhanhua; Liu, Jing; Zou, Wei; Li, Xiaoyan; Wang, Yachen; An, Lijia

    2013-01-01

    Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebellum of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged (22–24 month old) rats was significantly lower than that in young (1 month old) and adult (4 months old) rats. pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebellum. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebellum. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging. PMID:25206583

  15. Deficits in parvalbumin and calbindin immunoreactive cells in the hippocampus of isolation reared rats.

    PubMed

    Harte, M K; Powell, S B; Swerdlow, N R; Geyer, M A; Reynolds, G P

    2007-07-01

    Post-mortem studies have provided evidence for abnormalities of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia. The calcium-binding proteins (CBPs), parvalbumin (PV), calbindin (CB) and calretinin (CR) can be used as markers for specific subpopulations of GABAergic neurons in the brain. Isolation rearing of rats is a non-pharmacological, non-lesion manipulation that leads to deficits in prepulse inhibition of the startle reflex (PPI) and other behavioural and neurochemical alterations reminiscent of schizophrenia. Female rats were reared in social housing (groups of three) or singly for 11 weeks post weaning and PPI was measured. Brains were removed and hippocampal CBP- containing neurons determined following immunocytochemical staining. Compared to socially housed rats, isolated rats exhibited PPI deficits and reductions in PV and CB-immunoreactive cells in the hippocampus, with no significant change in CR. These findings demonstrate selective abnormalities of sub-populations of GABAergic interneurons in the hippocampus of isolation reared rats, which resemble the neuronal deficits seen in this region in schizophrenia.

  16. 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.

  17. [Effect of Acupuncture Intervention on Expression of NF-κB Signal Pathway in the Hippocampus of Chronic Stress-induced Depression Rats].

    PubMed

    Shao, Run-hui; Jin, Shu-ying; Lu, Jun; Hu, Li; Tu, Ya

    2015-10-01

    To observe the influence of acupuncture intervention on the expression of pivotal pro-inflammatory molecules nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) of NF-κB inflammatory signal pathway in the hippocampus of depression rats, so as to explore its mechanism underlying improvement of depression. Thirty-six male Sprague-Dawley rats were randomly divided into four groups: control, model, acupuncture, and medication (fluoxetine, Flu) (n = 9 rats in each group). The depression model was established by using chronic unpredictable stress stimuli combined with solitary feeding for 28 days. Acupuncture treatment was applied to "Baihui" (GV 20) and "Neiguan" (PC 6) once every other day for 28 days. Fluoxetine was given to rats of the medication group (10 mg/kg) by gavage (p. o.) everyday for 28 days before the stress stimulation. The expression of NF-κB protein in the hippocampus tissue was detected by Western blot, and the contents of COX-2 and PGE2 were detected by ELISA. Compared to the control group, the levels of NF-κB protein expression, COX-2 and PGE2 contents in the hippocampus were significantly increased in the model group (P < 0.01). Compared to the model group, the levels of NF-κB protein expression, COX-2 and PGE2 contents in the hippocampus were significantly down-regulated in both the acupuncture and medication groups (P < 0.05; P < 0.01). There was no significant differences between the acupuncture and medication groups in the NF-κB protein expression, and COX-2 and PGE2 contents (P > 0.05). Acupuncture intervention can effectively reduce hippocampal NF-κB expression, and COX-2 and PGE2 levels in depression rats, which may contribute to its anti-depressant effect by inhibiting pro-inflammatory pathway to protect the neurons of hippocampus.

  18. The spiking component of oscillatory extracellular potentials in the rat hippocampus

    PubMed Central

    Schomburg, Erik W.; Anastassiou, Costas A.; Buzsáki, György; Koch, Christof

    2012-01-01

    When monitoring neural activity using intracranial electrical recordings, researchers typically consider the signals to have two primary components: fast action potentials (AP) from neurons near the electrode, and the slower local field potential (LFP), thought to be dominated by postsynaptic currents integrated over a larger volume of tissue. In general, a decrease in signal power with increasing frequency is observed for most brain rhythms. 100–200 Hz oscillations in the rat hippocampus, including ‘fast gamma’ or ‘epsilon’ oscillations and sharp wave-ripples (SPW-R), are one exception, showing an increase in power with frequency within this band. We have employed detailed biophysical modeling to investigate the composition of extracellular potentials during fast oscillations in rat CA1. We find that postsynaptic currents exhibit a decreasing ability to generate large amplitude oscillatory signals at high frequencies, whereas phase-modulated spiking shows the opposite trend. Our estimates indicate that APs and postsynaptic currents contribute similar proportions of the power contained in 140–200 Hz ripples, and the two combined generate a signal that closely resembles in vivo SPW-Rs. Much of the AP-generated signal originates from neurons further than 100 μm from the recording site, consistent with ripples appearing similarly strong regardless of whether or not they contain recognizable APs. Additionally, substantial power can be generated in the 90–150 Hz epsilon band by the APs from rhythmically firing pyramidal neurons. Thus, high frequency LFPs may generally contain signatures of local cell assembly activation. PMID:22915121

  19. Dendritic morphology of neurons in prefrontal cortex and ventral hippocampus of rats with neonatal amygdala lesion.

    PubMed

    Vázquez-Roque, Rubén Antonio; Solis, Oscar; Camacho-Abrego, Israel; Rodríguez-Moreno, Antonio; Cruz, Fidel De La; Zamudio, Sergio; Flores, Gonzalo

    2012-05-01

    Neonatal basolateral amygdala (nBLA) lesions in rats have been widely used as a neurodevelopmental model that mimics schizophrenia-like behaviors. Recently, we reported that nBLA lesions result in significant decreases in the dendritic spine number of layer 3 prefrontal cortex (PFC) pyramidal cells and medium spiny neurons of the nucleus accumbens (NAcc), which all changes after puberty. At present, we aimed to evaluate the effect of this lesion in pyramidal neurons of CA1 of the ventral hippocampus (VH) and layer 5 of the PFC. In order to assess the effects of nBLA lesions on the dendritic morphology of the PFC and VH neurons, we carried out nBLA lesions in rats on postnatal day (PD) 7, and then we studied the dendritic morphology of these two limbic subregions at prepubertal (PD35) and postpubertal (PD60) ages. Dendritic characteristics were measured by Golgi-Cox procedure followed by Sholl analysis. We also evaluated the effects of nBLA lesions on the prepulse inhibition (PPI) and acoustic startle responses. The nBLA lesion induced a significant increase in dendritic length of layer 5 pyramidal neurons of the PFC at both ages, with a decrease in the dendritic spines density after puberty. The spine density of CA1 VH pyramidal neurons showed significant decreases at both ages. PPI was decreased in adulthood in the animals with an nBLA lesion. These results show that an nBLA lesion alters the dendritic morphology at the level of the PFC and VH in distinct ways before puberty, suggesting a disconnection between these limbic structures at an early age, and increasing our understanding of the implications of the VH in early amygdala dysfunction in schizophrenia. Copyright © 2011 Wiley Periodicals, Inc.

  20. Gene Expression Profile of Calcium/Calmodulin-Dependent Protein Kinase IIα in Rat's Hippocampus during Morphine Withdrawal

    PubMed Central

    Ahmadi, Shamseddin; Amiri, Shahin; Rafieenia, Fatemeh; Rostamzadeh, Jalal

    2013-01-01

    Introduction Calcium/calmodulin-dependent protein kinase II (CaMKII) which is highly expressed in the hippocampus is known to play a pivotal role in reward-related memories and morphine dependence. Methods In the present study, repeated morphine injections once daily for 7 days was done to induce morphine tolerance in male Wistar rats, after which gene expression profile of α-isoform of CaMKII (CaMKIIα) in the hippocampus was evaluated upon discontinuation of morphine injection over 21 days of morphine withdrawal. Control groups received saline for 7 consecutive days. For gene expression study, rats’ brains were removed and the hippocampus was dissected in separate groups on days 1, 3, 7, 14, and 21 since discontinuation of of morphine injection. A semi-quantitative RT-PCR method was used to evaluate the gene expression profile. Results Tolerance to morphine was verified by a significant decrease in morphine analgesia in a hotplate test on day 8 (one day after the final repeated morphine injections). Results showed that gene expression of CaMKIIα at mRNA level on day 1, 3, 7, 14 and 21 of morphine withdrawal was significantly altered as compared to the saline control group. Post hoc Tukey's test revealed a significantly enhanced CaMKIIα gene expression on day 14. Discussion It can be concluded that CaMKIIα gene expression during repeated injections of morphine is increased and this increase continues up to 14 days of withdrawal then settles at a new set point. Therefore, the strong morphine reward-related memory in morphine abstinent animals may, at least partly be attributed to, the up-regulation of CaMKIIα in the hippocampus over 14 days of morphine withdrawal. PMID:25337341

  1. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats.

    PubMed

    Eid, Tore; Ghosh, Arko; Wang, Yue; Beckström, Henning; Zaveri, Hitten P; Lee, Tih-Shih W; Lai, James C K; Malthankar-Phatak, Gauri H; de Lanerolle, Nihal C

    2008-08-01

    An excess of extracellular glutamate in the hippocampus has been linked to the generation of recurrent seizures and brain pathology in patients with medically intractable mesial temporal lobe epilepsy (MTLE). However, the mechanism which results in glutamate excess in MTLE remains unknown. We recently reported that the glutamate-metabolizing enzyme glutamine synthetase is deficient in the hippocampus in patients with MTLE, and we postulated that this deficiency is critically involved in the pathophysiology of the disease. To further explore the role of glutamine synthetase in MTLE we created a novel animal model of hippocampal glutamine synthetase deficiency by continuous (approximately 28 days) microinfusion of methionine sulfoximine (MSO: 0.625 to 2.5 microg/h) unilaterally into the hippocampus in rats. This treatment led to a deficiency in hippocampal glutamine synthetase activity by 82-97% versus saline. The majority (>95%) of the MSO-treated animals exhibited recurrent seizures that continued for several weeks. Some of the MSO-treated animals exhibited neuropathological features that were similar to mesial temporal sclerosis, such as hippocampal atrophy and patterned loss of hippocampal neurons. However, many MSO-treated animals displayed only minimal injury to the hippocampus, with no clear evidence of mesial temporal sclerosis. These findings support the hypothesis that a deficiency in hippocampal glutamine synthetase causes recurrent seizures, even in the absence of classical mesial temporal sclerosis, and that restoration of glutamine synthetase may represent a novel approach to therapeutic intervention in this disease.

  2. Colocalization of cannabinoid receptor 1 with somatostatin and neuronal nitric oxide synthase in rat brain hippocampus.

    PubMed

    Zou, Shenglong; Kumar, Ujendra

    2015-10-05

    Somatostatin (SST), a growth hormone inhibitory peptide, is expressed in different parts of the brain and functions as a neurotransmitter and neuromodulator. In the central nervous system (CNS), SST inhibits Ca(2+) influx and regulates neuronal excitability in the hippocampus, the brain region which plays a major role in seizure, as well as cognitive and memory function. Much like SST, cannabinoid receptor 1 (CB1 receptor) is also widely distributed in the CNS, associated with memory function ad exerts inhibitory effects on seizure. It is unknown whether overlapping functional activities of SST and CB1 receptor are also associated with coexpression in the hippocampus. In the present study, we determined the colocalization between SST and CB1 receptor in adult rat brain hippocampus. In the CNS, the majority of SST positive interneurons coexpress neuronal nitric oxide synthase (nNOS). Accordingly, colocalization studies were also performed to determine whether nNOS positive neurons display comparable colocalization with CB1 receptor. The findings suggested that SST and nNOS are expressed in most interneurons whereas CB1 receptor is present in both interneurons and projection neurons in hippocampal regions. The distinct neuronal populations either expressing CB1 receptor, SST and nNOS alone or colocalization were observed in a region specific manner. Taken together, the observations described here anticipate the possibility of crosstalk between somatostatin subtypes and CB1 receptor in regulation of physiological activities in the hippocampus. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. 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.

  4. The effects of doxepin on stress-induced learning, memory impairments, and TNF-α level in the rat hippocampus

    PubMed Central

    Azadbakht, Ali Ahmad; Radahmadi, Maryam; Javanmard, Shaghayegh Haghjooye; Reisi, Parham

    2015-01-01

    Stress has a profound impact on the nervous system and causes cognitive problems that are partly related to the inflammatory effects. Besides influencing the content of neurotransmitters, antidepressants such as doxepin are likely to have anti-inflammatory, anti-oxidative, and anti-apoptotic effects. Therefore, the present study investigated the effects of doxepin on passive avoidance learning and the levels of tumor necrosis factor-alpha (TNF-α) in the rat hippocampus following repeated restraint stress. Male Wistar rats were divided into five groups. Chronic stress was induced by keeping animals within an adjustable restraint chamber for 6 h every day for 21 successive days. In stress-doxepin group, stressed rats were given 1, 5 and 10 mg/kg of doxepin intraperitoneally (i.p) for 21 days and before placing them in restraint chamber. Healthy animals who served as control group and stressed rats received normal saline i.p. For evaluation of learning and memory, initial latency and step-through latency were determined using passive avoidance learning test. TNF-α levels were measured in hippocampus by enzyme-linked immunosorbant assay (ELISA) at the end of experiment. Induced stress considerably decreased the step through latencies in the rats (P<0.05) but doxepin administration prevented these changes. Stress-doxepin groups did not reveal any differences compared to control group at any given doses. TNF-α level was increased significantly (P<0.05) in stress group. Only the low dose of doxepin (1 mg/kg) decreased TNF-α level. The present findings indicated that learning and memory are impaired in stressful conditions and doxepin prevented memory deficit. It seems that inflammation may involve in induced stress memory deficits, and that doxepin is helpful in alleviating the neural complications due to stress. PMID:26752995

  5. Cholinergic and GABAergic receptor functional deficit in the hippocampus of insulin-induced hypoglycemic and streptozotocin-induced diabetic rats.

    PubMed

    Sherin, A; Anu, J; Peeyush, K T; Smijin, S; Anitha, M; Roshni, B T; Paulose, C S

    2012-01-27

    Neurotransmitter receptor functional regulation plays an important role in controlling the excitability and responsiveness of hippocampal neurons. Deregulation of its function is associated with seizure generation, motor deficits, and memory impairment. In the present study we investigated the changes in hippocampal cholinergic and GABA receptor binding and gene expression in insulin-induced hypoglycemic and streptozotocin-induced diabetic rats. Expression of cholinergic enzymes; acetylcholine esterase (AChE) and choline acetyltransferase (ChAT) upregulated and downregulated, respectively, in diabetic group, which was further exacerbated by hypoglycemia. Total muscarinic receptor, muscarinic M1, and GABA maximal binding (B(max)) significantly decreased in hypoglycemic and diabetic rats. In hypoglycemic group, the B(max) showed further decline compared with diabetes. Muscarinic M3 receptor B(max) and gene expression upregulated in hypoglycemic and diabetic group. Alpha7 nicotinic acetylcholine receptor (α7 nAChR) expression significantly downregulated in hypoglycemic and diabetic rats. Gene expression of glutamate decarboxylase (GAD), GABAAα1, and GABAB in hypoglycemic and diabetic rats downregulated, with more significant decrease in hypoglycemic group. Present findings show altered cholinergic, muscarinic, nicotinic receptor expression and thereby function. Decreased GABA receptor expression is associated with decline in GABAergic neurotransmission. Thus cholinergic receptor dysfunction and decreased GABAergic neuroprotective inhibitory function in the hippocampus of hypoglycemic and diabetic rats account for the increased vulnerability of hippocampus predisposing to neuronal damage, which is suggested to contribute to cognitive impairment and memory deficit reported in hypoglycemia and diabetes. Also, recurrent hypoglycemia in diabetes exacerbates the hippocampal dysfunction induced by diabetes, which has clinical significance in diabetes therapy.

  6. The effects of doxepin on stress-induced learning, memory impairments, and TNF-α level in the rat hippocampus.

    PubMed

    Azadbakht, Ali Ahmad; Radahmadi, Maryam; Javanmard, Shaghayegh Haghjooye; Reisi, Parham

    2015-01-01

    Stress has a profound impact on the nervous system and causes cognitive problems that are partly related to the inflammatory effects. Besides influencing the content of neurotransmitters, antidepressants such as doxepin are likely to have anti-inflammatory, anti-oxidative, and anti-apoptotic effects. Therefore, the present study investigated the effects of doxepin on passive avoidance learning and the levels of tumor necrosis factor-alpha (TNF-α) in the rat hippocampus following repeated restraint stress. Male Wistar rats were divided into five groups. Chronic stress was induced by keeping animals within an adjustable restraint chamber for 6 h every day for 21 successive days. In stress-doxepin group, stressed rats were given 1, 5 and 10 mg/kg of doxepin intraperitoneally (i.p) for 21 days and before placing them in restraint chamber. Healthy animals who served as control group and stressed rats received normal saline i.p. For evaluation of learning and memory, initial latency and step-through latency were determined using passive avoidance learning test. TNF-α levels were measured in hippocampus by enzyme-linked immunosorbant assay (ELISA) at the end of experiment. Induced stress considerably decreased the step through latencies in the rats (P<0.05) but doxepin administration prevented these changes. Stress-doxepin groups did not reveal any differences compared to control group at any given doses. TNF-α level was increased significantly (P<0.05) in stress group. Only the low dose of doxepin (1 mg/kg) decreased TNF-α level. The present findings indicated that learning and memory are impaired in stressful conditions and doxepin prevented memory deficit. It seems that inflammation may involve in induced stress memory deficits, and that doxepin is helpful in alleviating the neural complications due to stress.

  7. Hyperammonemia compromises glutamate metabolism and reduces BDNF in the rat hippocampus.

    PubMed

    Galland, Fabiana; Negri, Elisa; Da Ré, Carollina; Fróes, Fernanda; Strapazzon, Liliane; Guerra, Maria Cristina; Tortorelli, Lucas Silva; Gonçalves, Carlos-Alberto; Leite, Marina Concli

    2017-09-01

    Ammonia is putatively the major toxin associated with hepatic encephalopathy (HE), a neuropsychiatric manifestation that results in cognitive impairment, poor concentration and psychomotor alterations. The hippocampus, a brain region involved in cognitive impairment and depressive behavior, has been studied less than neocortical regions. Herein, we investigated hippocampal astrocyte parameters in a hyperammonemic model without hepatic lesion and in acute hippocampal slices exposed to ammonia. We also measured hippocampal BDNF, a neurotrophin commonly related to synaptic plasticity and cognitive deficit, and peripheral S100B protein, used as a marker for brain damage. Hyperammonemia directly impaired astrocyte function, inducing a decrease in glutamate uptake and in the activity of glutamine synthetase, in turn altering the glutamine-glutamate cycle, glutamatergic neurotransmission and ammonia detoxification itself. Hippocampal BDNF was reduced in hyperammonemic rats via a mechanism that may involve astrocyte production, since the same effect was observed in astrocyte cultures exposed to ammonia. Ammonia induced a significant increase in S100B secretion in cultured astrocytes; however, no significant changes were observed in the serum or in cerebrospinal fluid. Data demonstrating hippocampal vulnerability to ammonia toxicity, particularly due to reduced glutamate uptake activity and BDNF content, contribute to our understanding of the neuropsychiatric alterations in HE. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Sustained HSP25 Expression Induces Clasmatodendrosis via ER Stress in the Rat Hippocampus

    PubMed Central

    Kim, Ji-Eun; Hyun, Hye-Won; Min, Su-Ji; Kang, Tae-Cheon

    2017-01-01

    Heat shock protein (HSP) 25 (murine/rodent 25 kDa, human 27 kDa) is one of the major astroglial HSP families, which has a potent anti-apoptotic factor contributing to a higher resistance of astrocytes to the stressful condition. However, impaired removals of HSP25 decrease astroglial viability. In the present study, we investigated whether HSP25 is involved in astroglial apoptosis or clasmatodendrosis (autophagic astroglial death) in the rat hippocampus induced by status epilepticus (SE). Following SE, HSP25 expression was transiently increased in astrocytes within the dentate gyrus (DG), while it was sustained in CA1 astrocytes until 4 weeks after SE. HSP25 knockdown exacerbated SE-induced apoptotic astroglial degeneration, but mitigated clasmatodendrosis accompanied by abrogation of endoplasmic reticulum (ER) stress without changed seizure susceptibility or severity. These findings suggest that sustained HSP25 induction itself may result in clasmatodendrosis via prolonged ER stress. To the best of our knowledge, the present study demonstrates for the first time the double-edge properties of HSP25 in astroglial death induced by SE. PMID:28275338

  9. 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.

  10. Propofol Mitigates Learning and Memory Impairment After Electroconvulsive Shock in Depressed Rats by Inhibiting Autophagy in the Hippocampus

    PubMed Central

    Li, Ping; Hao, Xue-chao; Luo, Jie; Lv, Feng; Wei, Ke; Min, Su

    2016-01-01

    Background The present study explored the effects of propofol on hippocampal autophagy and synaptophysin in depression-model rats undergoing electroconvulsive shock (ECS). Material/Methods The rat depression model was established by exposing Sprague-Dawley rats to stress for 28 consecutive days. Forty rats were assigned randomly into the depression group (group D; no treatment), the ECS group (group E), the propofol group (group P), and the propofol + ECS group (group PE). Open field tests and sucrose preference tests were applied to evaluate the depression behavior; and Morris water maze tests were used to assess the learning and memory function of the rats. Western blotting was used to detect the expression of Beclin-1 and LC3-II/I; and ELISA was applied to assess the expression of synaptophysin. Results Rats in group E and group PE scored higher in the open field and sucrose preference tests compared with those in group D. Furthermore, rats in group E also had a longer escape latency, a shorter space exploration time, and increased expression of Beclin-1, LC3-II/I, and synaptophysin. Compared with group E, rats in group PE possessed a shorter escape latency, a longer space exploration time, reduced expression of Beclin-1, LC3-II/I, and synaptophysin. Conclusions Propofol could inhibit excessive ECS-induced autophagy and synaptophysin overexpression in the hippocampus, thus protecting the learning and memory functions in depressed rats after ECS. The inhibitory effects of propofol on the overexpression of synaptophysin may result from its inhibitory effects on the excessive induction of autophagy. PMID:27203836

  11. Mauritia flexuosa L. protects against deficits in memory acquisition and oxidative stress in rat hippocampus induced by methylmercury exposure.

    PubMed

    Leão, Luana K R; Herculano, Anderson M; Maximino, Caio; Brasil Costa, Alódia; Gouveia, Amauri; Batista, Evander O; Rocha, Fernando F; Crespo-Lopez, Maria Elena; Borges, Rosivaldo; Oliveira, Karen

    2017-06-01

    Methylmercury (MeHg) is the most toxic form of mercury that can affect humans through the food chain by bioaccumulation. Human organism is capable of triggering visual and cognitive disorders, neurodegeneration, as well as increased production of reactive species of O2 and depletion of natural anti-oxidant agents. In this context, Mauritia flexuosa L., a fruit rich in compounds with anti-oxidant properties, emerged as an important strategy to prevent the MeHg damages. So, this work has aimed to elucidate the protective effect of Mauritia flexuosa L. on the damage caused by the exposure of rats to MeHg. In order to evaluate the effect of MeHg on rat aversive memory acquisition and panic-like behavior, we have used elevated T-maze apparatus and after behavioral test, the hippocampus was removed to perfom lipid peroxidation. Our results demonstrated that the exposure to MeHg caused deficits in inhibitory avoidance acquisition (aversive conditioning) and in the learning process, and increased levels of lipid peroxidation in hippocampus tissue. However, the pretreatment with feed enriched with Mauritia flexuosa L. showed a protective effect against cognitive deficits caused by MeHg and also prevented the occurrence of cytoplasmic membrane damage induced by lipid peroxidation in the hippocampal region. Therefore, this study suggests that Mauritia flexuosa L. represents an important strategy to prevent neurocytotoxics and behavioral effects of MeHg.

  12. Stress and vitamin D: altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats.

    PubMed

    Jiang, Pei; Zhang, Wen-Yuan; Li, Huan-De; Cai, Hua-Lin; Liu, Yi-Ping; Chen, Lin-Yao

    2013-10-01

    Exposure to stressful life events is associated with the onset of major depression and increases the risk of cardiac morbidity and mortality. While recent evidence has indicated the existence of an interrelationship between local vitamin D (VD) metabolism and many aspects of human physiology including brain and heart function, much is still unknown concerning the biological link between VD signaling and stress-induced depressive behavior and cardiac dysfunction. In the present study, we observed the VD intracrine system in the hippocampus and myocardium of chronic unpredictable mild stress (CUMS) exposed rats. After 4 weeks of CUMS procedure, rats were induced to a depressive-like state and the cytochromes P450 enzymes involved in VD activating and catabolizing (CYP27B1 and CYP24A1 respectively) and VD receptor (VDR) were assessed by real time RT-PCR and western blot in the hippocampus, myocardium and kidney. In the hippocampus of depressed rats, CYP27B1, CYP24A1 and VDR expression were significantly increased and the local status of 1,25-dihydroxyvitamin D (1,25(OH)2D) was higher compared with controls. Furthermore, hippocampal mRNA levels of VD target genes (calbindin-d28k, neurotrophin-3) and RXRα (heterodimeric partner of VDR) were upregulated in response to chronic stress. Similar to the hippocampus, CUMS also induced CYP27B1/CYP24A1/VDR expression in the myocardium. However, renal metabolism of VD and serum1,25(OH)2D status were unchanged. Meanwhile, sertraline treatment could partly normalize the stress-induced alterations of VD metabolism. In conclusion, this study firstly showed a co-elevated expression of CYP27B1/CYP24A1/VDR in both the hippocampus and myocardium of CUMS rats, which suggests VD signaling may be involved in the compensatory mechanism that protect from stress-induced deteriorating effects on the brain and heart.

  13. Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat

    PubMed Central

    Gilbert, Mary E.; Sui, Li

    2008-01-01

    Background Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development. Objectives The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate. Methods Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus. Results At the highest perchlorate dose, triiodothyronine (T3) and thyroxine (T4) were reduced in pups on postnatal day 21. T4 in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T4 were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T3. Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. Conclusions Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate. PMID:18560531

  14. Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats.

    PubMed

    Maren, S; Aharonov, G; Fanselow, M S

    1997-11-01

    Electrolytic lesions of the dorsal hippocampus (DH) produce deficits in both the acquisition and expression of conditional fear to contextual stimuli in rats. To assess whether damage to DH neurons is responsible for these deficits, we performed three experiments to examine the effects of neurotoxic N-methyl-D-aspartate (NMDA) lesions of the DH on the acquisition and expression of fear conditioning. Fear conditioning consisted of the delivery of signaled or unsignaled footshocks in a novel conditioning chamber and freezing served as the measure of conditional fear. In Experiment 1, posttraining DH lesions produced severe retrograde deficits in context fear when made either 1 or 28, but not 100, days following training. Pretraining DH lesions made 1 week before training did not affect contextual fear conditioning. Tone fear was impaired by DH lesions at all training-to-lesion intervals. In Experiment 2, posttraining (1 day), but not pretraining (1 week), DH lesions produced substantial deficits in context fear using an unsignaled shock procedure. In Experiment 3, pretraining electrolytic DH lesions produced modest deficits in context fear using the same signaled and unsignaled shock procedures used in Experiments 1 and 2, respectively. Electrolytic, but not neurotoxic, lesions also increased pre-shock locomotor activity. Collectively, this pattern of results reveals that neurons in the DH are not required for the acquisition of context fear, but have a critical and time-limited role in the expression of context fear. The normal acquisition and expression of context fear in rats with neurotoxic DH lesions made before training may be mediated by conditioning to unimodal cues in the context, a process that may rely less on the hippocampal memory system.

  15. Forced Treadmill Exercise Prevents Spatial Memory Deficits in Aged Rats Probably Through the Activation of Na(+), K(+)-ATPase in the Hippocampus.

    PubMed

    Vanzella, Cláudia; Sanches, Eduardo Farias; Odorcyk, Felipe Kawa; Nicola, Fabrício; Kolling, Janaína; Longoni, Aline; Dos Santos, Tiago Marcon; Wyse, Angela Terezinha de Souza; Netto, Carlos Alexandre

    2017-02-16

    Regular physical activity has shown to improve the quality of life and to prevent age-related memory deficits. Memory processing requires proper regulation of several enzymes such as sodium-potassium adenosine triphosphatase (Na(+), K(+)-ATPase) and acetylcholinesterase (AChE), which have a pivotal role in neuronal transmission. The present study investigated the effects of a treadmill running protocol in young (3 months), mature (6 months) and aged (22 months) Wistar rats, on: (a) cognitive function, as assessed in the Water maze spatial tasks; (b) Na(+), K(+)-ATPase and AChE activities in the hippocampus following cognitive training alone or treadmill running combined with cognitive training. Animals of all ages were assigned to naïve (with no behavioral or exercise training), sedentary (non-exercised, with cognitive training) and exercised (20 min of daily running sessions, 3 times per week for 4 weeks and with cognitive training) groups. Cognition was assessed by reference and working memory tasks run in the Morris Water maze; 24 h after last session of behavioral testing, hippocampi were collected for biochemical analysis. Results demonstrated that: (a) a moderate treadmill running exercise prevented spatial learning and memory deficits in aged rats; (b) training in the Water maze increased both Na(+), K(+)-ATPase and AChE activities in the hippocampus of mature and aged rats; (c) aged exercised rats displayed an even further increase of Na(+), K(+)-ATPase activity in the hippocampus, (d) enzyme activity correlated with memory performance in aged rats. It is suggested that exercise prevents spatial memory deficits in aged rats probably through the activation of Na(+), K(+)-ATPase in the hippocampus.

  16. Cannabinoid CB(1) receptor expression and affinity in the rat hippocampus following bilateral vestibular deafferentation.

    PubMed

    Baek, Jean Ha; Zheng, Yiwen; Darlington, Cynthia L; Smith, Paul F

    2011-01-10

    Numerous studies have shown that bilateral vestibular deafferentation (BVD) results in spatial memory deficits and hippocampal dysfunction in rats and humans. Since cannabinoid CB(1) receptors are well known to regulate synaptic plasticity in the hippocampus, we investigated whether BVD resulted in changes in CB(1) receptor expression and affinity in the rat hippocampus at 1, 3 and 7 days post-surgery, using a combination of Western blotting and radioligand binding. Using Western blotting, we found that CB(1) receptor expression was significantly lower in BVD animals compared to sham controls only in the CA3 area across the 3 time points (P=0.03). CB(1) receptor expression decreased significantly over time for both the BVD and sham animals (P=0.000). The radioligand binding assays showed no significant change in the IC(50) of the CB(1) receptor for the cannabinoid CB(1)/CB(2) receptor agonist, WIN55,212-2. These results suggest that the CB(1) receptor down-regulates in the CA3 region of the hippocampus following BVD, but with no changes in the affinity of the CB(1) receptor for WIN55,212-2.

  17. Sleep deprivation reduces proliferation of cells in the dentate gyrus of the hippocampus in rats

    PubMed Central

    guzmán-marín, Ruben; Suntsova, Natalia; Stewart, Darya R; Gong, Hui; Szymusiak, Ronald; McGinty, Dennis

    2003-01-01

    The dentate gyrus (DG) of the adult hippocampus gives rise to progenitor cells, which have the potential to differentiate into neurons. To date it is not known whether sleep or sleep loss has any effect on proliferation of cells in the DG. Male rats were implanted for polysomnographic recording, and divided into treadmill sleep-deprived (SD), treadmill control (TC) and cage control (CC) groups. SD and TC rats were kept for 96 h on a treadmill that moved either for 3 s on/12 s off (SD group) or for 15 min on/60 min off (TC group) to equate total movement but permit sustained rest periods in TC animals. To label proliferating cells the thymidine analogue 5-bromo-2′-deoxyuridine (BrdU) was injected after the first 48 h of the experimental procedure in all groups (50 mg kg−1, i.p.). The percentage of time awake per day was 93.2 % in the SD group vs. 59.6 % in the TC group and 49.9 % in the CC group (P < 0.001). Stereological analysis showed that the number of BrdU-positive cells in the DG of the dorsal hippocampus was reduced by 54 % in the SD group in comparison with the TC and by 68 % in comparison with the CC group. These results suggest that sleep deprivation reduces proliferation of cells in the DG of the dorsal hippocampus. PMID:12679377

  18. The similarity of astrocytes number in dentate gyrus and CA3 subfield of rats hippocampus.

    PubMed

    Jahanshahi, Mehrdad; Sadeghi, Y; Hosseini, A; Naghdi, N

    2007-01-01

    The dentate gyrus is a part of hippocampal formation that it contains granule cells, which project to the pyramidal cells and interneurons of the CA3 subfield of the hippocampus. Astrocytes play a more active role in neuronal activity, including regulating ion flux currents, energy production, neurotransmitter release and synaptogenesis. Astrocytes are the only cells in the brain that contain the energy molecule glycogen. The close relationship between dentate gyrus and CA3 area can cause the similarity of the number of astrocytes in these areas. In this study 5 male albino wistar rats were used. Rats were housed in large plastic cage in animal house and were maintained under standard conditions, after histological processing, The 7 microm slides of the brains were stained with PTAH staining for showing the astrocytes. This staining is specialized for astrocytes. We showed that the number of astrocytes in different (ant., mid., post) parts of dentate gyrus and CA3 of hippocampus is the same. For example, the anterior parts of two area have the most number of astrocytes and the middle parts of two area have the least number of astrocytes. We concluded that dentate gyrus and CA3 area of hippocampus have the same group of astrocytes.

  19. Altered expression of GABAA receptors (α4, γ2 subunit), potassium chloride cotransporter 2 and astrogliosis in tremor rat hippocampus.

    PubMed

    Mao, Xiaoyuan; Ma, Ping; Cao, Danfeng; Sun, Chunyan; Ji, Zhong; Min, Dongyu; Sun, Hongli; Xie, Ni; Cai, Jiqun; Cao, Yonggang

    2011-11-25

    Impaired GABAergic inhibitory neurotransmission plays an essential role in the pathogenesis of epilepsy. GABA(A) receptor (GABA(A)R), potassium chloride cotransporter 2 (KCC2) and astrocytes are of particular importance to GABAergic transmission and thus involved in the development of increased seizure susceptibility. The tremor rat (TRM: tm/tm), a genetic mutant discovered in a Kyoto-Wistar colony, can manifest both absence-like seizures and tonic convulsions without any external stimuli. So far, there are no reports that can elucidate the effects of GABA(A)R (α4, γ2 subunit), KCC2 and astrocytes on TRMs. The present study was undertaken to detect the expressions of GABA(A)R α4, GABA(A)R γ2 and KCC2 in TRMs hippocampus at mRNA and protein levels. In this work, mRNA and protein expressions of GABA(A)R α4 were significantly elevated while GABA(A)R γ2 and KCC2 were both evidently decreased in TRMs hippocampus by real-time RT-PCR and western blot, respectively. Furthermore, a dramatic elevation of KCC2 protein level was found after cerebroventricular injection with K252a to TRMs than that in the DMSO-treated TRMs. Besides, our present study also demonstrated that GFAP (a major component of astrocyte) immunoreactivity was much more intense in TRMs hippocampal CA1, CA3 and DG regions than that in control group with immnohistochemistry and confocal microscopic analyses. The protein expression of GFAP was also markedly elevated in TRMs hippocampus, suggesting that astrogliosis appeared in the TRM model. These data demonstrate that altered expressions of GABA(A)R (α4, γ2) and KCC2 and astrogliosis observed in TRMs hippocampus may provide us good therapeutic targets for the treatment of genetic epilepsy.

  20. Effects of subchronic aluminum exposure on spatial memory, ultrastructure and L-LTP of hippocampus in rats.

    PubMed

    Zhang, Lifeng; Jin, Cuihong; Liu, Qiufang; Lu, Xiaobo; Wu, Shengwen; Yang, Jinghua; Du, Yanqiu; Zheng, Linlin; Cai, Yuan

    2013-01-01

    Epidemiological investigations have indicated that aluminum (Al), as an important environmental neurotoxicant, could cause damage to the cognitive function which was closely related with neurodegenerative diseases. Long-term potentiation (LTP) is one form of synaptic plasticity in association with cognitive function. Previous studies have demonstrated that Al impaired early phase long-term potentiation (E-LTP) in vivo and in vitro. However, Al-induced damage to late phase long-term potentiation (L-LTP) has poorly been studied. The present study was designed to observe the effects of subchronic Al exposure on the spatial memory, hippocampus ultrastructure and L-LTP in rats. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation from parturition to weaning for 3 weeks and then fed with the distilled water containing 0, 0.2%, 0.4% and 0.6% aluminum chloride (AlCl3) respectively from weaning to postnatal 3 months. The levels of Al in blood and hippocampus were quantitated by atomic absorption spectrophotometer. Morris water maze test was performed to study spatial memory. The induction and maintenance of L-LTP in area of Schaffer collateral- CA1 synapse was recorded by extracellular microelectrode recording technology in hippocampus of experimental rats. Hippocampus was collected for transmission electron microscopy observation. The results showed that the Al concentrations in blood and hippocampus of Al-exposed rats were higher than those of the control rats. Al could impair spatial memory ability of rats. Neuronal and synaptic ultrastructure from Al-exposed rats presented pathological changes; the incidence of L-LTP has a decrease trend while population spike (PS) amplitude was much smaller significantly stimulated by high-frequency stimulation (HFS) in Al-exposed rats. Our findings showed that Al exposure caused spatial memory damage, under which the neuronal and synaptic ultrastructure changes maybe were their

  1. Alteration of conditioned emotional response and conditioned taste aversion after neonatal ventral hippocampus lesions in rats.

    PubMed

    Angst, Marie-Josée; Macedo, Carlos Eduardo; Guiberteau, Thierry; Sandner, Guy

    2007-04-27

    Sprague-Dawley rats were submitted to bilateral ventral hippocampus lesions 7 days after birth according to the Lipska and Weinberger's procedure for modeling schizophrenia. The aim of the present work was to better characterize their learning capacity. A double latent inhibition study was conducted using respectively conditioned taste aversion and conditioned emotional response. In the background of this evaluation, locomotion under apomorphine and startle reactions, inhibited or not by prepulses, was also evaluated. Our experimental methods were the same as those used in previous studies from the laboratory which were found to be sensitive to pharmacological manipulations and shown by others to be unaffected by lesions of the ventral hippocampus carried out in adult rats. In contrast, neonatally lesioned rats, once adults (over 60 days old), were hyper-responsive to noise--i.e., the startle response to a 105 db(A) noise pulse was enhanced--and hyperactive under apomorphine (0.7 mg/kg). The prepulse inhibition properties of the startle remained unchanged. Lesioned rats showed a deficit but not a suppression of conditioning, similar in both tests, but latent inhibition was preserved. Such observations complement the already known memory deficit produced in this neurodevelopmental model of schizophrenia.

  2. Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study.

    PubMed

    Elsner, Viviane Rostirola; Lovatel, Gisele Agustini; Moysés, Felipe; Bertoldi, Karine; Spindler, Christiano; Cechinel, Laura Reck; Muotri, Alysson Renato; Siqueira, Ionara Rodrigues

    2013-02-01

    Regular exercise improves learning and memory, including during aging process. Interestingly, the imbalance of epigenetic mechanisms has been linked to age-related cognitive deficits. However, studies about epigenetic alterations after exercise during the aging process are rare. In this preliminary study we investigated the effect of aging and exercise on DNA methyltransferases (DNMT1 and DNMT3b) and H3-K9 methylation levels in hippocampus from 3 and 20-months aged Wistar rats. The animals were submitted to two exercise protocols: single session or chronic treadmill protocol. DNMT1 and H3-K9 methylation levels were decreased in hippocampus from aged rats. The single exercise session decreased both DNMT3b and DNMT1 levels in young adult rats, without any effect in the aged group. Both exercise protocols reduced H3-K9 methylation levels in young adult rats, while the single session reversed the changes on H3-K9 methylation levels induced by aging. Together, these results suggest that an imbalance on DNMTs and H3-K9 methylation levels might be linked to the brain aging process and that the outcome to exercise seems to vary through lifespan.

  3. Dopamine receptor dysregulation in hippocampus of aged rats underlies chronic pulsatile L-Dopa treatment induced cognitive and emotional alterations.

    PubMed

    Hernández, Vito S; Luquín, Sonia; Jáuregui-Huerta, Fernando; Corona-Morales, Aleph A; Medina, Mauricio P; Ruíz-Velasco, Silvia; Zhang, Limei

    2014-07-01

    L-Dopa is the major symptomatic therapy for Parkinson's disease, which commonly occurs in elderly patients. However, the effects of chronic use on mood and cognition in old subjects remain elusive. In order to compare the effects of a chronic pulsatile L-Dopa treatment on emotional and cognitive functions in young (3 months) and old (18 months) intact rats, an L-Dopa/carbidopa treatment was administered every 12 h over 4 weeks. Rats were assessed for behavioural despair (repeated forced swimming test, RFST), anhedonia (sucrose preference test, SPT) and spatial learning (Morris water maze, MWM) in the late phase of treatment (T). Neuronal expression of Fos in the hippocampus at the early and late phases of T, as well as after MWM was studied. The density and ratio of dopamine D5r, D3r and D2r receptors were also evaluated in the hippocampus using immunohistochemistry and confocal microscopy. Young rats showed similar patterns during behavioural tests, whereas aged treated rats showed increased immobility counts in RFST, diminished sucrose liquid intake in SPT, and spatial learning impairment during MWM. Fos expression was significantly blunted in the aged treated group after MWM. The density of D5r, D3r and D2r was increased in both aged groups. The treatment reduced the ratio of D5r/D3r and D5r/D2r in both groups. Moreover, aged treated subjects had significant lower values of D5r/D3r and higher values of D5r/D2r when compared with young treated subjects. These results indicate that chronic L-Dopa treatment in itself could trigger emotional and cognitive dysfunctions in elderly subjects through dopamine receptor dysregulation.

  4. Lovastatin decreases the synthesis of inflammatory mediators during epileptogenesis in the hippocampus of rats submitted to pilocarpine-induced epilepsy.

    PubMed

    Gouveia, T L F; Scorza, F A; Iha, H A; Frangiotti, M I B; Perosa, S R; Cavalheiro, E A; Silva, J A; Feliciano, R S; de Almeida, A C; Naffah-Mazzacoratti, M G

    2014-07-01

    Statins may act on inflammatory responses, decreasing oxidative stress and also reducing brain inflammation in several brain disorders. Epileptogenesis is a process in which a healthy brain becomes abnormal and predisposed to generating spontaneous seizures. We previously reported that lovastatin could prevent neuroinflammation in pilocarpine-induced status epilepticus (SE). In this context, this study investigated the long-lasting effects of lovastatin on mRNA expression of proinflammatory cytokines (interleukin-1β, tumor necrosis factor α, interleukin-6) and the antiinflammatory cytokine IL-10 in the hippocampus during epileptogenesis by immunohistochemistry and real time polymerase chain reaction (RT-PCR) during the latent and chronic phases in the epilepsy model induced by pilocarpine in rats. For these purposes, four groups of rats were employed: saline (CONTROL), lovastatin (LOVA), pilocarpine (PILO), and pilocarpine plus lovastatin (PILO+LOVA). After pilocarpine injection (350mg/kg, i.p.), the rats were treated with 20mg/kg of lovastatin via an esophagic probe 2h after SE onset. All surviving rats were continuously treated during 15days, twice/day. The pilocarpine plus lovastatin group showed a significant decrease in the levels of IL-1β, TNF-α, and IL-6 during the latent phase and a decreased expression of IL-1β and TNF-α in the chronic phase when compared with the PILO group. Moreover, lovastatin treatment also induced an increased expression of the antiinflammatory cytokine, IL-10, in the PILO+LOVA group when compared with the PILO group in the chronic phase. Thus, our data suggest that lovastin may reduce excitotoxicity during epileptogenesis induced by pilocarpine by increasing the synthesis of IL-10 and decreasing proinflammatory cytokines in the hippocampus.

  5. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

    PubMed Central

    Amrein, Irmgard; Becker, Anton S.; Engler, Stefanie; Huang, Shih-hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K.

    2014-01-01

    African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents. PMID

  6. Rapid regulation of sialidase activity in response to neural activity and sialic acid removal during memory processing in rat hippocampus.

    PubMed

    Minami, Akira; Meguro, Yuko; Ishibashi, Sayaka; Ishii, Ami; Shiratori, Mako; Sai, Saki; Horii, Yuuki; Shimizu, Hirotaka; Fukumoto, Hokuto; Shimba, Sumika; Taguchi, Risa; Takahashi, Tadanobu; Otsubo, Tadamune; Ikeda, Kiyoshi; Suzuki, Takashi

    2017-04-07

    Sialidase cleaves sialic acids on the extracellular cell surface as well as inside the cell and is necessary for normal long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4-methylumbelliferyl-α-d-N-acetylneuraminic acid (4MU-Neu5Ac) or 5-bromo-4-chloroindol-3-yl-α-d-N-acetylneuraminic acid (X-Neu5Ac) and Fast Red Violet LB was increased by high-K(+)-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDA receptors, or NMDA receptors. The increase in sialidase activity with neural excitation appears to be caused not by secreted sialidase or by an increase in sialidase expression but by a change in the subcellular localization of sialidase. Astrocytes as well as neurons are also involved in the neural activity-dependent increase in sialidase activity. Sialidase activity visualized with a benzothiazolylphenol-based sialic acid derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe for sialidase activity, at the CA3 stratum lucidum of rat acute hippocampal slices was immediately increased in response to LTP-inducible high-frequency stimulation on a time scale of seconds. To obtain direct evidence for sialic acid removal on the extracellular cell surface during neural excitation, the extracellular free sialic acid level in the hippocampus was monitored using in vivo microdialysis. The free sialic acid level was increased by high-K(+)-induced membrane depolarization. Desialylation also occurred during hippocampus-dependent memory formation in a contextual fear-conditioning paradigm. Our results show that neural activity-dependent desialylation by sialidase may be involved in hippocampal memory processing. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Parvalbumin-positive GABAergic interneurons are increased in the dorsal hippocampus of the dystrophic mdx mouse.

    PubMed

    Del Tongo, Claudia; Carretta, Donatella; Fulgenzi, Gianluca; Catini, Claudio; Minciacchi, Diego

    2009-12-01

    Duchenne muscular dystrophy (DMD) is characterized by variable alterations of the dystrophin gene and by muscle weakness and cognitive impairment. We postulated an association between cognitive impairment and architectural changes of the hippocampal GABAergic system. We investigated a major subpopulation of GABAergic neurons, the parvalbumin-immunopositive (PV-I) cells, in the dorsal hippocampus of the mdx mouse, an acknowledged model of DMD. PV-I neurons were quantified and their distribution was compared in CA1, CA2, CA3, and dentate gyrus in wild-type and mdx mice. The cell morphology and topography of PV-I neurons were maintained. Conversely, the number of PV-I neurons was significantly increased in the mdx mouse. The percent increase of PV-I neurons was from 45% for CA2, up to 125% for the dentate gyrus. In addition, the increased parvalbumin content in the mdx hippocampus was confirmed by Western blot. A change in the hippocampus processing abilities is the expected functional counterpart of the modification displayed by PV-I GABAergic neurons. Altered hippocampal functionality can be responsible for part of the cognitive impairment in DMD.

  8. Hippocampus and Retrograde Amnesia in the Rat Model: A Modest Proposal for the Situation of Systems Consolidation

    ERIC Educational Resources Information Center

    Sutherland, Robert J.; Sparks, Fraser T.; Lehmann, Hugo

    2010-01-01

    The properties of retrograde amnesia after damage to the hippocampus have been explicated with some success using a rat model of human medial temporal lobe amnesia. We review the results of this experimental work with rats focusing on several areas of consensus in this growing literature. We evaluate the theoretically significant hypothesis that…

  9. Hippocampus and Retrograde Amnesia in the Rat Model: A Modest Proposal for the Situation of Systems Consolidation

    ERIC Educational Resources Information Center

    Sutherland, Robert J.; Sparks, Fraser T.; Lehmann, Hugo

    2010-01-01

    The properties of retrograde amnesia after damage to the hippocampus have been explicated with some success using a rat model of human medial temporal lobe amnesia. We review the results of this experimental work with rats focusing on several areas of consensus in this growing literature. We evaluate the theoretically significant hypothesis that…

  10. Endogenous neurotrophins are required for the induction of GABAergic long-term potentiation in the neonatal rat hippocampus.

    PubMed

    Gubellini, Paolo; Ben-Ari, Yehezkel; Gaïarsa, Jean-Luc

    2005-06-15

    In the developing rat hippocampus, GABAergic synapses undergo a Ca2+-dependent long-term potentiation (LTP(GABA-A)); this form of synaptic plasticity is induced in CA3 pyramidal neurons by delivering repetitive depolarizing pulses (DPs) to the recorded neuron, and it is expressed as a long-lasting increase in the frequency and amplitude of spontaneous GABA(A) receptor-mediated postsynaptic currents. In the present study, we examined the role of endogenous tropomyosin-related kinase receptor B (TrkB) receptor ligands and associated protein tyrosine kinases (PTKs) in the induction of LTP(GABA-A). The application of Lavendustin A, a broad spectrum PTK inhibitor, blocked the induction of LTP(GABA-A), whereas Lavendustin B, its inactive form, had no effect. Moreover, k-252a and k-252b, two alkaloids that inhibit the kinase activity of the Trk receptor family, also prevented the induction of LTP(GABA-A). On hippocampal slices incubated with the soluble form of TrkB receptor IgG (TrkB-IgG), which prevents the activation of TrkB receptors by endogenous ligands, DPs failed to induce LTP(GABA-A), whereas the incubation with TrkA-IgG or TrkC-IgG had no such effect. Altogether, these data indicate that endogenous TrkB ligands and associated PTK activity are necessary for the induction of GABAergic LTP in the developing rat hippocampus.

  11. ERK activation in the amygdala and hippocampus induced by fear conditioning in ethanol withdrawn rats: modulation by MK-801.

    PubMed

    Bertotto, María Eugenia; Maldonado, Noelia Martina; Bignante, Elena Anahi; Gorosito, Silvana Vanesa; Cambiasso, María Julia; Molina, Víctor Alejandro; Martijena, Irene Delia

    2011-12-01

    The extracellular signal-regulated kinase (ERK) pathway, which can be activated by NMDA receptor stimulation, is involved in fear conditioning and drug addiction. We have previously shown that withdrawal from chronic ethanol administration facilitated the formation of contextual fear memory. In order to explore the neural substrates and the potential mechanism involved in this effect, we examined: 1) the ERK1/2 activation in the central (CeA) and basolateral (BLA) nuclei of the amygdala and in the dorsal hippocampus (dHip), 2) the effect of the NMDA receptor antagonist MK-801 on fear conditioning and ERK activation and 3) the effect of the infusion of U0126, a MEK inhibitor, into the BLA on fear memory formation in ethanol withdrawn rats. Rats made dependent via an ethanol-containing liquid diet were subjected to contextual fear conditioning on day 3 of ethanol withdrawal. High basal levels of p-ERK were found in CeA and dHip from ethanol withdrawn rats. ERK activation was significantly increased both in control (60min) and ethanol withdrawn rats (30 and 60min) in BLA after fear conditioning. Pre-training administration of MK-801, at a dose that had no effect on control rats, prevented the increase in ERK phosphorylation in BLA and attenuated the freezing response 24h later in ethanol withdrawn rats. Furthermore, the infusion of U0126 into the BLA, but not the CeA, before fear conditioning disrupted fear memory formation. These results suggest that the increased fear memory can be linked to changes in ERK phosphorylation, probably due to NMDA receptor activation in BLA in ethanol withdrawn rats.

  12. 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.

  13. Non-granule PSA-NCAM immunoreactive neurons in the rat hippocampus.

    PubMed

    Nacher, Juan; Blasco-Ibáñez, José M; McEwen, Bruce S

    2002-03-15

    The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) continues to be expressed in the adult hippocampus, mainly in a subset of neurons located in the innermost portion of the granule cell layer. PSA-NCAM immunoreactive neurons have also been described outside this layer in humans, where they are severely reduced in schizophrenic brains. Given this important clinical implication, we were interested in finding whether similar neurons existed in the adult rat hippocampus and to characterize their distribution, morphology and phenotype. PSA-NCAM immunocytochemistry reveals labeled neurons in the subiculum, fimbria, alveus, hilus, and stratum oriens, lucidum and radiatum of CA3 and CA1. They are mainly distributed in the ventral hippocampus, and have polygonal or fusiform somata with multipolar or bipolar morphology. These neurons show long straight dendrites, which reach several strata and even enter the fimbria and the alveus. These dendrites are often varicose, appear devoid of excrescences and apparently do not show spines. Most of these neurons display GABA immunoreactivity and further analysis has shown that a subpopulation expresses calretinin, but not somatostatin, neuropeptide Y, parvalbumin, calbindin or NADPH diaphorase. Our study demonstrates that there is an important subpopulation of PSA-NCAM immunoreactive neurons, many of which can be considered interneurons, outside the rat granule cell layer, probably homologous to those described in the human hippocampus. The presence of the polysialylated form of NCAM in these neurons could indicate that they are undergoing continuous remodeling during adulthood and may have an important role in hippocampal structural plasticity.

  14. Theta synchronization between the hippocampus and the nucleus incertus in urethane-anesthetized rats.

    PubMed

    Cervera-Ferri, Ana; Guerrero-Martínez, Juan; Bataller-Mompeán, Manuel; Taberner-Cortes, Alida; Martínez-Ricós, Joana; Ruiz-Torner, Amparo; Teruel-Martí, Vicent

    2011-06-01

    Oscillatory coupling between distributed areas can constitute a mechanism for neuronal integration. Theta oscillations provide temporal windows for hippocampal processing and only appear during certain active states of animals. Since previous studies have demonstrated that nucleus incertus (NI) contributes to the generation of hippocampal theta activity, in this paper, we evaluated the oscillatory coupling between both structures. We compared hippocampal and NI field potentials that were simultaneously recorded in urethane-anesthetized rats. Electrical and cholinergic stimulations of the reticularis pontis oralis nucleus have been used as hippocampal theta generation models. The spectral analyses reveal that electrical stimulation induced an increase in theta oscillations in both channels, whose frequencies depended on the intensity of stimulation. The intensity range used simultaneously increased the normalized spectral energy in the fast theta band (6-12 Hz) in HPC and NI. Frequencies within the theta range were found to be very similar in both channels. In order to validate coupling, spectral coherence was inspected. The data reveal that coherence in the high theta band also increased while stimuli were applied. Cholinergic activation progressively increased the main frequency in both structures to reach an asymptotic period with stable peak frequency in the low theta range (3-6 Hz), which could be first observed in NI and lasted about 1,500 s. Coherence in this band reached values close to 1. Taken together, these results support an electrophysiological and functional coupling between the hippocampus and the reticular formation, suggesting NI to be part of a distributed network working at theta frequencies.

  15. Expression of apoptosis-regulatory genes in the hippocampus of rat neonates born to mothers with diabetes.

    PubMed

    Haghir, Hossein; Hami, Javad; Lotfi, Nassim; Peyvandi, Mostafa; Ghasemi, Simagol; Hosseini, Mehran

    2017-04-01

    Diabetes during pregnancy impairs the development of the central nervous system (CNS) and causes cognitive and behavioral abnormalities in offspring. However, the exact mechanism by which the maternal diabetes affects the development of the brain remains to be elucidated. The aim of the present study was to investigate the effects of maternal diabetes in pregnancy on the expression of Bcl-2 and Bax genes and the numerical density of degenerating dark neurons (DNs) in the hippocampus of offspring at the first postnatal two weeks. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was sacrificed at P0, P7, and P14. Our findings demonstrated a significant down-regulation in the hippocampal expression of Bcl-2 in the diabetic group newborns (P < 0.05). In contrast, the mRNA expression of Bax was markedly up-regulated in the offspring born to diabetic dams at all of studied time-points (P < 0.05). Moreover, we found a striking increase in the numerical density of DNs in the various subfields of hippocampus of diabetic group pups (P < 0.05). The results of the present study revealed that maternal hyperglycemia during gestational period may result in disturbances in the expression of Bcl-2 and Bax genes as two important genes in neuronal apoptosis regulation and induces the production of DNs in the developing hippocampus of neonatal rats. These disturbances may be a reason for the cognitive, structural, and behavioral anomalies observed in offspring born to diabetic mothers. Furthermore, the control of maternal glycaemia by insulin administration in most cases normalized these negative impacts.

  16. Effects of the selective norepinephrine reuptake inhibitor reboxetine on norepinephrine and serotonin transmission in the rat hippocampus.

    PubMed

    Szabo, S T; Blier, P

    2001-12-01

    Given that norepinephrine (NE) and serotonin (5-HT) neurons are implicated in the mechanisms of action of antidepressant drugs and both project to the hippocampus, the impact of acute and long-term administration of the selective NE inhibitor reboxetine was assessed on CA(3) pyramidal neuron firing in this postsynaptic structure. Cumulative injections of reboxetine (1-4 mg/kg, i.v.) dose-dependently increased the recovery time of the firing of these neurons following iontophoretic applications of NE, but not 5-HT. In rats treated with reboxetine for 2.5 mg/kg/day for 21 days, a robust increase in the recovery time following NE applications was observed, and a small but significant prolongation occurred following 5-HT applications. In controls and reboxetine-treated rats, 1 and 5 Hz stimulations of the afferent 5-HT bundle to the hippocampus, which allows determination of terminal 5-HT(1B) autoreceptor sensitivity, produced similar frequency-dependent decreases in pyramidal neuron firing in both groups. However, after low and high doses of clonidine (10 and 400 microg/kg, i.v.), which assesses alpha(2)-adrenergic auto- and heteroreceptor sensitivity, respectively, only the effect of the high dose of clonidine was attenuated. Interestingly, administration of the selective 5-HT(1A) receptor antagonist WAY 100,635 induced a 140% increase in basal pyramidal neuron firing in reboxetine as compared to saline-treated rats. This increase in tonic activation of postsynaptic 5-HT(1A) receptors might be attributable in part to a desensitization of alpha(2)-adrenergic heteroreceptors, presumably resulting from sustained NE reuptake inhibition. These results indicate that even a selective NE reuptake inhibitor can modulate 5-HT transmission.

  17. Decreased Neuronal Bursting and Phase Synchrony in the Hippocampus of Streptozotocin Diabetic Rats

    PubMed Central

    Xie, Kangning; Li, Guoliang

    2014-01-01

    Diabetic encephalopathy is one of the complications of diabetes. Cognitive dysfunction is the main consequence. Previous findings from neuroanatomical and in vitro electrophysiological studies showed that the structure and function of the hippocampus is impaired in diabetes, which may underlie the cognitive dysfunction induced by diabetes. However the study of electrophysiological abnormality of hippocampal neurons in intact networks is sparse. In the current study, we recorded the spontaneous firing of neurons in hippocampal CA1 area in anesthetized streptozotozin (STZ)-diabetic and age-matched control rats. Profound reduction in burst activity was found in diabetic rats. Compared to control rats, the intra-burst inter-spike intervals were prolonged significantly in diabetic rats, while the burst ratio and the mean number of spikes within a burst decreased significantly. Treatment with APP 17-mer peptide retarded the effects of diabetes on these parameters. In addition, the average PLV of diabetic rats was lower than that of control rats. These findings provide in vivo electrophysiological evidence for the impairment of hippocampal function in STZ-diabetic rats, and may have some implications in the mechanisms associated with cognitive deficits in diabetes. PMID:25093193

  18. Theta band power increases in the posterior hippocampus predict successful episodic memory encoding in humans.

    PubMed

    Lin, Jui-Jui; Rugg, Michael D; Das, Sandhitsu; Stein, Joel; Rizzuto, Daniel S; Kahana, Michael J; Lega, Bradley C

    2017-10-01

    Functional differences in the anterior and posterior hippocampus during episodic memory processing have not been examined in human electrophysiological data. This is in spite of strong evidence for such differences in rodent data, including greater place cell specificity in the dorsal hippocampus, greater sensitivity to the aversive or motivational content of memories in ventral regions, connectivity analyses identifying preferential ventral hippocampal connections with the amygdala, and gene expression analyses identifying a dorsal-ventral gradient. We asked if memory-related oscillatory patterns observed in human hippocampal recordings, including the gamma band and slow-theta (2.5-5 Hz) subsequent memory effects, would exhibit differences along the longitudinal axis and between hemispheres. We took advantage of a new dataset of stereo electroencephalography patients with simultaneous, robotically targeted anterior, and posterior hippocampal electrodes to directly compare oscillatory subsequent memory effects during item encoding. This same data set allowed us to examine left-right connectivity and hemispheric differences in hippocampal oscillatory patterns. Our data suggest that a power increase during successful item encoding in the 2.5-5 Hz slow-theta frequency range preferentially occurs in the posterior hippocampus during the first 1,000 ms after item presentation, while a gamma band power increase is stronger in the dominant hemisphere. This dominant-nondominant pattern in the gamma range appears to reverse during item retrieval, however. Intrahippocampal phase coherence was found to be stronger during successful item encoding. Our phase coherence data are also consistent with existing reports of a traveling wave for theta oscillations propagating along the septotemporal (longitudinal) axis of the human hippocampus. We examine how our findings fit with theories of functional specialization along the hippocampal axis. © 2017 Wiley Periodicals, Inc.

  19. Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum.

    PubMed

    Chen, Hsiao-Jou Cortina; Spiers, Jereme G; Sernia, Conrad; Lavidis, Nickolas A

    2016-01-01

    Chronic mild stress has been shown to cause hippocampal neuronal nitric oxide synthase (NOS) overexpression and the resultant nitric oxide (NO) production has been implicated in the etiology of depression. However, the extent of nitrosative changes including NOS enzymatic activity and the overall output of NO production in regions of the brain like the hippocampus and striatum following acute stress has not been characterized. In this study, outbred male Wistar rats aged 6-7 weeks were randomly allocated into 0 (control), 60, 120, or 240 min stress groups and neural regions were cryodissected for measurement of constitutive and inducible NOS enzymatic activity, nitrosative status, and relative gene expression of neuronal and inducible NOS. Hippocampal constitutive NOS activity increased initially but was superseded by the inducible isoform as stress duration was prolonged. Interestingly, hippocampal neuronal NOS and interleukin-1β mRNA expression was downregulated, while the inducible NOS isoform was upregulated in conjunction with other inflammatory markers. This pro-inflammatory phenotype within the hippocampus was further confirmed with an increase in the glucocorticoid-antagonizing macrophage migration inhibitory factor, Mif, and the glial surveillance marker, Ciita. This indicates that despite high levels of glucocorticoids, acute stress sensitizes a neuroinflammatory response within the hippocampus involving both pro-inflammatory cytokines and inducible NOS while concurrently modulating the immunophenotype of glia. Furthermore, there was a delayed increase in striatal inducible NOS expression while no change was found in other pro-inflammatory mediators. This suggests that short term stress induces a generalized increase in inducible NOS signaling that coincides with regionally specific increased markers of adaptive immunity and inflammation within the brain.

  20. Methylphenidate Decreases ATP Levels and Impairs Glutamate Uptake and Na(+),K(+)-ATPase Activity in Juvenile Rat Hippocampus.

    PubMed

    Schmitz, Felipe; Pierozan, Paula; Rodrigues, André F; Biasibetti, Helena; Grings, Mateus; Zanotto, Bruna; Coelho, Daniella M; Vargas, Carmen R; Leipnitz, Guilhian; Wyse, Angela T S

    2016-11-14

    The study of the long-term neurological consequences of early exposure with methylphenidate (MPH) is very important since this psychostimulant has been widely misused by children and adolescents who do not meet full diagnostic criteria for ADHD. The aim of this study was to examine the effect of early chronic exposure with MPH on amino acids profile, glutamatergic and Na(+),K(+)-ATPase homeostasis, as well as redox and energy status in the hippocampus of juvenile rats. Wistar male rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 45th day of age. Results showed that MPH altered amino acid profile in the hippocampus, decreasing glutamine levels. Glutamate uptake and Na(+),K(+)-ATPase activity were decreased after chronic MPH exposure in the hippocampus of rats. No changes were observed in the immunocontents of glutamate transporters (GLAST and GLT-1), and catalytic subunits of Na(+),K(+)-ATPase (α1, α2, and α3), as well as redox status. Moreover, MPH provoked a decrease in ATP levels in the hippocampus of chronically exposed rats, while citrate synthase, succinate dehydrogenase, respiratory chain complexes activities (II, II-III, and IV), as well as mitochondrial mass and mitochondrial membrane potential were not altered. Taken together, our results suggest that chronic MPH exposure at early age impairs glutamate uptake and Na(+),K(+)-ATPase activity probably by decreasing in ATP levels observed in rat hippocampus.

  1. Learning impairment caused by a toxin produced by Pfiesteria piscicida infused into the hippocampus of rats.

    PubMed

    Levin, Edward D; Blackwelder, W Paul; Glasgow, Howard B; Burkholder, JoAnn M; Moeller, Peter D R; Ramsdell, John S

    2003-01-01

    Pfiesteria piscicida, an estuarine dinoflagellate, which has been shown to kill fish, has also been associated with neurocognitive deficits in humans. With a rat model, we have demonstrated the cause-and-effect relationship between Pfiesteria exposure and learning impairment. In several studies, we have replicated the finding in Sprague-Dawley rats that exposure to fixed acute doses of Pfiesteria cells or filtrates caused radial-arm maze learning impairment. Recently, this finding of Pfiesteria-induced learning impairment in rats has been independently replicated in another laboratory as well. We have demonstrated significant Pfiesteria-induced learning impairment in both the win-shift and repeated-acquisition tasks in the radial-arm maze and in reversal learning in a visual operant signal detection task. These learning impairments have been seen as long as 10 weeks after a single acute exposure to Pfiesteria. In the current study, we used a hydrophilic toxin isolated from clonal P. piscicida cultures (PfTx) and tested its effect when applied locally to the ventral hippocampus on repeated acquisition of rats in the radial-arm maze. Toxin exposure impaired choice accuracy in the radial-arm maze repeated acquisition procedure. The PfTx-induced impairment was seen at the beginning of the session and the early learning deficit was persistent across 6 weeks of testing after a single administration of the toxin. Eventually, with enough practice, in each session, the PfTx-exposed rats did learn that session's problem as did control rats. This model has demonstrated the cause-and-effect relationship between exposure to a hydrophilic toxin produced by P. piscicida and learning impairment, and specifically that the ventral hippocampus was critically involved.

  2. Structural Changes of Amyloid Beta in Hippocampus of Rats Exposed to Ozone: A Raman Spectroscopy Study

    PubMed Central

    Rivas-Arancibia, Selva; Rodríguez-Martínez, Erika; Badillo-Ramírez, Isidro; López-González, Ulises; Saniger, José M.

    2017-01-01

    The aim of this work was to study the effect of oxidative stress on the structural changes of the secondary peptide structure of amyloid beta 1–42 (Aβ 1–42), in the dentate gyrus of hippocampus of rats exposed to low doses of ozone. The animals were exposed to ozone-free air (control group) and 0.25 ppm ozone during 7, 15, 30, 60, and 90 days, respectively. The samples were studied by: (1) Raman spectroscopy to detect the global conformational changes in peptides with α-helix and β-sheet secondary structure, following the deconvolution profile of the amide I band; and (2) immunohistochemistry against Aβ 1–42. The results of the deconvolutions of the amide I band indicate that, ozone exposure causes a progressively decrease in the abundance percentage of α-helix secondary structure. Furthermore, the β-sheet secondary structure increases its abundance percentage. After 60 days of ozone exposure, the β-sheet band is identified in a similar wavenumber of the Aβ 1–42 peptide standard. Immunohistochemistry assays show an increase of Aβ 1–42 immunoreactivity, coinciding with the conformational changes observed in the Raman spectroscopy of Aβ 1–42 at 60 and 90 days. In conclusion, oxidative stress produces changes in the folding process of amyloid beta peptide structure in the dentate gyrus, leading to its conformational change in a final β-sheet structure. This is associated to an increase in Aβ 1–42 expression, similar to the one that happens in the brain of Alzheimer’s Disease (AD) patients. PMID:28588448

  3. 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

  4. Strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae), decreases serotonin levels in rat hippocampus.

    PubMed

    Farias, F M; Passos, C S; Arbo, M D; Barros, D M; Gottfried, C; Steffen, V M; Henriques, A T

    2012-09-01

    Psychotria is a complex genus whose neotropical species are known by the presence of glucosidic monoterpene indole alkaloids. These compounds are able to display a large range of effects on the central nervous system, such as anxiolytic, antidepressant, analgesic, and impairment of learning and memory acquisition. The aims of this study were to investigate the effects displayed by strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae) leaves, on monoamine levels in rat hippocampus and on monoamine oxidase activity. A significance (p<0.01) of 83.5% reduction in 5-HT levels was observed after intra-hippocampal injection (20 μg/μl). After treatment by intraperitoneal route (10 mg/kg), a 63.4% reduction in 5-HT levels and a 67.4% reduction in DOPAC values were observed. The results indicate that strictosidinic acid seems to act on 5-HT system in rat hippocampus, possibly inhibiting precursor enzymes of 5-HT biosynthesis. The decrease verified in DOPAC levels suggests a role of strictosidinic acid in the dopaminergic transmission, probably due to an inhibition of monoamine oxidase activity, confirmed by the enzymatic assay, which demonstrated an inhibitory effect on MAO A in rat brain mitochondria. Copyright © 2012 Elsevier B.V. All rights reserved.