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Sample records for rat hippocampus gaba

  1. Dual role of GABA in the neonatal rat hippocampus.

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    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.

  2. Acute desensitization of presynaptic GABA(B)-mediated inhibition and induction of epileptiform discharges in the neonatal rat hippocampus

    NARCIS (Netherlands)

    Tosetti, P; Bakels, R; Colin-Le Brun, [No Value; Ferrand, N; Gaiarsa, JL; Caillard, O

    2004-01-01

    The consequences of sustained activation of GABA(B) receptors on GABA(B)-mediated inhibition and network activity were investigated in the neonatal rat hippocampus using whole-cell and extracellular field recordings. GABA(B)-mediated presynaptic control of gamma-aminobutyric acid (GABA) release prog

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

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    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.

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

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    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.

  5. Early expression of GABA(A) receptor delta subunit in the neonatal rat hippocampus.

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    Didelon, F; Mladinic', M; Cherubini, E; Bradbury, A

    2000-12-01

    The cDNA library screening strategy was used to identify the genes encoding for GABA(A) receptor subunits in the rat hippocampus during development. With this technique, genes encoding eleven GABA(A) receptor subunits were identified. The alpha5 subunit was by far the most highly expressed, followed by the gamma2, alpha2 and alpha4 subunits respectively. The expression of the beta2, alpha1, gamma1, beta1 and beta3 subunits was moderate, although that of the alpha3 and delta subunits was weak. In situ hybridization experiments, using digoxigenin-labeled cRNA probes, confirmed that the delta subunit was expressed in the neonatal as well as in the adult hippocampus, and is likely to form functional receptors in association with other subunits of the GABA(A) receptor. When the more sensitive RT-PCR approach was used, the gamma3 subunit was also detected, suggesting that this subunit is present in the hippocampus during development but at low levels of expression. The insertion of the delta subunit into functional GABA(A) receptors may enhance the efficacy of GABA in the immediate postnatal period when this amino acid is still exerting a depolarizing and excitatory action.

  6. Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri.

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    Mathew, Jobin; Gangadharan, Gireesh; Kuruvilla, Korah P; Paulose, C S

    2011-01-01

    In the present study, alterations of the General GABA and GABA(A) receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B(max) (P Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.

  7. Exposure to novelty and forced swimming evoke stressor-dependent changes in extracellular GABA in the rat hippocampus.

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    de Groote, L; Linthorst, A C E

    2007-09-07

    In the hippocampus, a brain structure critically important in the stress response, GABA controls neuronal activity not only via synaptic inhibition, but also via tonic inhibition through stimulation of extrasynaptic GABA receptors. The extracellular level of GABA may represent a major determinant for tonic inhibition and, therefore, it is surprising that its responsiveness to stress has hardly been investigated. To clarify whether hippocampal extracellular GABA levels change in response to acute stress, we conducted an in vivo microdialysis study in rats. We found that dialysate GABA levels respond to various neuropharmacological manipulations such as reuptake inhibition, elevated concentrations of K(+), tetrodotoxin and baclofen, indicating that a large proportion of hippocampal extracellular GABA depends on neuronal release and that GABA re-uptake plays a role in determining the extracellular levels of this neurotransmitter. Next, rats were exposed to a novel cage or to forced swimming in 25 degrees C water. Interestingly, these two stressors resulted in opposite effects. Novelty caused a fast increase in GABA (120% of baseline), whereas forced swimming resulted in a profound decrease (70% of baseline). To discriminate between the psychological and physical aspects (i.e. the effects on body temperature) of forced swimming, another group of animals was forced to swim at 35 degrees C. This stressor, like novelty, caused an increase in hippocampal GABA, suggesting a stimulatory effect of psychological stress. The effects of novelty could not be blocked by the corticotropin-releasing factor receptor antagonist D-Phe-CRF(12-41). These results are the first to demonstrate stressor-dependent changes in hippocampal extracellular GABA; an observation which may be of particular significance for GABAergic tonic inhibition of hippocampal neurons.

  8. Timing of the developmental switch in GABA(A) mediated signaling from excitation to inhibition in CA3 rat hippocampus using gramicidin perforated patch and extracellular recordings.

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    Tyzio, Roman; Holmes, Gregory L; Ben-Ari, Yehezkiel; Khazipov, Roustem

    2007-01-01

    The timing of the developmental switch in the GABA(A) mediated responses from excitatory to inhibitory was studied in Wistar rat CA3 hippocampal pyramidal cells using gramicidin perforated patch-clamp and extracellular recordings. Gramicidin perforated patch recordings revealed a gradual developmental shift in the reversal potential of synaptic and isoguvacine-induced GABA(A) mediated responses from -55 +/- 4 mV at postnatal days P0-2 to -74 +/- 3 mV at P13-15 with a midpoint of disappearance of the excitatory effects of GABA at around P8. Extracellular recordings in CA3 pyramidal cell layer revealed that the effect of isoguvacine on multiple unit activity (MUA) switched from an increase to a decrease at around P10. The effect of synaptic GABA(A) mediated responses on MUA switched from an increase to a decrease at around P8. It is concluded that the developmental switch in the action of GABA via GABA(A) receptors from excitatory to inhibitory occurs in Wistar rat CA3 pyramidal cells at around P8-10, an age that coincides with the transition from immature to mature hippocampal rhythms. We propose that excitatory GABA contributes to enhanced excitability and ictogenesis in the neonatal rat hippocampus.

  9. Double Labeling Immunoelectron Microscopic Study on the Synaptic Connections between Glutamic Acid Neurons and GABA Neurons in the Hippocampus of Rats

    Institute of Scientific and Technical Information of China (English)

    ZHU Changgeng; CAI Qiuyun; LIU Qingying; WEI Ying

    2000-01-01

    In order to explore the roles of different neurotransmitters in epileptic pathogenesis,the synaptic connections between glutamic acid (Glu) neurons and GABA neurons in normal rat hippocampus were studied by pre-embedding double labeling immunoelectron microscopy. The GABA immunoreaction was first demonstrated by chromogen DAB, then the Glu immunoreaction was demonstrated by molybdic acid-TMB method. After being stabilized by DAB-cobalt chloride,the sections were processed for electron microscopic embedding. Under electron microscope, there were many Glu immunoreaction-positive neurons in the pyramidal layer of hippocampal CA1 area and some GABA immunoreaction-positive neurons with pyramidal or polygonal perikarya in the pyramidal, polymorphic and radiant layer of CA1 area. There were also symmetric dendro-axonic synapses formed by GABA-positive dendrites and Glu-positive axons in the polymorphic layer and symmetric axo-dendritic synapses formed by GABA-positive axons and Glu-positive dendrites in the radiant layer. In addition, there were symmetric autoregulatory axo-dendritic synapses between Glu-positive axons and dendrites and autoregulatory axo-axonic synapses (both symmetric and asymmetric) between GABA-positive axons. Above mentioned results, for the first time,showed that there were complex synaptic regulatory relationships between excitatory Glu neurons and inhibitory GABA neurons in the hippocampal CA1 area, thereby, providing ultrastructural evidence for different neurotransmitters participating in epileptic pathogenesis.

  10. Inhibition of GABA A receptor improved special memory impairment in the local model of demyelination in rat hippocampus.

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    Mousavi Majd, Alireza; Ebrahim Tabar, Forough; Afghani, Arghavan; Ashrafpour, Sahand; Dehghan, Samaneh; Gol, Mohammad; Ashrafpour, Manouchehr; Pourabdolhossein, Fereshteh

    2017-09-01

    Cognitive impairment and memory deficit are common features in multiple Sclerosis patients. The mechanism of memory impairment in MS is unknown, but neuroimaging studies suggest that hippocampal demyelination is involved. Here, we investigate the role of GABA A receptor on spatial memory in the local model of hippocampal demyelination. Demyelination was induced in male Wistar rats by bilaterally injection of lysophosphatidylcholine (LPC) 1% into the CA1 region of the hippocampus. The treatment groups were received daily intraventricular injection of bicuculline (0.025, 0.05μg/2μl/animal) or muscimol (0.1, 0.2μg/2μl/animal) 5days after LPC injection. Morris Water Maze was used to evaluate learning and memory in rats. We used Luxol fast blue staining and qPCR to assess demyelination extention and MBP expression level respectively. Immunohistochemistry (IHC) for CD45 and H&E staining were performed to assess inflammatory cells infiltration. Behavioral study revealed that LPC injection in the hippocampus impaired learning and memory function. Animals treated with both doses of bicuculline improved spatial learning and memory function; however, muscimol treatment had no effect. Histological and MBP expression studies confirmed that demylination in LPC group was maximal. Bicuculline treatment significantly reduced demyelination extension and increased the level of MBP expression. H&E and IHC results showed that bicuculline reduced inflammatory cell infiltration in the lesion site. Bicuculline improved learning and memory and decreased demyelination extention in the LPC-induced hippocampal demyelination model. We conclude that disruption of GABAergic homeostasis in hippocampal demyelination context may be involved in memory impairment with the implications for both pathophysiology and therapy. Copyright © 2017. Published by Elsevier B.V.

  11. Early sequential formation of functional GABA(A) and glutamatergic synapses on CA1 interneurons of the rat foetal hippocampus.

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    Hennou, Sonia; Khalilov, Ilgam; Diabira, Diabé; Ben-Ari, Yehezkel; Gozlan, Henri

    2002-07-01

    During postnatal development of CA1 pyramidal neurons, GABAergic synapses are excitatory and established prior to glutamatergic synapses. As interneurons are generated before pyramidal cells, we have tested the hypothesis that the GABAergic interneuronal network is operative before glutamate pyramidal neurons and provides the initial patterns of activity. We patch-clamp recorded interneurons in foetal (69 neurons) and neonatal P0 (162 neurons) hippocampal slices and performed a morphofunctional analysis of biocytin-filled neurons. At P0, three types of interneurons were found: (i) non-innervated "silent" interneurons (5%) with no spontaneous or evoked synaptic currents; (ii) G interneurons (17%) with GABA(A) synapses only; and (iii) GG interneurons with GABA and glutamatergic synapses (78%). Relying on the neuronal capacitance, cell body size and arborization of dendrites and axons, the three types of interneurons correspond to three stages of development with non-innervated neurons and interneurons with GABA(A) and glutamatergic synapses being, respectively, the least and the most developed. Recordings from both pyramidal neurons and interneurons in foetuses (E18-20) revealed that the majority of interneurons (65%) had functional synapses whereas nearly 90% of pyramidal neurons were quiescent. Therefore, interneurons follow the same GABA-glutamate sequence of synapse formation but earlier than the principal cells. Interneurons are the source and the target of the first synapses formed in the hippocampus and are thus in a position to modulate the development of the hippocampus in the foetal stage.

  12. Substance P receptor expression by inhibitory interneurons of the rat hippocampus: enhanced detection using improved immunocytochemical methods for the preservation and colocalization of GABA and other neuronal markers.

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    Sloviter, R S; Ali-Akbarian, L; Horvath, K D; Menkens, K A

    2001-02-12

    subregions were found to be SPR-immunoreactive, including the PV-positive interneurons of the dentate hilus and hippocampus, and the SS-positive cells of area CA1, both of which were previously reported to lack SPR-LI. Only minor proportions of hippocampal interneurons appeared clearly devoid of detectable SPR-LI. These results demonstrate for the first time that all identified interneuron subpopulations of the rat hippocampus are GABA-immunoreactive, and that many inhibitory interneurons of all subtypes in all subregions of the rat hippocampus express SPRs constitutively.

  13. Involvement of GABA(B) receptors of the dorsal hippocampus on the acquisition and expression of morphine-induced place preference in rats.

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    Zarrindast, Mohammad-Reza; Massoudi, Roohollah; Sepehri, Houri; Rezayof, Ameneh

    2006-01-30

    In the present study, effects of intra-hippocampal CA1 (intra-CA1) injections of GABA(B) receptor agonist and antagonist on the acquisition and expression of morphine-induced place preference in male Wistar rats have been investigated. Subcutaneous administration of different doses of morphine sulphate (0.5-6 mg/kg) produced a dose-dependent conditioned place preference (CPP). Using a 3-day schedule of conditioning, it was found that the GABA(B) receptor agonist, baclofen (0.5-2 microg/rat; intra-CA1), or the GABA(B) receptor antagonist, phaclofen (1-3 microg/rat; intra-CA1), did not produce a significant place preference or place aversion. Intra-CA1 administration of baclofen (1 and 2 microg/rat; intra-CA1) decreased the acquisition of CPP induced by morphine (3 mg/kg; s.c.). On the other hand, intra-CA1 injection of phaclofen (1 and 2 microg/rat; intra-CA1) in combination with a lower dose of morphine (1 mg/kg) elicited a significant CPP. The response of baclofen (2 microg/rat; intra-CA1) was reversed by phaclofen (4 and 6 microg/rat; intra-CA1). Furthermore, intra-CA1 administration of baclofen but not phaclofen before testing significantly decreased the expression of morphine (3 mg/kg; s.c.)-induced place preference. Baclofen or phaclofen injections had no effects on locomotor activity on the testing sessions. It is concluded that the GABA(B) receptors in dorsal hippocampus may play an active role in morphine reward.

  14. Traumatic brain injury and the effects of diazepam, diltiazem, and MK-801 on GABA-A receptor subunit expression in rat hippocampus

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    Meyer Rebecca C

    2010-05-01

    Full Text Available Abstract Background Excitatory amino acid release and subsequent biochemical cascades following traumatic brain injury (TBI have been well documented, especially glutamate-related excitotoxicity. The effects of TBI on the essential functions of inhibitory GABA-A receptors, however, are poorly understood. Methods We used Western blot procedures to test whether in vivo TBI in rat altered the protein expression of hippocampal GABA-A receptor subunits α1, α2, α3, α5, β3, and γ2 at 3 h, 6 h, 24 h, and 7 days post-injuy. We then used pre-injury injections of MK-801 to block calcium influx through the NMDA receptor, diltiazem to block L-type voltage-gated calcium influx, or diazepam to enhance chloride conductance, and re-examined the protein expressions of α1, α2, α3, and γ2, all of which were altered by TBI in the first study and all of which are important constituents in benzodiazepine-sensitive GABA-A receptors. Results Western blot analysis revealed no injury-induced alterations in protein expression for GABA-A receptor α2 or α5 subunits at any time point post-injury. Significant time-dependent changes in α1, α3, β3, and γ2 protein expression. The pattern of alterations to GABA-A subunits was nearly identical after diltiazem and diazepam treatment, and MK-801 normalized expression of all subunits 24 hours post-TBI. Conclusions These studies are the first to demonstrate that GABA-A receptor subunit expression is altered by TBI in vivo, and these alterations may be driven by calcium-mediated cascades in hippocampal neurons. Changes in GABA-A receptors in the hippocampus after TBI may have far-reaching consequences considering their essential importance in maintaining inhibitory balance and their extensive impact on neuronal function.

  15. Spontaneous release of GABA activates GABAB receptors and controls network activity in the neonatal rat hippocampus.

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    McLean, H A; Caillard, O; Khazipov, R; Ben-Ari, Y; Gaiarsa, J L

    1996-08-01

    giant glutamatergic potentials were observed in simultaneously recorded CA3 pyramidal cells and interneurons. CGP 35348 (0.5 mM) progressively increased the duration of these bicuculline-induced glutamatergic bursts leading to the simultaneous appearance of ictal discharges in both pyramidal cells and interneurons. 6. These results suggest that in the neonatal CA3 hippocampal region, when synchronous giant polysynaptic GABAergic PSPs are present (i.e., under basal, control conditions), spontaneously released GABA reaches a critical level and activates GABAB receptors on both pyramidal cells and interneurons thus regulating the level of glutamatergic and GABAergic activity in the CA3 neuronal network.

  16. Dual effect of beta-amyloid on α7 and α4β2 nicotinic receptors controlling the release of glutamate, aspartate and GABA in rat hippocampus.

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    Elisa Mura

    Full Text Available BACKGROUND: We previously showed that beta-amyloid (Aβ, a peptide considered as relevant to Alzheimer's Disease, is able to act as a neuromodulator affecting neurotransmitter release in absence of evident sign of neurotoxicity in two different rat brain areas. In this paper we focused on the hippocampus, a brain area which is sensitive to Alzheimer's Disease pathology, evaluating the effect of Aβ (at different concentrations on the neurotransmitter release stimulated by the activation of pre-synaptic cholinergic nicotinic receptors (nAChRs, α4β2 and α7 subtypes. Particularly, we focused on some neurotransmitters that are usually involved in learning and memory: glutamate, aspartate and GABA. METHODOLOGY/FINDINGS: WE USED A DUAL APPROACH: in vivo experiments (microdialysis technique on freely moving rats in parallel to in vitro experiments (isolated nerve endings derived from rat hippocampus. Both in vivo and in vitro the administration of nicotine stimulated an overflow of aspartate, glutamate and GABA. This effect was greatly inhibited by the highest concentrations of Aβ considered (10 µM in vivo and 100 nM in vitro. In vivo administration of 100 nM Aβ (the lowest concentration considered potentiated the GABA overflow evoked by nicotine. All these effects were specific for Aβ and for nicotinic secretory stimuli. The in vitro administration of either choline or 5-Iodo-A-85380 dihydrochloride (α7 and α4β2 nAChRs selective agonists, respectively elicited the hippocampal release of aspartate, glutamate, and GABA. High Aβ concentrations (100 nM inhibited the overflow of all three neurotransmitters evoked by both choline and 5-Iodo-A-85380 dihydrochloride. On the contrary, low Aβ concentrations (1 nM and 100 pM selectively acted on α7 subtypes potentiating the choline-induced release of both aspartate and glutamate, but not the one of GABA. CONCLUSIONS/SIGNIFICANCE: The results reinforce the concept that Aβ has relevant

  17. Postsynaptic GABA(B) Receptors Contribute to the Termination of Giant Depolarizing Potentials in CA3 Neonatal Rat Hippocampus

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    Khalilov, Ilgam; Minlebaev, Marat; Mukhtarov, Marat; Juzekaeva, Elvira; Khazipov, Roustem

    2017-01-01

    During development, hippocampal CA3 network generates recurrent population bursts, so-called Giant Depolarizing Potentials (GDPs). GDPs are characterized by synchronous depolarization and firing of CA3 pyramidal cells followed by afterhyperpolarization (GDP-AHP). Here, we explored the properties of GDP-AHP in CA3 pyramidal cells using gramicidin perforated patch clamp recordings from neonatal rat hippocampal slices. We found that GDP-AHP occurs independently of whether CA3 pyramidal cells fire action potentials (APs) or remain silent during GDPs. However, the amplitude of GDP-AHP increased with the number of APs the cells fired during GDPs. The reversal potential of the GDP-AHP was close to the potassium equilibrium potential. During voltage-clamp recordings, current-voltage relationships of the postsynaptic currents activated during GDP-AHP were characterized by reversal near the potassium equilibrium potential and inward rectification, similar to the responses evoked by the GABA(B) receptor agonists. Finally, the GABA(B) receptor antagonist CGP55845 strongly reduced GDP-AHP and prolonged GDPs, eventually transforming them to the interictal and ictal-like discharges. Together, our findings suggest that the GDP-AHP involves two mechanisms: (i) postsynaptic GABA(B) receptor activated potassium currents, which are activated independently on whether the cell fires or not during GDPs; and (ii) activity-dependent, likely calcium activated potassium currents, whose contribution to the GDP-AHP is dependent on the amount of firing during GDPs. We propose that these two complementary inhibitory postsynaptic mechanisms cooperate in the termination of GDP. PMID:28701925

  18. Subcellular fractionation on Percoll gradient of mossy fiber synaptosomes: evoked release of glutamate, GABA, aspartate and glutamate decarboxylase activity in control and degranulated rat hippocampus.

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    Taupin, P; Ben-Ari, Y; Roisin, M P

    1994-05-02

    Using discontinuous density gradient centrifugation in isotonic Percoll sucrose, we have characterized two subcellular fractions (PII and PIII) enriched in mossy fiber synaptosomes and two others (SII and SIII) enriched in small synaptosomes. These synaptosomal fractions were compared with those obtained from adult hippocampus irradiated at neonatal stage to destroy granule cells and their mossy fibers. Synaptosomes were viable as judged by their ability to release aspartate, glutamate and GABA upon K+ depolarization. After irradiation, compared to the control values, the release of glutamate and GABA was decreased by 57 and 74% in the PIII fraction, but not in the other fractions and the content of glutamate, aspartate and GABA was also decreased in PIII fraction by 62, 44 and 52% respectively. These results suggest that mossy fiber (MF) synaptosomes contain and release glutamate and GABA. Measurement of the GABA synthesizing enzyme, glutamate decarboxylase, exhibited no significant difference after irradiation, suggesting that GABA is not synthesized by this enzyme in mossy fibers.

  19. Stress-restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus

    DEFF Research Database (Denmark)

    Harvey, Brian H; Oosthuizen, Frasia; Brand, Linda

    2004-01-01

    activation. CONCLUSIONS: Stress-restress-mediated glucocorticoid release activates iNOS, followed by a reactive downregulation of hippocampal NMDA receptors and dysregulation of inhibitory GABA pathways. The role of NO in neuronal toxicity, and its regulation by glutamate and GABA has important implications...

  20. Effects of the 5-HT1B receptor antagonist NAS-181 on extracellular levels of acetylcholine, glutamate and GABA in the frontal cortex and ventral hippocampus of awake rats: a microdialysis study.

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    Hu, Xiao Jing; Wang, Fu-Hua; Stenfors, Carina; Ogren, Sven Ove; Kehr, Jan

    2007-09-01

    The purpose of this study was to investigate the effects of the 5-HT(1B) receptor antagonist NAS-181 ((R)-(+)-2-(3-morpholinomethyl-2H-chromen-8-yl) oxymethyl-morpholine methanesulfonate) on cholinergic, glutamatergic and GABA-ergic neurotransmission in the rat brain in vivo. Extracellular levels of acetylcholine, glutamate and GABA were monitored by microdialysis in the frontal cortex (FC) and ventral hippocampus (VHipp) in separate groups of freely moving rats. NAS-181 (1, 5 or 10 mg/kg, s.c.) caused a dose-dependent increase in ACh levels, reaching the maximal values of 500% (FC) and 230% (VHipp) of controls at 80 min post-injection. On the contrary, NAS-181 injected at doses of 10 or 20 mg/kg s.c. had no effect on basal extracellular levels of Glu and GABA in these areas. The present data suggest that ACh neurotransmission in the FC and VHipp, the brain structures strongly implicated in cognitive function, is under tonic inhibitory control of 5-HT(1B) heteroreceptors localized at the cholinergic terminals in these areas.

  1. Further evidence for involvement of the dorsal hippocampus serotonergic and γ-aminobutyric acid (GABA)ergic pathways in the expression of contextual fear conditioning in rats.

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    Almada, Rafael C; Albrechet-Souza, Lucas; Brandão, Marcus L

    2013-12-01

    Intra-dorsal hippocampus (DH) injections of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a serotonin-1A (5-hydroxytryptamine (5-HT)-1A) receptor agonist, were previously shown to inhibit the expression of contextual fear when administered six hours after conditioning. However, further understanding of the consolidation and expression of aversive memories requires investigations of these and other mechanisms at distinct time points and the regions of the brain to which they are transferred. Thus, the purpose of the present study was to investigate the role of DH serotonergic and γ-aminobutyric acid (GABA)ergic mechanisms in the expression of contextual fear 24 h after conditioning, reflected by fear-potentiated startle (FPS) and freezing behavior. The recruitment of the amygdala and medial prefrontal cortex (mPFC) in these processes was also evaluated by measuring Fos protein immunoreactivity. Although intra-DH injections of 8-OH-DPAT did not produce behavioral changes, muscimol reduced both FPS and the freezing response. Fos protein immunoreactivity revealed that contextual fear promoted wide activation of the mPFC, which was significantly reduced after intra-DH infusions of muscimol. The present findings, together with previous data, indicate that in contrast to 5-HT, which appears to play a role during the early phases of contextual aversive memory consolidation, longer-lasting GABA-mediated mechanisms are recruited during the expression of contextual fear memories.

  2. Localization of GABA(B) (R1) receptors in the rat hippocampus by immunocytochemistry and high resolution autoradiography, with specific reference to its localization in identified hippocampal interneuron subpopulations.

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    Sloviter, R S; Ali-Akbarian, L; Elliott, R C; Bowery, B J; Bowery, N G

    1999-11-01

    Immunocytochemical and autoradiographic methods were used to localize the GABA(B) receptor in the normal rat hippocampus. GABA(B) receptor 1-like immunoreactivity (GBR1-LI) was most intense in presumed GABAergic interneurons of all hippocampal subregions. It was also present throughout the hippocampal neuropil, where it was most intense in the dendritic strata of the dentate gyrus, which are innervated by the perforant pathway and inhibitory dentate hilar cells, and in strata oriens and radiatum of area CA3. The dendritic regions of area CA1 exhibited less GBR1-LI than area CA3. GBR1-LI was detectable in the somata of CA1 pyramidal cells, but was minimal or undetectable within the somata of dentate granule cells and CA3 pyramidal cells. GBR1-LI was similarly minimal in the dentate hilar neuropil, and in stratum lucidum, the two regions that contain granule cell axons and terminals. Nor was GBR1-LI detectable in the inhibitory basket cell fiber systems that surround hippocampal principal cell somata. Fluorescence co-localization studies indicated that significant proportions of interneurons expressing somatostatin, neuropeptide Y, cholecystokinin, calbindin, or calretinin also expressed GBR1-LI constitutively. Conversely, parvalbumin-positive GABAergic basket cells of the dentate gyrus and hippocampus, which form GABA(A) receptor-mediated inhibitory axo-somatic synapses, rarely contained detectable GBR1-LI. High resolution autoradiography with the GABA(B) receptor antagonist CGP 62349 revealed a close correspondence between receptor ligand binding and GBR1-LI, with several notable exceptions. Ligand binding closely matched GBR1-LI throughout the hippocampal, cortical, thalamic, and cerebellar neuropil. However, the hippocampal interneuron somata and dendrites that exhibited the most intense GBR1-LI, and the GBR1-positive somata of CA1 pyramidal cells, did not exhibit a similar density of [3H]-CGP 62349 binding. These data clarify the relationship between

  3. Comparative immunohistochemical localisation of GABA(B1a), GABA(B1b) and GABA(B2) subunits in rat brain, spinal cord and dorsal root ganglion.

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    Charles, K J; Evans, M L; Robbins, M J; Calver, A R; Leslie, R A; Pangalos, M N

    2001-01-01

    GABA(B) receptors are G-protein-coupled receptors mediating the slow onset and prolonged synaptic actions of GABA in the CNS. The recent cloning of two genes, GABA(B1) and GABA(B2), has revealed a novel requirement for GABA(B) receptor signalling. Studies have demonstrated that the two receptor subunits associate as a GABA(B1)/GABA(B2) heterodimer to form a functional GABA(B) receptor. In this study we have developed polyclonal antisera specific to two splice variants of the GABA(B1) subunit, GABA(B1a) and GABA(B1b), as well as an antiserum to the GABA(B2) subunit. Using affinity-purified antibodies derived from these antisera we have mapped out the distribution profile of each subunit in rat brain, spinal cord and dorsal root ganglion. In brain the highest areas of GABA(B1a), GABA(B1b) and GABA(B2) subunit expression were found in neocortex, hippocampus, thalamus, cerebellum and habenula. In spinal cord, GABA(B1) and GABA(B2) subunits were expressed in the superficial layers of the dorsal horn, as well as in motor neurones in the deeper layers of the ventral horn. GABA(B) receptor subunit immunoreactivity in dorsal root ganglion suggested that expression of GABA(B1b) was restricted to the large diameter neurones, in contrast to GABA(B1a) and GABA(B2) subunits which were expressed in both large and small diameter neurones. Although expression levels of GABA(B1) and GABA(B2) subunits varied we found no areas in which GABA(B1) was expressed in the absence of GABA(B2). This suggests that most, if not all, GABA(B1) immunoreactivity may represent functional GABA(B) receptors. Although our data are in general agreement with functional studies, some discrepancies in GABA(B1) subunit expression occurred with respect to other immunohistochemical studies. Overall our data suggest that GABA(B) receptors are widely expressed throughout the brain and spinal cord, and that GABA(B1a) and GABA(B1b) subunits can associate with GABA(B2) to form both pre- and post-synaptic receptors.

  4. Epileptogenic actions of GABA and fast oscillations in the developing hippocampus.

    Science.gov (United States)

    Khalilov, Ilgam; Le Van Quyen, Michel; Gozlan, Henri; Ben-Ari, Yehezkel

    2005-12-08

    GABA excites immature neurons and inhibits adult ones, but whether this contributes to seizures in the developing brain is not known. We now report that in the developing, but not the adult, hippocampus, seizures beget seizures only if GABAergic synapses are functional. In the immature hippocampus, seizures generated with functional GABAergic synapses include fast oscillations that are required to transform a naive network to an epileptic one: blocking GABA receptors prevents the long-lasting sequels of seizures. In contrast, in adult neurons, full blockade of GABA(A) receptors generates epileptogenic high-frequency seizures. Therefore, purely glutamatergic seizures are not epileptogenic in the developing hippocampus. We suggest that the density of glutamatergic synapses is not sufficient for epileptogenesis in immature neurons; excitatory GABAergic synapses are required for that purpose. We suggest that the synergistic actions of GABA and NMDA receptors trigger the cascades involved in epileptogenesis in the developing hippocampus.

  5. GABA and Glutamate are not colocalized in mossy fiber terminals of developing rodent hippocampus

    OpenAIRE

    Xiong, Guoxiang; Zhang, Lei; Mojsilovic-Petrovic, Jelena; Arroyo, Edguardo; Elkind, Jaclynn; Kundu, Suhali; Johnson, Brian; Smith, Colin J.; Cohen, Noam A.; Grady, Sean M.; Cohen, Akiva S.

    2012-01-01

    It has been hypothesized that, in the developing rodent hippocampus, mossy fiber terminals release GABA together with glutamate. Here, we used transgenic glutamic acid decarboxylase-67 (GAD67)-GFP expressing mice and multi-label immunohistochemistry to address whether glutamatergic and GABAergic markers are colocalized. We demonstrate that in the dentate gyrus, interneurons positive for GABA/GAD are sparsely distributed along the edge of the hilus, in a different pattern than the densely pack...

  6. Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus

    Directory of Open Access Journals (Sweden)

    Paul David Whissell

    2015-09-01

    Full Text Available Cholecystokinin (CCK- and parvalbumin (PV-expressing neurons constitute the two major populations of perisomatic GABAergic neurons in the cortex and the hippocampus. As CCK- and PV-GABA neurons differ in an array of morphological, biochemical and electrophysiological features, it has been proposed that they form distinct inhibitory ensembles which differentially contribute to network oscillations and behaviour. However, the relationship and balance between CCK- and PV-GABA neurons in the inhibitory networks of the brain is currently unclear as the distribution of these cells has never been compared on a large scale. Here, we systemically investigated the distribution of CCK- and PV-GABA cells across a wide number of discrete forebrain regions using an intersectional genetic approach. Our analysis revealed several novel trends in the distribution of these cells. While PV-GABA cells were more abundant overall, CCK-GABA cells outnumbered PV-GABA cells in several subregions of the hippocampus, medial prefrontal cortex and ventrolateral temporal cortex. Interestingly, CCK-GABA cells were relatively more abundant in secondary/association areas of the cortex (V2, S2, M2, and AudD/AudV than they were in corresponding primary areas (V1, S1, M1 and Aud1. The reverse trend was observed for PV-GABA cells. Our findings suggest that the balance between CCK- and PV-GABA cells in a given cortical region is related to the type of processing that area performs; inhibitory networks in the secondary cortex tend to favour the inclusion of CCK-GABA cells more than networks in the primary cortex. The intersectional genetic labelling approach employed in the current study expands upon the ability to study molecularly defined subsets of GABAergic neurons. This technique can be applied to the investigation of neuropathologies which involve disruptions to the GABAergic system, including schizophrenia, stress, maternal immune activation and autism.

  7. Blocking GABA(A) inhibition reveals AMPA- and NMDA-receptor-mediated polysynaptic responses in the CA1 region of the rat hippocampus.

    Science.gov (United States)

    Crépel, V; Khazipov, R; Ben-Ari, Y

    1997-04-01

    We have investigated the conditions required to evoke polysynaptic responses in the isolated CA1 region of hippocampal slices from Wistar adult rats. Experiments were performed with extracellular and whole cell recording techniques. In the presence of bicuculline (10 microM), 6-cyano-7-nitroquinoxaline-2-3-dione (10 microM), glycine (10 microM), and a low external concentration of Mg2+ (0.3 mM), electrical stimulation of the Schaffer collaterals/commissural pathway evoked graded N-methyl-D-aspartate (NMDA)-receptor-mediated late field potentials in the stratum radiatum of the CA1 region. These responses were generated via polysynaptic connections because their latency varied strongly and inversely with the stimulation intensity and they were abolished by a high concentration of divalent cations (7 mM Ca2+). These responses likely were driven by local collateral branches of CA1 pyramidal cell axons because focal application of tetrodotoxin (30 microM) in the stratum oriens strongly reduced the late synaptic component and antidromic stimulation of CA1 pyramidal cells could evoke the polysynaptic response. Current-source density analysis suggested that the polysynaptic response was generated along the proximal part of the apical dendrites of CA1 pyramidal cells (50-150 microm below the pyramidal cell layer in the stratum radiatum). In physiological concentration of Mg2+ (1.3 mM), the pharmacologically isolated NMDA-receptor-mediated polysynaptic response was abolished. In control artificial cerebrospinal fluid (with physiological concentration of Mg2+), bicuculline ( 10 microM) generated a graded polysynaptic response. Under these conditions, this response was mediated both by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA receptors. In the presence of D-2-amino-5-phosphonovalerate (50 microM), the polysynaptic response could be mediated by AMPA receptors, although less efficiently. In conclusion, suppression of gamma-aminobutyric acid

  8. Suanzaoren decoction on the cognitive function and NA,GABA, 5-HT in hippocampus on sleep deprived rats%酸枣仁汤对睡眠剥夺大鼠认知功能及海马NA,GABA,5-HT的影响

    Institute of Scientific and Technical Information of China (English)

    杨波; 岳明

    2015-01-01

    目的:观察复方酸枣仁汤(SZRT)对睡眠剥夺(SD)大鼠认知功能及海马NA ,GABA ,5‐HT含量的影响。方法:行为学筛选合格的雄性大鼠50只分为对照组、睡眠剥夺组、酸枣仁汤(SZRT )21.0g/kg ,10.50g/kg ,5.25 g/kg剂量组,建立睡眠剥夺大鼠动物模型,进行7d连续睡眠剥夺,1d1次,Y‐型电迷宫测定学习记忆,Elisa法检测海马中去甲肾上腺素(N A ),γ‐氨基丁酸(GABA),5‐羟色胺(5‐HT)的含量。结果:与睡眠剥夺组相比,SZRT 21.0g/kg组大鼠的学习记忆的能力改善,NA的含量降低,GABA和5‐HT 含量升高。结论:酸枣仁汤(SZRT )可改善睡眠剥夺大鼠认知功能,与改变单胺类递质作用有关。%Objective:To investigate the effects of Suanzaoren Decoction on the cognitive function in sleep de‐prived rats and the content of NA ,GABA ,5‐HT in hippocampus .Methods:After screening ,selection behavior qualified in rats ,50 male rats were randomly divided into control group ,sleep deprivation group ,SZRT 21 .0g/kg ,10 .50g/kg ,5 .25 g/kg dose group ,The models of sleep deprived were established with modified multiple platform method for seven days , drugs were given once daily .Determine the learning and memory of rats by Y‐type maze ,determine the the content of NA , GABA ,5‐HT in hippocampus by Elisa .Results:Compared with sleep deprivation group ,SZRT 21 .0g/kg dose group could improve learning and memory ,decrease the content of NA ,increase the content GABA ,5‐HT in hippocampal .Conclusion :Suanzaoren Decoction can improve the learning and memory in rats after sleep deprivation ,may be related to change mono‐amine transmitters .

  9. Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus.

    Science.gov (United States)

    Tyzio, Roman; Minlebaev, Marat; Rheims, Sylvain; Ivanov, Anton; Jorquera, Isabelle; Holmes, Gregory L; Zilberter, Yuri; Ben-Ari, Yehezkiel; Khazipov, Rustem

    2008-05-01

    During postnatal development of the rat hippocampus, gamma-aminobutyric acid (GABA) switches its action on CA3 pyramidal cells from excitatory to inhibitory. To characterize the underlying changes in the GABA reversal potential, we used somatic cell-attached recordings of GABA(A) and N-methyl-D-aspartate channels to monitor the GABA driving force and resting membrane potential, respectively. We found that the GABA driving force is strongly depolarizing during the first postnatal week. The strength of this depolarization rapidly declines with age, although GABA remains slightly depolarizing, by a few millivolts, even in adult neurons. Reduction in the depolarizing GABA driving force was due to a progressive negative shift of the reversal potential of GABA currents. Similar postnatal changes in GABA signalling were also observed using the superfused hippocampus preparation in vivo, and in the hippocampal interneurons in vitro. We also found that in adult pyramidal cells, somatic GABA reversal potential is maintained at a slightly depolarizing level by bicarbonate conductance, chloride-extrusion and chloride-loading systems. Thus, the postnatal excitatory-to-inhibitory switch in somatic GABA signalling is associated with a negative shift of the GABA reversal potential but without a hyperpolarizing switch in the polarity of GABA responses. These results also suggest that in adult CA3 pyramidal cells, somatic GABAergic inhibition takes place essentially through shunting rather than hyperpolarization. Apparent hyperpolarizing GABA responses previously reported in the soma of CA3 pyramidal cells are probably due to cell depolarization during intracellular or whole-cell recordings.

  10. Mechanisms of induction and expression of long-term depression at GABAergic synapses in the neonatal rat hippocampus.

    Science.gov (United States)

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

    1999-09-01

    Synaptic plasticity at excitatory glutamatergic synapses is believed to be instrumental in the maturation of neuronal networks. Using whole-cell patch-clamp recordings, we have studied the mechanisms of induction and expression of long-term depression at excitatory GABAergic synapses in the neonatal rat hippocampus (LTD(GABA-A)). We report that the induction of LTD(GABA-A) requires a GABA(A) receptor-mediated membrane depolarization, which is necessary to remove the Mg(2+) block from postsynaptic NMDA receptors. LTD(GABA-A) is associated with an increase in the coefficient of variation of evoked GABA(A) receptor-mediated synaptic currents and a decrease in the frequency, but not amplitude, of Sr(2+)-induced asynchronous GABA(A) quantal events. We conclude that LTD(GABA-A) induction requires the activation of both GABA(A) and NMDA postsynaptic receptors and that its expression is likely presynaptic.

  11. Differential effects of phosphonic analogues of GABA on GABA(B) autoreceptors in rat neocortical slices.

    Science.gov (United States)

    Ong, J; Marino, V; Parker, D A; Kerr, D I

    1998-04-01

    The effects of five phosphonic derivatives of GABA on the release of [3H]-GABA from rat neocortical slices, preloaded with [3H]-GABA, were investigated. Phaclofen and 4-aminobutylphosphonic acid (4-ABPA) increased the overflow of [3H] evoked by electrical stimulation (2 Hz) in a concentration-dependent manner, with similar potencies (phaclofen EC50=0.3 mmol/l, 4-ABPA EC50=0.4 mmol/l). At 3 mmol/l, phaclofen increased the release of [3H]-GABA by 82.6+/-8.6%, and 4-ABPA increased the release by 81.3+/-9.0%. 2-Amino-ethylphosphonic acid (2-AEPA) increased the overflow of [3H] by 46.8+/-10.9% at the highest concentration tested (3 mmol/l). In contrast, the lower phosphonic homologue 3-aminopropylphosphonic acid (3-APPA), and 2-amino-2-(p-chlorophenyl)-ethylphosphonic acid (2-CPEPA), a baclofen analogue, did not modify the stimulated overflow. These results suggest that phaclofen, 4-ABPA and 2-AEPA are antagonists at GABA(B) autoreceptors, the latter being the weakest antagonist, whilst neither 3-APPA nor 2-CPEPA are active at these receptors. Since phaclofen, 4-ABPA and 2-CPEPA are antagonists and 3-APPA a partial agonist/antagonist on GABA(B) heteroreceptors, the lack of effect of 3-APPA and 2-CPEPA on [3H]-GABA release in this study suggests that GABA(B) autoreceptors may be pharmacologically distinct from the heteroreceptors.

  12. GABA modulates baroreflex in the ventral tegmental area in rat.

    Science.gov (United States)

    Hatam, Masoumeh; Rasoulpanah, Minoo; Nasimi, Ali

    2015-12-01

    There are some reports demonstrating the cardiovascular functions of the ventral tegmental area (VTA). About 20-30% of the VTA neurons are GABAergic, which might play a role in baroreflex modulation. This study was performed to find the effects of GABA(A), GABA(B) receptors and reversible synaptic blockade of the VTA on baroreflex. Drugs were microinjected into the VTA of urethane anesthetized rats, and the maximum change of blood pressure and the gain of the reflex bradycardia in response to intravenous phenylephrine (Phe) injection were compared with the preinjection and the control values. Microinjection of bicuculline methiodide (BMI, 100 pmol/100 nl), a GABA(A) antagonist, into the VTA strongly decreased the Phe-induced hypertension, indicating that GABA itself attenuated the baroreflex. Muscimol, a GABA(A) agonist (30 mM, 100 nl), produced no significant changes. Baclofen, a GABA(B) receptor agonist (1000 pmole/100 nl), moderately attenuated the baroreflex, however phaclofen, a GABA(B) receptor antagonist (1000 pmole/100 nl), had no significant effect. In conclusion, for the first time, we demonstrated that GABA(A) receptors of the VTA strongly attenuate and GABA(B) receptors of the VTA moderately attenuate baroreflex in rat. © 2015 Wiley Periodicals, Inc.

  13. Dysbindin Deficiency Modifies the Expression of GABA Neuron and Ion Permeation Transcripts in the Developing Hippocampus

    Science.gov (United States)

    Larimore, Jennifer; Zlatic, Stephanie A.; Arnold, Miranda; Singleton, Kaela S.; Cross, Rebecca; Rudolph, Hannah; Bruegge, Martha V.; Sweetman, Andrea; Garza, Cecilia; Whisnant, Eli; Faundez, Victor

    2017-01-01

    The neurodevelopmental factor dysbindin is required for synapse function and GABA interneuron development. Dysbindin protein levels are reduced in the hippocampus of schizophrenia patients. Mouse dysbindin genetic defects and other mouse models of neurodevelopmental disorders share defective GABAergic neurotransmission and, in several instances, a loss of parvalbumin-positive interneuron phenotypes. This suggests that mechanisms downstream of dysbindin deficiency, such as those affecting GABA interneurons, could inform pathways contributing to or ameliorating diverse neurodevelopmental disorders. Here we define the transcriptome of developing wild type and dysbindin null Bloc1s8sdy/sdy mouse hippocampus in order to identify mechanisms downstream dysbindin defects. The dysbindin mutant transcriptome revealed previously reported GABA parvalbumin interneuron defects. However, the Bloc1s8sdy/sdy transcriptome additionally uncovered changes in the expression of molecules controlling cellular excitability such as the cation-chloride cotransporters NKCC1, KCC2, and NCKX2 as well as the potassium channel subunits Kcne2 and Kcnj13. Our results suggest that dysbindin deficiency phenotypes, such as GABAergic defects, are modulated by the expression of molecules controlling the magnitude and cadence of neuronal excitability.

  14. Regional GABA concentration and (/sup 3/H)-diazepam binding in rat brain following repeated electroconvulsive shock

    Energy Technology Data Exchange (ETDEWEB)

    Bowdler, J.M.; Green, A.R.; Minchin, M.C.W.; Nutt, D.J. (Radcliffe Infirmary, Oxford (UK))

    1983-01-01

    It has been confirmed that 24 hours following a series of electroconvulsive shocks (ECS) given once daily for 10 days (ECS x 10) to rats there is an increase in GABA concentration in the corpus striatum. A similar change was seen after the ECS had been given to rats anaesthetised with halothane, or when 5 ECS were given spread out over 10 days, the rats being anaesthetised during the ECS. A daily convulsion for 10 days elicited by flurothyl exposure resulted in an increased striatal GABA concentration, but also increased the GABA concentration in the hypothalamus, hippocampus and cortex. The increase in striatal GABA concentration was present 24 hours after ECS daily for 5 days or 3 days after ECS daily for 10 days. No change in (/sup 3/H)-diazepam binding was seen in hippocampus, cortex or corpus striatum 24 hours after the last of 10 once daily ECS. The increase in striatal GABA concentration was therefore seen at all times when enhanced monoaminemediated behaviours have been demonstrated following seizures.

  15. Binge Toluene Exposure Alters Glutamate, Glutamine and GABA in the Adolescent Rat Brain as Measured by Proton Magnetic Resonance Spectroscopy*

    Science.gov (United States)

    Perrine, Shane A.; O'Leary-Moore, Shonagh K.; Galloway, Matthew P.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Despite the high incidence of toluene abuse in adolescents, little is known regarding the effect of binge exposure on neurochemical profiles during this developmental stage. In the current study, the effects of binge toluene exposure during adolescence on neurotransmitter levels were determined using high-resolution proton magnetic resonance spectroscopy ex vivo at 11.7 T. Adolescent male Sprague-Dawley rats were exposed to toluene (0, 8,000 , or 12,000 ppm) for 15 min twice daily from postnatal day 28 (P28) through P34 and then euthanized either one or seven days later (on P35 or P42) to assess glutamate, glutamine, and GABA levels in intact tissue punches from the medial prefrontal cortex (mPFC), anterior striatum and hippocampus. In the mPFC, toluene reduced glutamate one day after exposure, with no effect on GABA, while after seven days, glutamate was no longer affected but there was an increase in GABA levels. In the hippocampus, neither GABA nor glutamate was altered one day after exposure, whereas seven days after exposure, increases were observed in GABA and glutamate. Striatal glutamate and GABA levels measured after either one or seven days were not altered after toluene exposure. These findings show that one week of binge toluene inhalation selectively alters these neurotransmitters in the mPFC and hippocampus in adolescent rats, and that some of these effects endure at least one week after the exposure. The results suggest that age-dependent, differential neurochemical responses to toluene may contribute to the unique behavioral patterns associated with drug abuse among older children and young teens. PMID:21126832

  16. Expression of somatostatin mRNA and peptide in rat hippocampus after cerebral ischemia

    DEFF Research Database (Denmark)

    Bering, Robert; Johansen, Flemming Fryd

    1993-01-01

    Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology......Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology...

  17. Postsynaptic blockade of inhibitory postsynaptic currents by plasmin in CA1 pyramidal cells of rat hippocampus.

    Science.gov (United States)

    Mizutani, A; Tanaka, T; Saito, H; Matsuki, N

    1997-06-27

    We have shown previously that plasmin facilitated the generation of long-term potentiation (LTP) in CA1 and dentate region of rat hippocampus. In the present study, we investigated the effects of plasmin on postsynaptic currents in CA1 pyramidal neurons of rat hippocampal slices. Plasmin (100 nM) had no effect on NMDA nor on non-NMDA receptor-mediated excitatory postsynaptic currents. However, plasmin significantly decreased GABA(A) receptor-mediated inhibitory postsynaptic currents. This effect of plasmin disappeared when intracellular Ca2+ was strongly chelated with BAPTA. Furthermore, plasmin attenuated the GABA-induced currents in CA1 pyramidal cells. These results suggest that the STP-enhancing effect of plasmin is due to a blockade of postsynaptic GABA(A) responses and that an increase in intracellular Ca2+ by plasmin may be involved in its mechanism.

  18. In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain.

    Science.gov (United States)

    Hoekzema, Elseline; Rojas, Santiago; Herance, Raúl; Pareto, Deborah; Abad, Sergio; Jiménez, Xavier; Figueiras, Francisca P; Popota, Foteini; Ruiz, Alba; Flotats, Núria; Fernández, Francisco J; Rocha, Milagros; Rovira, Mariana; Víctor, Víctor M; Gispert, Juan D

    2012-07-01

    The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA(A) receptor. To visualize BDZ site availability, [(11)C]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [(11)C]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduced radioligand uptake were detected in the bilateral hippocampus, cerebellum, midbrain, and bilateral frontal and parieto-occipital cortex. Our results support the pertinence of voxel-wise quantification in the analysis of microPET data. Moreover, these findings indicate that the aging process involves declines in neural BDZ recognition site availability, proposed to reflect alterations in GABA(A) receptor subunit polypeptide expression.

  19. Characterization of GABA/sub A/ receptor-mediated /sup 36/chloride uptake in rat brain synaptoneurosomes

    Energy Technology Data Exchange (ETDEWEB)

    Luu, M.D.; Morrow, A.L.; Paul, S.M.; Schwartz, R.D.

    1987-09-07

    ..gamma..-Aminobutyric acid (GABA) receptor-mediated /sup 36/chloride (/sup 36/Cl/sup -/) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated /sup 36/Cl/sup -/ uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated /sup 36/Cl/sup -/ uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated /sup 36/Cl/sup -/ uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br/sup -/>Cl/sup -/greater than or equal toNO/sub 3//sup -/>I/sup -/greater than or equal toSCN/sup -/>>C/sub 3/H/sub 5/OO/sup -/greater than or equal toClO/sub 4//sup -/>F/sup -/, consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl/sup -/ channel. 43 references, 4 figures, 3 tables.

  20. Proteomic analysis of hippocampus in the rat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bo; WANG Ren-zhi; LIAN Zhi-gang; YAO Yong

    2004-01-01

    Objective To analyze the protein expression in the rat hippocampus by the proteomic approach.Methods Proteins from hippocampal tissue homogenates of the rat were separated by two-dimensional gel electrophoresis(2-DE),and stained with colloidal Coomassie blue to produce a high-resolution map of the rat hippocampus proteome.Selected proteins from this map were digested with trypsin,and the resulting tryptic peptides were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).The mass spectrometric data were used to identify the proteins through searches of the NCBI protein sequence database.Results 37 prominent proteins with various functional characteristics were identified.The identified brain protein classes covered metabolism enzymes,cytoskeleton proteins,heat shock proteins,antioxidant proteins,signalling proteins,proteasome-related proteins,neuron-specific proteins and glial-associated proteins.Furthermore,3 hypothetical proteins,unknown proteins so far only proposed from their nucleic acid structure,were identified.Conclusion This study provides the first unbiased characterization of proteins of the rat hippocampus and will be used for future studies of differential protein expression in rat models of neurological disorders.

  1. Endogenous neurotrophins are required for the induction of GABAergic long-term potentiation in the neonatal rat hippocampus.

    Science.gov (United States)

    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.

  2. Characteristics of gamma-aminobutyric acid (GABA receptors in the rat central nervous system.

    Directory of Open Access Journals (Sweden)

    Kuroda,Hiroo

    1983-04-01

    Full Text Available Characteristics of gamma-aminobutyric acid (GABA were investigated in the rat central nervous system by radioreceptor assay (RRA. Scatchard analysis revealed that the rat brain had two distinct GABA binding sites with an apparent dissociation constant (Kd of 11.7 nM and 34.7 nM. The highest level of specific [3H]-GABA binding was found in the rat cerebellum. Imidazole acetic acid, a potent GABA agonist, was effective in displacing [3H]-GABA binding but beta-alanine was slightly effective in inhibiting [3H]-GABA binding. Muscimol, the most potent GABA agonist, has been used as a ligand to characterize the postsynaptic GABA receptors. However, the maximal binding capacity (Bmax of muscimol-RRA was about 3 times larger than that of GABA-RRA, suggesting that muscimol might label not only GABA receptors but other unknown receptors as well. An endogenous inhibitor of GABA receptor binding was purified from the P2 fraction of rat brain with 0.05% Triton X-100. The endogenous inhibitor was competitive with GABA on GABA binding sites. The inhibition by the endogenous inhibitor of GABA receptor binding was blocked by the allosteric effect of diazepam. In the presence of diazepam, [3H]-GABA binding with the endogenous inhibitor was larger than that with GABA, whereas there was no difference in the absence of diazepam. This indicated that the endogenous inhibitor was not GABA itself. The molecular weight of the endogenous inhibitor was estimate by gel filtration to be less than 3,000 daltons.

  3. INHIBITORY EFFECT OF BACLOFEN ON GABA-ACTIVATED CURRENT IN MECHANICALLY ISOLATED PYRAMIDAL CELLS OF RAT HIPPOCAMPUS%Baclofen对机械分离的大鼠海马锥体细胞GABA-激活电流的抑制作用

    Institute of Scientific and Technical Information of China (English)

    甘志强; 罗加烈; 郑少萍; 李之望

    2004-01-01

    在机械分离的海马锥体细胞上,应用全细胞膜片钳技术.证明大多数细胞(88.5%,46/52)对GABA敏感.10-5~10-3mol/L的GABA引起一剂量依赖性、有明显去敏感作用的内向电流.预加3×10-5 mol/L baclofen(GABAB受体的特异性激动剂)30 s后再加GABA,84.8%(39/46)的细胞GABA-激活电流被抑制,其中仅有一个细胞(2.2%,1/46)GABA-激活电流幅值增强,13%(6/46)的细胞GABA-激活电流幅值无变化.预加baclofen后,GABA-激活电流量-效曲线明显下移.预加baclofen前后IGABA量效曲线的Kd值非常接近(1.0X10-4 vs1.4×10-4mol/L).经saclofen预处理可消除baclofen对GABA-激活电流的抑制.这与我室以往在外周神经元上的研究结果一致.本文结果不仅证明了GABAA和GABAB受体在海马锥体细胞上的共存,而且也证明了GABAB受体激活后对GABAA受体功能抑制这一现象无论在外周或中枢神经系统均具有普遍性.

  4. GABA in Paraventricular Nucleus Regulates Adipose Afferent Reflex in Rats.

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    Lei Ding

    Full Text Available Chemical stimulation of white adipose tissue (WAT induces adipose afferent reflex (AAR, and thereby causes a general sympathetic activation. Paraventricular nucleus (PVN is important in control of sympathetic outflow. This study was designed to investigate the role of γ-aminobutyric acid (GABA in PVN in regulating the AAR.Experiments were carried out in anesthetized rats. Renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP were continuously recorded. AAR was evaluated by the RSNA and MAP responses to electrical stimulation of the right epididymal WAT (eWAT afferent nerve. Electrical stimulation of eWAT afferent nerve increase RSNA. Bilateral microinjection of the GABAA receptor agonist isoguvacine or the GABAB receptor agonist baclofen attenuated the AAR. The effect of isoguvacine on the AAR was greater than that of baclofen. The GABAA receptor antagonist gabazine enhanced the AAR, while the GABAB receptor antagonist CGP-35348 had no significant effect on the AAR. Bilateral PVN microinjection of vigabatrin, a selective GABA-transaminase inhibitor, to increase endogenous GABA levels in the PVN abolished the AAR. The inhibitory effect of vigabatrin on the AAR was attenuated by the pretreatment with gabazine or CGP-35348. Pretreatment with combined gabazine and CGP-35348 abolished the effects of vigabatrin.Activation of GABAA or GABAB receptors in the PVN inhibits the AAR. Blockade of GABAA receptors in the PVN enhances the AAR. Endogenous GABA in the PVN plays an important role in regulating the AAR.

  5. Developmental changes in GABAergic actions and seizure susceptibility in the rat hippocampus.

    Science.gov (United States)

    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.

  6. GABA mediated excitation in immature rat CA3 hippocampal neurons.

    Science.gov (United States)

    Cherubini, E; Rovira, C; Gaiarsa, J L; Corradetti, R; Ben Ari, Y

    1990-01-01

    Intracellular recordings from rat hippocampal neurons in vitro during the first postnatal week revealed the presence of spontaneous giant depolarizing potentials (GDPs). These were generated by the synchronous discharge of a population of neurons. GDPs reversed polarity at -27 and -51 mV when recorded with KCl or K-methylsulphate filled electrodes, respectively. GDPs were blocked by the GABAA receptor antagonist bicuculline (10 microM). Iontophoretic or bath applications of GABA (10-300 microM) in the presence of tetrodotoxin (1 microM), induced a membrane depolarization or in voltage clamp experiments an inward current which reversed polarity at the same potential as GDPs. The response to GABA was blocked in a non-competitive manner by bicuculline (10 microM) and did not desensitize. GABA mediated GDPs were presynaptically modulated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Their frequency was reduced or blocked by NMDA receptor antagonists and by the rather specific non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The frequency of GDPs was enhanced by glycine and D-serine (10-30 microM) in a strychnine insensitive manner. This effect was blocked by AP-5, suggesting that it was mediated by the allosteric modulatory site of the NMDA receptor. These observations suggest that most of the 'excitatory' drive in immature neurons is mediated by GABA acting on GABAA receptors; furthermore excitatory amino acids modulate the release of GABA by a presynaptic action on GABAergic interneurons.

  7. GABA B receptor subunit expression in glia.

    Science.gov (United States)

    Charles, K J; Deuchars, J; Davies, C H; Pangalos, M N

    2003-09-01

    GABA(B) receptor subunits are widely expressed on neurons throughout the CNS, at both pre- and postsynaptic sites, where they mediate the late, slow component of the inhibitory response to the major inhibitory neurotransmitter GABA. The existence of functional GABA(B) receptors on nonneuronal cells has been reported previously, although the molecular composition of these receptors has not yet been described. Here we demonstrate for the first time, using immunohistochemistry the expression of GABA(B1a), GABA(B1b), and GABA(B2) on nonneuronal cells of the rat CNS. All three principle GABA(B) receptor subunits were expressed on these cells irrespective of whether they had been cultured or found within brain tissue sections. At the ultrastructural level GABA(B) receptor subunits were expressed on astrocytic processes surrounding both symmetrical and assymetrical synapses in the CA1 subregion of the hippocampus. In addition, GABA(B1a), GABA(B1b), and GABA(B2) receptor subunits were expressed on activated microglia in culture but were not found on myelin forming oligodendrocytes in the white matter of rat spinal cord. Together these data demonstrate that the obligate subunits of functional GABA(B) receptors are expressed in astrocytes and microglia in the rat CNS.

  8. GABA transporter subtype 1 and GABA transporter subtype 3 modulate glutamatergic transmission via activation of presynaptic GABA(B) receptors in the rat globus pallidus.

    Science.gov (United States)

    Jin, Xiao-Tao; Paré, Jean-Francois; Smith, Yoland

    2012-08-01

    The intra-pallidal application of γ-aminobutyric acid (GABA) transporter subtype 1 (GAT-1) or GABA transporter subtype 3 (GAT-3) transporter blockers [1-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid hydrochloride (SKF 89976A) or 1-[2-[tris(4-methoxyphenyl)methoxy]ethyl]-(S)-3-piperidinecarboxylic acid (SNAP 5114)] reduces the activity of pallidal neurons in monkey. This effect could be mediated through the activation of presynaptic GABA(B) heteroreceptors in glutamatergic terminals by GABA spillover following GABA transporter (GAT) blockade. To test this hypothesis, we applied the whole-cell recording technique to study the effects of SKF 89976A and SNAP 5114 on evoked excitatory postsynaptic currents (eEPSCs) in the presence of gabazine, a GABA(A) receptor antagonist, in rat globus pallidus slice preparations. Under the condition of postsynaptic GABA(B) receptor blockade by the intra-cellular application of N-(2,6-dimethylphenylcarbamoylmethyl)-triethylammonium bromide (OX314), bath application of SKF 89976A (10 μM) or SNAP 5114 (10 μM) decreased the amplitude of eEPSCs, without a significant effect on its holding current and whole cell input resistance. The inhibitory effect of GAT blockade on eEPSCs was blocked by (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl)phosphinic acid, a GABA(B) receptor antagonist. The paired-pulse ratio of eEPSCs was increased, whereas the frequency, but not the amplitude, of miniature excitatory postsynaptic currents was reduced in the presence of either GAT blocker, demonstrating a presynaptic effect. These results suggest that synaptically released GABA can inhibit glutamatergic transmission through the activation of presynaptic GABA(B) heteroreceptors following GAT-1 or GAT-3 blockade. In conclusion, our findings demonstrate that presynaptic GABA(B) heteroreceptors in putative glutamatergic subthalamic afferents to the globus pallidus are sensitive to increases in extracellular GABA induced

  9. Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes.

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    Suresh K Mendu

    Full Text Available γ-Aminobutyric acid (GABA is the most prominent neuroinhibitory transmitter in the brain, where it activates neuronal GABA-A receptors (GABA-A channels located at synapses and outside of synapses. The GABA-A receptors are primary targets of many clinically useful drugs. In recent years, GABA has been shown to act as an immunomodulatory molecule. We have examined in human, mouse and rat CD4(+ and CD8(+ T cells which subunit isoforms of the GABA-A channels are expressed. The channel physiology and drug specificity is dictated by the GABA-A receptor subtype, which in turn is determined by the subunit isoforms that make the channel. There were 5, 8 and 13 different GABA-A subunit isoforms identified in human, mouse and rat CD4(+ and CD8(+ T cells, respectively. Importantly, the γ2 subunit that imposes benzodiazepine sensitivity on the GABA-A receptors, was only detected in the mouse T cells. Immunoblots and immunocytochemistry showed abundant GABA-A channel proteins in the T cells from all three species. GABA-activated whole-cell transient and tonic currents were recorded. The currents were inhibited by picrotoxin, SR95531 and bicuculline, antagonists of GABA-A channels. Clearly, in both humans and rodents T cells, functional GABA-A channels are expressed but the subtypes vary. It is important to bear in mind the interspecies difference when selecting the appropriate animal models to study the physiological role and pharmacological properties of GABA-A channels in CD4(+ and CD8(+ T cells and when selecting drugs aimed at modulating the human T cells function.

  10. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    Science.gov (United States)

    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 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.

  11. Control of GABA Release at Mossy Fiber-CA3 Connections in the Developing Hippocampus.

    Science.gov (United States)

    Safiulina, Victoria F; Caiati, Maddalena D; Sivakumaran, Sudhir; Bisson, Giacomo; Migliore, Michele; Cherubini, Enrico

    2010-01-01

    In this review some of the recent work carried out in our laboratory concerning the functional role of GABAergic signalling at immature mossy fibres (MF)-CA3 principal cell synapses has been highlighted. While in adulthood MF, the axons of dentate gyrus granule cells release onto CA3 principal cells and interneurons glutamate, early in postnatal life they release GABA, which exerts into targeted cells a depolarizing and excitatory action. We found that GABA(A)-mediated postsynaptic currents (MF-GPSCs) exhibited a very low probability of release, were sensitive to L-AP4, a group III metabotropic glutamate receptor agonist, and revealed short-term frequency-dependent facilitation. Moreover, MF-GPSCs were down regulated by presynaptic GABA(B) and kainate receptors, activated by spillover of GABA from MF terminals and by glutamate present in the extracellular medium, respectively. Activation of these receptors contributed to the low release probability and in some cases to synapses silencing. By pairing calcium transients, associated with network-driven giant depolarizing potentials or GDPs (a hallmark of developmental networks thought to represent a primordial form of synchrony between neurons), generated by the synergistic action of glutamate and GABA with MF activation increased the probability of GABA release and caused the conversion of silent synapses into conductive ones suggesting that GDPs act as coincident detector signals for enhancing synaptic efficacy. Finally, to compare the relative strength of CA3 pyramidal cell output in relation to their MF glutamatergic or GABAergic inputs in adulthood or in postnatal development, respectively, a realistic model was constructed taking into account different biophysical properties of these synapses.

  12. Sodium-independent, bicuculline-sensitive (/sup 3/H)GABA binding to isolated rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Minuk, G.Y.; Bear, C.E.; Sarjeant, E.J.

    1987-05-01

    To determine whether hepatocytes possess specific receptor sites for gamma-aminobutyric acid (GABA), a potent amino acid neurotransmitter, (/sup 3/H)GABA, was added to sodium-free suspensions of Percoll-purified hepatocytes derived from collagenase-perfused rat livers under various experimental conditions and in the presence or absence of specific GABA receptor agonists (muscimol) and antagonists (bicuculline). The effects of GABA, muscimol, and bicuculline on hepatocyte resting membrane potentials were also determined. Specific binding of (/sup 3/H)GABA to hepatocytes was a consistent finding. GABA-hepatocyte interactions were reversible and temperature dependent. Muscimol and bicuculline inhibited binding in a dose-dependent manner (IC50, 30 nM and 50 microM, respectively), whereas strychnine (1.0-100 microM), a nonspecific central nervous system stimulant, had no appreciable effect. Both GABA and muscimol (100 microM) caused significant hyperpolarization of hepatocyte resting membrane potential (delta PD 5.4 +/- 3.1 and 22.2 +/- 16.2 mV, respectively, means +/- SD, P less than 0.0005). Bicuculline (100 microM) inhibited the effect of muscimol (P less than 0.05). The results of this study suggest that specific GABA receptor sites exist on the surface of isolated rat hepatocytes. The presence of such sites raises the possibility that, in addition to adrenergic and cholinergic innervation, hepatic function may be influenced by GABA-ergic neurotransmitter mechanisms.

  13. Distribution of GABA-like immunoreactivity in the rat amygdaloid complex.

    Science.gov (United States)

    Nitecka, L; Ben-Ari, Y

    1987-12-01

    The distribution of GABA-like (GABA-Li) immunoreactivity in the rat amygdaloid complex was studied by using an anti-GABA antibody. GABA-Li positive neurons and processes were present in every nucleus of the complex. Three patterns of immunoreactivity were revealed: (1) the intercalated masses and the lateral olfactory tract nucleus exhibited the most intense staining of the neuropil, and virtually every neuron was labeled, (2) the central and medial nuclei contained intensely labeled neuropil and moderately labeled neurons, and (3) in the remaining nuclei, the neuropil was weakly labeled, and relatively numerous GABA-Li neurons were present. Our results suggest that: (1) the intercalated masses and lateral olfactory tract nucleus consist of large aggregates of GABA-Li immunoreactive neurons, and (2) the lateral, basal dorsal, and the posterior cortical nuclei may constitute a significant source of GABAergic connections to other amygdaloid nuclei, in particular to the medial and central nuclei.

  14. GABAB receptor blockade enhances theta and gamma rhythms in the hippocampus of behaving rats.

    Science.gov (United States)

    Leung, L Stan; Shen, Bixia

    2007-01-01

    The participation of GABA(B) receptors in hippocampal EEG generation was studied by intracerebroventricular (icv) and intracerebral infusions of GABA(B) receptor antagonist p-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid (CGP35348) in freely behaving rats. During awake-immobility, icv CGP35348 induced a theta rhythm and increased gamma waves (30-100 Hz) in the hippocampus. The immobility theta peaked at 6-7 Hz and had a theta phase in CA1 stratum radiatum of approximately 160 degrees with reference to the theta at the alveus, when compared with approximately 130 degrees during walking. Immobility theta power peaks at 6-7 Hz was also found in normal rats, and it was detected in 27% of the EEG segments during immobility. Incidence of immobility theta increased to 87.5% after 480 nmol of CGP35348 icv. Muscarinic antagonist scopolamine (5 mg/kg, ip) suppressed the induction of immobility theta and the gamma power increase after icv CGP35348. CGP35348 icv did not significantly change the hippocampal theta power at 7-8 Hz during walking (theta fundamental), but it increased power at 12-15 Hz, at the second harmonic of theta. CGP35348 icv also increased 30-50 Hz gamma power during walking. Medial septal infusion of CGP35348 (12 nmol in 0.4 microl) increased the power and the frequency of the hippocampal theta second harmonic during walking, but did not increase gamma activity. Infusion of CGP35348 (8 nmol in 0.4 microl) in the hippocampus increased the local gamma activity at 30-100 Hz, but did not induce immobility theta or affect the walking theta rhythm. In conclusion, icv GABA(B) receptor blockade increased an atropine-sensitive input that generated an immobility theta rhythm, while GABA(B) receptor blockade of the medial septum increased atropine-resistant theta harmonics possibly generated by apical dendritic spikes. GABA(B) receptor blockade may enhance cognitive task performance by activating hippocampal theta and gamma rhythms in behaving rats.

  15. Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.

    Science.gov (United States)

    Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie-Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania

    2015-12-01

    Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life.

  16. Deficits in parvalbumin and calbindin immunoreactive cells in the hippocampus of isolation reared rats.

    Science.gov (United States)

    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.

  17. Spontaneous synaptic activity is required for the formation of functional GABAergic synapses in the developing rat hippocampus.

    Science.gov (United States)

    Colin-Le Brun, Isabelle; Ferrand, Nadine; Caillard, Olivier; Tosetti, Patrizia; Ben-Ari, Yehezkel; Gaïarsa, Jean-Luc

    2004-08-15

    Here we examine the role of the spontaneous synaptic activity generated by the developing rat hippocampus in the formation of functional gamma-aminobutyric acid (GABA) synapses. Intact hippocampal formations (IHFs) were dissected at birth and incubated for 1 day in control or tetrodotoxin (TTX)-supplemented medium at 25 degrees C. After the incubation, miniature GABA(A)-mediated postsynaptic currents (mGABA(A)-PSCs) were recorded in whole-cell voltage-clamped CA3 pyramidal neurones from IHF-derived slices. After 1 day in vitro in control medium, the frequency of mGABA(A)-PSCs was similar to that recorded in acute slices obtained 1 day after birth, but significantly higher than the frequency recorded from acute slices just after birth. These results suggest that the factors required in vivo for the formation of functional GABAergic synapses are preserved in the IHFs in vitro. The frequency increase was prevented when IHFs were incubated for 1 day with TTX. TTX treatment affected neither the morphology of CA3 pyramidal neurones nor cell viability. The TTX effects were reproduced when IHFs were incubated in the presence of glutamatergic or GABAergic ionotropic receptor antagonists or in high divalent cationic medium. The present results indicate that the spontaneous synaptic activity generated by the developing hippocampus is a key player in the formation of functional GABAergic synapses, possibly via network events requiring both glutamatergic and GABAergic receptors.

  18. Control of GABA release at single mossy fiber-CA3 connections in the developing hippocampus

    Directory of Open Access Journals (Sweden)

    Victoria F Safiulina

    2010-02-01

    Full Text Available In this review some of the recent work carried out in our laboratory concerning the functional role of GABAergic signalling at immature mossy fibres (MF-CA3 principal cell synapses has been highlighted. While in adulthood MF, the axons of dentate gyrus granule cells release onto CA3 principal cells and interneurons glutamate, early in postnatal life they release GABA, which exerts into targeted cells a depolarizing and excitatory action. We found that GABAA-mediated postsynaptic currents (MF-GPSCs exhibited a very low probability of release, were sensitive to L-AP4, a group III metabotropic glutamate receptor agonist, and revealed short-term frequency-dependent facilitation. Moreover, MF-GPSCs were down regulated by presynaptic GABAB and kainate receptors, activated by spillover of GABA from MF terminals and by glutamate present in the extracellular medium, respectively. Activation of these receptors contributed to the low release probability and in some cases to synapses silencing. By pairing calcium transients, associated with network-driven giant depolarizing potentials or GDPs (a hallmark of developmental networks thought to represent a primordial form of synchrony between neurons, generated by the synergistic action of glutamate and GABA with MF activation increased the probability of GABA release and caused the conversion of silent synapses into conductive ones suggesting that GDPs act as coincident detector signals for enhancing synaptic efficacy. Finally, to compare the relative strength of CA3 pyramidal cell output in relation to their MF glutamatergic or GABAergic inputs in adulthood or in postnatal development, respectively, a realistic model was constructed taking into account different biophysical properties of these synapses.

  19. Effect of nitric oxide donor SNAP on GABA release from rat brain nerve terminals

    Directory of Open Access Journals (Sweden)

    A. S. Tarasenko

    2016-10-01

    Full Text Available In this work we investigated the effect of nanomolar concentrations of nitric oxide on the release of gamma-aminobutyric acid (GABA from rat brain nerve terminals using a radioisotope method with [3H]GABA and a spectrofluorimetric method with Ca2+-sensitive probe Fluo-4 AM. It was shown that in the presen­ce of dithiothreitol (DTT, nitric oxide donor SNAP at concentration, in which it produces NO in the nanomolar range, caused Ca2+-independent [3H]GABA release from nerve terminals. The applications of 4-aminopyridine (4-AP and nipecotic acid (NA, as the inducers of GABA release from vesicular and cytoplasmic pools, showed that the maximum of SNAP/+DTT-induced [3H]GABA release was registered at 10th min of incubation and coincided in time with significant increase (almost double in NA-induced [3H]GABA release. At this time point, 4-AP-induced release of [3H]GABA was drastically reduced. At the 15th min of incubation of nerve terminals with SNAP/+DTT, the opposite picture was observed: the decrease in NA- and increase in 4-AP-induced [3H]GABA release. Thus, nitric oxide in the form of S-nitrosothiols at nanomolar concentrations causes Ca2+-independent GABA leakage from synaptic vesicles into cytosol with subsequent release from nerve terminals. The reuptake of the neurotransmitter and its re-accumulation in synaptic vesicles occur later.

  20. Regulation of /sup 3/H-dopamine release by presynaptic GABA and glutamate heteroreceptors in rat brain nucleus accumbens synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Kovalev, G.I.; Hetey, L.

    1987-06-01

    The aim of this investigation was a neurochemical study of the effect of agonists of different types of GABA receptors - muscimol (type A receptor), baclofen (type B receptor), delta-aminolevulinic acid (DALA; GABA autoreceptor), and also of GABA itself - on tritium-labelled dopamine release, stimulated by potassium cations, from synaptosomes of the nuclei accumbenes of the rat brain.

  1. THE SIGNIFICANCE OF EXTRACELLULAR GABA IN THE SUBSTANTIA-NIGRA OF THE RAT DURING SEIZURES AND ANTICONVULSANT TREATMENTS

    NARCIS (Netherlands)

    SAYIN, U; TIMMERMAN, W; WESTERINK, BHC

    1995-01-01

    The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA (vigabatrin) on the extracellular content of GABA was determined by microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4-6-fold

  2. THE SIGNIFICANCE OF EXTRACELLULAR GABA IN THE SUBSTANTIA-NIGRA OF THE RAT DURING SEIZURES AND ANTICONVULSANT TREATMENTS

    NARCIS (Netherlands)

    SAYIN, U; TIMMERMAN, W; WESTERINK, BHC

    1995-01-01

    The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA (vigabatrin) on the extracellular content of GABA was determined by microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4-6-fold inc

  3. Cold-induced thermogenesis mediated by GABA in the preoptic area of anesthetized rats.

    Science.gov (United States)

    Osaka, Toshimasa

    2004-08-01

    Bilateral microinjections of GABA (300 mM, 100 nl) or the GABA(A) receptor agonist muscimol (100 microM, 100 nl) into the preoptic area (POA) of the hypothalamus increased the rate of whole body O(2) consumption (VO(2)) and the body core (colonic) temperature of urethane-chloralose-anesthetized, artificially ventilated rats. The most sensitive site was the dorsomedial POA at the level of the anterior commissure. The GABA-induced thermogenesis was accompanied by a tachycardic response and electromyographic (EMG) activity recorded from the femoral or neck muscles. Pretreatment with muscle relaxants (1 mg/kg pancuronium bromide + 4 mg/kg vecuronium bromide i.v.) prevented GABA-induced EMG activity but had no significant effect on GABA-induced thermogenesis. However, pretreatment with the beta-adrenoceptor propranolol (5 mg/kg i.v.) greatly attenuated the GABA-induced increase in VO(2) and tachycardic responses. Accordingly, the GABA-induced increase in VO(2) reflected mainly nonshivering thermogenesis. On the other hand, cooling of the shaved back of the rat by contact with a plastic bag containing 28 degrees C water also elicited thermogenic, tachycardic, and EMG responses. Bilateral microinjections of the GABA(A) receptor antagonist bicuculline (500 microM, 100 nl), but not the vehicle saline, into the POA blocked these skin cooling-induced responses. These results suggest that GABA and GABA(A) receptors in the POA mediate cold information arising from the skin for eliciting cold-induced thermogenesis.

  4. Changes of GABA A Receptor α1 Subunit mRNA and [3H] Flunirazepam Binding in Animal Model of Status Epileptic Rats

    Institute of Scientific and Technical Information of China (English)

    Qinchi Lu

    2000-01-01

    OBJECTIVE: In the present study, we determinded whether status epilepticus or prolonged limbic seizures ( induced by pilocarpine) altered GABA A receptor αl subunit gene expression m the hippocanpus. BACKGROUND: A decrease in GABAergic inhibition during epileptogenesis plays an imprortant role in the development of persistent hyperexcitability observed during chronic epilepsy. METHODS: Stares epilepticus was reduced in male adult rats by a single i.p. injection ofpilocarpine (320-340 mg/kg). Rats that survived status epilepticus ( definded as continous seizure activity in the EcoG for at least 40 min) for 1 h and 2 h were sacrificed for GABA A receptor gene expression and binding assay. In situ hybridization was used to measure regional mRNA levels, and [3H] flunirazepam used to label the benzodiazepine binding sites. RESULTS: We found that 2h after the onset of seizure, GABA A receptor α1 m RNA decresed significarntly in the CA1 and CA3 fields of hippocampus. No significant change in ctl mRNA was observed in the dentate gyrus. However, [3H] flunirazepam binding decreased uniformly in CA l, CA3 and dentate gyrus 2h after status epfileptius. 1 h ofcontinuous seizures did not produce any significant change in either αl mRNA or [3H] flunirazepam birding in any of the hippocampal regions studied. Cresyl violet staining of the brain hippocampus areas lh or 2h after the seizure-onset. DISCUSSION: The above changes make the brain more susceptible for the development of chronic epilepsy. CONCLUSION: These results suggest that status epilepticus-induced decreased in GABA A recepor αl gene expression and [3H] flunirazepam binding in the hippocampus.

  5. Segregation of acetylcholine and GABA in the rat superior cervical ganglia: functional correlation.

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    Diana eElinos

    2016-04-01

    Full Text Available Sympathetic neurons have the capability to segregate their neurotransmitters (NTs and co-transmitters to separate varicosities of single axons; furthermore, in culture, these neurons can even segregate classical transmitters. In vivo sympathetic neurons employ acetylcholine (ACh and other classical NTs such as gamma aminobutyric acid (GABA. Herein, we explore whether these neurons in vivo segregate these classical NTs in the superior cervical ganglia of the rat. We determined the topographical distribution of GABAergic varicosities, somatic GABAA receptor, as well as the regional distribution of the segregation of ACh and GABA. We evaluated possible regional differences in efficacy of ganglionic synaptic transmission, in the sensitivity of GABAA receptor to GABA and to the competitive antagonist picrotoxin (PTX. We found that sympathetic preganglionic neurons in vivo do segregate ACh and GABA. GABAergic varicosities and GABAA receptor expression showed a rostro-caudal gradient along ganglia; in contrast, segregation exhibited a caudo-rostral gradient. These uneven regional distributions in expression of GABA, GABAA receptors, and level segregation correlate with stronger synaptic transmission found in the caudal region. Accordingly, GABAA receptors of rostral region show larger sensitivity to GABA and PTX. These results suggest the presence of different types of GABAA receptors in each region that result in a different regional levels of endogenous GABA inhibition. Finally, we discuss a possible correlation of these different levels of GABA modulation and the function of the target organs innervated by rostral and caudal ganglionic neurons.

  6. The effects of thioperamide on extracellular levels of glutamate and GABA in the rat prefrontal cortex.

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    Welty, Natalie; Shoblock, James R

    2009-12-01

    Histamine H3 receptors (H3R) are presynaptic heteroreceptors that negatively modulate the release of histamine and other neurotransmitters such as acetylcholine. Blocking H3 receptors with antagonists/inverse agonists has been shown to be procognitive and this effect has often been associated with increases in acetylcholine transmission. H3 receptors are abundantly expressed in the prefrontal cortex, an area associated with cognitive performance. While the procognitive effects of H3 receptor antagonists/inverse agonists may depend on alterations to acetylcholine or histamine release, other transmitters involved in cognitive processing such as glutamate and gamma-aminobutyric acid (GABA) may also be involved. The purpose of the present study was to examine the effects of thioperamide, an H3 receptor antagonist, on extracellular levels of glutamate and GABA in the prefrontal cortex. By means of in vivo microdialysis on freely moving Sprague Dawley rats, samples were collected and assayed via high-performance liquid chromatography coupled to electrochemical detection. Replacement of calcium with magnesium revealed that the release of GABA, but not glutamate, was calcium-dependent. Thioperamide (10-20 mg/kg) did not affect basal glutamate or GABA release. Perfusion with a high concentration of potassium (100 mM) increased GABA, but not glutamate, release and thioperamide (20 mg/kg) attenuated the effects of high potassium on GABA release. These data indicate that H3 receptors in the prefrontal cortex can enhance stimulated GABA release, but do not regulate basal levels of glutamate or GABA.

  7. Temperature dependence and GABA modulation of (TH)triazolam binding in the rat brain

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    Earle, M.E.; Concas, A.; Wamsley, J.K.; Yamamura, H.I.

    1987-07-27

    The hypnotic triazolam (TZ), a triazolobenzodiazepine displays a short physiological half life and has been used for the treatment of insomnia related to anxiety states. The authors major objectives were the direct measurement of the temperature dependence and the gamma-aminobutyric acid (GABA) effect of (TH)TZ binding in the rat brain. Saturation studies showed a shift to lower affinity with increasing temperatures (K/sub d/ = 0.27 +/- 08 nM at 0C; K/sub d/ = 1.96 +/- 0.85 nM at 37C) while the B/sub max/ values remained unchanged (1220 +/- 176 fmoles/mg protein at 0C and 1160 +/- 383 fmoles/mg protein at 37C). Saturation studies of (TH)TZ binding in the presence or absence of GABA (100 M) showed a GABA-shift. At 0C the K/sub d/ values were (K/sub d/ = 0.24 +/- 0.03 nM/-GABA; K/sub d/ = 0.16 +/- 0.04/+GABA) and at 37C the K/sub d/ values were (K/sub d/ = 1.84 +/- 0.44 nM/-GABA; K/sub d/ = 0.95 +/- 0.29 nM/+GABA). In contrast to reported literature, the authors findings show that TZ interacts with benzodiazepine receptors with a temperature dependence and GABA-shift consistent with predicted behavior for benzodiazepine agonists. 20 references, 3 tables.

  8. GABA-ERGIC NEURONS IN THE RAT STRIATUM UNDER NORMAL AND ISCHEMIC INJURY

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    E.S. Petrova

    2013-09-01

    Full Text Available Gamma-aminobutyric acid (GABA is a major inhibitory neurotransmitter in the central nervous system. Enzyme glutamate decarboxylase (GAD-67 is a marker of GABA-ergic neurons. The purpose of this study is to examine the distribution of GAD-67-immunopositive neurons in the striatum of rats under experimental conditions, reproducing brief focal cerebral ischemia. Endovascular occlusion of the left middle cerebral artery in rats was performed. Duration of circulatory disorders was 30 min, the time of reperfusion was 48 hours. With counting GAD-67-immunopositive neurons in the striatum was found that the number of GABA-ergic neurons in the striatum ipsilateral hemisphere is reduced by 40%. In the contralateral hemisphere, the distribution and structure of the neurons is not different from controls. It is shown that GABA-ergic neurons are less susceptible to damage, as compared to other neurons phenotypes.

  9. MORPHOLOGICAL CHANGES IN THE HIPPOCAMPUS OF RATS IN ACCELERATED AGING

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    K. Yu. Maksimova

    2014-01-01

    Full Text Available The aim of this work was the analysis of structural changes with age in the hippocampus of senescenceaccelerated OXYS rats when signs of accelerated brain aging are missing (age 14 days, developments (age 5 months, and active progresses (age 15 months. The study was performed on 15 OXYS rats and 15 Wistar rats (as a control. After dislocation, brains were dissected, fixed with 10% formalin, embedded in paraffin, and serially cut in coronal sections (5μm thickness. These sections were stained with Cresyl violet and examined with a photomicroscope (Carl Zeiss Axiostar plus, Germany. The total number of hippocampal pyramidal cells in the CA1, CA3 and the dentate gyrus regions were estimated in 14-dayold, 5and 15-month-old OXYS and Wistar rats (n = 5 on the 5 slices of each brain sections. The number of neurons with chromatolysis, hyperchromatic with darkly stained cytoplasm and shrunken neurons were calculated as degenerative neurons. The pictures obtained with the program Carl Zeiss Axio Vision 8.0 with increasing 10  100, determined the average area bodies and nuclei of neurons (mkm2. The significant structural changes of neurons in the CA1, CA3 and dentate gyrus regions of the hippocampus in OXYS rats at 5 month of age are revealed by light microscopy. This results indicates the early develop neurodegeneration in OXYS rats. The most pronounced morphological changes occur in the CA1 region of the hippocampus of OXYS rats and irreversible. The degenerative changes of neurons in the hippocampus increases by the age of 15 months. Morphometric analysis of the average area of bodies and the nuclei of hippocampal neurons in CA1, CA3 and the dentate gyrus regions of OXYS and Wistar rats at 14 days of age showed no significant interline differences. At 5 months of age in the CA1 region of the hippocampus of OXYS rats was determined a significantly lower average body size and nuclei of pyramidal neurons compared with Wistar rats. With age, these

  10. Non-granule PSA-NCAM immunoreactive neurons in the rat hippocampus.

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    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.

  11. Activation of presynaptic and postsynaptic ryanodine-sensitive calcium stores is required for the induction of long-term depression at GABAergic synapses in the neonatal rat hippocampus.

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

    2000-09-01

    The role of internal calcium stores in the induction of long-term depression at GABAergic synapses was investigated in the neonatal rat hippocampus. Whole-cell recordings of CA3 pyramidal neurons were performed on hippocampal slices from neonatal (2-4 d old) rats. In control conditions, tetanic stimulation (TS) evoked an NMDA-dependent long-term depression of GABA(A) receptor-mediated postsynaptic responses (LTD(GABA-A)). LTD(GABA-A) was prevented when the cells were loaded with ruthenium red, a blocker of Ca2+-induced Ca2+ release (CICR) stores, whereas loading the cells with heparin, a blocker of IP3-induced Ca2+ release stores, had no effect. The effects of ryanodine, another compound that interferes with CICR stores, were also investigated. Intracellular injection of ryanodine prevented the induction of LTD(GABA-A) only when the TS was preceded by depolarizing pulses that increase intracellular Ca2+ concentration. When applied in the bath, ryanodine prevented the induction of LTD(GABA-A). Altogether, these results suggest that ryanodine acts as a Ca2+-dependent blocker of CICR stores and that the induction of LTD(GABA-A) required the activation of both presynaptic and postsynaptic CICR stores.

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

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    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

  13. Ethanol affects network activity in cultured rat hippocampus: mediation by potassium channels.

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    Eduard Korkotian

    Full Text Available 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.

  14. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters.

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    Jolivalt, Corinne G; Lee, Corinne A; Ramos, Khara M; Calcutt, Nigel A

    2008-11-15

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored the role of the GABA(A) receptor in rats with painful diabetic neuropathy. KCC2 protein levels were significantly reduced in the spinal cord of diabetic rats, while levels of NKCC1 and the GABA(A) receptor were unchanged. Spinal delivery of the GABA(A) receptor antagonist bicuculline reduced formalin-evoked flinching in diabetic rats and also dose-dependently alleviated tactile allodynia. GABA(A) receptor-mediated rate-dependent depression of the spinal H reflex was absent in the spinal cord of diabetic rats. Control rats treated with the KCC2 blocker DIOA, mimicked diabetes by showing increased formalin-evoked flinching and diminished rate- dependent depression. The ability of bicuculline to alleviate allodynia and formalin-evoked hyperalgesia in diabetic rats is consistent with a reversal of the properties of GABA predicted by reduced spinal KCC2 and suggests that reduced KCC2 expression and increased GABA release contribute to spinally mediated hyperalgesia in diabetes.

  15. Neuronal mechanisms of the anoxia-induced network oscillations in the rat hippocampus in vitro.

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    Dzhala, V; Khalilov, I; Ben-Ari, Y; Khazipov, R

    2001-10-15

    1. A spindle of fast network oscillations precedes the ischaemia-induced rapid depolarisation in the rat hippocampus in vivo. However, this oscillatory pattern could not be reproduced in slices and the underlying mechanisms remain poorly understood. We have found that anoxia-induced network oscillations (ANOs, 20-40 Hz, lasting for 1-2 min) can be reproduced in the intact hippocampi of postnatal day P7-10 rats in vitro, and we have examined the underlying mechanisms using whole-cell and extracellular field potential recordings in a CA3 pyramidal layer. 2. ANOs were generated at the beginning of the anoxic depolarisation, when pyramidal cells depolarised to subthreshold values. Maximal power of the ANOs was attained when pyramidal cells depolarised to -56 mV; depolarisation above -47 mV resulted in a depolarisation block of pyramidal cells and a waning of ANOs. 3. A multiple unit activity in extracellular field recordings was phase locked to the negative and ascending phases of ANOs. Pyramidal cells recorded in current-clamp mode generated action potentials with an average probability of about 0.05 per cycle. The AMPA receptor-mediated EPSCs and the GABA receptor-mediated IPSCs in CA3 pyramidal cells were also phase locked with ANOs. 4. ANOs were prevented by tetrodotoxin and glutamate receptor antagonists CNQX and APV, and were slowed down by the allosteric GABA(A) receptor modulator diazepam. In the presence of the GABA(A) receptor antagonist bicuculline, ANOs were transformed to epileptiform discharges. 5. In the presence of the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), the anoxia induced an epileptiform activity and no ANOs were observed. 6. In normoxic conditions, a rise of extracellular potassium to 10 mM induced an epileptiform activity. Increasing extracellular potassium in conjunction with a bath application of the adenosine A1 receptor agonist cyclopentyladenosine induced oscillations similar to ANOs. 7. Multisite

  16. Valerian inhibits rat hepatocarcinogenesis by activating GABA(A receptor-mediated signaling.

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    Anna Kakehashi

    Full Text Available Valerian is widely used as a traditional medicine to improve the quality of sleep due to interaction of several active components with the γ-aminobutyric acid (GABA A receptor (GABA(AR system. Recently, activation of GABA signaling in stem cells has been reported to suppress cell cycle progression in vivo. Furthermore, possible inhibitory effects of GABA(AR agonists on hepatocarcinogenesis have been reported. The present study was performed to investigate modulating effects of Valerian on hepatocarcinogenesis using a medium-term rat liver bioassay. Male F344 rats were treated with one of the most powerful Valerian species (Valeriana sitchensis at doses of 0, 50, 500 and 5000 ppm in their drinking water after initiation of hepatocarcinogenesis with diethylnitrosamine (DEN. Formation of glutathione S-transferase placental form positive (GST-P(+ foci was significantly inhibited by Valerian at all applied doses compared with DEN initiation control rats. Generation of 8-hydroxy-2'-deoxyguanosine in the rat liver was significantly suppressed by all doses of Valerian, likely due to suppression of Nrf2, CYP7A1 and induction of catalase expression. Cell proliferation was significantly inhibited, while apoptosis was induced in areas of GST-P(+ foci of Valerian groups associated with suppression of c-myc, Mafb, cyclin D1 and induction of p21(Waf1/Cip1, p53 and Bax mRNA expression. Interestingly, expression of the GABA(AR alpha 1 subunit was observed in GST-P(+ foci of DEN control rats, with significant elevation associated with Valerian treatment. These results indicate that Valerian exhibits inhibitory effects on rat hepatocarcinogenesis by inhibiting oxidative DNA damage, suppressing cell proliferation and inducing apoptosis in GST-P(+ foci by activating GABA(AR-mediated signaling.

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

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

    2008-08-15

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

  18. Modulatory effect of substance P on GABA-activated currents from rat dorsal root ganglion

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    Jun-qiang SI; Zhi-qin ZHANG; Chun-xia LI; Li-feng WANG; Yun-lei YANG; Zhi-wang LI

    2004-01-01

    AIM: To explore the modulatory effect of substance P (SP) on GABA-activated current of dorsal root ganglion (DRG) neurons in rat. METHODS: The whole-cell patch-clamp technique was used to record SP- and GABAactivated currents in neurons freshly dissociated from rat DRG neurons. Drugs were applied by rapid solution exchange. RESULTS: Application of SP (28/41, 68.5 %) and GABA (36/41, 88.2 %) could induce concentrationdependent inward current in some cells. SP-(10 μmol/L) and GABA (100 μmol/L)-activated inward currents were (244±83) pA (n=9) and (1.8±0.5) nA (n=13), respectively. The majority of GABA-activated current had obvious three processes, the peak value (Ip), the steady state (Iss) and the desensitization (Ia). The desensitization of GABAactivated current was a biphasic process, including fast and slow desensitization. However, pre-application of SP (0.001-1 μmol/L) could inhibit the GABA-activated inward current which was identified to be GABAA receptormediated current. The inhibitory effects were concentration-dependent. The inhibitory effect of SP on the peak value of GABA-activated current was more than the steady state of GABA-activated current. The inhibition of GABA-activated current by SP (0.1 μmol/L) was related to the time after application of SP, the inhibition of GABAactivated currents by SP reached the peak at about 4 min (49.8 %±7.2 %, n=7, P<0.01) and took about 12 min to get a full recovery. The inhibition of GABA-activated currents by SP was almost completely removed after blockade of PKC by H-7 with the re-patch clamp. CONCLUSION: Pre-application of SP exerts a more strong inhibitory effect on the peak value of GABA-activated current than the steady state of GABA-activated current.

  19. Benzodiazepine/GABA receptor complex during severe ethanol intoxication and withdrawal in the rat

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    Hemmingsen, R.; Braestrup, C.; Nielsen, M.; Barry, D.I. (Dept. of Psychiatry, Rigshospitalet, Copenhagen, St. Hans Mental Hospital, Roskilde, and Ferrosan Research Laboratory, Soeborg, Denmark)

    1982-01-01

    The benzodiazepine/GABA (gammaaminobutyric acid) receptor complex was investigated during severe ethanol intoxication and withdrawal in the rat. The intragastric intubation technique was used to establish physical ethanol dependence in the animals. Cerebral cortex from male Wistar rats was studied 1) after 31/2 days of severe ethanol intoxication, 2) during the ethanol withdrawal reaction and 3) in a control group. The effect of GABA-ergic activation by muscimol and THIP (4,5,6,7-tetrahydroisoxazole(5,4-c)pyridin-3-01) on /sup 3/H-diazepam binding was unchanged during ethanol intoxication and withdrawal, as was the affinity constant (Ksub(D)) and the maximal number of binding sites (Bsub(max)) for /sup 3/H-flunitrazepam. In conclusion, the benzodiazepine/GABA receptor complex is unlikely to play any causual part in physical ethanol dependence.

  20. CHANGES OF ZINC CONTAMINATION IN HIPPOCAMPUS CELLS OF ADRENALECTOMIZED RATS

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    Bondaruyk О.А.

    2013-09-01

    Full Text Available Adrenalectomy causes the decline of zinc maintenance in the neurons of hippocampus and B cells of pancreas that has been observed in experiments on rats. The loss of zinc of these cells has been partly compensated by the injection of adrenalin and prednizolon to the adrenalectomized animals. The increase of zinc maintenance in these cells has been caused by the sharp-stress process due to the simultaneous physical activity and immobilization. The given data prove the participation of adrenal glands in the mechanism of zinc exchanges regulation in central (hippocampus and peripheral (cells B of pancreas zinc-containing organs of animals.

  1. Changes in mACh, NMDA and GABA(A) receptor binding after lateral fluid-percussion injury: in vitro autoradiography of rat brain frozen sections.

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    Sihver, S; Marklund, N; Hillered, L; Långström, B; Watanabe, Y; Bergström, M

    2001-08-01

    Adult rats were subjected to a moderate lateral fluid percussion injury (FPI), followed by survival periods of 2 and 12 h. Regional NMDA subtype glutamate, muscarinic acetylcholine and GABA(A) receptor binding in various brain regions was analysed by quantitative in vitro autoradiography and short-lived positron emission tomography tracers [11C]cyano-dizocilpine, 4-N-[11C]methylpiperidylbenzilate (4-N-[11C]MPB), and [11C]flumazenil, respectively. The binding potential (BP, Bmax/KD) was calculated. The data with [11C]cyano-dizocilpine showed a significant decrease in BP bilaterally for the frontoparietal cortex and hippocampus at both time points, in comparison with that of the sham-operated controls. At 12 h the decrease was significantly more prominent for the ipsilateral cortex and hippocampus than for the contralateral side. The BP of 4-N-[11C]MPB was significantly decreased after 2 h for the trauma-side hippocampus, and after 12 h it had decreased for the trauma-site cortex and the bilateral hippocampus. The [11C]flumazenil exhibited a significant decrease in BP for the trauma-site cortex and the underlying hippocampus by 2 h after the traumatic brain injury. After 12 h a significantly decreased BP was observed only for the trauma-site cortex. The finding of a decreased BP demonstrates the involvement of these receptor systems in the development of cellular dysfunction, which is widespread and not limited to the site of lateral FPI.

  2. Repeated dose of ketamine effect to the rat hippocampus tissue

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    Mehtap Okyay Karaca

    2015-01-01

    Full Text Available Aim: We aimed to determine the neurotoxic effect of repeated ketamine administration on brain tissue and if neurotoxic effect was present, whether this effect continued 16 days later using histological stereological method, a quantitative and objective method. Materials and Methods: Female rats were divided into three groups, each containing five rats. Rats in Group I were given 0.9% saline solution 4 times a day for 5 days. The rats in Groups II and III were given ketamine as intraperitoneal injections. Rats in Groups I and II were sacrificed on 5 th day while the ones in Group III on 21 st day. Cornu ammonis (CA and gyrus dentatus (GD regions in hippocampus tissue of rats were studied using optic fractionation method. Findings: There were significantly less number of cells in hippocampal CA and GD regions of rats from Groups II and III compared to the ones from Group I. Difference in cell number was also significantly higher in Group III than in Group II, but this difference was not as pronounced as the one between Groups III and I. Conclusion: Repeated ketamine doses caused neurotoxicity in rat hippocampus.

  3. Axonal sorting of Kir3.3 defines a GABA-containing neuron in the CA3 region of rodent hippocampus.

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    Grosse, Gisela; Eulitz, Dirk; Thiele, Theodor; Pahner, Ingrid; Schröter, Sascha; Takamori, Shigeo; Grosse, Johannes; Wickman, Kevin; Tapp, Rosemarie; Veh, Rüdiger W; Ottersen, Ole Petter; Ahnert-Hilger, Gudrun

    2003-11-01

    Hippocampal interneurons comprise a heterogeneous group of locally acting GABAergic neurons. In addition to their variability in cotransmitter content and receptor profile, they express a variety of potassium channels that specify their individual properties. Here we describe a new type of large GABA-containing neuron in rodent hippocampus that is characterized by an axonal sorting of the potassium channel Kir3.3. The parent cell bodies of the Kir3.3-positive axons are located in CA3, as assessed by primary cultures derived from hippocampal subareas. At postnatal day 14 these neurons appear at the border between stratum oriens and stratum pyramidale of CA3, from where their axons pass through stratum pyramidale to join the mossy fiber tract. In adult hippocampus, high levels of Kir3.3 channel protein exist in axons that run with the mossy fiber tract. Kir3.3 and the vesicular GABA transporter could be identified in subpopulations of large synaptic terminals that probably derive from Kir3.3 neurons. Axonal sorting of Kir3.3 appears to be typical of a group of large inhibitory neurons, including Purkinje cells and a novel type of interneuron in CA3. Kir3.3 neurons might modulate the activity of CA3 circuitries and consequently memory processing in the hippocampus.

  4. Effect of ethanol administration and withdrawal on GABA receptor binding in rat cerebral cortex

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    Volicer, L.; Biagioni, T.M.

    1982-01-01

    Sodium independent GABA receptor binding was measured in synaptosomes prepared from cerebral cortex of rats made ethanol dependent by three daily ethanol administrations. In rats sacrificed 1 hour after the last ethanol dose there was a lower number of low affinity binding sites and lower affinity of the high affinity binding than in controls. The decreased affinity was present only in rats who showed symptoms of ethanol withdrawal during the course of ethanol administration. In rats sacrificed during ethanol withdrawal the affinity of the high affinity binding was lower than in controls and other binding characteristics were unchanged. This decreased binding was normalized by repeated Triton X-100 incubations indicating involvement of an endogenous inhibitor in this ethanol effect. Acute ethanol administration did not change GABA receptor binding.

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

    Institute of Scientific and Technical Information of China (English)

    Eduardo; Ferreira; de; Castro-Neto; Rafael; Henrique; da; Cunha; Dartiu; Xavier; da; Silveira; Mauricio; Yonamine; Telma; Luciana; Furtado; Gouveia; Esper; Abro; Cavalheiro; Débora; Amado; Maria; da; Graa; Naffah-Mazzacoratti

    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 ℃ 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 vs2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION: Our data suggest

  6. Hypocretin/orexin antagonism enhances sleep-related adenosine and GABA neurotransmission in rat basal forebrain.

    Science.gov (United States)

    Vazquez-DeRose, Jacqueline; Schwartz, Michael D; Nguyen, Alexander T; Warrier, Deepti R; Gulati, Srishti; Mathew, Thomas K; Neylan, Thomas C; Kilduff, Thomas S

    2016-03-01

    Hypocretin/orexin (HCRT) neurons provide excitatory input to wake-promoting brain regions including the basal forebrain (BF). The dual HCRT receptor antagonist almorexant (ALM) decreases waking and increases sleep. We hypothesized that HCRT antagonists induce sleep, in part, through disfacilitation of BF neurons; consequently, ALM should have reduced efficacy in BF-lesioned (BFx) animals. To test this hypothesis, rats were given bilateral IgG-192-saporin injections, which predominantly targets cholinergic BF neurons. BFx and intact rats were then given oral ALM, the benzodiazepine agonist zolpidem (ZOL) or vehicle (VEH) at lights-out. ALM was less effective than ZOL at inducing sleep in BFx rats compared to controls. BF adenosine (ADO), γ-amino-butyric acid (GABA), and glutamate levels were then determined via microdialysis from intact, freely behaving rats following oral ALM, ZOL or VEH. ALM increased BF ADO and GABA levels during waking and mixed vigilance states, and preserved sleep-associated increases in GABA under low and high sleep pressure conditions. ALM infusion into the BF also enhanced cortical ADO release, demonstrating that HCRT input is critical for ADO signaling in the BF. In contrast, oral ZOL and BF-infused ZOL had no effect on ADO levels in either BF or cortex. ALM increased BF ADO (an endogenous sleep-promoting substance) and GABA (which is increased during normal sleep), and required an intact BF for maximal efficacy, whereas ZOL blocked sleep-associated BF GABA release, and required no functional contribution from the BF to induce sleep. ALM thus induces sleep by facilitating the neural mechanisms underlying the normal transition to sleep.

  7. A gene-environment study of cytoglobin in the human and rat hippocampus

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Elfving, Betina; Müller, Heidi Kaastrup;

    2013-01-01

    Cygb to be up regulated by hypoxic stress. This study addresses three main questions related to Cygb expression in the hippocampus: 1) Is the rat hippocampus a valid neuroanatomical model for the human hippocampus; 2) What is the degree of co-expression of Cygb and neuronal nitric oxide synthase (n......NOS) in the rat hippocampus; 3) The effect of chronic restraint stress (CRS) on Cygb and nNOS expression....

  8. Subchronic toxicity evaluation of γ-aminobutyric acid (GABA) in rats.

    Science.gov (United States)

    Takeshima, Kazuhito; Yamatsu, Atsushi; Yamashita, Yusuke; Watabe, Kazuya; Horie, Noriko; Masuda, Kazuyuki; Kim, Mujo

    2014-06-01

    γ-Aminobutyric acid (GABA) is an amino acid compound contained in vegetables such as tomatoes and also widely distributed in mammals. GABA acts as an inhibitory neurotransmitter and promotes parasympathetic activity to provide several beneficial effects, for instance, relaxation, anti-stress, and insomnia. GABA, produced via a fermentation process, has been available as a functional food ingredient. As part of a program to assess its safety, GABA was administered by oral gavage at doses of 500, 1250, and 2500mg/kg body weight to groups of 10 male and 10 female Sprague-Dawley rats for 13weeks. Treatment was not associated with the test substance-related mortality and appeared to be well tolerated. There were no toxicologically and statistically significant changes in urinalysis, hematology, clinical chemistry parameters, and in necropsy findings. A few statistically significant changes in food consumption and body weights were noted in the male groups while any significant changes were not noted in female groups. There was no effect of treatment on organ weights or on the results of the histopathological examinations. The results of toxicity evaluation support the safety use of GABA and the potential use as a functional food ingredient.

  9. Sleep duration varies as a function of glutamate and GABA in rat pontine reticular formation.

    Science.gov (United States)

    Watson, Christopher J; Lydic, Ralph; Baghdoyan, Helen A

    2011-08-01

    The oral part of the pontine reticular formation (PnO) is a component of the ascending reticular activating system and plays a role in the regulation of sleep and wakefulness. The PnO receives glutamatergic and GABAergic projections from many brain regions that regulate behavioral state. Indirect, pharmacological evidence has suggested that glutamatergic and GABAergic signaling within the PnO alters traits that characterize wakefulness and sleep. No previous studies have simultaneously measured endogenous glutamate and GABA from rat PnO in relation to sleep and wakefulness. The present study utilized in vivo microdialysis coupled on-line to capillary electrophoresis with laser-induced fluorescence to test the hypothesis that concentrations of glutamate and GABA in the PnO vary across the sleep/wake cycle. Concentrations of glutamate and GABA were significantly higher during wakefulness than during non-rapid eye movement sleep and rapid eye movement sleep. Regression analysis revealed that decreases in glutamate and GABA accounted for a significant portion of the variance in the duration of non-rapid eye movement sleep and rapid eye movement sleep episodes. These data provide novel support for the hypothesis that endogenous glutamate and GABA in the PnO contribute to the regulation of sleep duration.

  10. Chronic infusions of GABA into the medial prefrontal cortex induce spatial alternation deficits in aged rats.

    Science.gov (United States)

    Meneses, S; Galicia, O; Brailowsky, S

    1993-10-21

    It has been proposed that functions associated with the prefrontal cortex could change as a consequence of aging. Previous experiments in young rats have demonstrated that anatomical lesions or chronic GABA infusions into this area produce deficits in spatial delayed alternation tasks. The present study examines the effect of chronic (7 days) GABA or saline infusion into the prefrontal cortex on the performance of delayed alternation task in old rats (24 months). The results suggested that aged rats needed more sessions to acquire the delayed alternation task. GABA infusions into the prefrontal cortex produced deficits in spatial alternation tasks similar to those previously observed in young rats. Performance rapidly recovered after the infusion period. Histological analysis showed similar lesion size in both groups. The results suggest that aged prefrontal cortex and/or related areas participating in the acquisition of the delayed alternation task are more sensitive to aging processes. Furthermore, the prefrontal cortex is important for the retention of a previously learned spatial delayed alternation task. The structures involved in functional recovery from these deficits appear to be fully functional in aged rats.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  13. Metabolic changes in rat prefrontal cortex and hippocampus induced by chronic morphine treatment studied ex vivo by high resolution 1H NMR spectroscopy.

    Science.gov (United States)

    Gao, Hongchang; Xiang, Yun; Sun, Ninglei; Zhu, Hang; Wang, Yaqiang; Liu, Maili; Ma, Yuanye; Lei, Hao

    2007-01-01

    Ex vivo(1)H NMR spectroscopy was used to measure changes in the concentrations of cerebral metabolites in the prefrontal cortex (PFC) and hippocampus of rats subjected to repeated morphine treatment known to cause tolerance/dependence. The results show that repeated morphine exposure induces significant changes in the concentrations of a number of cerebral metabolites, and such changes are region specific. After 10 days of repeated morphine treatment, the concentration of gamma-aminobutyric acid (GABA) increased significantly in the PFC (20+/-11%), but decreased in the hippocampus (-31+/-12%), compared to control. In contrast, the glutamate (Glu) concentrations in both the PFC (-15+/-8%) and hippocampus (-13+/-4%) decreased significantly. Significant changes were also observed in the concentrations of hippocampal glutamine (Gln), myo-inositol, taurine, and N-acetyl aspartate. These morphine-induced changes were reversed during a subsequent 5-day withdrawal period. It is suggested that the observed concentration changes for Glu, Gln and GABA are most likely the result of a shift in the steady-state equilibrium of the Gln-Glu-GABA metabolic cycle. Changes in the metabolism of this neurotransmitter system might be part of the adaptive measures taken by the central nervous system in response to repeated morphine exposure and subsequent withdrawal.

  14. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters

    OpenAIRE

    2008-01-01

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored th...

  15. Effects of rhynchophylline on monoamine transmitters of striatum and hippocampus in cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    LUYuan-Fu; XIEXiao-Long; WUQin; WENGuo-Rong; YANGSu-Fen; SHIJing-Shan

    2004-01-01

    AIM To investigate the effects of rhynchophylline ( Rhy on monoamine transmitters and its metabolites in striatum and hippocampus of cerebral ischemic rats. METItODS The cerebral ischemic injury of rat was induced by middle cerebral artery occlusion (MCAO). The extracellular fluid of striatum and hippocampus in cerebral ischemic rats was collected by using

  16. Chronic infusions of GABA into the medial frontal cortex of the rat induce a reversible delayed spatial alternation deficit.

    Science.gov (United States)

    Di Scala, G; Meneses, S; Brailowsky, S

    1990-10-30

    The effects of bilateral infusions of GABA into the medial frontal cortex of the rat were studied in a delayed spatial alternation task. It was found that GABA (500 mM, 1 microliter/h during 7 days) impaired the performance of the rats in the previously learned task. Upon interruption of the treatment, the animals rapidly recovered normal performance scores. The results show that GABA infusions produce functional deficits similar to those produced by lesions of the frontal cortex. Moreover, the deficits are reversible upon interruption of the treatment. This technique may therefore be a useful tool for studying frontal lobe functions and the involvement of GABAergic mechanisms in cognitive processes.

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

    Science.gov (United States)

    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.

  18. Proteomic Analysis of Rat Hippocampus under Simulated Microgravity

    Science.gov (United States)

    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

  19. GABA(A) receptor activation in the CA1 area of the dorsal hippocampus impairs consolidation of conditioned contextual fear in C57BL/6J mice.

    Science.gov (United States)

    Misane, Ilga; Kruis, Ayla; Pieneman, Anton W; Ögren, Sven Ove; Stiedl, Oliver

    2013-02-01

    Local infusion of the GABA(A) receptor agonist muscimol is used for reversible inactivation of septohippocampal brain structures associated with cognitive functions. However, information on the effective duration, affected processes and site(s) of action of muscimol in the hippocampus is lacking. Therefore, the dose- and time-dependent effects of bilateral dorsohippocampal infusion of muscimol (0.01-2.0 μg/mouse) below the CA1 area were examined on processing of fear memory in male C57BL/6J mice. Infusion of muscimol 15 min-6 h but not 9 h or 24 h before training impaired conditioned context-dependent fear tested 24 h or 48 h after training. Post-training infusion of muscimol also impaired context-dependent fear when applied either 4 h or 6 h after training, although with lower efficacy. Muscimol was ineffective when administered immediately, 1 h or 24 h after training. Infusion of muscimol 15 min before training impaired context-dependent fear 4-6 h after training indicating preserved short-term but impaired long-term memory. Regardless of infusion time and dose, muscimol had no effect on tone-dependent (cued) fear memory. The impairment by the fluorescently-labeled muscimol-bodipy (5.3 μg/mouse) were similar to those of an equimolar dose of muscimol (1 μg/mouse). The distribution profile after local infusion indicated that muscimol-bodipy (5.3 μg/mouse) was confined to the CA1 area of the dorsal hippocampus. These results demonstrated that GABA(A) receptor activation in the CA1 area of the dorsal hippocampus causes a long-term memory impairment of conditioned context-dependent fear mediated by a long-lasting (≥6 h) muscimol action most likely affecting consolidation processes.

  20. Chronic baclofen desensitizes GABA(B)-mediated G-protein activation and stimulates phosphorylation of kinases in mesocorticolimbic rat brain.

    Science.gov (United States)

    Keegan, Bradley M T; Beveridge, Thomas J R; Pezor, Jeffrey J; Xiao, Ruoyu; Sexton, Tammy; Childers, Steven R; Howlett, Allyn C

    2015-08-01

    The GABAB receptor is a therapeutic target for CNS and neuropathic disorders; however, few preclinical studies have explored effects of chronic stimulation. This study evaluated acute and chronic baclofen treatments on GABAB-activated G-proteins and signaling protein phosphorylation as indicators of GABAB signaling capacity. Brain sections from rats acutely administered baclofen (5 mg/kg, i.p.) showed no significant differences from controls in GABAB-stimulated GTPγS binding in any brain region, but displayed significantly greater phosphorylation/activation of focal adhesion kinase (pFAK(Tyr397)) in mesocorticolimbic regions (caudate putamen, cortex, hippocampus, thalamus) and elevated phosphorylated/activated glycogen synthase kinase 3-β (pGSK3β(Tyr216)) in the prefrontal cortex, cerebral cortex, caudate putamen, nucleus accumbens, thalamus, septum, and globus pallidus. In rats administered chronic baclofen (5 mg/kg, t.i.d. for five days), GABAB-stimulated GTPγS binding was significantly diminished in the prefrontal cortex, septum, amygdala, and parabrachial nucleus compared to controls. This effect was specific to GABAB receptors: there was no effect of chronic baclofen treatment on adenosine A1-stimulated GTPγS binding in any region. Chronically-treated rats also exhibited increases in pFAK(Tyr397) and pGSK3β(Tyr216) compared to controls, and displayed wide-spread elevations in phosphorylated dopamine- and cAMP-regulated phosphoprotein-32 (pDARPP-32(Thr34)) compared to acutely-treated or control rats. We postulate that those neuroadaptive effects of GABAB stimulation mediated by G-proteins and their sequelae correlate with tolerance to several of baclofen's effects, whereas sustained signaling via kinase cascades points to cross-talk between GABAB receptors and alternative mechanisms that are resistant to desensitization. Both desensitized and sustained signaling pathways should be considered in the development of pharmacotherapies targeting the GABA

  1. Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system.

    Science.gov (United States)

    Vaz, G C; Bahia, A P C O; de Figueiredo Müller-Ribeiro, F C; Xavier, C H; Patel, K P; Santos, R A S; Moreira, F A; Frézard, F; Fontes, M A P

    2015-01-29

    Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 μL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P nervous system. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Effects of aluminium exposure on brain glutamate and GABA systems: an experimental study in rats.

    Science.gov (United States)

    Nayak, P; Chatterjee, A K

    2001-12-01

    It has been postulated that the neurotoxic effects of aluminium could be mediated through glutamate, an excitatory amino acid. Hence the effects of aluminium administration (at a dose of 4.2mg/kg body weight daily as aluminium chloride, hexahydrate, intraperitoneally, for 4 weeks) on glutamate and gamma-amino butyrate (GABA), an inhibitory amino acid, and related enzyme activities in different regions of the brain were studied in albino rats. The glutamate level increased significantly in the cerebrum, thalamic area, midbrain-hippocampal region and cerebellum in response to in vivo aluminium exposure. The aluminium insult also caused significant increases in glutamate alpha-decarboxylase activity in all the brain regions. However, on aluminium insult, the GABA content was not significantly changed except in the thalamic area, where it was elevated. On the contrary, the GABA-T activities of all the regions were reduced significantly in all regions except the midbrain-hippocampal region. However, the succinic semi-aldehyde content of all brain regions increased, often significantly. The aluminium-induced modification of the enzyme activities may be either due to the direct impact of aluminium or due to aluminium-induced changes in the cellular environment. The aluminium-induced differential regional accumulation of glutamate or other alterations in enzymes of the glutamate-GABA system may be one of the causes of aluminium-induced neurotoxicity.

  3. Interneurons containing calretinin are specialized to control other interneurons in the rat hippocampus.

    Science.gov (United States)

    Gulyás, A I; Hájos, N; Freund, T F

    1996-05-15

    Spine-free calretinin-immunoreactive (CR-IR) interneurons form a subpopulation of GABAergic cells in the rat hippocampus. A characteristic feature of these cells--located in all areas and layers--is the frequent dendro-dendritic and axo-dendritic contacts they form with each other. In this study we examined in detail the connectivity of these neurons by reconstructing their dendritic and axonal arbor and by identifying their postsynaptic targets. Radially running dendrites of CR-IR cells, located in different layers, intermingled into long braids. An average cell was in contact with dendrites of three to seven other CR-IR cells. Reconstruction of the dendritic trees from six consecutive sections demonstrated that at least 15 cells may participate in a dendro-dendritically connected cluster. Electron microscopical examination revealed that regularly spaced zonula adherentia connect the touching dendrites. The postsynaptic targets of CR-IR neurons have been examined using postembedding immunogold staining for GABA. CR-containing GABA-immunoreactive axons of local origin formed multiple symmetrical synaptic contacts (two to five) exclusively on GABAergic dendrites (CR-negative as well as CR-positive). Two to 10 CR-IR axons may converge onto a single CR-IR neuron, often from cells belonging to the same dendro-dendritically connected cluster. Using double immunocytochemistry, CR-IR cells were shown to heavily innervate calbindin D28k-containing interneurons and VIP-containing basket cells but avoided the parvalbumin-containing basket and axo-axonic cells. The unique connectivity of CR-IR cells may enable them to play a crucial role in the generation of synchronous, rhythmic hippocampal activity by controlling other interneurons terminating on different dendritic and somatic compartments of principal cells.

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

    Science.gov (United States)

    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 neuronal apoptosis in rats, and then affect hippocampal synaptic plasticity.

  5. Sex differences in diazepam effects and parvalbumin-positive GABA neurons in trait anxiety Long Evans rats.

    Science.gov (United States)

    Ravenelle, Rebecca; Neugebauer, Nichole M; Niedzielak, Timothy; Donaldson, S Tiffany

    2014-08-15

    In clinical populations, prevalence rates for a number of anxiety disorders differ between males and females and gonadal hormones are thought to contribute to these differences. While these hormones have been shown to modulate the anxiolytic effects of the benzodiazepine agonist diazepam in some models, findings are inconsistent. Here, we tested for sex differences in response to anxiogenic stimuli following a 30-min diazepam (1.0mg/kg) pre-treatment in male and female rats showing high (HAn) and low (LAn) anxiety-like behavior on the elevated plus maze. Acute diazepam administration resulted in decreased anxiety-like behavior only in HAn males as demonstrated by a significant increase in percent open arm time in the elevated plus maze (EPM). Immunohistochemical analysis for parvalbumin (PV; a calcium-binding protein that selectively stains GABAergic neurons) in central amygdala (CeA), caudate putamen (CPu) and the hippocampus indicated the number of GABAergic interneurons in these areas differed across sex and anxiety trait. In the CPu, females had significantly more PV-immunoreactive (IR) cells than males, and LAn females had greater PV-IR neurons than HAn females. In the CeA, males displayed an increased number of PV-IR neurons compared to females, with no differences found between LAn and HAn. Further, trait differences were evident in the CA2 region of the hippocampus, regardless of sex. Taken together, these data suggest that gonadal hormones and trait anxiety may influence the sensitivity to the anti-anxiety effects of diazepam and these differences may be due in part to the distribution of GABA-containing interneurons.

  6. Traumatic brain injury impairs synaptic plasticity in hippocampus in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bao-liang; CHEN Xin; TAN Tao; YANG Zhuo; CARLOS Dayao; JIANG Rong-cai; ZHANG Jian-ning

    2011-01-01

    Background Traumatic brain injury (TBl) often causes cognitive deficits and remote symptomatic epilepsy.Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBl may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control (n=20) and TBl groups (n=20). Long-term potentiation,extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus (DG), but a significantly decreased excitability in the cornu ammonis 1 (CA1) area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area.Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.

  7. Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Supavilai, P.; Karobath, M.

    1985-02-04

    GABA, THIP and muscimol enhance spontaneous and inhibit electrically induced release of tritium labelled compounds from rat striatal slices which have been pre-labelled with /sup 3/H-choline. Baclofen is inactive in this model. Muscimol can inhibit electrically induced release of tritiated material by approximately 75% with half maximal effects at 2 ..mu..M. The response to muscimol can be blocked by the GABA antagonists bicuculline methobromide, picrotoxin, anisatin, R 5135 and CPTBO (cyclopentylbicyclophosphate). Drugs which act on the benzodiazepine receptor (BR) require the presence of muscimol to be effective and they modulate the effects of muscimol in a bidirectional manner. Thus BR agonists enhance and inverse BR agonists attenuate the inhibitory effects of muscimol on electrically induced release. Ro15-1788, a BR antagonist, does not modulate the inhibitory effects of muscimol but antagonizes the actions of clonazepam, a BR agonist, and of DMCM, an inverse BR agonist. These results demonstrate that a GABA/benzodiazepine receptor complex can modulate acetylcholine release from rat striatal slices in vitro. 24 references, 3 figures, 5 table.

  8. Heterogenous GABA(B) receptor-mediated pathways are involved in the local GABAergic system of the rat trigeminal ganglion: possible involvement of KCTD proteins.

    Science.gov (United States)

    Hayasaki, H; Sohma, Y; Kanbara, K; Otsuki, Y

    2012-08-30

    It is well known that Gamma-aminobutyric acid (GABA) plays an important role in signal transduction in the central nervous system. However, the function of GABA in the peripheral nervous system, including sensory ganglions, is still unclear. In this study we have characterized the expression, cellular distribution, and function of GABA(B) receptor subunits, and the recently discovered GABA(B) auxiliary subunits, K(+) channel tetramerization domain-containing (KCTD) proteins, in rat trigeminal ganglion (TG) neuronal cells, which are devoid of synapses. We found heterogeneous expression of both GABA(B1) and GABA(B2) subunits, and a near-plasma membrane localization of KCTD12. In addition, we found that GABA(B2) subunits correlated with KCTD16. Whole-cell current-clamp recordings showed that responses to the GABA(B) receptor agonist, baclofen, were variable and both increases and decreases in excitability were observed. This correlated with observed differences in voltage-dependent K(+) current responses to baclofen in voltage-clamped TG neuronal cells. The functional diversity of the GABA(B)ergic regulation on the excitability of the TG neuronal cell bodies could be due to the heterogenous expression of KCTD proteins, and subsequent regulation of plasma membrane K(+) channels. Taken together with our previous demonstration of a local GABA(A) receptor-mediated system in rat TG, we provide an updated GABAergic model in the rat TG that incorporates both GABA(A)- and GABA(B)-receptor systems.

  9. Loss of Parvalbumin in the Hippocampus of MAM Schizophrenia Model Rats Is Attenuated by Peripubertal Diazepam

    OpenAIRE

    Du, Yijuan; Grace, Anthony A.

    2016-01-01

    Background: Loss of parvalbumin interneurons in the hippocampus is a robust finding in schizophrenia brains. Rats exposed during embryonic day 17 to methylazoxymethanol acetate exhibit characteristics consistent with an animal model of schizophrenia, including decreased parvalbumin interneurons in the ventral hippocampus. We reported previously that peripubertal administration of diazepam prevented the emergence of pathophysiology in adult methylazoxymethanol acetate rats. Methods: We used an...

  10. Conformational basis for the Li(+)-induced leak current in the rat gamma-aminobutyric acid (GABA) transporter-1

    DEFF Research Database (Denmark)

    MacAulay, Nanna; Zeuthen, Thomas; Gether, Ulrik

    2002-01-01

    The rat gamma-aminobutyric acid transporter-1 (GAT-1) was expressed in Xenopus laevis oocytes and the substrate-independent Li(+)-induced leak current was examined using two-electrode voltage clamp. The leak current was not affected by the addition of GABA and was not due to H(+) permeation. The ...... of Na(+) restrains the transporter from moving into a leak conductance mode as well as allowing maintenance of GABA-elicited transport-associated current....

  11. Role of gamma-aminobutyricacidB(GABA(B)) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus.

    Science.gov (United States)

    Lee, Han Kyu; Seo, Young Jun; Choi, Seong Soo; Kwon, Min Soo; Shim, Eon Jeong; Lee, Jin Young; Suh, Hong Won

    2005-12-31

    Kainic acid (KA) is well-known as an excitatory, neurotoxic substance. In mice, KA administered intracerebroventricularly (i.c.v.) lead to morphological damage of hippocampus expecially concentrated on the CA3 pyramidal neurons. In the present study, the possible role of gamma-aminobutyric acid B (GABA(B)) receptors in hippocampal cell death induced by KA (0.1 microg) administered i.c.v. was examined. 5-Aminovaleric acid (5-AV; GABA(B) receptors antagonist, 20 mug) reduced KA-induced CA3 pyramidal cell death. KA increased the phosphorylated extracellular signal-regulated kinase (p-ERK) and Ca(2+)/calmodulin-dependent protein kinase II (p-CaMK II) immunoreactivities (IRs) 30 min after KA treatment, and c-Fos, c-Jun IR 2 h, and glial fibrillary acidic protein (GFAP), complement receptor type 3 (OX-42) IR 1 day in hippocampal area in KA-injected mice. 5-AV attenuated KA-induced p-CaMK II, GFAP and OX-42 IR in the hippocampal CA3 region. These results suggest that p-CaMK II may play as an important regulator on hippocampal cell death induced by KA administered i.c.v. in mice. Activated astrocytes, which was presented by GFAP IR, and activated microglia, which was presented by the OX-42 IR, may be a good indicator for measuring the cell death in hippocampal regions by KA excitotoxicity. Furthermore, it showed that GABA(B) receptors appear to be involved in hippocampal CA3 pyramidal cell death induced by KA administered i.c.v. in mice.

  12. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters

    Science.gov (United States)

    Jolivalt, Corinne G.; Lee, Corinne A.; Ramos, Khara M.; Calcutt, Nigel A.

    2008-01-01

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored the role of the GABAA receptor in rats with painful diabetic neuropathy. KCC2 protein levels were significantly reduced in the spinal cord of diabetic rats while levels of NKCC1 and the GABAA receptor were unchanged. Spinal delivery of the GABAA receptor antagonist bicuculline reduced formalin-evoked flinching in diabetic rats and also dose-dependently alleviated tactile allodynia. GABAA receptor-mediated rate-dependent depression of the spinal H reflex was absent in the spinal cord of diabetic rats. Control rats treated with the KCC2 blocker DIOA, mimicked diabetes by showing increased formalin-evoked flinching and diminished rate dependent depression. The ability of bicuculline to alleviate allodynia and formalin-evoked hyperalgesia in diabetic rats is consistent with a reversal of the properties of GABA predicted by reduced spinal KCC2 and suggests that reduced KCC2 expression and increased GABA release contribute to spinally-mediated hyperalgesia in diabetes. PMID:18755547

  13. Neurotransmitter evaluation in the hippocampus of rats after intracerebral injection of TsTX scorpion toxin

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    ALA Nencioni

    2009-01-01

    Full Text Available TsTX is an α-type sodium channel toxin that stimulates the discharge of neurotransmitters from neurons. In the present study we investigated which neurotransmitters are released in the hippocampus after TsTX injection and if they are responsible for electrographic or histopathological effects. Microdialysis revealed that the toxin increased glutamate extracellular levels in the hippocampus; however, levels of gamma-aminobutyric acid (GABA, glycine, 5-hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA and 3,4-dihydroxyphenylacetic acid (DOPAC were not significantly altered. Neurodegeneration in pyramidal cells of hippocampus and electroencephalographic alterations caused by the toxin were blocked by pretreatment with riluzole, a glutamate release inhibitor. The present results suggest a specific activity of TsTX in the hippocampus which affects only glutamate release.

  14. Developmental changes in GABAergic actions and seizure susceptibility in the rat hippocampus.

    OpenAIRE

    Khazipov, Roustem; Khalilov, Ilgam; Tyzio, Roman; Morozova, Elena; Ben-Ari, Yezekiel; Holmes, Gregory,

    2004-01-01

    International audience; 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...

  15. Neurocalcin-immunoreactive cells in the rat hippocampus are GABAergic interneurons.

    Science.gov (United States)

    Martínez-Guijarro, F J; Briñón, J G; Blasco-Ibáñez, J M; Okazaki, K; Hidaka, H; Alonso, J R

    1998-01-01

    Neurocalcin (NC) is a recently described calcium-binding protein isolated and characterized from bovine brain. NC belongs to the neural calcium-sensor proteins defined by the photoreceptor cell-specific protein recoverin that have been proposed to be involved in the regulation of calcium-dependent phosphorylation in signal transduction pathways. We analyzed the distribution and morphology of the NC-immunoreactive (IR) neurons in the rat dorsal hippocampus and the coexistence of NC with GABA and different neurochemical markers which label perisomatic inhibitory cells [parvalbumin (PV) and cholecystokinin (CCK)], mid-proximal dendritic inhibitory cells [calbindin D28k (CB)], distal dendritic inhibitory cells [somatostatin (SOM) and neuropeptide Y (NPY)], and interneurons specialized to innervate other interneurons [calretinin (CR) and vasoactive intestinal polypeptide (VIP)]. NC-IR cells were present in all layers of the dentate gyrus and hippocampal fields. In the dentate gyrus, NC-IR cells were concentrated in the granule cell layer, especially in the hilar border, whereas in the CA fields they were most frequently found in the stratum radiatum. NC-IR cells were morphologically heterogeneous and exhibited distinctive features of non-principal cells. In the dentate gyrus, pyramidal-like, multipolar and fusiform (horizontal and vertical) cells were found. In the CA3 region most NC-IR cells were multipolar, but vertical and horizontal fusiform cells also appeared. In the CA1 region, where NC-IR cells showed most frequently vertically arranged dendrites, multipolar, bitufted and fusiform (vertical and horizontal) cells could be distinguished. All the NC-IR cells were found to be GABA-IR in all hippocampal layers and regions, and they represented about 19% of the GABA-positive cells. NC/CB, NC/CR and NC/VIP double-labeled cells were found in all hippocampal regions, and represented 29%, 24% and 18% of the NC-IR cells, respectively. NC and CCK did not coexist in the

  16. Long-Lasting Effects of GABA Infusion Into the Cerebral Cortex of the Rat

    Science.gov (United States)

    Montiel, Teresa; Almeida, Daniel; Arango, Iván; Calixto, Eduardo; Casasola, César; Brailowsky, Simón

    2000-01-01

    In electrophysiological terms, experimental models of durable information storage in the brain include long-term potentiation (LTP), long-term depression, and kindling. Protein synthesis correlates with these enduring processes. We propose a fourth example of long-lasting information storage in the brain, which we call the GABA-withdrawal syndrome (GWS). In rats, withdrawal of a chronic intracortical infusion of GABA, a ubiquitous inhibitory neurotransmitter, induced epileptogenesis at the infusion site. This overt GWS lasted for days. Anisomycin, a protein synthesis inhibitor, prevented the appearance of GWS in vivo. Hippocampal and neocortical slices showed a similar post-GABA hyperexcitability in vitro and an enhanced susceptibility to LTP induction. One to four months after the epileptic behavior disappeared, systemic administration of a subconvulsant dose of pentylenetetrazol produced the reappearance of paroxysmal activity. The long-lasting effects of tonic GABAA receptor stimulation may be involved in long-term information storage processes at the cortical level, whereas the cessation of GABAA receptor stimulation may be involved in chronic pathological conditions, such as epilepsy. Furthermore, we propose that GWS may represent a common key factor in the addiction to GABAergic agents (for example, barbiturates, benzodiazepines, and ethanol). GWS represents a novel form of neurono-glial plasticity. The mechanisms of this phenomenon remain to be understood. PMID:10709209

  17. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

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    Mathew Jobin

    2012-02-01

    Full Text Available Abstact Background Gamma amino butyric acid (GABA, the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. Methods In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. Results Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P Aά1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P Aά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. Conclusions Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.

  18. Cellular and network mechanisms generating spontaneous population events in the immature rat hippocampus

    OpenAIRE

    SipilÀ, Sampsa

    2006-01-01

    Distinct endogenous network events, generated independently of sensory input, are a general feature of various structures of the immature central nervous system. In the immature hippocampus, these type of events are seen as "giant depolarizing potentials" (GDPs) in intracellular recordings in vitro. GABA, the major inhibitory neurotransmitter of the adult brain, has a depolarizing action in immature neurons, and GDPs have been proposed to be driven by GABAergic transmission. Moreover, GDPs ha...

  19. Donor/Recipient Enhancement of Memory in Rat Hippocampus

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    Sam A Deadwyler

    2013-12-01

    Full Text Available The critical role of the mammalian hippocampus in the formation, translation and retrieval of memory has been documented over many decades. There are many theories of how the hippocampus operates to encode events and a precise mechanism was recently identified in rats performing a short-term memory task which demonstrated that successful information encoding was promoted via specific patterns of activity generated within ensembles of hippocampal neurons. In the study presented here these ‘representations’ were extracted via a customized nonlinear multi-input multi-output (MIMO mathematical model which allowed prediction of successful performance on specific trials within the testing session. A unique feature of this characterization was demonstrated when successful information encoding patterns were derived online from well-trained donor animals during difficult long-delay trials and delivered via online electrical stimulation to synchronously tested naïve recipient animals never before exposed to the delay feature of the task. By transferring such model-derived trained (donor animal hippocampal firing patterns via stimulation to coupled naïve recipient animals, their task performance was facilitated in a direct donor-recipient manner. This provides the basis for utilizing extracted appropriate neural information from one brain to induce, recover, or enhance memory related processing in the brain of another subject.

  20. Effect of maternal diabetes on gliogensis in neonatal rat hippocampus

    Science.gov (United States)

    Sadeghi, Akram; Esfandiary, Ebrahim; Hami, Javad; Khanahmad, Hossein; Hejazi, Zahra; Razavi, Shahnaz

    2016-01-01

    Background: Diabetes in pregnancy is a common metabolic disorder associated with various adverse outcomes in the offspring including impairments in attention and memory and alterations in social behavior. Glial cells are proven to have a critical role in normal function of neurons, and alteration in their activity could contribute to disturbance in the brain function. The aim of this study was to investigate the effect of maternal diabetes on hippocampal mRNA expression and distribution pattern of glial fibrillary acidic protein (GFAP) immunoreactive glial cells in the dentate gyrus (DG) of rat neonate at postnatal day 14 (P14). Materials and Methods: Wistar female rats were randomly allocated in control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by injection of streptozotocin from 4 weeks before gestation until parturition. After delivery, the male offspring was euthanized at P14. Results: Our results showed a significant higher level of hippocampal GFAP expression and an increase in the mean number of GFAP positive cells in the DG of diabetic group offspring (P 0.05). Conclusion: The present study revealed that diabetes during pregnancy strongly increased the glial cells production in the developing rat hippocampus. PMID:27656611

  1. Sleep and GABA levels in the oral part of rat pontine reticular formation are decreased by local and systemic administration of morphine.

    Science.gov (United States)

    Watson, C J; Lydic, R; Baghdoyan, H A

    2007-01-05

    Morphine, a mu-opioid receptor agonist, is a commonly prescribed treatment for pain. Although highly efficacious, morphine has many unwanted side effects including disruption of sleep and obtundation of wakefulness. One mechanism by which morphine alters sleep and wakefulness may be by modulating GABAergic signaling in brain regions regulating arousal, including the pontine reticular nucleus, oral part (PnO). This study used in vivo microdialysis in unanesthetized Sprague-Dawley rat to test the hypothesis that mu-opioid receptors modulate PnO GABA levels. Validation of the high performance liquid chromatographic technique used to quantify GABA was obtained by dialyzing the PnO (n=4 rats) with the GABA reuptake inhibitor nipecotic acid (500 microM). Nipecotic acid caused a 185+/-20% increase in PnO GABA levels, confirming chromatographic detection of GABA and demonstrating the existence of functional GABA transporters in rat PnO. Morphine caused a concentration-dependent decrease in PnO GABA levels (n=25 rats). Coadministration of morphine (100 microM) with naloxone (1 microM), a mu-opioid receptor antagonist, blocked the morphine-induced decrease in PnO GABA levels (n=5 rats). These results show for the first time that mu-opioid receptors in rat PnO modulate GABA levels. A second group of rats (n=6) was used to test the hypothesis that systemically administered morphine also decreases PnO GABA levels. I.v. morphine caused a significant (PPnO GABA levels relative to control i.v. infusions of saline. Finally, microinjections followed by 2 h recordings of electroencephalogram and electromyogram tested the hypothesis that PnO morphine administration disrupts sleep (n=8 rats). Morphine significantly (PPnO.

  2. Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

    Directory of Open Access Journals (Sweden)

    E.F. Collares

    2005-01-01

    Full Text Available Dipyrone administered intravenously (iv or intracerebroventricularly (icv delays gastric emptying (GE in rats. Gamma-aminobutyric acid (GABA is the most potent inhibitory neurotransmitter of the central nervous system. The objective of the present study was to determine the effect of icv baclofen, a GABA B receptor agonist, on delayed GE induced by dipyrone. Adult male Wistar rats received a saline test meal containing phenol red as a marker. GE was indirectly evaluated by determining the percent of gastric retention (%GR of the meal 10 min after orogastric administration. In the first experiment, the animals were injected iv with vehicle (Civ or 80 mg/kg (240 µmol/kg dipyrone (Dp iv, followed by icv injection of 10 µl vehicle (bac0, or 0.5 (bac0.5, 1 (bac1 or 2 µg (bac2 baclofen. In the second experiment, the animals were injected icv with 5 µl vehicle (Cicv or an equal volume of a solution containing 4 µmol (1333.2 µg dipyrone (Dp icv, followed by 5 µl vehicle (bac0 or 1 µg baclofen (bac1. GE was determined 10 min after icv injection. There was no significant difference between control animals from one experiment to another concerning GR values. Baclofen at the doses of 1 and 2 µg significantly reduced mean %GR induced by iv dipyrone (Dp iv bac1 = 35.9% and Dp iv bac2 = 26.9% vs Dp iv bac0 = 51.8%. Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean %GR: Dp icv bac1 = 30.4% vs Dp icv bac0 = 54.2%. The present results suggest that dipyrone induces delayed GE through a route in the central nervous system that is blocked by the activation of GABA B receptors.

  3. Midazolam inhibits neophobia-induced Fos expression in the rat hippocampus.

    Science.gov (United States)

    Wisłowska-Stanek, A; Zienowicz, M; Lehner, M; Taracha, E; Bidziński, A; Maciejak, P; Skórzewska, A; Szyndler, J; Płaźnik, A

    2006-01-01

    The effect of midazolam on expression of c-Fos protein was examined in the rat hippocampus, following the open field test of neophobia. It was found that pretreatment of rats with midazolam, at the dose of 0.5 mg/kg, enhanced rat exploratory behavior, and inhibited neophobia related stimulation of c-Fos in the CA-1 and CA-3 areas of the hippocampus. The presented results provide new immunocytochemical data on the involvement of hippocampus in emotional processes related to neophobia, and indicate a possible site of action of benzodiazepines.

  4. In vivo neurochemical evidence that newly synthesised GABA activates GABA(B), but not GABA(A), receptors on dopaminergic nerve endings in the nucleus accumbens of freely moving rats

    NARCIS (Netherlands)

    Saigusa, T.; Aono, Y.; Sekino, R.; Uchida, T.; Takada, K.; Oi, Y.; Koshikawa, N.; Cools, A.R.

    2012-01-01

    GABA released from accumbal GABAergic interneurons plays an inhibitory role in the regulation of dopamine efflux through GABA(B) and GABA(A) receptors located on accumbal dopaminergic nerve endings. The cytosolic newly synthesised GABA alters vesicular GABA levels and, accordingly, the amount of GAB

  5. Effect of pregabalin on apoptotic regulatory genes in hippocampus of rats with chronic temporal lobe epilepsy

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    ZHANG Yi-dan

    2012-04-01

    Full Text Available Objective To observe the effect of pregabalin on the expression of Bcl-2 and Bax in hippocampus of chronic epileptic rats induced by pilocarpine, to explore the anti-epileptic pharmacology mechanism of pregabalin, and its anti-apoptotic effect on hippocampal neurons of rats. Methods The model of chronic temporal lobe epileptic rats induced by lithium-pilocarpine was established, then the rats in pregabalin treatment group received intraperitoneal injection of pregabalin (40 mg/kg once daily for three weeks. The expression of Bcl-2 and Bax in hippocampus of all rats was detected by immunohistochemical technique and Western blotting. Results Compared with normal saline group rats, the expression of Bcl-2 and Bax in hippocampus of rats with chronic temporal lobe epilepsy was significantly increased (P = 0.000, for all. Pregabalin can down-regulate the expression of Bax and up-regulate the expression of Bcl-2 in hippocampus of rats compared to model group rats (P = 0.000, for all. Conclusion Pregabalin may have the effects of inhibiting cell apoptosis and protecting neurons through lowing Bax level and increasing Bcl-2 level in hippocampus of chronic temporal lobe epileptic rats.

  6. Brain-derived neurotrophic factor (BDNF) enhances GABA transport by modulating the trafficking of GABA transporter-1 (GAT-1) from the plasma membrane of rat cortical astrocytes.

    Science.gov (United States)

    Vaz, Sandra H; Jørgensen, Trine N; Cristóvão-Ferreira, Sofia; Duflot, Sylvie; Ribeiro, Joaquim A; Gether, Ulrik; Sebastião, Ana M

    2011-11-25

    The γ-aminobutyric acid (GABA) transporters (GATs) are located in the plasma membrane of neurons and astrocytes and are responsible for termination of GABAergic transmission. It has previously been shown that brain derived neurotrophic factor (BDNF) modulates GAT-1-mediated GABA transport in nerve terminals and neuronal cultures. We now report that BDNF enhances GAT-1-mediated GABA transport in cultured astrocytes, an effect mostly due to an increase in the V(max) kinetic constant. This action involves the truncated form of the TrkB receptor (TrkB-t) coupled to a non-classic PLC-γ/PKC-δ and ERK/MAPK pathway and requires active adenosine A(2A) receptors. Transport through GAT-3 is not affected by BDNF. To elucidate if BDNF affects trafficking of GAT-1 in astrocytes, we generated and infected astrocytes with a functional mutant of the rat GAT-1 (rGAT-1) in which the hemagglutinin (HA) epitope was incorporated into the second extracellular loop. An increase in plasma membrane of HA-rGAT-1 as well as of rGAT-1 was observed when both HA-GAT-1-transduced astrocytes and rGAT-1-overexpressing astrocytes were treated with BDNF. The effect of BDNF results from inhibition of dynamin/clathrin-dependent constitutive internalization of GAT-1 rather than from facilitation of the monensin-sensitive recycling of GAT-1 molecules back to the plasma membrane. We therefore conclude that BDNF enhances the time span of GAT-1 molecules at the plasma membrane of astrocytes. BDNF may thus play an active role in the clearance of GABA from synaptic and extrasynaptic sites and in this way influence neuronal excitability.

  7. Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced primary and secondary hypersensitivity in rats

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Erichsen, Helle K; Brown, David T

    2012-01-01

    this concept being tested in humans. Prior to assessing the efficacy of GABA-A receptor PAMs in a human volunteer pain model we have compared compounds capable of variously modulating GABA-A receptor function in comparable rat models of capsaicin-induced acute nocifensive flinching behaviour and secondary...... mechanical hypersensitivity. The subtype-selective PAM NS11394 (0.3-10 mg/kg), and the non-selective PAM diazepam (1-5 mg/kg) variously reduced capsaicin-induced secondary mechanical hypersensitivity (180 min post-injection). However, the low efficacy subtype-selective PAM TPA023 (3-30 mg/kg) was completely......, albeit at doses previously shown to impair locomotor function. Our data indicate that GABA-A receptor PAMs with optimal selectivity and efficacy profiles reduce centrally-mediated mechanical hypersensitivity in capsaicin-injected rats, an observation that we expect can translate directly to human...

  8. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

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    Khushbu Jain

    2015-01-01

    Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

  9. Behavioral deficit and decreased GABA receptor functional regulation in the cerebellum of epileptic rats: effect of Bacopa monnieri and bacoside A.

    Science.gov (United States)

    Mathew, Jobin; Peeyush Kumar, T; Khan, Reas S; Paulose, C S

    2010-04-01

    In the present study, the effects of Bacopa monnieri and its active component, bacoside A, on motor deficit and alterations of GABA receptor functional regulation in the cerebellum of epileptic rats were investigated. Scatchard analysis of [(3)H]GABA and [(3)H]bicuculline in the cerebellum of epileptic rats revealed a significant decrease in B(max) compared with control. Real-time polymerase chain reaction amplification of GABA(A) receptor subunits-GABA(Aalpha1), GABA(Aalpha5,) and GABA(Adelta)-was downregulated (Pbacoside A reversed these changes to near-control levels. Our results suggest that changes in GABAergic activity, motor learning, and memory deficit are induced by the occurrence of repetitive seizures. Treatment with B. monnieri and bacoside A prevents the occurrence of seizures thereby reducing the impairment of GABAergic activity, motor learning, and memory deficit.

  10. Reduction of GABA/sub B/ receptor binding induced by climbing fiber degeneration in the rat cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K.; Fukuda, H.

    1985-07-22

    When the rat cerebellar climbing fibers degenerated, as induced by lesioning the inferior olive with 3-acetylpyridine (3-AP), GABA/sub B/ receptor binding determined with /sup 3/H-(+/-)baclofen was reduced in the cerebellum but not in the cerebral cortex of rats. Computer analysis of saturation data revealed two components of the binding sites, and indicated that decrease of the binding in the cerebellum was due to reduction in receptor density, mainly of the high-affinity sites, the B/sub max/ of which was reduced to one-third that in the control animals. In vitro treatment with 3-AP, of the membranes prepared from either the cerebellum or the cerebral cortex, induced no alteration in the binding sites, thereby indicating that the alteration of GABA/sub B/ sites induced by in vivo treatment with 3-AP is not due to a direct action of 3-AP on the receptor. GABA/sub A/ and benzodiazepine receptor binding labelled with /sup 3/H-muscimol and /sup 3/H-diazepam, respectively, in both of brain regions was not affected by destruction of the inferior olive. These results provide evidence that some of the GABA/sub B/ sites but neither GABA/sub A/ nor benzodiazepine receptors in the cerebellum are located at the climbing fiber terminals. 28 references, 4 figures, 2 tables.

  11. Evaluation of GABA Receptors of Ventral Tegmental Area in Cardiovascular Responses in Rat

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    Minoo Rasoulpanah

    2015-07-01

    Full Text Available Background: The ventral tegmental area (VTA is well known for its role in cardiovascular control. It is demonstrated that about 20-30% of the VTA neurons are GABAergic though their role in cardiovascular control is not yet understood. This study is carried out to find the effects of GABA A and GABA B receptors on cardiovascular response of the VTA. Methods: Experiments were performed on urethane anesthetized male Wistar rats. Drugs were microinjected unilaterally into the VTA. The average changes in mean arterial pressure (MAP and heart rate (HR were compared between the case and the control groups using t test and with the pre-injection values using paired t test. Results: Microinjection of muscimol, a GABAA agonist (500, 1500 and 2500 pmol/100nl into the VTA had no significant effect on MAP and HR compared with the saline group and pre-injection values. Injection of bicuculline methiodide (BMI, 100 and 200 pmol/100 nl, a GABAA antagonist, caused a significant increase in the MAP (11.1±1.95mmHg, P<0.5 and a decrease in HR (-32.07±10.2, P<0.01. Microinjection of baclofen a GABAB receptor agonist (500 or 1000 pmole/100 nl and phaclofen a GABAB receptor antagonist (500 or 1000 pmole/100 nl had no significant effects on MAP and HR. Conclusion: For the first time it was demonstrated that GABA system of the VTA inhibits the cardiovascular system through the activation of GABAA but not the GABAB receptors.

  12. Oxo-4-methylpentanoic acid directs the metabolism of GABA into the Krebs cycle in rat pancreatic islets.

    Science.gov (United States)

    Hernández-Fisac, Inés; Fernández-Pascual, Sergio; Ortsäter, Henrik; Pizarro-Delgado, Javier; Martín del Río, Rafael; Bergsten, Peter; Tamarit-Rodriguez, Jorge

    2006-11-15

    OMP (oxo-4-methylpentanoic acid) stimulates by itself a biphasic secretion of insulin whereas L-leucine requires the presence of L-glutamine. L-Glutamine is predominantly converted into GABA (gamma-aminobutyric acid) in rat islets and L-leucine seems to promote its metabolism in the 'GABA shunt' [Fernández-Pascual, Mukala-Nsengu-Tshibangu, Martín del Río and Tamarit-Rodríguez (2004) Biochem. J. 379, 721-729]. In the present study, we have investigated how 10 mM OMP affects L-glutamine metabolism to uncover possible differences with L-leucine that might help to elucidate whether they share a common mechanism of stimulation of insulin secretion. In contrast with L-leucine, OMP alone stimulated a biphasic insulin secretion in rat perifused islets and decreased the islet content of GABA without modifying its extracellular release irrespective of the concentration of L-glutamine in the medium. GABA was transaminated to L-leucine whose intracellular concentration did not change because it was efficiently transported out of the islet cells. The L-[U-14C]-Glutamine (at 0.5 and 10.0 mM) conversion to 14CO2 was enhanced by 10 mM OMP within 30% and 70% respectively. Gabaculine (250 microM), a GABA transaminase inhibitor, suppressed OMP-induced oxygen consumption but not L-leucine- or glucose-stimulated respiration. It also suppressed the OMP-induced decrease in islet GABA content and the OMP-induced increase in insulin release. These results support the view that OMP promotes islet metabolism in the 'GABA shunt' generating 2-oxo-glutarate, in the branched-chain alpha-amino acid transaminase reaction, which would in turn trigger GABA deamination by GABA transaminase. OMP, but not L-leucine, suppressed islet semialdehyde succinic acid reductase activity and this might shift the metabolic flux of the 'GABA shunt' from gamma-hydroxybutyrate to succinic acid production.

  13. Depletion of polyamines prevents the neurotrophic activity of the GABA-agonist THIP in cultured rat cerebellar granule cells

    DEFF Research Database (Denmark)

    Abraham, J H; Hansen, Gert Helge; Seiler, N

    1993-01-01

    Effects of polyamine depletion by alpha-difluoromethylornithine (DFMO) were studied on the GABA-agonist mediated enhancement of the morphological development of cultured rat cerebellar granule cells. An increase in the number of neurite extending cells and in the cytoplasmic density of organelles...... endoplasmic reticulum, Golgi apparatus and different types of vesicles was prevented by the exposure to DFMO....

  14. Electrical stimulation of the substantia nigra reticulata : Detection of neuronal extracellular GABA in the ventromedial thalamus and its regulatory mechanism using microdialysis in awake rats

    NARCIS (Netherlands)

    Timmerman, W; Westerink, BHC

    1997-01-01

    A combination of electrical stimulation and microdialysis was used to study the nigrothalamic gamma aminobutyric acid (GABA)ergic system and its regulatory mechanisms in awake rats. Extracellular GABA levels in the ventromedial nucleus of the thalamus were detected in S-min fractions collected befor

  15. Glucocorticoids modulate the NGF mRNA response in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2001-02-23

    Nerve growth factor (NGF) expression in the rat hippocampus is increased after experimental traumatic brain injury (TBI) and is neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the expression of NGF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury and in situ hybridisation to evaluate the expression of NGF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomised rats (with or without CORT replacement). TBI increased expression of NGF mRNA in sham-ADX rats, but not in ADX rats. Furthermore, CORT replacement in ADX rats restored the increase in NGF mRNA induced by TBI. These findings suggest that glucocorticoids have an important role in the induction of hippocampal NGF mRNA after TBI.

  16. GABAergic gene expression in postmortem hippocampus from alcoholics and cocaine addicts; corresponding findings in alcohol-naive P and NP rats.

    Directory of Open Access Journals (Sweden)

    Mary-Anne Enoch

    Full Text Available BACKGROUND: By performing identical studies in humans and rats, we attempted to distinguish vulnerability factors for addiction from neurobiological effects of chronic drug exposure. We focused on the GABAergic system within the hippocampus, a brain region that is a constituent of the memory/conditioning neuronal circuitry of addiction that is considered to be important in drug reinforcement behaviors in animals and craving and relapse in humans. METHODOLOGY: Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, alcohol preferring (P and non-preferring (NP rats selectively bred for extremes of alcohol-seeking behavior that also show a general addictive tendency. A pathway-targeted analysis of 25 GABAergic genes encoding proteins implicated in GABA synthesis, metabolism, synaptic transmission and re-uptake was undertaken. PRINCIPAL FINDINGS: Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10⁻¹⁴, 7×10⁻¹¹ respectively. Principal FDR-corrected findings were that GABBR1 was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in NSF, implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. GABRG2, encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with GPHN, encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (GAD1, GAD2, alcoholics (GABRA2 and P rats (ABAT, GABRG3. CONCLUSIONS/SIGNIFICANCE: Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA

  17. Regulation of GABA(A and glutamate receptor expression, synaptic facilitation and long-term potentiation in the hippocampus of prion mutant mice.

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    Alejandra Rangel

    Full Text Available BACKGROUND: Prionopathies are characterized by spongiform brain degeneration, myoclonia, dementia, and periodic electroencephalographic (EEG disturbances. The hallmark of prioniopathies is the presence of an abnormal conformational isoform (PrP(sc of the natural cellular prion protein (PrP(c encoded by the Prnp gene. Although several roles have been attributed to PrP(c, its putative functions in neuronal excitability are unknown. Although early studies of the behavior of Prnp knockout mice described minor changes, later studies report altered behavior. To date, most functional PrP(c studies on synaptic plasticity have been performed in vitro. To our knowledge, only one electrophysiological study has been performed in vivo in anesthetized mice, by Curtis and coworkers. They reported no significant differences in paired-pulse facilitation or LTP in the CA1 region after Schaffer collateral/commissural pathway stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Here we explore the role of PrP(c expression in neurotransmission and neural excitability using wild-type, Prnp -/- and PrP(c-overexpressing mice (Tg20 strain. By correlating histopathology with electrophysiology in living behaving mice, we demonstrate that both Prnp -/- mice but, more relevantly Tg20 mice show increased susceptibility to KA, leading to significant cell death in the hippocampus. This finding correlates with enhanced synaptic facilitation in paired-pulse experiments and hippocampal LTP in living behaving mutant mice. Gene expression profiling using Illumina microarrays and Ingenuity pathways analysis showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission were co-regulated in Prnp -/- and Tg20 mice. Lastly, RT-qPCR of neurotransmission-related genes indicated that subunits of GABA(A and AMPA-kainate receptors are co-regulated in both Prnp -/- and Tg20 mice. CONCLUSIONS/SIGNIFICANCE: Present results demonstrate that PrP(c is necessary for the

  18. Effects of thyroid status on the characteristics of alpha sub 1 -, alpha sub 2 -, beta, imipramine and GABA receptors in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Sandrini, M.; Marrama, D.; Vergoni, A.V.; Bertolini, A. (Univ. of Modena (Italy))

    1991-01-01

    The effects of a chronic treatment with L-triiodothyronine or with propylthiouracil on the characteristics of alpha{sub 1}, alpha{sub 2}, beta, imipramine and GABA binding sites in different brain areas of the adult rat have been studied. T{sub 3}-treatment caused an increase in the number of ({sup 3}H)dihydroalprenolol and a decrease in the number of ({sup 3}H)muscimol binding sites in the cerebral cortex. PTU-treatment caused a decrease in the number of ({sup 3}H)prazosin, ({sup 3}H)yohimbine and ({sup 3}H)dihydroalprenolol binding sites in the cerebral cortex, while the number of ({sup 3}H)imipramine binding sites was reduced in the cerebral cortex and hypothalamus, and increased in the hippocampus. Affinity constants were never modified. Concurrent experiments showed that the in vitro addition of T{sub 3} and PTU did not influence the binding of any of the ligands employed to control rat brain membranes. The present data further support the view that neurotransmission in the CNS is influenced by the thyroid status.

  19. Activity- and age-dependent GABAergic synaptic plasticity in the developing rat hippocampus.

    Science.gov (United States)

    Gubellini, P; Ben-Ari, Y; Gaïarsa, J L

    2001-12-01

    Activity-dependent plasticity of GABAergic synaptic transmission was investigated in rat hippocampal slices obtained between postnatal day (P) 0-15 using the whole-cell patch-clamp recording technique. Spontaneous GABA(A) receptor-mediated postsynaptic currents (sGABA(A)-PSCs) were isolated in the presence of ionotropic glutamate receptor antagonists. A conditioning protocol relevant to the physiological condition, consisting of repetitive depolarizing pulses (DPs) at 0.1 Hz, was able to induce long-lasting changes in both frequency and amplitude of sGABA(A)-PSCs between P0 and P8. Starting from P12, DPs were unable to induce any form of synaptic plasticity. The effects of DPs were tightly keyed to the frequency at which they were delivered. When delivered at a lower (0.05 Hz) or higher (1 Hz) frequency, DPs failed to induce any long-lasting change in the frequency or amplitude of sGABA(A)-PSCs. In two cases, DPs were able to activate sGABA(A)-PSCs in previously synaptically silent cells at P0-1. These results show that long-term changes in GABAergic synaptic activity can be induced during a restricted period of development by a conditioning protocol relevant to the physiological condition. It is suggested that such activity-induced modifications may represent a physiological mechanism for the functional maturation of GABAergic synaptic transmission.

  20. Cell type-specific synaptic dynamics of synchronized bursting in the juvenile CA3 rat hippocampus.

    Science.gov (United States)

    Aradi, Ildiko; Maccaferri, Gianmaria

    2004-10-27

    Spontaneous synchronous bursting of the CA3 hippocampus in vitro is a widely studied model of physiological and pathological network synchronization. The role of inhibitory conductances during network bursting is not understood in detail, despite the fact that several antiepileptic drugs target GABA(A) receptors. Here, we show that the first manifestation of a burst event is a cell type-specific flurry of GABA(A) receptor-mediated inhibitory input to pyramidal cells, but not to stratum oriens horizontal interneurons. Moreover, GABA(A) receptor-mediated synaptic input is proportionally smaller in these interneurons compared with pyramidal cells. Computational models and dynamic-clamp studies using experimentally derived conductance waveforms indicate that both these factors modulate spike timing during synchronized activity. In particular, the different kinetics and the larger strength of GABAergic input to pyramidal cells defer action potential initiation and contribute to the observed delay of firing, so that the interneuronal activity leads the burst cycle. In contrast, excitatory inputs to both neuronal populations during a burst are kinetically similar, as required to maintain synchronicity. We also show that the natural pattern of activation of inhibitory and excitatory conductances during a synchronized burst cycle is different within the same neuronal population. In particular, GABA(A) receptor-mediated currents activate earlier and outlast the excitatory components driving the bursts. Thus, cell type-specific balance and timing of GABA(A) receptor-mediated input are critical to set the appropriate spike timing in pyramidal cells and interneurons and coordinate additional neurotransmitter release modulating burst strength and network frequency.

  1. Chronaxie Measurements in Patterned Neuronal Cultures from Rat Hippocampus.

    Science.gov (United States)

    Stern, Shani; Agudelo-Toro, Andres; 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.

  2. Chronaxie Measurements in Patterned Neuronal Cultures from Rat Hippocampus.

    Directory of Open Access Journals (Sweden)

    Shani Stern

    Full Text Available 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.

  3. Morphine Withdrawal Modifies Prion Protein Expression in Rat Hippocampus

    Science.gov (United States)

    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

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

    OpenAIRE

    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 t...

  5. Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin

    DEFF Research Database (Denmark)

    Brust, P; Christensen, Thomas; Diemer, Nils Henrik

    1992-01-01

    The extracellular amino acid concentrations in the left and right dorsal hippocampus of male rats were studied before and during application of vasopressin into the right hippocampus. The method of intracerebral microdialysis was used for both arginine vasopressin administration and monitoring...... of the composition of the extracellular fluid. The concentrations of 16 amino acids were measured by HPLC in the perfusate samples. The level of taurine declined 20% in the right hippocampus during perfusion with vasopressin, whereas o-phosphoethanolamine decreased in both sides, the left 20% and the right 24...

  6. Roles of forebrain GABA receptors in controlling vasopressin secretion and related phenomena under basal and hyperosmotic circumstances in conscious rats.

    Science.gov (United States)

    Yamaguchi, Ken'ichi; Yamada, Takaho

    2008-09-05

    Although the anteroventral third ventricular region (AV3V), a forebrain area essential for homeostatic responses, includes receptors for gamma-aminobutyric acid (GABA), the roles of these receptors in controlling vasopressin (AVP) secretion and related phenomena have not been clarified as yet. This study aimed to pursue this problem in conscious rats implanted with indwelling catheters. Cerebral injection sites were determined histologically. Applications of bicuculline, a GABA(A) receptor antagonist, to the AV3V induced prompt and marked augmentations in plasma AVP, osmolality, glucose, arterial pressure and heart rate, without affecting plasma electrolytes. Such phenomena did not occur when phaclofen, a GABA(B) receptor antagonist, was applied to the AV3V. All of the effects of AV3V-administered bicuculline were abolished by preadministration of the GABA(A) receptor agonist muscimol. Preadministration of either MK-801 or NBQX, ionotropic glutamatergic receptor antagonists, was also potent to abolish the AVP response to AV3V bicuculline. When hypertonic saline was infused intravenously, plasma AVP increased progressively, in parallel with rises in plasma osmolality, sodium and arterial pressure. AV3V application of muscimol or baclofen, a GABA(B) receptor agonist, was found to abolish the response of plasma AVP, without inhibiting that of the osmolality or sodium. The response of arterial pressure was also blocked by muscimol treatment, but not by baclofen treatment. Based on these results, we concluded that, under basal conditions, GABA receptors in the AV3V or vicinity may tonically operate to attenuate AVP secretion and cardiovascular functions through mechanisms associated with glutamatergic activity, and that plasma hyperosmolality may cause facilitation of AVP release by decreasing forebrain GABAergic activity.

  7. [GABA--the basic mediator of excitation in the early stages of hippocampal development].

    Science.gov (United States)

    Khazipov, R N; Zefirov, A L; Ben-Ari, E

    1998-01-01

    GABA is the principal neurotransmitter of inhibition in the adult mammalian brain. However, at early stages of development, including embryonic period and first week of postnatal life, GABA plays the role of main neurotransmitter of excitation. The paradoxical excitatory effect of GABA is due to an inversed chloride gradient and therefore a depolarizing direction of GABA-A receptor mediated responses. In addition, another type of GABAergic inhibition mediated by postsynaptic GABA-B receptors is not functional at early stage of life. In the neonatal rat hippocampus, GABA, acting via GABA-A receptors, activates voltage gated sodium and calcium channels and potentiates the activity of NMDA receptors by reducing their voltage dependent Mg2+ block. The temporal window when GABA exerts excitatory actions coincides with a particular pattern of activity of hippocampal neuronal network that is characterized by periodical giant depolarizing potentials (GDPs) reminiscent of interictal-like epileptiform discharges. Recent studies have shown that GDPs result from the synchronous discharge of GABAergic interneurons and principal glutamatergic pyramidal cells and are mediated by the synergistic excitatory actions of GABA-A and glutamate receptors. GDPs provide synchronous intracellular Ca2+ oscillations and may therefore be implicated in hebbian modulation of developing synapses and activity-dependent formation of the hippocampal network.

  8. Glucocorticoids modulate BDNF mRNA expression in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2000-10-20

    Brain-derived neurotrophic factor (BDNF) expression in rat hippocampus is increased after experimental traumatic brain injury (TBI) and may be neuroprotective. Glucocorticoids are important regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) on the expression of BDNF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury (FPI) and in situ hybridization to evaluate the expression of BDNF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomized rats (with or without corticosterone replacement). FPI and ADX independently increased expression of BDNF mRNA. In animals undergoing FPI, prior ADX caused further elevation of BDNF mRNA and this upregulation was prevented by corticosterone replacement in ADX rats. These findings suggest that glucocorticoids are involved in the modulation of the BDNF mRNA response to TBI.

  9. Mathematical Identification of a Neuronal Network Consisting of GABA and DA in Striatal Slices of the Rat Brain

    Directory of Open Access Journals (Sweden)

    L. Ramrath

    2009-01-01

    Full Text Available High frequency stimulation (HFS has been used to treat various neurological and psychiatric diseases. Although further disorders are under investigation to extend the clinical application of HFS, the complex effect of HFS within a neuronal network is still unknown. Thus, it would be desirable to find a theoretical model that allows an estimation of the expected effect of applied HFS. Based on the neurochemical analysis of effects of the γ-aminobutyric acid (GABAA receptor antagonist bicuculline, the D2-like receptor antagonist sulpiride and the D1-like receptor antagonist SCH-23390 on HFS evoked GABA and dopamine (DA release from striatal slices of the rat brain, a mathematical network model is proposed including the neurotransmitters GABA, DA and glutamate (GLU. The model reflects inhibitory and excitatory interactions of the neurotransmitters outflow in the presence of HFS. Under the assumption of linear interactions and static measurements, the model is expressed analytically. Numerical identification of inhibition and excitation is performed on a basis of real outflow levels of GABA and DA in the rat striatum. Results validate the nature of the proposed model. Therefore, this leads to an analytical model of the interactions within distinct neural network components of the rat striatum.

  10. Postsynaptic targets of somatostatin-immunoreactive interneurons in the rat hippocampus.

    Science.gov (United States)

    Katona, I; Acsády, L; Freund, T F

    1999-01-01

    Two characteristic interneuron types in the hippocampus, the so-called hilar perforant path-associated cells in the dentate gyrus and stratum oriens/lacunosum-moleculare neurons in the CA3 and CA1 regions, were suggested to be involved in feedback circuits. In the present study, interneurons identical to these cell populations were visualized by somatostatin-immunostaining, then reconstructed, and processed for double-immunostaining and electron microscopy to establish their postsynaptic target selectivity. A combination of somatostatin-immunostaining with immunostaining for GABA or other interneuron markers revealed a quasi-random termination pattern. The vast majority of postsynaptic targets were GABA-negative dendritic shafts and spines of principal cells (76%), whereas other target elements contained GABA (8%). All of the examined neurochemically defined interneuron types (parvalbumin-, calretinin-, vasoactive intestinal polypeptide-, cholecystokinin-, substance P receptor-immunoreactive neurons) received innervation from somatostatin-positive boutons. Recent anatomical and electrophysiological data showed that the main excitatory inputs of somatostatin-positive interneurons originate from local principal cells. The present data revealed a massive GABAergic innervation of distal dendrites of local principal cells by these feedback driven neurons, which are proposed to control the efficacy and plasticity of entorhinal synaptic input as a function of local principal cell activity and synchrony.

  11. Effects of motilin in the hippocampus on the interdigestive migrating motor complex in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Mei; DONG Lei; DUAN Zhong-ping; ZHU Wen-yi; CUI Yang; LEI Li

    2005-01-01

    Objective :To explore the effects of motilin in the hippocampus on the interdigestive migrating motor complex (MMC) in rats. Methods: Adult SD rats of either sex were used; 0.5 μl motilin (0. 74mmol/L) was injected into the guide cannula which was stereotaxically implanted into the hippocampus previously. Then the MMC was recorded by a RM6240B multilead physiological recording system. Results: (1) MMC characteristics of normal rats' duodenum: the frequency of phase Ⅲ was (18. 1 ± 0. 4)bursts/min; the amplitude of phase Ⅲ was (260. 5±42.3)μV; the duration of phase Ⅲ was (354. 1±21.6) s; MMC cycle duration was (690.2±58.7)s. (2) After motilin was injected into the hippocampus,the duodenal MMC cycle duration was decreased significantly. However, the amplitude of phase Ⅲ and the frequency of phase Ⅲ were increased. But there were no effects on the duration of phase Ⅲ. Frequency of phase Ⅲ percentage change was much more than amplitude of phase Ⅲ percentage change (57.2±2.8 vs39.3± 5. 2). (3) Effects of motilin in the hippocampus on MMC were completely abolished by subdiaphragmal vagotomy. (4) Effects of motilin in the hippocampus on MMC were unaffected by intravenously injected atropine, phentolamine or propranolol. (5) The anti-motilin serum partly abolished the effects of motilin in the hippocampus on MMC. Conclusion: Motilin in the hippocampus has effects on the duodenal MMC cycle duration, the amplitude of phase Ⅲ and the frequency of phase Ⅲ. Motilin in the hippocampus plays an important role in duodenal MMC.

  12. [The distribution of GABA-ergic neurons in rat neocortex in the postnatal period after the perinatal hypoxia].

    Science.gov (United States)

    Khozhaĭ, L I; Otelin, V A

    2014-01-01

    The distribution of GABA-ergic neurons in different areas of the neocortex (frontal, sensorimotor, visual cortex) was studied in Wistar rats at different time periods of postnatal development after their exposure to perinatal hypoxia. To identify these neurons, the antibodies against GAD-67, the marker of GABA-ergic neurons, were used. It was found that the exposure to perinatal hypoxia caused a significant reduction in the number of GAD-67-expressing neurons in both upper and deep layers of the cortex in juvenile age (day 20 of postnatal period), that persisted until the prepubertal period (day 40). In experimental animals at postnatal day 40, the numbers of neurons that synthesized GAD-67, were two times lower in each of the layers of the neocortex than those in control animals. It is suggested that a drastic reduction in the number of GABA-ergic neurons in the neocortex could be a result of the damaging effects of acute perinatal hypoxia on the processes of progenitor cell migration from the subventricular zone, or on the synthesis of the factors controlling these migration processes as well as on GABA-ergic neuron maturation, leading to a delay of GAD-67 expression.

  13. Enhanced pyridoxal 5'-phosphate synthetic enzyme immunoreactivities do not contribute to GABAergic inhibition in the rat hippocampus following pilocarpine-induced status epilepticus.

    Science.gov (United States)

    Kwak, S-E; Kim, J-E; Kim, D-W; Kwon, O-S; Choi, S-Y; Kang, T-C

    2009-03-31

    To comprehend the role of pyridoxal 5'-phosphate (PLP) in epilepsy or seizure, we investigated whether the expressions of two PLP synthetic enzymes (pyridoxal kinase, PLK; pyridoxine-5'-phosphate oxidase, PNPO) are altered in the hippocampus and whether changes in paired-pulse responses in the hippocampus are associated with altered PLP synthetic enzyme expressions following status epilepticus (SE). PLK and PNPO immunoreactivities were significantly increased in the rat hippocampus accompanied by reductions in paired-pulse inhibition at 1 day and 1 week after SE. Four weeks after SE, PLK and PNPO immunoreactivities in dentate granule cells were similar to those in control animals, while their immunoreactivities were markedly reduced in Cornu Ammonis 1 (CA1) pyramidal cells due to neuronal loss. Linear regression analysis identified a direct proportional relationship between PLK/PNPO immunoreactivity and normalized population spike amplitude ratio in the dentate gyrus and the CA1 region as excluded the data obtained from 4 weeks after SE. These findings indicate that the upregulation of PLK and PNPO immunoreactivities in principal neurons may not be involved in gamma-aminobutyric acid (GABA)ergic inhibition, but rather in enhanced excitability during epileptogenic periods.

  14. Sex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress

    Directory of Open Access Journals (Sweden)

    Sanoara Mazid

    2016-12-01

    Full Text Available Drug addiction requires associative learning processes that critically involve hippocampal circuits, including the opioid system. We recently found that acute and chronic stress, important regulators of addictive processes, affect hippocampal opioid levels and mu opioid receptor trafficking in a sexually dimorphic manner. Here, we examined whether acute and chronic stress similarly alters the levels and trafficking of hippocampal delta opioid receptors (DORs. Immediately after acute immobilization stress (AIS or one-day after chronic immobilization stress (CIS, the brains of adult female and male rats were perfusion-fixed with aldehydes. The CA3b region and the dentate hilus of the dorsal hippocampus were quantitatively analyzed by light microscopy using DOR immunoperoxidase or dual label electron microscopy for DOR using silver intensified immunogold particles (SIG and GABA using immunoperoxidase. At baseline, females compared to males had more DORs near the plasmalemma of pyramidal cell dendrites and about 3 times more DOR-labeled CA3 dendritic spines contacted by mossy fibers. In AIS females, near-plasmalemmal DOR-SIGs decreased in GABAergic hilar dendrites. However, in AIS males, near-plasmalemmal DOR-SIGs increased in CA3 pyramidal cell and hilar GABAergic dendrites and the percentage of CA3 dendritic spines contacted by mossy fibers increased to about half that seen in unstressed females. Conversely, after CIS, near-plasmalemmal DOR-SIGs increased in hilar GABA-labeled dendrites of females whereas in males plasmalemmal DOR-SIGs decreased in CA3 pyramidal cell dendrites and near-plasmalemmal DOR-SIGs decreased hilar GABA-labeled dendrites. As CIS in females, but not males, redistributed DOR-SIGs near the plasmalemmal of hilar GABAergic dendrites, a subsequent experiment examined the acute affect of oxycodone on the redistribution of DOR-SIGs in a separate cohort of CIS females. Plasmalemmal DOR-SIGs were significantly elevated on hilar

  15. Sex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress.

    Science.gov (United States)

    Mazid, Sanoara; Hall, Baila S; Odell, Shannon C; Stafford, Khalifa; Dyer, Andreina D; Van Kempen, Tracey A; Selegean, Jane; McEwen, Bruce S; Waters, Elizabeth M; Milner, Teresa A

    2016-12-01

    Drug addiction requires associative learning processes that critically involve hippocampal circuits, including the opioid system. We recently found that acute and chronic stress, important regulators of addictive processes, affect hippocampal opioid levels and mu opioid receptor trafficking in a sexually dimorphic manner. Here, we examined whether acute and chronic stress similarly alters the levels and trafficking of hippocampal delta opioid receptors (DORs). Immediately after acute immobilization stress (AIS) or one-day after chronic immobilization stress (CIS), the brains of adult female and male rats were perfusion-fixed with aldehydes. The CA3b region and the dentate hilus of the dorsal hippocampus were quantitatively analyzed by light microscopy using DOR immunoperoxidase or dual label electron microscopy for DOR using silver intensified immunogold particles (SIG) and GABA using immunoperoxidase. At baseline, females compared to males had more DORs near the plasmalemma of pyramidal cell dendrites and about 3 times more DOR-labeled CA3 dendritic spines contacted by mossy fibers. In AIS females, near-plasmalemmal DOR-SIGs decreased in GABAergic hilar dendrites. However, in AIS males, near-plasmalemmal DOR-SIGs increased in CA3 pyramidal cell and hilar GABAergic dendrites and the percentage of CA3 dendritic spines contacted by mossy fibers increased to about half that seen in unstressed females. Conversely, after CIS, near-plasmalemmal DOR-SIGs increased in hilar GABA-labeled dendrites of females whereas in males plasmalemmal DOR-SIGs decreased in CA3 pyramidal cell dendrites and near-plasmalemmal DOR-SIGs decreased hilar GABA-labeled dendrites. As CIS in females, but not males, redistributed DOR-SIGs near the plasmalemmal of hilar GABAergic dendrites, a subsequent experiment examined the acute affect of oxycodone on the redistribution of DOR-SIGs in a separate cohort of CIS females. Plasmalemmal DOR-SIGs were significantly elevated on hilar interneuron

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

    Science.gov (United States)

    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.

  17. Early repeated maternal separation induces alterations of hippocampus reelin expression in rats

    Indian Academy of Sciences (India)

    Jianlong Zhang; Lina Qin; Hu Zhao

    2013-03-01

    The long-term effects of repeated maternal separation (MS) during early postnatal life on reelin expression in the hippocampus of developing rats were investigated in the present study. MS was carried out by separating Wistar rat pups singly from their mothers for 3 h a day during postnatal days (PND) 2–14. Reelin mRNA and protein levels in the hippocampus were determined using qRT-PCR and Western blotting, at PND 22, PND 60 and PND 90. MS resulted in the loss of body weight in the developing rats, and reelin mRNA and protein levels in the hippocampus generally were down-regulated over the developing period, but the reelin mRNA and protein levels in the hippocampus of 90-day-old male rats were up-regulated. These findings suggest that the long-term effects of MS on the expression levels of hippocampal reelin mRNA and protein depends on the age at which the stressed rats’ brains were collected; reelin had important implications for the maternal-neonate interaction needed for normal brain development. In conclusion, repeated MS occurring during early postnatal life may cause the alterations of hippocampal reelin expression with the increasing age of developing rats.

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

    Science.gov (United States)

    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.

  19. Expression of Toll-like receptor 4 in hippocampus of rat model with temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    PAN Li-ping

    2013-12-01

    Full Text Available Objective To investigate the expression of Toll-like receptor 4 (TLR4 protein in hippocampus of rat model with temporal lobe epilepsy after status epilepticus (SE and explore its function in the pathogenesis of temporal lobe epilepsy. Methods Rat model with temporal lobe epilepsy was induced by lithium chloride (LiCl-pilocarpine. Total protein was extracted from hippocampus and rat brain slices were obtained at different time points (0, 1, 6, 12, 24, 48 h and 7, 10, 30, 50 d after SE. Western blotting and immunohistochemical staining were used for detection of the expression of TLR4 in the hippocampus. Results The results of Western blotting showed the TLR4 protein expression at 0, 1, 6, 12, 24, 48 h and 7, 10, 30 d after SE was higher than that in the control group (P 0.05. Conclusion TLR4 protein was mainly expressed in cytoplasm of pyramidal cells in CA3 area of hippocampus. TLR4 protein expression in the hippocampus was increased in varying degrees at different observation time points after SE, indicating that TLR4 may play an important role in the development of epilepsy.

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

    Directory of Open Access Journals (Sweden)

    Jeanine Manuella Kamsu

    Full Text Available 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.

  1. Regulation of Astroglia on Synaptic Plasticity in the CA1 Region of Rat Hippocampus

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The regulation of astroglia on synaptic plasticity in the CA1 region of rat hippocampus was examined. Rats were divided into three groups: the newly born (<24 h), the juvenile (28-30days) and the adult groups (90-100 days), with each group having 20 animals. The CA1 region of rat hippocampus was immunohistochemically and electron-microscopically examined, respectively,for the growth of astroglia and the ultrastructure of synapses. The high performance liquid chromatography was employed to determine the cholesterol content of rat hippocampus. In the newly-born rats, a large number of neurons were noted in the hippocampal CA1 region of the newly-born rats,and few astroglia and no synaptic structure were observed. In the juvenile group, a few astroglias and some immature synapses were found, which were less than those in adult rats (P<0.01). The cholesterol content was 2.92±0.03 mg/g, 11.20± 3.41 mg/g and 12.91 ± 1.25 mg/g for newly born, the juvenile and the adult groups, respectively, with the differences among them being statistically significant (P<0.01). Our study suggests that the astrocytes may play an important role in the synaptic formation and functional maturity of hippocampal neurons, which may be related to the secretion of cholesterol from astrocytes.

  2. Mitochondrial plasticity of the hippocampus in a generic rat model of depression after antidepressant treatment

    DEFF Research Database (Denmark)

    Chen, Fenghua; Wegener, Gregers; Madsen, Torsten Meldgaard;

    2012-01-01

    investigated the changes in mitochondrial plasticity and its correlation to morphological alterations of neuroplasticity in the hippocampus, both associated with a depressive phenotype, and after treatment, with antidepressant imipramine. Design-based stereological methods were used to estimate the number...... and volume of mitochondria in CA1 of the hippocampus in two different strains of rats, the Sprague-Dawley (SD) and Flinders rats, which display a genetic susceptibility to depressive behavior, the Flinders-sensitive line (FSL) and their corresponding controls, the Flinders-resistant line (FRL). Results...... of mitochondrial plasticity in the hippocampus and antidepressant treatment may counteract with the structural impairments. Moreover, the changes in mitochondrial morphology and number are a consistent feature of neuroplasticity. Synapse, 2013. © 2012 Wiley Periodicals, Inc....

  3. Corticosterone modulation of neurotransmitter receptors in rat hippocampus: a quantitative autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A. (Hoffmann-La Roche, Inc., Nutley, NJ (USA). Dept. of Pharmacology); Rainbow, T.C. (Pennsylvania Univ., Philadelphia (USA). School of Medicine); McEwen, B.S. (Rockefeller Univ., New York (USA))

    1985-04-22

    The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on neurotransmitter receptors was studied in dorsal hippocampus of rat using quantitative autoradiography. ADX for one week causes an increase in (/sup 3/H)5-HT binding to 5-HT/sub 1/ receptors which is significant in the CA1 cell field. CORT treatment of ADX rats for 3-5 days results in localized reductions of (/sup 3/H)5-HT binding including a partial reversal of the increase observed after ADX in CA1. CORT treatment of ADX animals also decreases binding of (/sup 3/H)QNB to muscarinic receptors in the dorsal hippocampus, with a significant effect in an area designated as subiculum. No influence of CORT was detected on (/sup 3/H)prazosin binding to alpha/sub 1/ adrenergic receptors in dorsal hippocampus. Possible mechanisms for hormone effects on neurotransmitter receptor levels are discussed.

  4. Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray

    Directory of Open Access Journals (Sweden)

    Shin Minkyu

    2010-11-01

    Full Text Available Abstract Background The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. Results We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine. a selective serotonin reuptake inhibitor (fluoxetine, a monoamine oxidase inhibitor (phenelzine and psychoactive herbal extracts of Nelumbinis Semen (NS. To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFβ, was significantly enhanced. Conclusions These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.

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

    Science.gov (United States)

    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 anti-aging property of EPO. PMID:26261574

  6. Progenitor cells from the CA3 region of the embryonic day 19 rat hippocampus generate region-specific neuronal phenotypes in vitro.

    Science.gov (United States)

    Shetty, Ashok K

    2004-01-01

    Progenitor cells that endure in different regions of the CNS after the initial neurogenesis can be expanded in culture and used as a source of donor tissue for grafting in neurodegenerative diseases. However, the proliferation and differentiation characteristics of residual neural progenitor cells from distinct regions of the CNS are mostly unknown. This study elucidated the characteristics of progenitor cells that endure in the CA3 region of the hippocampus after neurogenesis, by in vitro analyses of cells that are responsive to epidermal growth factor (EGF) or fibroblast growth factor-2 (FGF-2) in the embryonic day 19 (E19) rat hippocampus. Isolated cells from the E19 CA3 region formed neurospheres in the presence of either EGF or FGF-2, but the yield of neurospheres was greater with FGF-2 exposure, Differentiation cultures revealed a greater yield of neurons from FGF-2 neurospheres (60%) than from EGF neurospheres (35%). Exposure to brain-derived neurotrophic factor (BDNF) enhanced the yield of neurons from EGF neurospheres but had no consequence on FGF-2 neurospheres. A large number of neurons from EGF/FGF-2 neurospheres demonstrated clearly palpable morphological features of CA3 pyramidal neurons and lacked gamma-aminobutyric acid (GABA) expression. However, a fraction of neurons (17-20%) from EGF/FGF-2 neurospheres expressed GABA, and exposure to BDNF increased the number of GABAergic neurons (30%) from EGF neurospheres. Neurons from EGF/FGF-2 neurospheres also contained smaller populations of calbindin- and calretinin-positive interneuron-like cells. Thus, progenitor cells responsive to FGF-2 are prevalent in the CA3 region of the E19 rat hippocampus and give rise to a greater number of neurons than progenitor cells responsive to EGF. However, both FGF-2- and EGF-responsive progenitor cells from E19 CA3 region are capable of giving rise to CA3 field-specific phenotypic neurons. These results imply that progenitor cells that persist in the hippocampus after

  7. Membrane voltage modulates the GABA(A) receptor gating in cultured rat hippocampal neurons.

    Science.gov (United States)

    Pytel, Maria; Mercik, Katarzyna; Mozrzymas, Jerzy W

    2006-02-01

    The kinetics of GABAergic currents in neurons is known to be modulated by the membrane voltage but the underlying mechanisms have not been fully explored. In particular, the impact of membrane potential on the GABA(A) receptor gating has not been elucidated. In the present study, the effect of membrane voltage on current responses elicited by ultrafast GABA applications was studied in cultured hippocampal neurons. The current to voltage relationship (I-V) for responses to saturating [GABA] (10 mM) showed an inward rectification (slope conductance at positive voltages was 0.62 +/- 0.05 of that at negative potentials). On the contrary, I-V for currents evoked by low [GABA] (1 microM) showed an outward rectification. The onset of currents elicited by saturating [GABA] was significantly accelerated at positive potentials. Analysis of currents evoked by prolonged applications of saturating [GABA] revealed that positive voltages significantly increased the rate and extent of desensitization. The onsets of current responses to non-saturating [GABA] were significantly accelerated at positive voltages indicating an enhancement of the binding rate. However, at low [GABA] at which the onset rate is expected to approach an asymptote set by opening/closing and unbinding rates, no significant modification of current onset by voltage was observed. Quantitative analysis based on model simulations indicated that the major effect of membrane depolarization was to increase the rates of binding, desensitization and of opening as well as to slightly reduce the rate of exit from desensitization. In conclusion, we provide evidence that membrane voltage affects the GABA(A) receptor microscopic gating.

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  10. Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

    Directory of Open Access Journals (Sweden)

    P S Santos

    2011-01-01

    Full Text Available Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p. with 0.9% saline (Control, pilocarpine (400 mg/kg, Pilocarpine, LA (10 mg/kg, LA, and the association of LA (10 mg/kg plus pilocarpine (400 mg/kg, that was injected 30 min before of administration of LA (LA plus pilocarpine. Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC. In pilocarpine group, it was observed a significant increase in glutamate content (37% and a decrease in taurine level (18% in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28% and augmented taurine content (32% in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

  11. Upregulation of voltage-activated potassium channels in hippocampus of Aβ25.35-treated rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-liangWANG; Ya-pingPAN

    2004-01-01

    AIM: Potassium channels dysfunction has been indicated in Alzheimer disease. In the present study, the mRNA and protein expression alterations and the functional changes ot VOltage- activated potassium channels were studied in rat hippocampus after a single intracerebro- ventricular injection of β-amyloid peptide 25-35 (Aβ25.35). METHODS: The expressions of mRNA

  12. Parvalbumin-Positive Neurons in Rat Dorsal Hippocampus Contain Muscarinic Acetylcholine Receptors

    NARCIS (Netherlands)

    Zee, E.A. van der; de Jong, Giena; Strosberg, A.D.; Luiten, P.G.M.

    1991-01-01

    The present study describes the colocalization of muscarinic acetylcholine receptors (mAChRs) and the calcium-binding protein parvalbumin (PARV) in nonpyramidal neurons of the rat dorsal hippocampus by means of dual-label immunocytochemistry. Fifty-two percent of all muscarinic cholinoceptive

  13. Morphology of CA3 non-pyramidal cells in the developing rat hippocampus.

    OpenAIRE

    Gaïarsa, Jean-Luc; Khalilov, Ilgam; Gozlan, Henri; Ben-Ari, Yehezkel

    2001-01-01

    International audience; Although several investigations have shown that the local GABAergic circuit in the rat hippocampus is functional very early in development, this result has not been yet completed by the investigation of the full dendritic and axonal arborization of the neonatal interneurones. In the present study, intracellular injection of biocytin was used to assess the branching pattern of interneurones in the hippocampal CA3 region of rat between 2 and 6 days of age. Based on their...

  14. Status epilepticus results in reversible neuronal injury in infant rat hippocampus: novel use of a marker

    OpenAIRE

    Chang, Daniel; Tallie Z. Baram

    1994-01-01

    Despite ready induction of severe limbic status epilepticus by systemic kainic acid (KA) in infant rats, excitotoxic neuronal injury has not been observed. The mechanisms of this resistance of the immature hippocampus to excitotoxicity are unknown. Acid fuchsin stain has been used as a marker of irreversibly injured neurons in the adult brain. We speculated that the dye might map reversibly injured neurons in the infant. Subsequent to KA-induced status epilepticus in 11-day-old rats, acid fuc...

  15. Memantine treatment reduces the expression of the K(+)/Cl(-) cotransporter KCC2 in the hippocampus and cerebral cortex, and attenuates behavioural responses mediated by GABA(A) receptor activation in mice.

    Science.gov (United States)

    Molinaro, Gemma; Battaglia, Giuseppe; Riozzi, Barbara; Di Menna, Luisa; Rampello, Liborio; Bruno, Valeria; Nicoletti, Ferdinando

    2009-04-10

    A 7-day treatment with memantine (25 mg/kg, i.p.), a drug that is currently prescribed for the treatment of Alzheimer's disease, increased the levels of brain-derived neurotrophic factor (BDNF) and reduced the expression of the neuron-specific K(+)/Cl(-) co-transporter, KCC2, in the hippocampus and cerebral cortex of mice. Knowing that KCC2 maintains low intracellular Cl(-) concentrations, which drive Cl(-) influx in response to GABA(A) receptor activation, we monitored the behavioural response to the GABA(A) receptor enhancer, diazepam, in mice pre-treated for 7 days with saline or 25 mg/kg of memantine. Memantine treatment substantially attenuated motor impairment induced by an acute challenge with diazepam (6 mg/kg, i.p.), as assessed by the rotarod test and the horizontal wire test. We suggest that a prolonged treatment with memantine induces changes in the activity of GABA(A) receptors that might contribute to the therapeutic and/or toxic effects of the drug.

  16. The Pattern of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampus of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Iraj Salehi

    2010-06-01

    Full Text Available Objective(sThe aim of this study was to evaluate the effects of regular exercise in preventing diabetes complication in the hippocampus of streptozotocin (STZ-induced diabetic rat.Materials and MethodsA total of 48 male wistar rats were divided into four groups (control, control exercise, diabetic and diabetic exercise. Diabetes was induced by injection of single dose of STZ. Exercise was performed for one hr every day, over a period of 8 weeks. The antioxidant enzymes (SOD, GPX, CAT and GR and oxidant indexes with brain-derived neurotrophic factor (BDNF protein and its mRNA and apoptosis were measured in hippocampus of rats. ResultsA significant decrease in antioxidant enzymes activities and increased malondialdehyde (MDA level were observed in diabetic rats (P= 0.004. In response to exercise, antioxidant enzymes activities increased (P= 0.004. In contrast, MDA level decreased in diabetic rats (P= 0.004. Induction of diabetes caused an increase of BDNF protein and its mRNA expression. In response to exercise, BDNF protein and its mRNA expression reduced in hippocampus of diabetic rats. ConclusionDiabetes induced oxidative stress and increased BDNF gene expression. Exercise ameliorated oxidative stress and decreased BDNF gene expression.

  17. Synchronized network activity in developing rat hippocampus involves regional hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function

    OpenAIRE

    Bender, Roland A.; Galindo, Rafael; Mameli, Manuel; Gonzalez-Vega, Rebeca; Valenzuela, C. Fernando; Tallie Z. Baram

    2005-01-01

    The principal form of synchronized network activity in neonatal hippocampus consists of low frequency ‘giant depolarizing potentials’ (GDPs). Whereas contribution of both GABA and glutamate to their generation has been demonstrated, full understanding of the mechanisms underlying these synchronized activity bursts remains incomplete. A contribution of the h-current, conducted by HCN channels, to GDPs has been a topic of substantial interest. Here we focus on HCN1, the prevalent HCN channel is...

  18. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    Energy Technology Data Exchange (ETDEWEB)

    Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

    2001-05-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  19. Lithium ameliorates lipopolysaccharide-induced neurotoxicity in the cortex and hippocampus of the adult rat brain.

    Science.gov (United States)

    Khan, Muhammad Sohail; Ali, Tahir; Abid, Muhammad Noman; Jo, Myeung Hoon; Khan, Amjad; Kim, Min Woo; Yoon, Gwang Ho; Cheon, Eun Woo; Rehman, Shafiq Ur; Kim, Myeong Ok

    2017-09-01

    Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor-kB (NF-KB) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α). We also analyzed that LiCl significantly abrogated activated gliosis via attenuation of specific markers for activated microglia, ionized calcium-binding adaptor molecule (Iba-1) and astrocytes, glial fibrillary acidic protein (GFAP) in both the cortex and hippocampus of the adult rat brain. Furthermore, we also observed that LiCl treatment significantly ameliorated the increase expression level of apoptotic neurodegeneration protein markers Bax/Bcl2, activated caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1) in the cortex and hippocampus regions of the LPS-treated adult rat brain. In addition, the morphological results of the fluoro-jade B (FJB) and Nissl staining showed that LiCl attenuated the neuronal degeneration in the cortex and hippocampus regions of the LPS-treated adult rat brain. Taken together, our Western blot and morphological results indicated that LiCl significantly prevents the LPS-induced neurotoxicity via attenuation of neuroinflammation and apoptotic neurodegeneration in the cortex and hippocampus of the adult rat brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Effects of the GABA(B) antagonist CGP 35348 on sleep-wake states, behaviour, and spike-wave discharges in old rats

    NARCIS (Netherlands)

    Puigcerver, A.; Luijtelaar, E.L.J.M. van; Drinkenburg, W.H.I.M.; Coenen, A.L.M.

    1996-01-01

    The GABA(B) antagonist CGP 35348 was intraperitoneally given in doses of 100, 300, and 900 mg/kg to old rats. These rats were earlier chronically provided with EEG and EMG electrodes. Sleep recordings based on visual inspection of EEG and EMG recordings were made for 3 h post injection, and

  1. Effects of the GABA(B) antagonist CGP 35348 on sleep-wake states, behaviour, and spike-wave discharges in old rats

    NARCIS (Netherlands)

    Puigcerver, A.; Luijtelaar, E.L.J.M. van; Drinkenburg, W.H.I.M.; Coenen, A.L.M.

    1996-01-01

    The GABA(B) antagonist CGP 35348 was intraperitoneally given in doses of 100, 300, and 900 mg/kg to old rats. These rats were earlier chronically provided with EEG and EMG electrodes. Sleep recordings based on visual inspection of EEG and EMG recordings were made for 3 h post injection, and spontane

  2. Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Daniel Reyes-Haro

    2016-01-01

    Full Text Available 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.

  3. Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus

    Science.gov (United States)

    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

  4. Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons.

    Science.gov (United States)

    Yang, Bo; Rajput, Padmesh S; Kumar, Ujendra; Sastry, Bhagavatula R

    2015-01-01

    The equilibrium potential for GABA-A receptor mediated currents (EGABA) in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K+/Cl- co-transporter (KCC2) but a relatively high expression of Na+-K+-Cl- cotransporter (NKCC1). Theta-burst stimulation (TBS) in stratum radiatum induces a negative shift in EGABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on EGABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs) are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus EGABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in EGABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS)-a-Methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in EGABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in EGABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary.

  5. Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons.

    Directory of Open Access Journals (Sweden)

    Bo Yang

    Full Text Available The equilibrium potential for GABA-A receptor mediated currents (EGABA in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K+/Cl- co-transporter (KCC2 but a relatively high expression of Na+-K+-Cl- cotransporter (NKCC1. Theta-burst stimulation (TBS in stratum radiatum induces a negative shift in EGABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on EGABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus EGABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in EGABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS-a-Methyl-4-carboxyphenylglycine (MCPG, a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in EGABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in EGABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary.

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

    Science.gov (United States)

    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 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.

  7. Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Gabriela Beatriz Acosta; María Alejandra Fernández; Diego Martín Roselló; María Luján Tomaro; Karina Balestrasse; Abraham Lemberg

    2009-01-01

    AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into shamoperated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions.

  8. Functional inactivation of the rat hippocampus disrupts avoidance of a moving object.

    Science.gov (United States)

    Telensky, Petr; Svoboda, Jan; Blahna, Karel; Bureš, Jan; Kubik, Stepan; Stuchlik, Ales

    2011-03-29

    The hippocampus is well known for its critical involvement in spatial memory and information processing. In this study, we examined the effect of bilateral hippocampal inactivation with tetrodotoxin (TTX) in an "enemy avoidance" task. In this paradigm, a rat foraging on a circular platform (82 cm diameter) is trained to avoid a moving robot in 20-min sessions. Whenever the rat is located within 25 cm of the robot's center, it receives a mild electrical foot shock, which may be repeated until the subject makes an escape response to a safe distance. Seventeen young male Long-Evans rats were implanted with cannulae aimed at the dorsal hippocampus 14 d before the start of the training. After 6 d of training, each rat received a bilateral intrahippocampal infusion of TTX (5 ng in 1 μL) 40 min before the training session on day 7. The inactivation severely impaired avoidance of a moving robot (n = 8). No deficit was observed in a different group of rats (n = 9) that avoided a stable robot that was only displaced once in the middle of the session, showing that the impairment was not due to a deficit in distance estimation, object-reinforcement association, or shock sensitivity. This finding suggests a specific role of the hippocampus in dynamic cognitive processes required for flexible navigation strategies such as continuous updating of information about the position of a moving stimulus.

  9. Bilateral injections of beta A(25-35) + IBO into the hippocampus disrupts acquisition of spatial learning in the rat.

    Science.gov (United States)

    Dornan, W A; Kang, D E; McCampbell, A; Kang, E E

    1993-11-18

    Focal deposits of beta-amyloid (beta A) in the hippocampus have been implicated in Alzheimer's disease. In this study we assessed the effects of bilateral injections into the hippocampus of beta A(25-35), a combination of beta A(25-35) with ibotenic acid (IBO), and IBO on spatial learning in the rat. Bilateral injections of beta A(25-35) into the hippocampus together with IBO (which by itself has no neurotoxic effects) produced a dramatic disruption in the acquisition of a spatial learning in the rat. Separate injections into the hippocampus of beta A(25-35) or the incubated form of beta A(25-35) alone failed to significantly affect maze acquisition in the rat. Histological examination revealed that only the combination of beta A(25-35) with IBO produced a lesion along with focal deposits in the hippocampus.

  10. Aging in the rat hippocampus is associated with widespread reductions in the number of glutamate decarboxylase-67 positive interneurons but not interneuron degeneration.

    Science.gov (United States)

    Stanley, Dirk P; Shetty, Ashok K

    2004-04-01

    Increased excitability of principal excitatory neurons is one of the hallmarks of aging in the hippocampus, signifying a diminution in the number and/or function of inhibitory interneurons with aging. To elucidate this, we performed comprehensive GABA-ergic interneuron cell counts in all layers of the dentate gyrus and the CA1 and CA3 subfields, using serial sections from adult, middle-aged and aged Fischer 344 rats. Sections were immunostained for glutamate decarboxylase-67 (GAD-67, a synthesizing enzyme of GABA) and GAD-67 immunopositive interneurons were counted using an unbiased cell counting method, the optical fractionator. Substantial declines in the absolute number of GAD-67 immunopositive interneurons were found in all hippocampal layers/subfields of middle-aged and aged animals, in comparison with the adult animals. However, the counts were comparable between the middle-aged and aged groups for all regions. Interestingly, determination of the absolute number of interneurons using neuron-specific nuclear antigen (NeuN) expression in the strata oriens and radiatum of CA1 and CA3 subfields revealed an analogous number of interneurons across the three age groups. Furthermore, the ratio of GAD-67 immunopositive and NeuN positive interneurons decreased from adult age to middle age but remained relatively static between middle age and old age. Collectively, the results underscore that aging in the hippocampus is associated with wide-ranging decreases in the number of GAD-67 immunopositive interneurons and most of the age-related changes in GAD-67 immunopositive interneuron numbers transpire by middle age. Additionally, this study provides novel evidence that age-related reductions in hippocampal GAD-67 immunopositive interneuron numbers are due to loss of GAD-67 expression in interneurons rather than interneuron degeneration.

  11. Study of the variations in apoptotic factors in hippocampus of male rats with posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Behrang Alani

    2013-01-01

    Full Text Available Background: Post-traumatic stress disorder (PTSD is a stress-related psychosomatic disorder caused by occurrence of a traumatic event and the hippocampus volume of the patients with Post-traumatic stress disorder decreased. However, the mechanisms that cause such damage are not well-understood. The aim of this study is to detect the expression of apoptosis-related Bax, Bcl-2, Caspase-3 and Insulin-like growth Factor-I proteins in the hippocampus region in the Predatory stress rats. Materials and Methods: A total of 70 male wistar rats were divided into Predatory stress groups of 1d, 2d, 3d, 7d, 14d, 30d and a normal control group (N = 10. Rats were subjected to 5 min of predatory stress and then exposed to the elevated plus-maze (EPM. Serum corticosterone and Insulin-like growth factor-1 level of Hippocampus were measured by ELISA technique. The expression of Bax, Bcl-2, and Caspase-3 were detected by western blotting. Results: Rats spent significantly more time in closed arms of the elevated plus maze (EPM than control group after exposure to stress. Serum levels of corticosterone significantly increased at 2d-3d. The expression of hippocampal IGF-1 was significantly up-regulated at 1d-2d after stress. Both Bax and the ratio of Bax/Bcl-2 significantly peaked at Predatory stress 2d-14d. Caspase3 was significantly active among 2d-30 compared to the normal control. Conclusion: The activation of caspase-3 in the stress groups indicates that apoptosis may be one of the reasons inducing hippocampus atrophy and play roles in the pathogenesis of PTSD. Increase in hippocampus levels of IGF-1 during early PTSD might be involved in the early molecular inhibitory mechanism of apoptosis in PTSD.

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

    Science.gov (United States)

    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.

  13. Differences in prefrontal cortex GABA/glutamate ratio after acute restraint stress in rats are associated with specific behavioral and neurobiological patterns.

    Science.gov (United States)

    Drouet, J-B; Fauvelle, F; Maunoir-Regimbal, S; Fidier, N; Maury, R; Peinnequin, A; Denis, J; Buguet, A; Canini, F

    2015-01-29

    In patients suffering from stress-related pathologies and depression, frontal cortex GABA and glutamate contents are reported to decrease and increase, respectively. This suggests that the GABA and/or glutamate content may participate in pathological phenotype expression. Whether differences in frontal cortex GABA and glutamate contents would be associated with specific behavioral and neurobiological patterns remains unclear, especially in the event of exposure to moderate stress. We hypothesized that an increase in prefrontal cortex GABA/glutamate ratio would be associated with a blunted prefrontal cortex activation, an enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activation and changes in behavior. Rats being restrained for 1-h were then tested in an open-field test in order to assess their behavior while under stress, and were sacrificed immediately afterward. The GABA/glutamate ratio was assessed by (1)H high-resolution magic angle spinning magnetic resonance spectroscopy ((1)H-HRMAS-MRS). The neurobiological response was evaluated through prefrontal cortex mRNA expression and plasma corticosterone levels. The stressed rats were distributed into two subgroups according to their high (H-G/g) or low (L-G/g) GABA/glutamate ratio. Compared to the L-G/g rats, the H-G/g rats exhibited a decrease in c-fos, Arc, Npas4, Nr4a2 mRNA expression suggesting blunted prefrontal cortex activation. They also showed a more pronounced stress with an enhanced rise in corticosterone, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), creatine kinase (CK) and lactate dehydrogenase (LDH) levels, as well as behavioral disturbances with decreased locomotion speed. These changes were independent from prefrontal cortex energetic status as mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) pathway activities were similar in both subpopulations. The differences in GABA/glutamate ratio in the frontal cortex observed

  14. Design-based estimation of neuronal number and individual neuronal volume in the rat hippocampus

    DEFF Research Database (Denmark)

    Hosseini-Sharifabad, Mohammad; Nyengaard, Jens Randel

    2007-01-01

    vertical sections from the hippocampus. The volume of hippocampal neurons was estimated using the rotator principle on 40 microm thick plastic vertical uniform random sections and corrected for tissue shrinkage. Application of the proposed new design should result in more accurate estimates of neuron......Tools recently developed in stereology were employed for unbiased estimation of the neuronal number and volume in three major subdivisions of rat hippocampus (dentate granular, CA1 and CA3 pyramidal layers). The optical fractionator is used extensively in quantitative studies of the hippocampus......; however, the classical optical fractionator design may be affected by tissue deformation in the z-axis of the section. In this study, we applied an improved optical fractionator design to estimate total number of neurons on 100 microm thick vibratome sections that had been deformed, in the z...

  15. Early expression of KCC2 in rat hippocampal cultures augments expression of functional GABA synapses.

    Science.gov (United States)

    Chudotvorova, Ilona; Ivanov, Anton; Rama, Sylvain; Hübner, Christian A; Pellegrino, Christophe; Ben-Ari, Yehezkel; Medina, Igor

    2005-08-01

    The development of GABAergic synapses is associated with an excitatory to inhibitory shift of the actions of GABA because of a reduction of [Cl-]i. This is due to a delayed postnatal expression of the K+ -Cl- cotransporter KCC2, which has low levels at birth and peaks during the first few postnatal weeks. Whether the expression of the cotransporter and the excitatory to inhibitory shift have other consequences on the operation of GABA(A) receptors and synapses is not yet known. We have now expressed KCC2 in immature neurones at an early developmental stage and determined the consequences on the formation of GABA and glutamate synapses. We report that early expression of the cotransporter selectively enhances GABAergic synapses: there is a significant increase of the density of GABA(A) receptors and synapses and an increase of the frequency of GABAergic miniature postsynaptic currents. The density of glutamate synapses and frequency of AMPA miniature postsynaptic currents are not affected. We conclude that the expression of KCC2 and the reduction of [Cl-]i play a critical role in the construction of GABAergic networks that extends beyond the excitatory to inhibitory shift of the actions of GABA.

  16. Connections between EM2-containing terminals and GABA/μ-opioid receptor co-expressing neurons in the rat spinal trigeminal caudal nucleus

    Science.gov (United States)

    Li, Meng-Ying; Wu, Zhen-Yu; Lu, Ya-Cheng; Yin, Jun-Bin; Wang, Jian; Zhang, Ting; Dong, Yu-Lin; Wang, Feng

    2014-01-01

    Endomorphin-2 (EM2) demonstrates a potent antinociceptive effect via the μ-opioid receptor (MOR). To provide morphological evidence for the pain control effect of EM2, the synaptic connections between EM2-immunoreactive (IR) axonal terminals and γ-amino butyric acid (GABA)/MOR co-expressing neurons in lamina II of the spinal trigeminal caudal nucleus (Vc) were investigated in the rat. Dense EM2-, MOR- and GABA-IR fibers and terminals were mainly observed in lamina II of the Vc. Within lamina II, GABA- and MOR-neuronal cell bodies were also encountered. The results of immunofluorescent histochemical triple-staining showed that approximately 14.2 or 18.9% of GABA-IR or MOR-IR neurons also showed MOR- or GABA-immunopositive staining in lamina II; approximately 45.2 and 36.1% of the GABA-IR and MOR-IR neurons, respectively, expressed FOS protein in their nuclei induced by injecting formalin into the left lower lip of the mouth. Most of the GABA/MOR, GABA/FOS, and MOR/FOS double-labeled neurons made close contacts with EM2-IR fibers and terminals. Immuno-electron microscopy confirmed that the EM2-IR terminals formed synapses with GABA-IR or MOR-IR dendritic processes and neuronal cell bodies in lamina II of the Vc. These results suggest that EM2 might participate in pain transmission and modulation by binding to MOR-IR and GABAergic inhibitory interneuron in lamina II of the Vc to exert inhibitory effect on the excitatory interneuron in lamina II and projection neurons in laminae I and III. PMID:25386121

  17. Serotonin receptor 5-HT5A in rat hippocampus decrease by leptin treatment.

    Science.gov (United States)

    García-Alcocer, Guadalupe; Rodríguez, Angelina; Moreno-Layseca, Paulina; Berumen, Laura C; Escobar, Jesica; Miledi, Ricardo

    2010-12-17

    5-Hydroxytryptamine (5-HT) is involved in a variety of different physiological processes and behaviors through the activation of equally diverse receptors subtypes. In this work we studied the changes on the expression of 5-HT(5A) receptors in rat hippocampus induced by leptin, an adipocyte-derived hormone that has been reported to participate in the modulation of food intake and in adult hippocampal neurogenesis. To study the effect of leptin on the 5-HT(5A) receptor gene expression a qRT-PCR was used and the distribution of those receptors in the hippocampus was visualized by immunohistochemistry. Rats were separated in four groups: control (untreated rats), leptin-treated, serotonin-treated and leptin+serotonin treated. The results showed that even though the 5-HT(5A) gene expression did not change in the hippocampus of any of the treated groups, in the rats treated with leptin and serotonin, the specific immunostaining for the 5-HT(5A) serotonin receptor decreased significantly in the dentate gyrus.

  18. Effects of carbon disulfide on the expression and activity of nitric oxide synthase in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Carbon disulfide (CS2) is a commonly used organic solvent. Many epidemiological investigations and animal experiments have indicated that learning and memory ability can be affected to different degrees after long-term exposure to CS2, but the mechanisms are still unclear. The aim of this study was to explore the possible mechanisms of CS2-related impairment of the learning and memory ability of rats, by investigating the effects of CS2 on nitric oxide synthase (NOS) activity and NOS mRNA expression in rat hippocampus. Methods Rat models of toxicity were generated by inhalation of various doses of CS2. After two months of inhaling intoxication, the activities of constitutive NOS (cNOS) and induced NOS (iNOS) in the hippocampus were measured. The levels of neuronal NOS (nNOS) mRNA and iNOS mRNA were measured by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results cNOS activity was significantly decreased compared with controls, while iNOS activity was changed only slightly. CS2 treatment significantly decreased nNOS mRNA levels, iNOS mRNA levels were significantly increased only at higher doses of CS2. Conclusion The effect of CS2 on learning and memory ability in rats is related to the activity of NOS and the expression of nNOS in the hippocampus.

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

    Science.gov (United States)

    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.

  20. Effect of anterior nucleus of thalamus stimulation on glucose metabolism in hippocampus of epileptic rats

    Institute of Scientific and Technical Information of China (English)

    LIU Huan-guang; YANG An-chao; MENG Da-wei; ZHANG Kai; ZHANG Jian-guo

    2012-01-01

    Background Electrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures.In this study,we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.Methods Three groups of rats were used:(1) a stimulation group (n=12),(2) a sham stimulation group (n=12) with seizures induced by stereotactic administration of kainic acid (KA),and (3) a control group (n=12) with sham surgery.Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT.High-frequency stimulation was performed in each group except the sham stimulation group.Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in thestimulation group.The concentrations of glucose,lactate,and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.Results The extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P=0.020,P=0.001; respectively).However,no significant difference in the concentration of glucose and pyruvate was found between these groups (P>0.05).Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P <0.05),but it did not influence the glucose metabolism in the contralateral hippocampus (P >0.05).Conclusions This study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation.These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

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

    Science.gov (United States)

    Maren, Stephen

    2014-02-01

    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.

  2. Effect of phenylsuccinate on potassium- and ischemia-induced release of glutamate in rat hippocampus monitored by microdialysis

    DEFF Research Database (Denmark)

    Christensen, Thomas; Bruhn, T; Diemer, Nils Henrik

    1991-01-01

    The extracellular concentration of glutamate in rat hippocampus during physiological conditions, elevated extracellular K+ and global ischemia was followed by microdialysis and subsequent determination of glutamate by HPLC. The effect of phenylsuccinate, an inhibitor of the mitochondrial dicarbox...

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

    Science.gov (United States)

    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.

  4. Localization of glucocorticoid receptor messenger ribonucleic acid in hippocampus of rat brain using in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. GABA B receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons.

    Science.gov (United States)

    Lei, Saobo; McBain, Chris J

    2003-01-15

    Hippocampal stratum radiatum inhibitory interneurons receive glutamatergic excitatory innervation via the recurrent collateral fibers of CA3 pyramidal neurons and GABAergic inhibition from other interneurons. We examined both presynaptic- and postsynaptic-GABA(B) receptor-mediated responses at both synapse types. Postsynaptic GABA(B) receptor-mediated responses were absent in recordings from young (P16-18) but present in recordings from older animals (> or =P30) suggesting developmental regulation. In young animals, the GABA(B) receptor agonist, baclofen, inhibited the amplitude of evoked EPSCs and IPSCs, an effect blocked by prior application of the selective antagonist CGP55845. Baclofen enhanced the paired-pulse ratio and coefficient of variation of evoked EPSCs and IPSCs, consistent with a presynaptic mechanism of regulation. In addition, baclofen reduced the frequency of miniature IPSCs but not mEPSCs. However, baclofen reduced the frequency of KCl-induced mEPSCs; an effect blocked by Cd(2+), implicating presynaptic voltage-gated Ca(2+) channels as a target for baclofen modulation. In contrast, although Cd(2+) prevented the KCl-induced increase in mIPSC frequency, it failed to block baclofen's reduction of mIPSC frequency. Whereas N- and P/Q-types of Ca(2+) channels contributed equally to GABA(B) receptor-mediated inhibition of EPSCs, more P/Q-type Ca(2+) channels were involved in GABA(B) receptor-mediated inhibition of IPSCs. Finally, baclofen blocked the frequency-dependent depression of EPSCs and IPSCs, but was less effective at blocking frequency-dependent facilitation of EPSCs. Our results demonstrate that presynaptic GABA(B) receptors are expressed on the terminals of both excitatory and inhibitory synapses onto CA3 interneurons and that their activation modulates essential components of the release process underlying transmission at these two synapse types.

  6. Acute Immobilization Stress Modulate GABA Release from Rat Olfactory Bulb: Involvement of Endocannabinoids—Cannabinoids and Acute Stress Modulate GABA Release

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    Alejandra Delgado

    2011-01-01

    Full Text Available We studied the effects of cannabinoids and acute immobilization stress on the regulation of GABA release in the olfactory bulb. Glutamate-stimulated 3H-GABA release was measured in superfused slices. We report that cannabinoids as WIN55, 212-2, methanandamide, and 2-arachidonoylglycerol were able to inhibit glutamate- and KCl-stimulated 3H-GABA release. This effect was blocked by the CB1 antagonist AM281. On the other hand, acute stress was able per se to increase endocannabinoid activity. This effect was evident since the inhibition of stimulated GABA release by acute stress was reversed with AM281 and tetrahydrolipstatin. Inhibition of the endocannabinoid transport or its catabolism showed reduction of GABA release, antagonized by AM281 in control and stressed animals. These results point to endocannabinoids as inhibitory modulators of GABA release in the olfactory bulb acting through an autocrine mechanism. Apparently, stress increases the endocannabinoid system, modulating GABAergic synaptic function in a primary sensory organ.

  7. Chronic ketamine produces altered distribution of parvalbumin-positive cells in the hippocampus of adult rats.

    Science.gov (United States)

    Sabbagh, Jonathan J; Murtishaw, Andrew S; Bolton, Monica M; Heaney, Chelcie F; Langhardt, Michael; Kinney, Jefferson W

    2013-08-29

    The underlying mechanisms of schizophrenia pathogenesis are not well understood. Increasing evidence supports the glutamatergic hypothesis that posits a hypofunction of the N-methyl D-aspartate (NMDA) receptor on specific gamma amino-butyric acid (GABA)-ergic neurons may be responsible for the disorder. Alterations in the GABAergic system have been observed in schizophrenia, most notably a change in the expression of parvalbumin (PV) in the cortex and hippocampus. Several reports also suggest abnormal neuronal migration may play a role in the etiology of schizophrenia. The current study examined the positioning and distribution of PV-positive cells in the hippocampus following chronic treatment with the NMDA receptor antagonist ketamine. A robust increase was found in the number of PV-positive interneurons located outside the stratum oriens (SO), the layer where most of these cells are normally localized, as well as an overall numerical increase in CA3 PV cells. These results suggest ketamine leads to an abnormal distribution of PV-positive cells, which may be indicative of aberrant migratory activity and possibly related to the Morris water maze deficits observed. These findings may also be relevant to alterations observed in schizophrenia populations.

  8. Sensitization to the conditioned rewarding effects of morphine modulates gene expression in rat hippocampus.

    Science.gov (United States)

    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.

  9. Neurochemical phenotype of cytoglobin‑expressing neurons in the rat hippocampus

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Fahrenkrug, Jan; Hannibal, Jens

    2014-01-01

    in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number...... of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic...... structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin- and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population...

  10. GABA is the principal fast-acting excitatory transmitter in the neonatal brain.

    Science.gov (United States)

    Leinekugel, X; Khalilov, I; McLean, H; Caillard, O; Gaiarsa, J L; Ben-Ari, Y; Khazipov, R

    1999-01-01

    gamma-aminobutyric acid (GABA) is the principal neurotransmitter of inhibition in the adult mammalian brain. However, at early stages of development, including the embryonic period and first week of postnatal life, GABA plays the role of main neurotransmitter of excitation. The paradoxical excitatory effect of GABA is caused by an inverted chloride gradient and, therefore, a depolarizing direction of GABA type A (GABAA) receptor mediated responses. In addition, another type of GABAergic inhibition mediated by postsynaptic GABA type B (GABAB) receptors is not functional at early stage of life. In the neonatal rat hippocampus, GABA, acting via GABAA receptors, activates voltage-gated sodium and calcium channels and potentiates the activity of N-methyl-D-aspartate (NMDA) receptors by reducing their voltage-dependent Mg2+ block. The temporal window when GABA exerts excitatory actions coincides with a particular pattern of activity of hippocampal neuronal network that is characterized by periodical giant depolarizing potentials (GDPs) reminiscent of interictal-like epileptiform discharges. Recent studies have shown that GDPs result from the synchronous discharge of GABAergic interneurons and principal glutamatergic pyramidal cells, and they are mediated by the synergistic excitatory actions of GABAA and glutamate receptors. GDPs provide synchronous intracellular Ca2+ oscillations and may, therefore, be implicated in hebbian modulation of developing synapses and activity-dependent formation of the hippocampal network.

  11. Morphological Effects of Hydroalcoholic Zingiber Officinalis Extract in the Murine Hippocampus of Male Rat Offspring

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    Ghodrati

    2016-02-01

    Full Text Available Background The hippocampus is responsible for memory. A diet full of antioxidants improves brain damage and cognitive function. Regard the antioxidant effects of zingiber officinalis (ginger and its flavonoids components. Objectives The aim of this study was to evaluate the effect of the extract of ginger on memory by using hippocampus tissue of the male offspring of rats. Materials and Methods In this study, 60 rats, 15 males and 45 females, were used. We separated pregnant female rats from males on the first day of pregnancy (determined by vaginal plug, and during days 16 - 18 of pregnancy, via intraperitoneal injection, three groups received hydroalcoholic extract of ginger, with low (200 mg/kg bw, medium (400 mg/kg bw, and high (800 mg/kg bw concentration doses. The control group did not receive anything, and the sham group received normal saline during these days. Then at day 50, the males offspring in each group were sacrificed, their brains were removed, and the hippocampus sections were prepared for microscopic studies. Data was analyzed by SPSS 20 and by using one-way ANOVA and then a Tukey post-test (P < 0.05 considered as the significance level. Results This research showed that the number and thickness of pyramidal and granular layers of the CA1 and dentate gyrus areas of the hippocampus had increased in male offspring according to the increase in the ginger extract dose. Conclusions It seems as though ginger extract, which contains compounds such as gingerols, shogaols, and zingerone, can affect memory ability in rats through these compounds’ antioxidant properties by affecting embryonic acetylcholine content and place cells.

  12. Growth hormone prevents neuronal loss in the aged rat hippocampus.

    Science.gov (United States)

    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.

  13. Astaxanthin rescues neuron loss and attenuates oxidative stress induced by amygdala kindling in adult rat hippocampus.

    Science.gov (United States)

    Lu, Yan; Xie, Tao; He, Xue-Xin; Mao, Zhuo-Feng; Jia, Li-Jing; Wang, Wei-Ping; Zhen, Jun-Li; Liu, Liang-Min

    2015-06-15

    Oxidative stress plays an important role in the neuronal damage induced by epilepsy. The present study assessed the possible neuroprotective effects of astaxanthin (ATX) on neuronal damage, in hippocampal CA3 neurons following amygdala kindling. Male Sprague-Dawley rats were chronically kindled in the amygdala and ATX or equal volume of vehicle was given by intraperitoneally. Twenty-four hours after the last stimulation, the rats were sacrificed by decapitation. Histopathological changes and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and reduced glutathione (GSH) were measured, cytosolic cytochrome c (CytC) and caspase-3 activities in the hippocampus were also recorded. We found extensive neuronal damage in the CA3 region in the kindling group, which was preceded by increases of ROS level and MDA concentration and was followed by caspase-3 activation and an increase in cytosolic CytC. Treatment with ATX markedly attenuated the neuronal damage. In addition, ATX significantly decreased ROS and MDA concentrations and increased GSH levels. Moreover, ATX suppressed the translation of CytC release and caspase-3 activation in hippocampus. Together, these results suggest that ATX protects against neuronal loss due to epilepsy in the rat hippocampus by attenuating oxidative damage, lipid peroxidation and inhibiting the mitochondrion-related apoptotic pathway.

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

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    Farzaneh Bagheri-abassi

    2015-07-01

    Full Text Available 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

  15. Cloning and Identification of Novel MicroRNAs from Rat Hippocampus

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    MicroRNAs (miRNAs) are small regulatory molecules post-transcriptionally suppressing mRNA activity. Many miRNAs in various organisms have been cloned but many unknown miRNAs remain to be identified. Here we describe the cloning of six new miRNAs from rat hippocampus. Among them, four were not found in the rat miRBase, but were identical to their human and/or mouse homolog, therefore they were designated as rno-miR-92b, rno-miR-146b, rno-let-7g, and rno-miR-551b. The other two were derived from the other arms of the known miRNA precursors of rno-miR-330 and rno-miR-384, and were not found in miRBase of all organisms. They were designated as rno-miR-330* and rno-miR-384*. The expression of these miRNAs was confirmed by RNA-tailing and primer-extension real-time reverse transcriptionpolymerase chain reaction. These six miRNAs were expressed at significantly higher levels in the hippocampus than in other tissues, including cerebral cortex, heart, liver, lung and kidney. miR-384* was 10 times more abundant than miR-384 in rat hippocampus, but little difference was found between miR-330* and miR-330 expression in the same tissue.

  16. EFFECT OF EXERCISE ON LEARNING, MEMORY AND LEVELS OF EPINEPHRINE IN RATS' HIPPOCAMPUS

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    Hojjatallah Alaei

    2003-09-01

    Full Text Available The aim of the present study was to investigate effect of exercise on learning and memory, long-term potentiation and levels of epinephrine in the rat hippocampus. Treadmill trained (one hour at 17 m·min-1 for 10 days and corresponding control rats went through spatial learning process on a Morris water maze for 8 days. The time to reach the platform (latency, the length of swim path, and the swim speed were used for the evaluation of spatial learning. Our results showed that physical activity produced a significant enhancement in spatial learning, with a decreased path length (p<0.05 and latency (p<0.05 to the platform in Morris water maze, without affecting the swim speed. Furthermore, the levels of the epinephrine were significantly increased (p<0.05 in hippocampus of the exercised rats. In conclusion our findings suggest that the enhanced learning by exercise may be mediated through the activation of adrenoceptors in the hippocampus and epinephrine may play an important role in potentiation of learning

  17. Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus.

    Science.gov (United States)

    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

  18. Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus.

    Directory of Open Access Journals (Sweden)

    Lidiane Dal Bosco

    Full Text Available 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

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

    Science.gov (United States)

    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.

  20. Effects of essential oil from Chamaecyparis obtusa on cytokine genes in the hippocampus of maternal separation rats.

    Science.gov (United States)

    Park, Hae Jeong; Kim, Su Kang; Kang, Won Sub; Woo, Jong-Min; Kim, Jong Woo

    2014-02-01

    We investigated the effects of an essential oil from Chamaecyparis obtusa (EOCO) on early life stress, using maternal separation (MS) rats and a microarray method to analyze the changes in gene expressions caused by EOCO in the hippocampus of MS rats. Rats in the MS groups were separated from their respective mothers from postnatal day (pnd) 14 to 28. Rats in the EOCO-treated groups were exposed to EOCO for 1 or 2 h by inhalation from pnd 21 to 28. The EOCO-treated MS rats showed decreased anxiety-related behaviors compared with the untreated MS rats in the elevated plus-maze (EPM) test. In the microarray analysis, we found that EOCO downregulated the expressions of cytokine genes such as Ccl2, Il6, Cxcl10, Ccl19, and Il1rl in the hippocampus of MS rats, and also confirmed that using reverse transcriptase - PCR. In particular, the expressions of Ccl2 and Il6 were predominantly decreased by EOCO in the hippocampus of MS rats. Interestingly, protein expression was also reduced by EOCO in MS rats. These results indicate that EOCO decreases MS-induced anxiety-related behaviors, and modulates cytokines, particularly Ccl2 and Il6, in the hippocampus of MS rats.

  1. Downregulation of caveolin-1 contributes to the synaptic plasticity deficit in the hippocampus of aged rats*******

    Institute of Scientific and Technical Information of China (English)

    Yang Liu; Zhanhua Liang; Jing Liu; Wei Zou; Xiaoyan Li; Yachen Wang; Lijia An

    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 cerebel um 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 cerebel um. 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 cerebel um. 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.

  2. Reduction of phosphorylated synapsin I (ser-553 leads to spatial memory impairment by attenuating GABA release after microwave exposure in Wistar rats.

    Directory of Open Access Journals (Sweden)

    Simo Qiao

    Full Text Available BACKGROUND: Abnormal release of neurotransmitters after microwave exposure can cause learning and memory deficits. This study investigated the mechanism of this effect by exploring the potential role of phosphorylated synapsin I (p-Syn I. METHODS: Wistar rats, rat hippocampal synaptosomes, and differentiated (neuronal PC12 cells were exposed to microwave radiation for 5 min at a mean power density of 30 mW/cm2. Sham group rats, synaptosomes, and cells were otherwise identically treated and acted as controls for all of the following post-exposure analyses. Spatial learning and memory in rats was assessed using the Morris Water Maze (MWM navigation task. The protein expression and presynaptic distribution of p-Syn I and neurotransmitter transporters were examined via western blotting and immunoelectron microscopy, respectively. Levels amino acid neurotransmitter release from rat hippocampal synaptosomes and PC12 cells were measured using high performance liquid chromatograph (HPLC at 6 hours after exposure, with or without synapsin I silencing via shRNA transfection. RESULTS: In the rat experiments, there was a decrease in spatial memory performance after microwave exposure. The expression of p-Syn I (ser-553 was decreased at 3 days post-exposure and elevated at later time points. Vesicular GABA transporter (VGAT was significantly elevated after exposure. The GABA release from synaptosomes was attenuated and p-Syn I (ser-553 and VGAT were both enriched in small clear synaptic vesicles, which abnormally assembled in the presynaptic terminal after exposure. In the PC12 cell experiments, the expression of p-Syn I (ser-553 and GABA release were both attenuated at 6 hours after exposure. Both microwave exposure and p-Syn I silencing reduced GABA release and maximal reduction was found for the combination of the two, indicating a synergetic effect. CONCLUSION: p-Syn I (ser-553 was found to play a key role in the impaired GABA release and cognitive

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

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466‐8550 (Japan); Department of Toxicology, Guangdong Prevention and Treatment Center for Occupational Diseases, Guangzhou 510‐300 (China); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514‐8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514‐8507 (Japan); Chang, Jie; Zhang, Lingyi; Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466‐8550 (Japan); Ichihara, Gaku, E-mail: gak@med.nagoya-u.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466‐8550 (Japan)

    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.

  4. Intracerebroventricular injection of lipopolysaccharide increases gene expression of connexin32 gap junction in rat hippocampus.

    Science.gov (United States)

    Abbasian, Mohammad; Sayyah, Mohammad; Babapour, Vahab; Mahdian, Reza

    2013-01-01

    Gap junctions are intercellular membrane channels that provide direct cytoplasmic continuity between adjacent cells. This communication can be affected by changes in expression of gap junctional subunits called Connexins (Cx). Changes in the expression and function of connexins are associated with number of brain neurodegenerative diseases. Neuroinflammation is a hallmark of various central nervous system (CNS) diseases, like multiple sclerosis, Alzheimer's disease and epilepsy. Neuroinflammation causes change in Connexins expression. Hippocampus, one of the main brain regions with a wide network of Gap junctions between different neural cell types, has particular vulnerability to damage and consequent inflammation. Cx32 - among Connexins- is expressed in hippocampal Olygodandrocytes and some neural subpopulations. Although multiple lines of evidence indicate that there is an association between neuroinflammation and the expression of connexin, the direct effect of neuroinflammation on the expression of connexins has not been well studied. In the present study, the effect of neuroinflammation induced by the Lipopolysaccharide (LPS) on Cx32 gene and protein expressions in rat hippocampus is evaluated. LPS (2.5µg/rat) was infused into the rat cerebral ventricles for 14 days. Cx32 mRNA and protein levels were measured by Real Time PCR and Western Blot after 1st, 7th and 14th injection of LPS in the hippocampus. Significant increase in Cx32 mRNA expression was observed after 7th injection of LPS (P < 0.001). However, no significant change was observed in Cx32 protein level. LPS seems to modify Cx32 GJ communication in the hippocampus at transcription level but not at translation or post-translation level. In order to have a full view concerning modification of Cx32 GJ communication, effect of LPS on Cx32 channel gating should also be determined.

  5. Effect of THIP and SL 76002, two clinically experimented GABA-mimetic compounds, on anterior pituitary GABA receptors and prolactin secretion in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Apud, J.A.; Masotto, C.; Racagni, G.

    1987-03-02

    In the present study, the ability of three direct GABA agonists, muscimol, THIP and SL 76002 to displace /sup 3/H-GABA binding from anterior pituitary and medio-basal hypothalamus membranes was evaluated. Further, the effect of both THIP and SL 76002 on baseline prolactin levels or after stimulation of hormone release with haloperidol has been also studied. Either muscimol, THIP or SL 76002 have shown to posses 7-, 7- and 3-fold higher affinity, respectively, for the central nervous system than for the anterior pituitary /sup 3/H-GABA binding sites. Moreover, THIP and SL 76002 have demonstrated to be respectively, 25- and 1000- fold less potent than muscimol in inhibiting /sup 3/H- GABA binding at the level of the anterior pituitary and about 25- and 2700-fold less potent at the level of the medio-basal hypothalamus. Under basal conditions, either THIP or SL 76002 were ineffective to reduce prolactin release. However, after stimulation of prolactin secretion through blockade of the dopaminergic neurotransmission with haloperidol (0.1 mg/kg), both THIP (10 mg/kg) and SL 76002 (200 mg/kg) significantly counteracted the neuroleptic-induced prolactin rise with a potency which is in line with their ability to inhibit /sup 3/H-GABA binding in the anterior pituitary. The present results indicate that both compounds inhibit prolactin release under specific experimental situations probably through a GABAergic mechanism. In view of the endocrine effects of these GABA-mimetic compounds, the possibility arises for an application of these type of drugs in clinical neuroendocrinology. 35 references, 3 figures, 2 tables.

  6. The expression of somatostatin receptors in the hippocampus of pilocarpine-induced rat epilepsy model.

    Science.gov (United States)

    Kwak, Sung-Eun; Kim, Ji-Eun; Choi, Hui-Chul; Song, Hong-Ki; Kim, Yeong-In; Jo, Seung-Mook; Kang, Tae-Cheon

    2008-01-01

    During the course of this study, we sought examine whether the expression of somatostatin receptors (SSTRs) is altered in the hippocampus following pilocarpine-induced status epilepticus (SE) in order to understand the role/function of SSTRs in the hippocampus after epileptogenic insults. SSTR1 and SSTR4 immunoreactivities were increased in the hippocampus at 1 week after SE. At 4 weeks after SE, SRIF1-family (SSTR 2A, SSTR2B, and SSTR5) immunoreactivity was increased only in neuropil. Both SSTR2A and 2B immunoreactivities were increased in CA2-3 pyramidal cells. However, SSTR3 and SSTR4 immunoreactivities were reduced in the CA1 pyramidal cells of epileptic rat due to neuronal loss. In addition, SSTR5 immunoreactivity was reduced in CA2 pyramidal cells and various interneurons. Both SSTR2B and SSTR4 immunoreactivities were increased within microglia following SE. Our findings suggest that increases in neuron-glial SSTR expressions may be closely related to the enhanced inhibition of the dentate gyrus and regulation of reactive microgliosis in the hippocampus of a pilocarpine model of temporal lobe epilepsy.

  7. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats.

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    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.

  8. Toxicological study of injuries of rat's hippocampus after lead poisoning by synchrotron microradiography and elemental mapping

    Energy Technology Data Exchange (ETDEWEB)

    Liang Feng [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Zhang Guilin, E-mail: glzhang@sinap.ac.c [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Xiao Xianghui; Cai Zhonghou; Lai, Barry [Advanced Photon Source, Argonne (United States); Hwu Yeukuang [Institute of Physics, Academia Sinica, Nankang, Taipei (China); Yan Chonghuai; Xu Jian [Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Children' s Environmental Health, Shanghai 200092 (China); Li Yulan; Tan Mingguang; Zhang Chuanfu [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Li Yan, E-mail: liyan@sinap.ac.c [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)

    2010-09-15

    The hippocampus, a major component of the brain, is one of the target nervous organs in lead poisoning. In this work, a rat's hippocampal injury caused by lead was studied. The lead concentrations in blood, bone and hippocampus collected from rats subject to lead poisoning were quantified by Inductively Coupled Plasma Mass Spectrometry while morphological information and elemental distributions in the hippocampus were obtained with synchrotron radiation X-ray phase contrast imaging and synchrotron radiation micro-beam X-ray fluorescence, respectively. For comparison, identical characterization of the specimens from the rats in the control group was done in parallel. Results show that the ratios between the lead content in the treated group and that in the control group of the hippocampus, bone, and blood are about 2.66, 236, and 39.6, respectively. Analysis also revealed that some health elements such as S, K, Cl and P increase in the regions with high lead content in the treated hippocampus. Morphological differences between the normal and lead-exposed hippocampus specimens in some local areas were observed. Explicitly, the structure of the lead-exposed hippocampus was tortuous and irregular, and the density of the neurons in the Dentate Gyrus was significantly lower than that from the control group. The study shows that the synchrotron radiation methods are very powerful for investigating structural injury caused by heavy metals in the nervous system.

  9. A threshold sodium current in pyramidal cells in rat hippocampus.

    Science.gov (United States)

    French, C R; Gage, P W

    1985-05-23

    Maintained, inward currents were activated by small depolarizations from the resting membrane potential (-50 to -60 mV) in voltage-clamped, pyramidal neurons in rat hippocampal slices. The currents were apparently Na currents as they were blocked by tetrodotoxin or removal of extracellular Na and were not affected by Cd. They showed little decrease in amplitude during prolonged depolarizations. The increase in Na conductance with depolarization was sigmoidal, with half-maximum conductance at about -50 mV, and saturated at -20 to -30 mV. This 'threshold' Na current may be involved in setting patterns of repetitive firing of action potentials.

  10. Activation of Nrf2-ARE signal pathway in hippocampus of amygdala kindling rats.

    Science.gov (United States)

    Wang, Wei; Wang, Wei-Ping; Zhang, Guo-Liang; Wu, Yan-Fen; Xie, Tao; Kan, Min-Chen; Fang, Hai-Bo; Wang, Hong-Chao

    2013-05-24

    Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of epilepsy. Therefore, antioxidant therapies have received considerable attention in epilepsy treatment. It is well known that the transcription factor NF-E2-related factor (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes under conditions of oxidative stress, which reduces oxidative stress and accumulation of toxic metabolites. However, whether Nrf2-ARE pathway is activated after seizure has not been studied. In the present study, Wistar rats were rapidly kindled in the amygdala. Twenty-four hours after the last seizure, the hippocampus of control, sham and kindled rats were examined for oxidative stress parameters (malondialdehyde and glutathione) by spectrophotometry, the expression of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) were determined using immunohistochemistry, Western blot and real-time fluorescence quantitative polymerase chain reaction (PCR). The results showed that the kindled seizures induced oxidative stress, the expression of Nrf2, HO-1 and NQO1 at protein or gene levels significantly increased in hippocampus after seizure. According to these results, it could be postulated that Nrf2-ARE signal pathway was activated in the hippocampus after seizure.

  11. Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus.

    Science.gov (United States)

    Hundahl, Christian Ansgar; Fahrenkrug, Jan; Hannibal, Jens

    2014-09-01

    Cytoglobin (Cygb), a novel oxygen-binding protein, is expressed in the majority of tissues and has been proposed to function in nitric oxide (NO) metabolism in the vasculature and to have cytoprotective properties. However, the overall functions of Cygb remain elusive. Cygb is also expressed in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin- and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population of Cygb neurons co-expressing nNOS. Furthermore, it was shown that the majority of neurons expressing somastostatin and vasoactive intestinal peptide also co-express Cygb and nNOS. Detailed information regarding the neurochemical phenotype of Cygb neurons in the hippocampus can be a valuable tool in determining the function of Cygb in the brain.

  12. Posthoc phosphorylation of proteins derived from ischemic rat hippocampus, striatum and neocortex.

    Science.gov (United States)

    Kirschenbaum, B; Pulsinelli, W A

    1990-03-12

    Disruption of the brain's protein phosphorylation system by ischemia may cause irreversible metabolic and structural alterations leading eventually to cell death. To examine the effect of ischemia on the phosphorylation state of brain proteins, tissue homogenates derived from the hippocampus, striatum and neocortex of normal rats and rats subjected to severe forebrain ischemia were phosphorylated with [gamma-32P]ATP. The phosphorylated proteins were separated by two-dimensional polyacrylamide gel electrophoresis and changes were assessed by autoradiography. Cerebral ischemia caused marked alterations of the phosphorylation state of many brain proteins; phosphorylation of some proteins was increased while phosphorylation of others was decreased. Despite differences in the sensitivity of the hippocampus, striatum and neocortex to ischemic injury the direction and approximate magnitude of protein phosphorylation changes caused by ischemia were similar in all three regions. Since the pattern of protein phosphorylation in the ischemia-vulnerable hippocampus was identical to that in the ischemia-resistant paramedian neocortex we conclude that abnormalities of protein phosphorylation may be necessary for ischemic injury to neurons but none are sufficient to explain the selective vulnerability of certain brain regions to ischemic damage.

  13. The similarity of astrocytes number in dentate gyrus and CA3 subfield of rats hippocampus.

    Science.gov (United States)

    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.

  14. Differential patterns of myosin Va expression during the ontogenesis of the rat hippocampus

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    L.S. Brinn

    2010-09-01

    Full Text Available Myosin Va is an actin-based, processive molecular motor protein highly enriched in the nervous tissue of vertebrates. It has been associated with processes of cellular motility, which include organelle transport and neurite outgrowth. The in vivo expression of myosin Va protein in the developing nervous system of mammals has not yet been reported. We describe here the immunolocalization of myosin Va in the developing rat hippocampus. Coronal sections of the embryonic and postnatal rat hippocampus were probed with an affinity-purified, polyclonal anti-myosin Va antibody. Myosin Va was localized in the cytoplasm of granule cells in the dentate gyrus and of pyramidal cells in Ammon's horn formation. Myosin Va expression changed during development, being higher in differentiating rather than already differentiated granule and pyramidal cells. Some of these cells presented a typical migratory profile, while others resembled neurons that were in the process of differentiation. Myosin Va was also transiently expressed in fibers present in the fimbria. Myosin Va was not detected in germinative matrices of the hippocampus proper or of the dentate gyrus. In conclusion, myosin Va expression in both granule and pyramidal cells showed both position and time dependency during hippocampal development, indicating that this motor protein is under developmental regulation.

  15. Changes of mRNA expression of enkephalin and prodynorphin in hippocampus of rats with chronic immobilization stress

    Institute of Scientific and Technical Information of China (English)

    Jia-Xu Chen; Wei Li; Xin Zhao; Jian-Xin Yang; Hong-Yan Xu; Zhu-Feng Wang; Guang-Xin Yue

    2004-01-01

    AIM: To observe the changes of enkephalin mRNA and prodynorphin mRNA in hippocampus of rats induced by chronic immobilization stress.METHODS: Thirty rats were randomly divided into three groups of 10 each: the normal control group (group A),the group induced by chronic immobilization stress for 7 d (group B) and the group induced by chronic immobilization stress for 21 d (group C). The changes of the enkephalin mRNA and prodynorphin mRNA in the rat hippocampus were detected by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: Expression levels of enkephalin mRNA and prodynorphin mRNA in rat hippocampus were significantly increased under chronic immobilization stress, and the expression of prodynorphin mRNA in the rat hippocampus in group C was remarkably higher than that in group B (0.624±0.026; n = 5; P<0.01).CONCLUSION: The increased enkephalin mRNA and prodynorphin mRNA gene expressions in rat hippocampus were involved in chronic stress.

  16. Impaired up-regulation of type II corticosteroid receptors in hippocampus of aged rats.

    Science.gov (United States)

    Eldridge, J C; Fleenor, D G; Kerr, D S; Landfield, P W

    1989-01-30

    Several recent investigations have reported a decline of rat hippocampal corticosteroid-binding receptors (CSRs) with aging. This decline has been proposed to be an initial cause (through disinhibition) of the elevated adrenal steroid secretion that apparently occurs with aging; however, it could instead be an effect of corticoid elevation (through down-regulation). In order to assess the effects of age on CSR biosynthetic capacity in the absence of down-regulatory influences of endogenous corticoids, as well as to study aging changes in CSR plasticity, we examined the up-regulation of hippocampal CSR that follows adrenalectomy (ADX). The rat hippocampus contains at least two types of CSR binding and differential analysis of types I and II CSR was accomplished by selective displacement of [3H]corticosterone with RU-28362, a specific type II agonist. In young (3 months old) Fischer-344 rat hippocampus, up-regulation of type II binding above 2-day ADX baseline was present by 3-7 days and increased still further by 8-10 days post-ADX; type I CSR density did not change significantly between 1 and 10 days post-ADX. However, in aged (24-26 months old) rats, type II CSR up-regulation did not occur over the 10 day post-ADX period. Thus, the age-related impairment of type II up-regulation may reflect an intrinsic deficit in CSR biosynthesis or lability that is independent of the acute endogenous adrenal steroid environment.

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

    Science.gov (United States)

    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.

  18. Alteration of conditioned emotional response and conditioned taste aversion after neonatal ventral hippocampus lesions in rats.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  1. Metabolomic analysis reveals metabolic disturbance in the cortex and hippocampus of subchronic MK-801 treated rats.

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    Liya Sun

    Full Text Available BACKGROUND: Although a number of proteins and genes relevant to schizophrenia have been identified in recent years, few are known about the exact metabolic pathway involved in this disease. Our previous proteomic study has revealed the energy metabolism abnormality in subchronic MK-801 treated rat, a well-established animal model for schizophrenia. This prompted us to further investigate metabolite levels in the same rat model to better delineate the metabolism dysfunctions and provide insights into the pathology of schizophrenia. METHODS: Metabolomics, a high-throughput investigatory strategy developed in recent years, can offer comprehensive metabolite-level insights that complement protein and genetic findings. In this study, we employed a nondestructive metabolomic approach (1H-MAS-NMR to investigate the metabolic traits in cortex and hippocampus of MK-801 treated rats. Multivariate statistics and ingenuity pathways analyses (IPA were applied in data processing. The result was further integrated with our previous proteomic findings by IPA analysis to obtain a systematic view on our observations. RESULTS: Clear distinctions between the MK-801 treated group and the control group in both cortex and hippocampus were found by OPLS-DA models (with R(2X = 0.441, Q(2Y = 0.413 and R(2X = 0.698, Q(2Y = 0.677, respectively. The change of a series of metabolites accounted for the separation, such as glutamate, glutamine, citrate and succinate. Most of these metabolites fell in a pathway characterized by down-regulated glutamate synthesis and disturbed Krebs cycle. IPA analysis further confirmed the involvement of energy metabolism abnormality induced by MK-801 treatment. CONCLUSIONS: Our metabolomics findings reveal systematic changes in pathways of glutamate metabolism and Krebs cycle in the MK-801 treated rats' cortex and hippocampus, which confirmed and improved our previous proteomic observation and served as a valuable reference to

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

    Science.gov (United States)

    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.

  3. Stereological method for objectively quantifying myelin sheaths in the rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Wei Lu; Shu Yang; Lin Chen; Xuan Qiu; Guohua Cheng; Yong Tang

    2011-01-01

    In the present study, tissue blocks were randomly sampled from the entire hippocampus of 6-week-old Long-Evans rats. Isotropic, uniform and random sections, 60 nm thick, were prepared by isector. Fifteen fields of view were randomly selected for each section and photographed using a transmission electron microscope. The mean internal and external diameters of the myelin sheaths were obtained by measuring the longest profile diameter perpendicular to its longest axis.The inner and outer perimeters of the myelin sheaths were estimated using the equidistant parallel test lines. The thickness of the myelin sheaths was estimated by direct orthogonal measurements in uniform, random locations. These stereological methods should permit an unbiased quantitative assessment of changes in the myelin sheaths of myelinated fibers in the hippocampus.

  4. In Vivo Effect of a 5-HT7 Receptor Agonist on 5-HT Neurons and GABA Interneurons in the Dorsal Raphe Nuclei of Sham and PD Rats.

    Science.gov (United States)

    Wang, Shuang; Zhao, Yan; Gao, Jie; Guo, Yufang; Wang, Xiang; Huo, Jian; Wei, Ping; Cao, Jian

    2017-03-01

    The 5-hydroxytryptamine (5-HT; serotonin) neurotransmission is severely affected by the degeneration of nigrostriatal dopaminergic neurons. Here, we report the effects of the systemic administration of the 5-HT7 receptor agonist AS-19. In sham rats, the mean response of the 5-HT neurons in the dorsal raphe nucleus (DRN) to systemic AS-19 was excitatory and the mean response of the γ-aminobutyric acid (GABA) interneurons was inhibitory. In Parkinson disease (PD) rats, the same dose did not affect the 5-HT neurons and only high doses (640 μg/kg intravenous) were able to the increase GABA interneuron activity. These results indicate that DRN 5-HT neurons and GABA interneurons are regulated by the activation of 5-HT7 receptors and that the degeneration of the nigrostriatal pathway leads to decreased responses of these neurons to AS-19, which in turn suggests that the 5-HT7 receptors on 5-HT neurons and GABA interneurons in PD rats are dysfunctional and downregulated.

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

    Science.gov (United States)

    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.

  6. Transcranial focal electrical stimulation reduces the convulsive expression and amino acid release in the hippocampus during pilocarpine-induced status epilepticus in rats.

    Science.gov (United States)

    Santana-Gómez, César E; Alcántara-González, David; Luna-Munguía, Hiram; Bañuelos-Cabrera, Ivette; Magdaleno-Madrigal, Víctor; Fernández-Mas, Rodrigo; Besio, Walter; Rocha, Luisa

    2015-08-01

    The aim of the present study was to evaluate the effects of transcranial focal electrical stimulation (TFS) on γ-aminobutyric acid (GABA) and glutamate release in the hippocampus under basal conditions and during pilocarpine-induced status epilepticus (SE). Animals were previously implanted with a guide cannula attached to a bipolar electrode into the right ventral hippocampus and a concentric ring electrode placed on the skull surface. The first microdialysis experiment was designed to determine, under basal conditions, the effects of TFS (300 Hz, 200 μs biphasic square pulses, for 30 min) on afterdischarge threshold (ADT) and the release of GABA and glutamate in the hippocampus. The results obtained indicate that at low current intensities (Status Epilepticus".

  7. The effects of neuroleptics on the GABA-induced Cl- current in rat dorsal root ganglion neurons: differences between some neuroleptics.

    Science.gov (United States)

    Yokota, Kenjiro; Tatebayashi, Hideharu; Matsuo, Tadashi; Shoge, Takashi; Motomura, Haruhiko; Matsuno, Toshiyuki; Fukuda, Akira; Tashiro, Nobutada

    2002-03-01

    1. Several neuroleptics inhibited the 3 microM gamma-aminobutyric acid induced-chloride current (GABA-current) on dissociated rat dorsal root ganglion neurons in whole-cell patch-clamp investigations. 2. The IC(50) for clozapine, zotepine, olanzapine, risperidone and chlorpromazine were 6.95, 18.26, 20.30, 106.01 and 114.56 microM, respectively. The values for the inhibitory effects of neuroleptics on the GABA (3 microM)-current, which were calculated by the fitting Hill's equations where the concentrations represent the mean therapeutic blood concentrations, were ranked clozapine>zotepine>chlorpromazine>olanzapine>risperidone. These inhibitory effects, weighted with the therapeutic concentrations of neuroleptics, were correlated with the clinical incidences of seizure during treatment with neuroleptics. 3. Clozapine reduced the picrotoxin-inhibiton, and may compete with a ligand of the t-butylbicyclophosphorothionate (TBPS) binding site. 4. Haloperidol and quetiapine did not affect the peak amplitude of the GABA (3 microM)-current. However, haloperidol reduced the clozapine-inhibition, and may antagonize ligand binding to TBPS binding site. 5. Neuroleptics including haloperidol and quetiapine enhanced the desensitization of the GABA (3 microM)-current. However, haloperidol and quetiapine at 100 microM inhibited the desensitization at the beginning of application. 6. Blonanserin (AD-5423) at 30 and 50 microM potentiated the GABA (3 microM)-current to 170.1+/-6.9 and 192.0+/-10.6% of the control current, respectively. Blonanserin shifted GABA concentration-response curve leftward. Blonanserin only partly negatively interacted with diazepam. The blonanserin-potentiation was not reversed by flumazenil. Blonanserin is not a benzodiazepine receptor agonist. 7. The various effects of neuroleptics on the GABA-current may be related to the clinical effects including modifying the seizure threshold.

  8. The effects of neuroleptics on the GABA-induced Cl− current in rat dorsal root ganglion neurons: differences between some neuroleptics

    Science.gov (United States)

    Yokota, Kenjiro; Tatebayashi, Hideharu; Matsuo, Tadashi; Shoge, Takashi; Motomura, Haruhiko; Matsuno, Toshiyuki; Fukuda, Akira; Tashiro, Nobutada

    2002-01-01

    Several neuroleptics inhibited the 3 μM γ-aminobutyric acid induced-chloride current (GABA-current) on dissociated rat dorsal root ganglion neurons in whole-cell patch-clamp investigations. The IC50 for clozapine, zotepine, olanzapine, risperidone and chlorpromazine were 6.95, 18.26, 20.30, 106.01 and 114.56 μM, respectively. The values for the inhibitory effects of neuroleptics on the GABA (3 μM)-current, which were calculated by the fitting Hill's equations where the concentrations represent the mean therapeutic blood concentrations, were ranked clozapine>zotepine>chlorpromazine>olanzapine>risperidone. These inhibitory effects, weighted with the therapeutic concentrations of neuroleptics, were correlated with the clinical incidences of seizure during treatment with neuroleptics. Clozapine reduced the picrotoxin-inhibiton, and may compete with a ligand of the t-butylbicyclophosphorothionate (TBPS) binding site. Haloperidol and quetiapine did not affect the peak amplitude of the GABA (3 μM)-current. However, haloperidol reduced the clozapine-inhibition, and may antagonize ligand binding to TBPS binding site. Neuroleptics including haloperidol and quetiapine enhanced the desensitization of the GABA (3 μM)-current. However, haloperidol and quetiapine at 100 μM inhibited the desensitization at the beginning of application. Blonanserin (AD-5423) at 30 and 50 μM potentiated the GABA (3 μM)-current to 170.1±6.9 and 192.0±10.6% of the control current, respectively. Blonanserin shifted GABA concentration-response curve leftward. Blonanserin only partly negatively interacted with diazepam. The blonanserin-potentiation was not reversed by flumazenil. Blonanserin is not a benzodiazepine receptor agonist. The various effects of neuroleptics on the GABA-current may be related to the clinical effects including modifying the seizure threshold. PMID:11906969

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

    Science.gov (United States)

    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.

  10. Methylmercury chloride damage to the adult rat hippocampus cannot be detected by proton magnetic resonance spectroscopy

    Institute of Scientific and Technical Information of China (English)

    Zhiyan Lu; Jinwei Wu; Guangyuan Cheng; Jianying Tian; Zeqing Lu; Yongyi Bi

    2014-01-01

    Previous studies have found that methylmercury can damage hippocampal neurons and accord-ingly cause cognitive dysfunction. However, a non-invasive, safe and accurate detection method for detecting hippocampal injury has yet to be developed. This study aimed to detect methylmer-cury-induced damage on hippocampal tissue using proton magnetic resonance spectroscopy. Rats were given a subcutaneous injection of 4 and 2 mg/kg methylmercury into the neck for 50 consecutive days. Water maze and pathology tests confirmed that cognitive function had been impaired and that the ultrastructure of hippocampal tissue was altered after injection. The results of proton magnetic resonance spectroscopy revealed that the nitrogen-acetyl aspartate/creatine, choline complex/creatine and myoinositol/creatine ratio in rat hippocampal tissue were unchanged. Therefore, proton magnetic resonance spectroscopy can not be used to determine structural damage in the adult rat hippocampus caused by methylmercury chloride.

  11. The proteome of neural stem cells from adult rat hippocampus

    Directory of Open Access Journals (Sweden)

    Fütterer Carsten D

    2003-06-01

    Full Text Available Abstract Background Hippocampal neural stem cells (HNSC play an important role in cerebral plasticity in the adult brain and may contribute to tissue repair in neurological disease. To describe their biological potential with regard to plasticity, proliferation, or differentiation, it is important to know the cellular composition of their proteins, subsumed by the term proteome. Results Here, we present for the first time a proteomic database for HNSC isolated from the brains of adult rats and cultured for 10 weeks. Cytosolic proteins were extracted and subjected to two-dimensional gel electrophoresis followed by protein identification through mass spectrometry, database search, and gel matching. We could map about 1141 ± 209 (N = 5 protein spots for each gel, of which 266 could be identified. We could group the identified proteins into several functional categories including metabolism, protein folding, energy metabolism and cellular respiration, as well as cytoskeleton, Ca2+ signaling pathways, cell cycle regulation, proteasome and protein degradation. We also found proteins belonging to detoxification, neurotransmitter metabolism, intracellular signaling pathways, and regulation of DNA transcription and RNA processing. Conclusions The HNSC proteome database is a useful inventory which will allow to specify changes in the cellular protein expression pattern due to specific activated or suppressed pathways during differentiation or proliferation of neural stem cells. Several proteins could be identified in the HNSC proteome which are related to differentiation and plasticity, indicating activated functional pathways. Moreover, we found a protein for which no expression has been described in brain cells before.

  12. Effect of developmental lead exposure on synaptic plasticity and N—methyl—D—aspartate receptor subunit in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    RuanDY; SuiL

    2002-01-01

    Chronic lead(Pb) exposure is known to be associated with learning and memory,and cognitive dysfunction in children.Previous studies have demonstrated that Pb exposure may impair neuronal process underlying synaptic plasticity via a direct interaction with N-methyl-D-aspartate (NMDA) receptors(NMDARs).The studies described here were carried out to investigate effect of developmental Pb exposure on long-term potentiation(LTP),long-tern depression(LTD) and NMDAs subunits in rat hippocampus.The results are listed as follows:(1)low-level Pb exposture can impair the induction and maintenance of LTP in vivo and in vitro;(2)the Pb-induced impairment of LTD magnitude was an age-related decline in area CA1 of rat hippocampus;(3)chronic Pb exposure affected two components,voltage-gated calcium channel-dependent LTD and NMDARs-dependent LTD,of LTD induction in area CA1 of rat hippocampus;(4)different effects of developmental Pb exposure on NMDA receptor NR1,NR2A,NR2B,NR2C,NR2D and NR3A subunits in area CA1,CA2,CA3 and CA4 of rat hippocampus were observed;(5)the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors enriched in area CA1,CA3 and dentate gyrus and kainite receptors enriched in area CA1 and dentate gyrus of rat hippocampus were impaired by Pb exposure.

  13. The effects of endomorphins on striatal [3H]GABA release induced by electrical stimulation: an in vitro superfusion study in rats.

    Science.gov (United States)

    Bagosi, Zsolt; Jászberényi, Miklós; Telegdy, Gyula

    2009-05-01

    The endomorphins (EM1 and EM2) are selective endogenous ligands for mu-opioid receptors (MOR1 and MOR2) with neurotransmitter and neuromodulator roles in mammals. In the present study we investigated the potential actions of EMs on striatal GABA release and the implication of different MORs in these processes. Rat striatal slices were preincubated with tritium-labelled GABA ([(3)H]GABA), pretreated with selective MOR1 and MOR2 antagonist beta-funaltrexamine and selective MOR1 antagonist naloxonazine and then superfused with the selective MOR agonists, EM1 and EM2. EM1 significantly decreased the striatal [(3)H]GABA release induced by electrical stimulation. Beta-funaltrexamine antagonized the inhibitory action of EM1, but naloxonazine did not affect it considerably. EM2 was ineffective, even in case of specific enzyme inhibitor diprotin A pretreatment. The results demonstrate that EM1 decreases GABA release in the basal ganglia through MOR2, while EM2 does not influence it.

  14. Effects of GABA receptor antagonists on thresholds of P23H rat retinal ganglion cells to electrical stimulation of the retina

    Science.gov (United States)

    Jensen, Ralph J.; Rizzo, Joseph F., III

    2011-06-01

    An electronic retinal prosthesis may provide useful vision for patients suffering from retinitis pigmentosa (RP). In animal models of RP, the amount of current needed to activate retinal ganglion cells (RGCs) is higher than in normal, healthy retinas. In this study, we sought to reduce the stimulation thresholds of RGCs in a degenerate rat model (P23H-line 1) by blocking GABA receptor mediated inhibition in the retina. We examined the effects of TPMPA, a GABAC receptor antagonist, and SR95531, a GABAA receptor antagonist, on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400 µm diameter electrode. Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average three-fold. Neither TPMPA nor SR95531, applied alone or in combination, had consistent effects on the stimulation thresholds of OFF-center RGCs. We suggest that the effects of the GABA receptor antagonists on ON-center RGCs may be attributable to blockage of GABA receptors on the axon terminals of ON bipolar cells.

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

    Science.gov (United States)

    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.

  16. Prenatal exposure to bacterial endotoxin reduces the number of GAD67- and reelin-immunoreactive neurons in the hippocampus of rat offspring.

    Science.gov (United States)

    Nouel, Dominique; Burt, Melissa; Zhang, Ying; Harvey, Louise; Boksa, Patricia

    2012-04-01

    Epidemiological studies implicate prenatal infection as a risk factor for the development of schizophrenia and autism. Subjects with schizophrenia and autism are reported to exhibit reduced levels of glutamic acid decarboxylase 67 (GAD67), a marker for GABA neurons, in various brain regions. Reduced levels of reelin, a secretory glycoprotein present in a subpopulation of GABA neurons, have also been found in these disorders. To test if prenatal infection can cause abnormalities in GAD67 and reelin in the brains of offspring, this study used a rat model of prenatal exposure to the bacterial endotoxin, lipopolysaccharide (LPS), and assessed numbers of GAD67-immunoreactive (GAD67+) and reelin-immunoreactive (reelin+) neurons in the hippocampus of offspring. In offspring at postnatal day 14 (PD14), GAD67+ cell counts were reduced in the dentate gyrus of the prenatal LPS group compared to prenatal saline controls, while at PD28, GAD67+ cells counts were reduced in the prenatal LPS group in both the dentate gyrus and the CA1. There was a decrease in the number of reelin+ cells in the prenatal LPS offspring compared to controls in the dentate gyrus at PD14. However using Western blotting, no significant effects of prenatal LPS on levels of GAD67 or reelin protein were observed in various brain regions at PD14. These findings support the idea that prenatal infection can cause reductions in postnatal expression of GAD67 and reelin, and in this way, possibly contribute to the pathophysiology of schizophrenia or autism. Copyright © 2011 Elsevier B.V. and ECNP. All rights reserved.

  17. Nicotine-stimulated release of [3H]norepinephrine is reduced in the hippocampus of an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat.

    Science.gov (United States)

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

    2014-07-14

    Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous, developmental disorder, and is one of the most common child-psychiatric disorders. It is also a risk factor for early smoking and adult nicotine dependence. Nicotine has been shown to improve symptoms associated with ADHD, including problems with attention, working memory and response inhibition. Norepinephrine, a neurotransmitter involved in attention, is highly implicated in ADHD, and often targeted in the treatment thereof. In the present study we investigated nicotine׳s effect on release of norepinephrine in the hippocampus of a validated rat model of ADHD, the spontaneously hypertensive rat (SHR), as well as in two control strains: Wistar-Kyoto rats (WKY) and Sprague-Dawley rats (SD). Hippocampal slices obtained from male SHR, WKY and SD (postnatal day 31-33) were pre-incubated with radioactively labelled norepinephrine ([3H]NE) and perfused with buffer. The slices were stimulated by exposure to different concentrations of nicotine (1, 10, 100 or 1000 µM) for 1 min at 2 intervals (S1 and S2, separated by 20 min). Following a 10 min wash, slices were stimulated with 25 mM potassium. Since glutamate and GABA receptor function differ in SHR and WKY, we investigated the possible involvement of AMPA and GABA(A) receptors in nicotine (100 µM)-stimulated release of hippocampal [3H]NE in each of the strains by blocking these receptors with CNQX (AMPA receptor antagonist, 10 µM) or bicuculline (GABAA receptor antagonist, 30 µM) respectively. Nicotine-stimulated release (S1) of [3H]NE from SHR hippocampal slices was less than that of WKY and SD, at 100 µM and 1000 µM nicotine, suggesting reduced density and/or function of nicotinic receptors in SHR hippocampus. Nicotine-stimulated release of [3H]NE in response to S2 was reduced compared to S1 in all strains, indicating desensitization of receptors involved in stimulation of [3H]NE by nicotine. Potassium-stimulated release of [3H]NE following the

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 8h/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.

  1. Dopamine-galanin receptor heteromers modulate cholinergic neurotransmission in the rat ventral hippocampus

    Science.gov (United States)

    Moreno, Estefanía; Vaz, Sandra H.; Cai, Ning-Sheng; Ferrada, Carla; Quiroz, César; Barodia, Sandeep; Kabbani, Nadine; Canela, Enric I.; McCormick, Peter J.; Lluis, Carme; Franco, Rafael; Ribeiro, Joaquim A; Sebastião, Ana M.; Ferré, Sergi

    2011-01-01

    Previous studies have shown that dopamine and galanin modulate cholinergic transmission in the hippocampus, but little is known about the mechanisms involved and their possible interactions. By using resonance energy transfer techniques in transfected mammalian cells we demonstrated the existence of heteromers between the dopamine D1-like receptors (D1 and D5) and galanin Gal1, but not Gal2 receptors. Within the D1-Gal1 and D5-Gal1 receptor heteromers, dopamine receptor activation potentiated and dopamine receptor blockade counteracted MAPK activation induced by stimulation of Gal1 receptors, while Gal1 receptor activation or blockade did not modify D1-like receptor-mediated MAPK activation. Ability of a D1-like receptor antagonist to block galanin-induced MAPK activation (cross-antagonism) was used as a “biochemical fingerprint” of D1-like-Gal1 receptor heteromers, allowing their identification in the rat ventral hippocampus. The functional role of D1-like-Gal receptor heteromers was demonstrated in synaptosomes from rat ventral hippocampus, where galanin facilitated acetylcholine release, but only with co-stimulation of D1-like receptors. Electrophysiological experiments in rat ventral hippocampal slices showed that these receptor interactions modulate hippocampal synaptic transmission. Thus, a D1-like receptor agonist, that was ineffective when administered alone, turned an inhibitory effect of galanin into an excitatory effect, an interaction that required cholinergic neurotransmission. Altogether, our results strongly suggest that D1-like-Gal1 receptor heteromers act as processors that integrate signals of two different neurotransmitters, dopamine and acetylcholine, to modulate hippocampal cholinergic neurotransmission. PMID:21593325

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

    Science.gov (United States)

    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.

  3. Ischemia leads to apoptosis--and necrosis-like neuron death in the ischemic rat hippocampus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Stadelmann, Christine; Bastholm, Lone

    2004-01-01

    pyramidal cells of the rat hippocampus. The earliest ischemic changes were found on day 2 and 3, reflected by an upregulation of phospho-c-Jun in a proportion of morphologically intact CA1 neurons, which matched the number of neurons that succumbed to ischemia at later time points. At day 3 and later 3...... and/or caspase-3 expression represented a minor fraction (neurons, while the vast majority followed a necrosis-like pathway. Our studies suggest that CA1 pyramidal cell death following transient forebrain ischemia may be initiated through c-Jun N-terminal kinase (JNK) pathway...

  4. Comparison of taurine, GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo

    Science.gov (United States)

    Deng, Yan; Wang, Wei; Yu, Pingfeng; Xi, Zhijiang; Xu, Lijian; Li, Xiaolong; He, Nongyue

    2013-04-01

    The purpose of this study is to determine if amino acid neurotransmitters such as gamma-aminobutyric acid (GABA), taurine, glutamate (Glu), and aspartate (Asp) can scavenge activated carbonyl toxicants. In vitro, direct reaction between malondialdehyde (MDA) and amino acids was researched using different analytical methods. The results indicated that scavenging activated carbonyl function of taurine and GABA is very strong and that of Glu and Asp is very weak in pathophysiological situations. The results provided perspective into the reaction mechanism of taurine and GABA as targets of activated carbonyl such as MDA in protecting nerve terminals. In vivo, we studied the effect of taurine and GABA as antioxidants by detecting MDA concentration and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. It was shown that MDA concentration was decreased significantly, and the activities of SOD and GSH-Px were increased significantly in the cerebral cortex and hippocampus of acute epileptic state rats, after the administration of taurine and GABA. The results indicated that the peripherally administered taurine and GABA can scavenge free radicals and protect the tissue against activated carbonyl in vivo and in vitro.

  5. Neonatal N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) treatment modifies the vulnerability to phenobarbital- and ethanol-evoked sedative-hypnotic effects in adult rats.

    Science.gov (United States)

    Bortel, Aleksandra; Słomian, Lucyna; Nitka, Dariusz; Swierszcz, Michał; Jaksz, Mirella; Adamus-Sitkiewicz, Beata; Nowak, Przemysław; Jośko, Jadwiga; Kostrzewa, Richard M; Brus, Ryszard

    2008-01-01

    To study the influence of the central noradrenergic system on sensitivity to sedative-hypnotic effects mediated by the aminobutyric acid (GABA) system, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg sc x2, P1 and P3]. At 10 weeks, loss of the righting reflex (LORR) was used as an index to study the acute sedative-hypnotic effects of phenobarbital (100 mg/kg ip) and ethanol (4 g/kg ip, 25% v/v). Additionally, GABA concentration in the medial prefrontal cortex (PFC), hippocampus, cerebellum and brainstem was estimated by an HPLC/ED method. Neonatal DSP-4 treatment diminished the sedative-hypnotic effects of both phenobarbital and ethanol in adult rats. While the endogenous GABA content in the PFC, hippocampus, brainstem and cerebellum of DSP-4-treated rats was not altered, phenobarbital significantly decreased GABA content of both intact and DSP-4-lesioned rats by approximately 40% in the hippocampus and by approximately 20% in other brain regions at 1 h. Ethanol reduced GABA content by approximately 15-30% but only in the hippocampus and brainstem of both intact and lesioned rats. These findings indicate that the noradrenergic system exerts a prominent influence on sedative-hypnotics acting via GABAergic systems in the brain without directly altering GABA levels in the brain.

  6. Generation of slow network oscillations in the developing rat hippocampus after blockade of glutamate uptake.

    Science.gov (United States)

    Cattani, Adriano Augusto; Bonfardin, Valérie Delphine; Represa, Alfonso; Ben-Ari, Yehezkel; Aniksztejn, Laurent

    2007-10-01

    Cell-surface glutamate transporters are essential for the proper function of early cortical networks because their dysfunction induces seizures in the newborn rat in vivo. We have now analyzed the consequences of their inhibition by DL-TBOA on the activity of the developing CA1 rat hippocampal network in vitro. DL-TBOA generated a pattern of recurrent depolarization with an onset and decay of several seconds' duration in interneurons and pyramidal cells. These slow network oscillations (SNOs) were mostly mediated by gamma-aminobutyric acid (GABA) in pyramidal cells and by GABA and N-methyl-D-aspartate (NMDA) receptors in interneurons. However, in both cell types SNOs were blocked by NMDA receptor antagonists, suggesting that their generation requires a glutamatergic drive. Moreover, in interneurons, SNOs were still generated after the blockade of NMDA-mediated synaptic currents with MK-801, suggesting that SNOs are expressed by the activation of extrasynaptic NMDA receptors. Long-lasting bath application of glutamate or NMDA failed to induce SNOs, indicating that they are generated by periodic but not sustained activation of NMDA receptors. In addition, SNOs were observed in interneurons recorded in slices with or without the strata pyramidale and oriens, suggesting that the glutamatergic drive may originate from the radiatum and pyramidale strata. We propose that in the absence of an efficient transport of glutamate, the transmitter diffuses in the extracellular space to activate extrasynaptic NMDA receptors preferentially present on interneurons that in turn activate other interneurons and pyramidal cells. This periodic neuronal coactivation may contribute to the generation of seizures when glutamate transport dysfunction is present.

  7. Spontaneous recurrent seizures in rats: amino acid and monoamine determination in the hippocampus.

    Science.gov (United States)

    Cavalheiro, E A; Fernandes, M J; Turski, L; Naffah-Mazzacoratti, M G

    1994-01-01

    Rats subjected to structural brain damage induced by sustained convulsions triggered by systemic administration of pilocarpine (PILO) are a useful model for investigation of the mechanisms essential for seizure generation and spread in rodents. After PILO administration, three distinct phases are observed: (a) an acute period of 1-2 days' duration corresponding to a pattern of repetitive limbic seizures and status epilepticus; (b) a seizure-free (silent) period characterized by a progressive return to normal EEG and behavior of 4-44 days' duration; and (c) a period of spontaneous recurrent seizures (SRS) starting 5-45 days after PILO administration and lasting throughout the animal's life. PILO (320-350 mg/kg intraperitoneally, i.p.) was administered to rats, and the content of hippocampal monoamines and amino acids was measured in the acute, silent, and SRS periods by liquid chromatography. Norepinephrine (NE) level was decreased during all periods whereas dopamine (DA) content was increased. Serotonin (5-hydroxytryptamine, 5-HT) was increased only in the acute period. Utilization rate measurement of monoamines showed increased NE consumption and decreased DA consumption during all phases. 5-HT utilization rate was increased only in the acute period. Amino acid content showed a decrease in aspartate (ASP) and glutamate (GLU) concentrations associated with increased gamma-aminobutyric acid (GABA) level during the acute period. The silent phase was characterized by a decrease in glycine (GLY) and GABA levels and an increase in GLU concentration. The SRS period showed an increase in all amino acid concentrations. These findings show important neurochemical changes in the course of establishment of an epileptic focus after brain damage induced by status epilepticus triggered by pilocarpine.

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

    Science.gov (United States)

    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.

  9. Expression and significance of GIT1 in hippocampus of lithium-pilocarpine-induced epileptic rats

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    Li-hua ZHENG

    2015-07-01

    Full Text Available Objective  To investigate the expression changes of G-protein-coupled receptor kinase-interacting protein 1 (GIT1 in lithium-pilocarpine-induced epileptic rat model and explore its role in the genesis and development of epilepsy.  Methods  The lithium-pilocarpine-induced model of status epilepticus (SE was established in 42 specific pathogen free (SPF male adult Wistar rats, and those rats were randomly divided into control group and 6 epilepsy groups (1, 3, 7, 14, 30, 60 d after SE. The expression of GIT1 mRNA was detected by fluroescent quantitative polymerase chain reaction (PCR, while the expression of GIT1 protein was examined by Western blotting and immunohistochemistry was applied to test the expression of CA1 region, dentate gyrus and parahippocampal cortex in rat hippocampus at different time points.  Results  GIT1 mRNA level rised in acute phase on 1st and 3rd day after SE (P = 0.012, 0.002, then increased continously in latency on 7th and 14th day (P = 0.003, 0.001, and reached the peak in chronic phase on 30th and 60th day (P = 0.000, for all. GIT1 protein expression rised in acute phase and increased continously in chronic phase, but there was no significant difference compared with control group (P > 0.05, for all. Then, it reached the peak in chronic phase (P = 0.000, for all. Until the 30th day, the GIT1 expression of CA1 region, dentate gyrus and parahippocampal cortex in the hippocampus of rats in 6 epilepsy groups was significantly higher than that of control group (P = 0.000, for all.  Conclusions  The up-regulated expression of GIT1 in the hippocampus of epileptic rat was probably involved in the formation process of chronic epilepsy by regulating cytoskeleton dynamic regrouping to influence excitatory neural networks. DOI: 10.3969/j.issn.1672-6731.2015.06.011

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

    Science.gov (United States)

    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

  11. Blockade of GABA, type A, receptors in the rat pontine reticular formation induces rapid eye movement sleep that is dependent upon the cholinergic system.

    Science.gov (United States)

    Marks, G A; Sachs, O W; Birabil, C G

    2008-09-22

    The brainstem reticular formation is an area important to the control of rapid eye movement (REM) sleep. The antagonist of GABA-type A (GABA(A)) receptors, bicuculline methiodide (BMI), injected into the rat nucleus pontis oralis (PnO) of the reticular formation resulted in a long-lasting increase in REM sleep. Thus, one factor controlling REM sleep appears to be the number of functional GABA(A) receptors in the PnO. The long-lasting effect produced by BMI may result from secondary influences on other neurotransmitter systems known to have long-lasting effects. To study this question, rats were surgically prepared for chronic sleep recording and additionally implanted with guide cannulas aimed at sites in the PnO. Multiple, 60 nl, unilateral injections were made either singly or in combination. GABA(A) receptor antagonists, BMI and gabazine (GBZ), produced dose-dependent increases in REM sleep with GBZ being approximately 35 times more potent than BMI. GBZ and the cholinergic agonist, carbachol, produced very similar results, both increasing REM sleep for about 8 h, mainly through increased period frequency, with little reduction in REM latency. Pre-injection of the muscarinic antagonist, atropine, completely blocked the REM sleep-increase by GBZ. GABAergic control of REM sleep in the PnO requires the cholinergic system and may be acting through presynaptic modulation of acetylcholine release.

  12. Mate Tea Prevents Oxidative Stress in the Blood and Hippocampus of Rats with Acute or Chronic Ethanol Administration

    Directory of Open Access Journals (Sweden)

    Bianca Scolaro

    2012-01-01

    Full Text Available Objective. The aim of this study was to evaluate the influence of acute and chronic intake of mate tea on the effects elicited by acute and chronic administration of ethanol. Methods. Oxidative stress was evaluated by measuring thiobarbituric acid-reactive substances (TBARS, as well as the activities of the antioxidant enzymes, catalase (CAT, glutathione peroxidase (GSH-Px, and superoxide dismutase (SOD in the hippocampus and blood of rats. Male Wistar rats were randomly assigned to four groups, for both acute and chronic treatment: (1 control group, (2 treated group, (3 intoxicated group, (4 and intoxicated group treated with mate tea. Results. Both ethanol administrations significantly increased TBARS in plasma and hippocampus of rats and altered antioxidant enzyme activities, changes which were reverted by mate tea administration. Conclusions. Data indicate that acute and chronic ethanol administration induced oxidative stress in hippocampus and blood and that mate tea treatment was able to prevent this situation.

  13. Expression of brain-derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs.

    Science.gov (United States)

    Bai, Ou; Chlan-Fourney, Jennifer; Bowen, Rudy; Keegan, David; Li, Xin-Min

    2003-01-01

    Typical and atypical antipsychotic drugs, though both effective, act on different neurotransmitter receptors and are dissimilar in some clinical effects and side effects. The typical antipsychotic drug haloperidol has been shown to cause a decrease in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal cell survival, differentiation, and neuronal connectivity. However, it is still unknown whether atypical antipsychotic drugs similarly regulate BDNF expression. We examined the effects of chronic (28 days) administration of typical and atypical antipsychotic drugs on BDNF mRNA expression in the rat hippocampus using in situ hybridization. Quantitative analysis revealed that the typical antipsychotic drug haloperidol (1 mg/kg) down-regulated BDNF mRNA expression in both CA1 (P BDNF mRNA expression in CA1, CA3, and dentate gyrus regions of the rat hippocampus compared with their respective controls (P BDNF mRNA expression in rat hippocampus.

  14. Correlations between cognitive impairment and brain‑derived neurotrophic factor expression in the hippocampus of post-stroke depression rats.

    Science.gov (United States)

    Zhang, Zhao-Hui; Wu, Li-Na; Song, Jing-Gui; Li, Wen-Qiang

    2012-10-01

    The aim of this study was to investigate the correlation between brain-derived neurotrophic factor (BDNF) expression and cognitive impairment in post‑stroke depression (PSD) rats and to explore the mechanism(s) involved in the process of cognitive impairment. A rat model of focal cerebral ischemia was established by occluding the middle cerebral artery (MCA). Rats were subjected to isolation-housing combined with chronic unexpected mild stress (CUMS) to establish a PSD rat model. The learning and memory abilities of the PSD rat model were evaluated by passive avoidance tests. Real‑time PCR and immunohistochemical methods were used to detect changes in BDNF mRNA and protein expression in the hippocampus. Passive avoidance defects were revealed in the PSD and depression groups. Passive avoidance defects were more evident in the PSD group compared with the depression group and the difference was statistically significant (PBDNF expression in the hippocampus was significantly lower in the PSD and depression groups compared with that in the normal control group (PBDNF expression was identified between the normal control and stroke groups (P>0.05) or between the PSD and the depression groups (P>0.05). The decrease in BDNF expression in the hippocampus of PSD rats may aggravate cognitive impairment, however, the degree of cognitive impairment cannot be reflected by the expression levels of BDNF in the hippocampus.

  15. Plasticity-related binding of GABA and muscarinic receptor sites in piriform cortex of rat: An autoradiographic study

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    Thomas, A.P.; Westrum, L.E. (Univ. of Washington, Seattle (USA))

    1989-09-01

    This study has used the recently developed in vitro quantitative autoradiographic technique to examine the effects of olfactory bulb (OB) removal on receptor-binding sites in the deafferented piriform cortex (PC) of the rat. The gamma-aminobutyric acid-benzodiazepine receptor (GABA-BZR)- and muscarinic cholinergic receptor (MChR)-binding sites in layer I of PC were localized using (3H)flunitrazepam and (3H)quinuclidinyl benzilate as ligands, respectively. From the resultant autoradiograms the optical densities were measured using a Drexel-DUMAS image analysis system. The densities of BZR and MChR-binding sites were markedly increased in the PC ipsilateral to the lesion as compared to the contralateral side in those subjects that were operated in adulthood (Postnatal Day 100, PN 100). Comparisons between the unoperated and PN 100 operated animals also showed significant increases in the deafferented PC. In the animals operated on the day of birth (PN 0) no significant differences were seen between the operated and the contralateral PC. The difference between the PN 0 deafferented PC and the unoperated controls shows a slight decrease in BZR density in the former group; however, in case of the MChR there is a slight increase on the side of the lesion. These results demonstrate that deafferentation of PC by OB removal appears to modulate both the BZR-binding sites that are coupled with the GABA-A receptor complex and the MChR-binding sites. The results also suggest that possibility of a role for these neurotransmitter receptor-binding sites in plasticity following deafferentation.

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

    Science.gov (United States)

    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.

  17. Neurogenesis by Activation of Inherent Neural Stem Cells in the Rat Hippocampus after Cerebral Infarction

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Ren-zhi Wang; Zhi-gang Lian; Yang Song; Yong Yao

    2009-01-01

    Objective To investigate the changes of neural stem cells (NSCs) in the rat hippocampus after cerebral infarction (CI) and to evaluate the neurogenesis caused by the activation of NSCs. Methods CI models of rats were made and rats were assigned to 6 groups: sham-operated, 1 day, 3 days, 7 days, 14 days, and 28 days after CI. The dynamic expression of bromodeoxyuridine (BrdU), polysialylated neural cell adhesion molecule (PSA-NCAM), glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU was used to mark the proliferated NSCs. PSA-NCAM was used to mark the plasticity of activated NSCs. GFAP and NeuN were used to mark the differentiated NSCs. Results Compared with the controls, the number of BrdU+ cells in the hippocampus increased significantly at 1 day after CI (P < 0.05), reached peak at 7 days after CI (P < 0.05), decreased but still elevated compared with the controls at 14 days after CI (P < 0.05), and nearly unchanged at 28 days after CI. The number of BrdU+/PSA-NCAM+ cells increased significantly at 7 days after CI (P < 0.05), reached peak at 14 days after CI (P < 0.05), and decreased but still elevated compared with the controls at 28 days after CI (P < 0.05). The number of BrdU+/PSA-NCAM+ cells was equal to 60% of the number of BrdU+ cells in all the same period. The number of BrdU+/NeuN+ cells in the hippocampus increased significantly at 14 days after CI (P < 0.05) and reached peak at 28 day after CI (P < 0.05). The number of BrdU+/GFAP+cells in the hippocampus nearly unchanged after CI. Conclusion CI can stimulate the proliferation of inherent NSCs, and most proliferated NSCs may differentiate into neurons and represent neural plasticity.

  18. Effects of neonatal. gamma. -ray irradiation on rat hippocampus: Pt. 1; Postnatal maturation of hippocampal cells

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    Represa, A.; Dessi, F.; Beaudoin, M.; Ben-Ari, Y. (Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France))

    1991-01-01

    The axons of dentate granule cells, the mossy fibres, establish synaptic contacts with the thorny excrescences of the apical dendrite of CA3 pyramidal neurons. Dentate granule cells develop postnatally in rats, whereas the CA3 pyramidal cells are generated before birth. In the present studies, using unilateral neonatal {gamma}-ray irradiation to destroy the granule cells in one hemisphere, we have studied the effect of mossy fibre deprivation on the development of their targets. We show that such ''degranulation'' prevents the normal development of giant thorny excrescences, suggesting that the development of thorny excrescences in CA3 pyramidal neurons is under the control of mossy fibres. In contrast, irradiation of the hippocampus of the neonatal rat does not affect the development of the dendritic arborization of CA3 pyramidal cells and their non-mossy dendritic spines. (author).

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 (PCA3-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.

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

    Science.gov (United States)

    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.

  2. Differential gene expression in the rat hippocampus during learning of an operant conditioning task.

    Science.gov (United States)

    Rapanelli, M; Frick, L R; Zanutto, B S

    2009-11-10

    Changes in transcription levels of brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate (cAMP) response element binding (CREB), Synapsin I, Ca(2+)/calmodulin-dependent protein kinase II (CamKII), activity-regulated cytoskeleton-associated protein (Arc), c-jun and c-fos have been associated to several learning paradigms in different brain areas. In this study, we measured mRNA expression in the hippocampus by real time (RT)-PCR mRNA levels of BDNF, CREB, Synapsin I, CamKII, Arc, c-jun and c-fos, during learning and operant conditioning task. Experimental groups were as follows: control (C, the animals never left the bioterium), when the animals reached 50-65% of the expected response (Incompletely Trained, IT), when animals reached 100% of the expected response with a latency time lower than 5 s (Trained, Tr), Box Control of Incompletely Trained (BCIT), animals spent the same time as the IT in the operant conditioning box and Box Control of Trained (BCTr) animals spent the same time as the Tr in the operant conditioning box. All rats were killed at the same time by cervical dislocation 15 min after training and hippocampi were removed and processed. We found increments of mRNA levels of most genes (BDNF, CREB, Synapsin I, Arc, c-jun and c-fos) in IT and Tr groups compared to their box controls, but increments in Tr were smaller compared with IT. These results describe a differential gene expression in the rat hippocampus when the animals are learning and when animals have already learned. Taking together the results presented herein with the known functions of these genes, we propose a link between changes in gene expression in the hippocampus and different degrees of cellular activation and plasticity during learning of an operant conditioning task.

  3. The essential oil of bergamot enhances the levels of amino acid neurotransmitters in the hippocampus of rat: implication of monoterpene hydrocarbons.

    Science.gov (United States)

    Morrone, Luigi A; Rombolà, Laura; Pelle, Cinzia; Corasaniti, Maria T; Zappettini, Simona; Paudice, Paolo; Bonanno, Giambattista; Bagetta, Giacinto

    2007-04-01

    The effects of bergamot essential oil (BEO) on the release of amino acid neurotransmitters in rat hippocampus have been studied by in vivo microdialysis and by in vitro superfusion of isolated nerve terminals. Intraperitoneal administration of BEO (100microl/kg) significantly elevated the extracellular concentration of aspartate, glycine and taurine in a Ca(2+)-dependent manner. A dose-relation study generated a bell-shaped curve. When perfused into the hippocampus via the dialysis probe (20microl/20min), BEO produced a significant increase of extracellular aspartate, glycine, taurine as well as of GABA and glutamate. The augmentation of all amino acids was Ca(2+)-independent. Focally injected 1:1 diluted BEO preferentially caused extracellular increase of glutamate. Interestingly, this release appeared to be strictly Ca(2+)-dependent. BEO concentration-dependently enhanced the release of [(3)H]D-aspartate from superfused hippocampal synaptosomes. Similar results were obtained by monitoring the BEO-evoked release of endogenous glutamate. At relatively high concentrations, the BEO-induced [(3)H]d-aspartate release was almost entirely prevented by the glutamate transporter blocker dl-threo-beta-benzyloxyaspartic acid (DL-TBOA) and was Ca(2+)-independent. At relatively low concentrations the release of [(3)H]D-aspartate was only in part ( approximately 50%) DL-TBOA-sensitive and Ca(2+)-independent; the remaining portion of release was dependent on extracellular Ca(2+). Interestingly, the monoterpene hydrocarbon-free fraction of the essential oil appeared to be inactive while the bergapten-free fraction superimposed the releasing effect of BEO supporting the deduction that psoralens may not be implicated. To conclude, BEO contains into its volatile fraction still unidentified monoterpene hydrocarbons able to stimulate glutamate release by transporter reversal and/or by exocytosis, depending on the dose administered.

  4. Effect of cholecystokinin on learning and memory, neuronal proliferation and apoptosis in the rat hippocampus

    Science.gov (United States)

    Reisi, Parham; Ghaedamini, Ali Reza; Golbidi, Mohammad; Shabrang, Moloud; Arabpoor, Zohreh; Rashidi, Bahman

    2015-01-01

    Background: Cholecystokinin (CCK) has roles in learning and memory, but the cellular mechanism is poorly understood. This study investigated the effect of CCK on spatial learning and memory, neuronal proliferation and apoptosis in the hippocampus in rats. Materials and Methods: Experimental groups were control and CCK. The rats received CKK octapeptide sulfated (CCK-8S, 1.6 μg/kg, i.p.) for 14 days. Spatial learning and memory were tested by Morris water maze and finally immunohistochemical study was performed; neurogenesis by Ki-67 method and apoptosis by Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL) assay in hippocampal dentate gyrus (DG). Results: Cholecystokinin increased Ki-67 positive cells and reduced TUNEL positive cells in the granular layer of hippocampal DG. CCK failed to have a significant effect on spatial learning and memory. Conclusion: Results indicate neuroprotective and proliferative effects of CCK in the hippocampus; however, other factors are probably involved until the newly born neurons achieve necessary integrity for behavioral changes. PMID:26623402

  5. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus.

    Science.gov (United States)

    Suderman, Matthew; McGowan, Patrick O; Sasaki, Aya; Huang, Tony C T; Hallett, Michael T; Meaney, Michael J; Turecki, Gustavo; Szyf, Moshe

    2012-10-16

    Early life experience is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, it is unlikely that such effects completely capture the evolutionarily conserved epigenetic mechanisms of early adaptation to environment. Here we present DNA methylation profiles spanning 6.5 million base pairs centered at the NR3C1 gene in the hippocampus of humans who experienced abuse as children and nonabused controls. We compare these profiles to corresponding DNA methylation profiles in rats that received differential levels of maternal care. The profiles of both species reveal hundreds of DNA methylation differences associated with early life experience distributed across the entire region in nonrandom patterns. For instance, methylation differences tend to cluster by genomic location, forming clusters covering as many as 1 million bases. Even more surprisingly, these differences seem to specifically target regulatory regions such as gene promoters, particularly those of the protocadherin α, β, and γ gene families. Beyond these high-level similarities, more detailed analyses reveal methylation differences likely stemming from the significant biological and environmental differences between species. These results provide support for an analogous cross-species epigenetic regulatory response at the level of the genomic region to early life experience.

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

    Science.gov (United States)

    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 Bax increased significantly compared to the control group at the doses of 1 ( p Bax was increased significantly compared to the control group at the doses of 2 and 4 mg/kg ( p Bax mRNA ratio induces cell apoptosis. Apoptotic effect of cadmium may be through the mitochondrial pathway by the activation of caspase-3/7.

  7. Greater glucocorticoid receptor activation in hippocampus of aged rats sensitizes microglia.

    Science.gov (United States)

    Barrientos, Ruth M; Thompson, Vanessa M; Kitt, Meagan M; Amat, Jose; Hale, Matthew W; Frank, Matthew G; Crysdale, Nicole Y; Stamper, Christopher E; Hennessey, Patrick A; Watkins, Linda R; Spencer, Robert L; Lowry, Christopher A; Maier, Steven F

    2015-03-01

    Healthy aging individuals are more likely to suffer profound memory impairments following an immune challenge than are younger adults. These challenges produce a brain inflammatory response that is exaggerated with age. Sensitized microglia found in the normal aging brain are responsible for this amplified response, which in turn interferes with processes involved in memory formation. Here, we examine factors that may lead aging to sensitize microglia. Aged rats exhibited higher corticosterone levels in the hippocampus, but not in plasma, throughout the daytime (diurnal inactive phase). These elevated hippocampal corticosterone levels were associated with increased hippocampal 11β-hydroxysteroid dehydrogenase type 1 protein expression, the enzyme that catalyzes glucocorticoid formation and greater hippocampal glucocorticoid receptor (GR) activation. Intracisternal administration of mifepristone, a GR antagonist, effectively reduced immune-activated proinflammatory responses, specifically from hippocampal microglia and prevented Escherichia coli-induced memory impairments in aged rats. Voluntary exercise as a therapeutic intervention significantly reduced total hippocampal GR expression. These data strongly suggest that increased GR activation in the aged hippocampus plays a critical role in sensitizing microglia.

  8. ISCHEMIC PRECONDITIONING RELIEVES ISCHEMIA/REPERFUSION INJURY OF HIPPOCAMPUS NEURONS IN RAT BY INHIBITING p53 AND BAX EXPRESSIONSA

    Institute of Scientific and Technical Information of China (English)

    Hui-min Liu; Jing-xin Li; Lian-bi Chen

    2007-01-01

    Objective To examine whether ischemic preconditioning (IPC) can protect neuron against delayed death in CA1 subfield of hippocampus following reperfusion of a lethal ischemia in rats, and explore the role of p53 and bax in this process.Methods We examined the effect of IPC on delayed neuron death, neuron apoptosis, expressions of p53 and bax gene in the CA1 area of hippocampus in the rats using HE staining, flow cytometry, RT-PCR, and immunohistochemis-try technique.Results IPC enhanced the quantity of survival cells in the CA1 region of hippocampus (216 ±9 cells/0. 72 mm2 vs. 30 ±5 cells/0. 72 mm2, P<0. 01), decreased the percentages of apoptotic neurons of hippocampus caused by is-chemia/reperfusion (2. 06% ±0.21% vs. 4.27% ±0. 08% , P<0. 01), and weakened the expressions of p53 and bax gene of hippocampus compared with ischemia/reperrusion without IPC.Conclusion IPC can protect the neurons in the CA1 region of hippocampus against apoptosis caused by ischemia/reperfusion, and this process may be related to the reduced expressions of p53 and bax.

  9. Bumetanide, an NKCC1 antagonist, does not prevent formation of epileptogenic focus but blocks epileptic focus seizures in immature rat hippocampus.

    Science.gov (United States)

    Nardou, Romain; Ben-Ari, Yehezkel; Khalilov, Ilgam

    2009-06-01

    Excitatory GABA action induced by high [Cl(-)](i) is thought to contribute to seizure generation in neonatal neurons although the mechanism of this effect remains unclear. We report that bumetanide, a NKCC1 antagonist, reduces driving force of GABA-mediated currents (DF(GABA)) in neonatal hippocampal neurons and blocks the giant depolarizing potentials (GDPs), a spontaneous pattern of network activity. In the preparation composed of two intact interconnected hippocampi, bumetanide did not prevent generation of kainate-induced seizures, their propagation to the contralateral hippocampus, and formation of an epileptogenic mirror focus. However, in the isolated mirror focus, bumetanide effectively blocked spontaneous epileptiform activity transforming it to the GDP-like activity pattern. Bumetanide partially reduced DF(GABA) and therefore the excitatory action of GABA in epileptic neurons. Therefore bumetanide is a potent anticonvulsive agent although it cannot prevent formation of the epileptogenic mirror focus. We suggest that an additional mechanism other than NKCC1-mediated contributes to the persistent increase of DF(GABA) in epileptic neurons.

  10. 虎门合剂对成瘾模型及戒断大鼠GABA免疫阳性神经元的影响%Influences from Traditional Chinese HuMen Composition on GABA Immune Positive Neurons of Morphine-Dependence and Withdrawal Rats

    Institute of Scientific and Technical Information of China (English)

    丁尤放; 林涵; 李树春

    2016-01-01

    目的:研究吗啡成瘾性和戒断大鼠在虎门合剂给药后GABA阳性神经元数量的变化。方法:通过提升传统建模方法建立大鼠成瘾模型和模型评估系统,同时利用免疫组化法观察虎门合剂给药后吗啡成瘾和戒断大鼠阳性细胞元的变化。结果:吗啡依赖大鼠海马CA1区和齿状回GABA阳性神经元数目明显减少,虎门合剂治疗组海马GABA阳性神经元数量和光密度均显著升高。结论:虎门合剂对吗啡损伤一般记忆的效应具有拮抗作用。%Objective To discuss the changes occurring in GABA positive neurons of morphine-dependence and withdrawal Rats after given HuMen Composition.Methods Rats addiction models and model evaluation system were established in the study through im-proving the traditional methods of building models.At the same time,immunohistochemical method was used to observe the changes occurring in positive neurons of morphine-dependence and withdrawal Rats after given HuMen Composition.Results the number of positive neurons is obviously decreased in hippocampus CA1 and Dentate Gyrus areas of morphine-dependent rats.In the treatment group of HuMen Composition,the number of hippocampus GABA and optical density are all increased respectively.Conclusion Hu-Men Composition may have certain antagonistic effect in curing damaged memory induced by morphine.

  11. Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Chun Yang

    2012-01-01

    Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

  12. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injur y in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Wangxin Zhang; Qiuling Zhang; Wen Deng; Yalu Li; Guoqing Xing; Xianjun Shi; Yifeng Du

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-ti-oxidative and anti-inlfammatory 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 ganoder-ma 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 fac-tor-αand interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. hTese results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-ti-inlfammatory actions.

  13. The bradycardic and hypotensive responses to serotonin are reduced by activation of GABA A receptors in the nucleus tractus solitarius of awake rats

    Directory of Open Access Journals (Sweden)

    J.C. Callera

    2005-07-01

    Full Text Available We investigated the effects of bilateral injections of the GABA receptor agonists muscimol (GABA A and baclofen (GABA B into the nucleus tractus solitarius (NTS on the bradycardia and hypotension induced by iv serotonin injections (5-HT, 2 µg/rat in awake male Holtzman rats. 5-HT was injected in rats with stainless steel cannulas implanted bilaterally in the NTS, before and 5, 15, and 60 min after bilateral injections of muscimol or baclofen into the NTS. The responses to 5-HT were tested before and after the injection of atropine methyl bromide. Muscimol (50 pmol/50 nl, N = 8 into the NTS increased basal mean arterial pressure (MAP from 115 ± 4 to 144 ± 6 mmHg, did not change basal heart rate (HR and reduced the bradycardia (-40 ± 14 and -73 ± 26 bpm at 5 and 15 min, respectively, vs -180 ± 20 bpm for the control and hypotension (-11 ± 4 and -14 ± 4 mmHg, vs -40 ± 9 mmHg for the control elicited by 5-HT. Baclofen (12.5 pmol/50 nl, N = 7 into the NTS also increased basal MAP, but did not change basal HR, bradycardia or hypotension in response to 5-HT injections. Atropine methyl bromide (1 mg/kg body weight injected iv reduced the bradycardic and hypotensive responses to 5-HT injections. The stimulation of GABA A receptors in the NTS of awake rats elicits a significant increase in basal MAP and decreases the cardiac Bezold-Jarisch reflex responses to iv 5-HT injections.

  14. Parvalbumin and neuropeptide Y expressing hippocampal GABA-ergic inhibitory interneuron numbers decline in a model of Gulf War illness.

    Science.gov (United States)

    Megahed, Tarick; Hattiangady, Bharathi; Shuai, Bing; Shetty, Ashok K

    2014-01-01

    Cognitive dysfunction is amongst the most conspicuous symptoms in Gulf War illness (GWI). Combined exposure to the nerve gas antidote pyridostigmine bromide (PB), pesticides and stress during the Persian Gulf War-1 (PGW-1) are presumed to be among the major causes of GWI. Indeed, our recent studies in rat models have shown that exposure to GWI-related (GWIR) chemicals and mild stress for 4 weeks engenders cognitive impairments accompanied with several detrimental changes in the hippocampus. In this study, we tested whether reduced numbers of hippocampal gamma-amino butyric acid (GABA)-ergic interneurons are among the pathological changes induced by GWIR-chemicals and stress. Animals were exposed to low doses of GWIR-chemicals and mild stress for 4 weeks. Three months after this exposure, subpopulations of GABA-ergic interneurons expressing the calcium binding protein parvalbumin (PV), the neuropeptide Y (NPY) and somatostatin (SS) in the hippocampus were stereologically quantified. Animals exposed to GWIR-chemicals and stress for 4 weeks displayed reduced numbers of PV-expressing GABA-ergic interneurons in the dentate gyrus and NPY-expressing interneurons in the CA1 and CA3 subfields. However, no changes in SS+ interneuron population were observed in the hippocampus. Furthermore, GABA-ergic interneuron deficiency in these animals was associated with greatly diminished hippocampus neurogenesis. Because PV+ and NPY+ interneurons play roles in maintaining normal cognitive function and neurogenesis, and controlling the activity of excitatory neurons in the hippocampus, reduced numbers of these interneurons may be one of the major causes of cognitive dysfunction and reduced neurogenesis observed in GWI. Hence, strategies that improve inhibitory neurotransmission in the hippocampus may prove beneficial for reversing cognitive dysfunction in GWI.

  15. Parvalbumin and Neuropeptide Y Expressing Hippocampal GABA-ergic Inhibitory Interneuron Numbers Decline in a Model of Gulf War illness

    Directory of Open Access Journals (Sweden)

    Tarick eMegahed

    2015-01-01

    Full Text Available Cognitive dysfunction is amongst the most conspicuous symptoms in Gulf war illness (GWI. Combined exposure to the nerve gas antidote pyridostigmine bromide, pesticides and stress during the Persian Gulf War-1 are presumed to be among the major causes of GWI. Indeed, our recent studies in rat models have shown that exposure to GWI-related (GWIR chemicals and mild stress for four weeks engenders cognitive impairments accompanied with several detrimental changes in the hippocampus. In this study, we tested whether reduced numbers of hippocampal gamma-amino butyric acid (GABA-ergic interneurons are among the pathological changes induced by GWIR-chemicals and stress. Animals were exposed to low doses of GWIR-chemicals and mild stress for four weeks. Three months after this exposure, subpopulations of GABA-ergic interneurons expressing the calcium binding protein parvalbumin (PV, the neuropeptide Y (NPY and somatostatin (SS in the hippocampus were stereologically quantified. Animals exposed to GWIR-chemicals and stress for four weeks displayed reduced numbers of PV-expressing GABA-ergic interneurons in the dentate gyrus and NPY-expressing interneurons in the CA1 and CA3 subfields. However, no changes in SS+ interneuron population were observed in the hippocampus. Furthermore, GABA-ergic interneuron deficiency in these animals was associated with greatly diminished hippocampus neurogenesis. Because PV+ and NPY+ interneurons play roles in maintaining normal cognitive function and neurogenesis, and controlling the activity of excitatory neurons in the hippocampus, reduced numbers of these interneurons may be one of the major causes of cognitive dysfunction and reduced neurogenesis observed in GWI. Hence, strategies that improve inhibitory neurotransmission in the hippocampus may prove beneficial for reversing cognitive dysfunction in GWI.

  16. Overexpression of neuropeptide Y induced by brain-derived neurotrophic factor in the rat hippocampus is long lasting.

    Science.gov (United States)

    Reibel, S; Vivien-Roels, B; Lê, B T; Larmet, Y; Carnahan, J; Marescaux, C; Depaulis, A

    2000-02-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampal neuroplasticity. In particular, BDNF upregulation in the hippocampus by epileptic seizures suggests its involvement in the neuronal rearrangements accompanying epileptogenesis. We have shown previously that chronic infusion of BDNF in the hippocampus induces a long-term delay in hippocampal kindling progression. Although BDNF has been shown to enhance the excitability of this structure upon acute application, long-term transcriptional regulations leading to increased inhibition within the hippocampus may account for its suppressive effects on epileptogenesis. Therefore, the long-term consequences of a 7-day chronic intrahippocampal infusion of BDNF (12 microg/day) were investigated up to 2 weeks after the end of the infusion, on the expression of neurotransmitters contained in inhibitory hippocampal interneurons and which display anti-epileptic properties. Our results show that BDNF does not modify levels of immunostaining for glutamic acid decarboxylase, the rate-limiting enzyme for gamma-aminobutyric acid (GABA) synthesis, and somatostatin. Conversely, BDNF induces a long-lasting increase of neuropeptide Y (NPY) in the hippocampus, measured by immunohistochemistry and radioimmunoassay, outlasting the end of the infusion by at least 7 days. The distribution of BDNF-induced neuropeptide Y immunoreactivity is similar to the pattern observed in animals submitted to hippocampal kindling, with the exception of mossy fibres which only become immunoreactive following seizure activity. The enduring increase of neuropeptide Y expression induced by BDNF in the hippocampus suggests that this neurotrophin can trigger long-term genomic effects, which may contribute to the neuroplasticity of this structure, in particular during epileptogenesis.

  17. Jiawei Wendan decoction affects mitogen-activated protein kinase signal pathway in the hippocampus of depression rats

    Institute of Scientific and Technical Information of China (English)

    Liping Zhang; Man Zhang; Li Wu; Meng Xia; Guangbin Li

    2011-01-01

    A previous study from our group showed that Jiawei Wendan decoction inhibits protein expression of interleukin-1β, 2, and 6, as well as plasma neuropeptide Y, P substance and somatostatin in the hippocampus of depression rat models. The present study analyzed the influence of Jiawei Wendan decoction on the mitogen-activated protein kinase signal transduction pathway in the hippocampus. Results demonstrated that Jiawei Wendan decoction effectively upregulated expression of small molecular G proteins, extracellular regulated kinase 1/2, and activated ribosomal S6 kinase protein in the rat hippocampus. In addition, Jiawei Wendan decoction exhibits antidepressant effects similar to fluoxetine. The underlying mechanisms were shown to be dependent on increased mitogen-activated protein kinase signal transduction pathway activity.

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

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    Luxen Andre

    2008-05-01

    Full Text Available Abstract 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

  19. Polygalasaponin F induces long-term potentiation in adult rat hippocampus via NMDA receptor activation

    Institute of Scientific and Technical Information of China (English)

    Feng SUN; Jian-dong SUN; Ning HAN; Chuang-jun LI; Yu-he YUAN; Dong-ming ZHANG; Nai-hong CHEN

    2012-01-01

    Aim:To investigate the effect and underlying mechanisms of polygalasaponin F (PGSF),a triterpenoid saponin isolated from Polygala japonica,on long-term potentiation (LTP)in hippocampus dentate gyrus (DG)of anesthetized rats.Methods:Population spike (PS)of hippocampal DG was recorded in anesthetized male Wistar rats.PGSF,the NMDAR inhibitor MK801 and the CaMKll inhibitor KN93 were intracerebroventricularly administered.Western blotting analysis was used to examine the phosphorylation expressions of NMDA receptor subunit 2B (NR2B),Ca2+/calmodulin-dependent kinase Ⅱ (CaMKII),extracellular signalregulated kinase (ERK),and cAMP response element-binding protein (CREB).Results:Intracerebroventricular administration of PGSF (1 and 10 μmol/L)produced long-lasting increase of PS amplitude in hippocampal DG in a dose-dependent manner.Pre-injection of MK801 (100 μmol/L)or KN93 (100 μmol/L)completely blocked PGSFinduced LTP.Furthermore,the phosphorylation of NR2B,CaMKII,ERK,and CREB in hippocampus was significantly increased 5-60min after LTP induction.The up-regulation of p-CaMKII expression could be completely abolished by pre-injection of MK801.The upregulation of p-ERK and p-CREB expressions could be partially blocked by pre-injection of KN93.Conclusion:PGSF could induce LTP in hippocampal DG in anesthetized rats via NMDAR activation mediated by CaMKII,ERK and CREB signaling pathway.

  20. [Effect of electroacupuncture on cellular structure of hippocampus in splenic asthenia pedo-rats].

    Science.gov (United States)

    Yang, Zhuo-xin; Zhuo, Yuan-yuan; Yu, Hai-bo; Wang, Ning

    2010-02-01

    To observe the effect of electroacupuncture (EA) on hippocampal structure in splenic asthenia pedo-rats. A total of 15 SD male rats were randomly assigned to normal control group (n=5), model group (n=5) and EA group (n=5). Splenic asthenic syndrome model was established by intragastric administration of rhubarb and intraperitoneal injection of Reserpine for 14 d. EA (1 mA, 3 Hz/iS Hz) was applied to bilateral "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 20 mm, once a day for 14 days. The cellular structure of hippocampus was observed by light microscope and transmission electron microscope. Optical microscopic observation showed that in normal control group, the cellular nucleus was distinct, and the granular cell layer well-arranged and tight. In model group, the intracellular space was widened, and the granular cell layer was out of order in the arrangement. In EA group, the celluldr nucleus and the granular cell layer were nearly normal. Results of the electronic microscope showed that cells in model group had a karyopyknosis with irregular appearance and clear incisure, and some of them presented dissolving and necrotic phenomena; and those in EA group were milder in injury, had nearly-normal nucleus with visible nucleoli and relatively-intact nuclear membrane. Regarding the cellular plasma, in comparison with rich normal organelles of control group, the mitochondria in model group were swelling, with vague, dissolved and broken cristae, while in EA group, majority of the organelles were well-kept, and slightly dissolved mitochondrial cristae found. In regard to the synaptic structure, in comparison with control group, synaptic apomorphosis and swelling mitochondria were found in model group While in EA group, milder swelling and hydropic degeneration were seen. Different from the distinct pre- and post-synaptic membrane and synaptic vesicles of control group, while those in EA group were nearly-normal. electroacupunture can effectively relieve splenasthenic

  1. REGION-SPECIFIC ALTERATIONS OF CALBINDIN-D28K IMMUNOREACTIVITY IN THE RAT HIPPOCAMPUS FOLLOWING ADRENALECTOMY AND CORTICOSTERONE TREATMENT

    NARCIS (Netherlands)

    KRUGERS, HJ; MEDEMA, RM; POSTEMA, F; KORF, J

    1995-01-01

    The aim of this study was (i) to compare the immunocytochemical distribution of the calcium-binding protein calbindin-D28k (CB) in the hippocampus of rats with the pattern of neurodegeneration following adrenalectomy (ADX) using silver impregnation, and (ii) to investigate the CB-immunoreactivity in

  2. Distribution of a GABAB-like receptor protein in the rat central nervous system.

    Science.gov (United States)

    Charles, K J; Calver, A R; Jourdain, S; Pangalos, M N

    2003-11-07

    Using a homology-based bioinformatics approach we have identified the human and rodent orthologues of a novel putative seven transmembrane G protein coupled receptor, termed GABA(BL). The amino acid sequence homology of these cDNAs compared to GABA(B1) and GABA(B2) led us to postulate that GABA(BL) may be a putative novel GABA(B) receptor subunit. We have developed a rabbit polyclonal antisera specific to the GABA(BL) protein and assessed the distribution of GABA(BL) in the rat CNS by immunohistochemistry. Protein expression was particularly dense in regions previously shown to contain known GABA(B) receptor subunits. Dense immunoreactivity was observed in the cortex, major subfields of the hippocampus and the dentate gyrus. GABA(BL) labelling was very conspicuous in the cerebellum, both in the granule cell layer and in Purkinje cells, and was also observed in the substantia gelatinosa and ventral horn motor neurons of the spinal cord. GABA(BL) immunoreactivity was also noted in a subset of parvalbumin positive hippocampal interneurons. Our data suggest a widespread distribution of GABA(BL) throughout the rat CNS.

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

    Directory of Open Access Journals (Sweden)

    Natalia Grion

    2016-02-01

    Full Text Available 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.

  4. ROLE OF NMDA, NICOTINIC, AND GABA RECEPTORS IN THE STEADY STATE VISUAL EVOKED POTENTIAL IN RATS.

    Science.gov (United States)

    This manuscript characterizes the receptor pathways involved in pattern-evoked potential generation in rats" NMDA and nicotinic acetylcholine receptors appear to be involved in the generation of the steady-state pattern evoked response in vivo." The pattern evok...

  5. Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat

    Energy Technology Data Exchange (ETDEWEB)

    Oleskevich, S.; Descarries, L.; Lacaille, J.C. (Universite de Montreal, Quebec (Canada))

    1989-11-01

    A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus.

  6. Dexamethasone induces different morphological changes in the dorsal and ventral hippocampus of rats.

    Science.gov (United States)

    Silva-Gómez, Adriana Berenice; Aguilar-Salgado, Yuritze; Reyes-Hernández, Diego Octavio; Flores, Gonzalo

    2013-01-01

    Dexamethasone (DEX), a synthetic glucocorticoid widely used in neurological illnesses because of its antiinflammatory properties, has many serious side effects, including severe psychiatric symptoms such as psychoses. The hippocampus is divided in the dorsal hippocampus (DH) and ventral hippocampus (VH) with each region having a subfield of CA1 and CA3 pyramidal layers. Great interest has recently emerged showing that the DH and VH are functionally different. In our work we determined whether, and what, changes occurred, after five days of DEX (0.2mg/kg) treatment, on the dendritic morphology of the CA1 and CA3 pyramidal neurons of the DH and VH of adult Sprague-Dawley rats. The dendritic morphology and characteristics were measured by using the Golgi-Cox procedure followed by a Sholl analysis. DEX decreased the number of dendritic spines of both apical and basolateral dendrites. Interestingly, this decrease was more pronounced in the VH. Only the VH neurons were affected by DEX with a decrease in their total dendritic length (TDL). An interesting point is that the VH neurons are longer that the DH neurons among the groups injected with saline only as the control. The length per branch order was only altered in the apical dendritic tree of the CA1 neurons. These data taken together show that the VH is more susceptible to DEX and its neurons are larger than the DH neurons. These results support previous observations related to differences between the DH and VH and suggest differences in the expression of the glucocorticoid receptors in connectivity and the space to elongate their dendritic arbor.

  7. Sleep-deprivation induces changes in GABA(B and mGlu receptor expression and has consequences for synaptic long-term depression.

    Directory of Open Access Journals (Sweden)

    Ramakrishna Tadavarty

    Full Text Available Long term depression (LTD in the CA1 region of the hippocampus, induced with a 20-Hz, 30 s tetanus to Schaffer collaterals, is enhanced in sleep-deprived (SD rats. In the present study, we investigated the role of metabotropic glutamate receptors (mGluRs, γ-aminobutyric acid (GABA B receptors (GABA(B-Rs and N-methyl-D-aspartic acid receptors (NMDARs in the LTD of the population excitatory postsynaptic potential (pEPSP. The requirement of Ca(2+ from L- and T-type voltage-gated calcium channels (VGCCs and intracellular stores was also studied. Results indicate that mGluRs, a release of Ca(2+ from intracellular stores and GABA(B-Rs are required for LTD. Interestingly, while mGlu1Rs seem to be involved in both short-term depression and LTD, mGlu5Rs appear to participate mostly in LTD. CGP 55845, a GABA(B-R antagonist, partially suppressed LTD in normally sleeping (NS rats, while completely blocking LTD in SD rats. Moreover, GS-39783, a positive allosteric modulator for GABA(B-R, suppressed the pEPSP in SD, but not NS rats. Since both mGluRs and GABA(B-Rs seem to be involved in the LTD, especially in SD rats, we examined if the receptor expression pattern and/or dimerization changed, using immunohistochemical, co-localization and co-immunoprecipitation techniques. Sleep-deprivation induced an increase in the expression of GABA(B-R1 and mGlu1αR in the CA1 region of the hippocampus. In addition, co-localization and heterodimerization between mGlu1αR/GABA(B-R1 and mGlu1αR/GABA(B-R2 is enhanced in SD rats. Taken together, our findings present a novel form of LTD sensitive to the activation of mGluRs and GABA(B-Rs, and reveal, for the first time, that sleep-deprivation induces alterations in the expression and dimerization of these receptors.

  8. Nicotine versus 6-hydroxy-l-nicotine against chlorisondamine induced memory impairment and oxidative stress in the rat hippocampus.

    Science.gov (United States)

    Hritcu, Lucian; Ionita, Radu; Motei, Diana Elena; Babii, Cornelia; Stefan, Marius; Mihasan, Marius

    2017-02-01

    6-Hydroxy-l-nicotine (6HLN), a nicotine derivative from nicotine degradation by Arthrobacter nicotinovorans pAO1 strain was found to improve behavioral deficits and to reverse oxidative stress in the rat hippocampus. Rats were given CHL (10mg/kg, i.p.) were used as an Alzheimer's disease-like model. The nicotine (0.3mg/kg) and 6HLN (0.3mg/kg) were administered alone or in combination in the CHL-treated rats. Memory-related behaviors were evaluated using Y-maze and radial arm-maze tests. The antioxidant enzymes activity and the levels of the biomarkers of oxidative stress were measured in the hippocampus. Statistical analyses were performed using two-way ANOVA and Tukey's post hoc test. F values for which pmemory deficits and oxidative stress enhancing were observed. Both nicotine and 6HLN administration attenuated the cognitive deficits and recovered the antioxidant capacity in the rat hippocampus of the CHL rat model. Our results suggest that 6HLN versus nicotine confers anti-amnesic properties in the CHL-induced a rat model of memory impairment via reversing cholinergic function and decreasing brain oxidative stress, suggesting the use of this compound as an alternative agent in AD treatment.

  9. Cellular and subcellular localization of Ras guanyl nucleotide-releasing protein in the rat hippocampus.

    Science.gov (United States)

    Pierret, P; Vallée, A; Mechawar, N; Dower, N A; Stone, J C; Richardson, P M; Dunn, R J

    2001-01-01

    Ras guanyl nucleotide-releasing protein (RasGRP) is a recently discovered Ras guanyl nucleotide exchange factor that is expressed in selected regions of the rodent CNS, with high levels of expression in the hippocampus. Biochemical studies suggest that RasGRP can activate the Ras signal pathway in response to changes in diacylglycerol and possibly calcium. To investigate potential sites for RasGRP signaling, we have determined the cellular and subcellular localization of RasGRP protein in adult rat hippocampus, and have also examined the appearance of RasGRP mRNA and protein during hippocampal development. RasGRP immunoreactivity is predominately localized to those neurons participating in the direct cortico-hippocampo-cortical loop. In both hippocampal and entorhinal neurons, RasGRP protein appeared to be localized to both dendrites and somata, but not to axons. Electron microscopy of hippocampal pyramidal cells confirmed RasGRP immunoreactivity in neuronal cell bodies and dendrites, where it appeared to be associated with microtubules. The localization of RasGRP to dendrites suggests a role for this pathway in the regulation of dendritic function. Examination of developing hippocampal structures indicated that RasGRP mRNA and protein appear synchronously during the first 2 weeks of postnatal development as these neurons become fully mature. This result indicates that the RasGRP signal transduction pathway is not required during early hippocampal development, but is a feature of mature neurons during the later stages of development.

  10. Antioxidant activity of Bacopa monniera in rat frontal cortex, striatum and hippocampus.

    Science.gov (United States)

    Bhattacharya, S K; Bhattacharya, A; Kumar, A; Ghosal, S

    2000-05-01

    The effect of a standardized extract of Bacopa monniera Linn. was assessed on rat brain frontal cortical, striatal and hippocampal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities, following administration for 7, 14 or 21 days. The effects induced by this extract (bacoside A content 82% +/- 0.5%), administered in doses of 5 and 10 mg/kg, orally, were compared with the effects induced by (-) deprenyl (2 mg/kg, p. o.) administered for the same time periods. Bacopa monniera (BM) induced a dose-related increase in SOD, CAT and GPX activities, in all the brain regions investigated, after 14 and 21 days of drug administration. On the contrary, deprenyl induced an increase in SOD, CAT and GPX activities in the frontal cortex and striatum, but not in the hippocampus, after treatment for 14 or 21 days. The results suggest that BM, like deprenyl, exhibits a significant antioxidant effect after subchronic administration which, unlike the latter, extends to the hippocampus as well. The results suggest that the increase in oxidative free radical scavenging activity by BM may explain, at least in part, the cognition- facilitating action of BM, recorded in Ayurvedic texts, and demonstrated experimentally and clinically.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 (pzinc significantly increased this by an additional 2-fold (pzinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (pzinc 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.

  13. Prefrontal cortex, hippocampus, and basolateral amygdala plasticity in a rat model of autism spectrum.

    Science.gov (United States)

    Sosa-Díaz, Nuvia; Bringas, Maria Elena; Atzori, Marco; Flores, Gonzalo

    2014-10-01

    We aimed to investigate the effect of prenatal administration of valproic acid (VPA) (500 mg/kg) at embryonic day 12.5 on the anatomical properties of the prefrontal cortex, hippocampus, and basolateral amygdala, at three different ages: immediately after weaning (postnatal day 21 [PD21]), prepubertal (PD35), and postpubertal (PD70) ages in a rat model of autistic spectrum disorder. Quantitative analysis of the thickness of the prefrontal cortex revealed a reduced size at all study ages in the cingulate 1 area of the prefrontal cortex and CA1 of the dorsal hippocampus in prenatally exposed animals compared to controls. At the level of the basolateral amygdala, a reduction in the size was observed at PD35 and PD70 in the VPA group. In addition, a reduced thickness was observed in the prelimbic region of the prefrontal cortex in VPA animals at PD35. Interestingly, no differences in cortical thickness were observed between control and VPA animals in the infralimbic region of the prefrontal at any age. Our results suggest that prenatal exposure to VPA differentially alters cortical limbic regions anatomical parameters, with implication in the autistic spectrum disorder.

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

    Science.gov (United States)

    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.

  15. [Reactive microglial changes in rat neocortex and hippocampus after exposure to acute perinatal hypoxia].

    Science.gov (United States)

    Khozhaĭ, L I; Otellin, V A

    2013-01-01

    The dynamics of reactive changes of a population density of microglial cells and the reversibility of their phenotypic forms were studied in the brain of neonatal rats at different time intervals after 1 hr-long exposure to acute normobaric hypoxia in the pressure chamber at the second postnatal day. Different areas of the neocortex (frontal, motor, somatosensory and visual) and of the hippocampus (CAI, CA3, CA4 and fascia dentata) were examined 1 hr, 3 hrs, 1 and 5 days after exposure to hypoxia. Microglial cells were demonstrated using an immunocytochemical staining with the monoclonal antibodies against Iba- 1 antigen. The results have shown that the reaction of microglia to acute hypoxia in both the neocortex and the hippocampus of the new-borns developed simultaneously and synchronously with the augmentation of cell death. The increase of a population density of amoeboid form of microglial cells in the brain areas studied was recorded already after 1 hour as a result of their migration from the subventricular region and the areas adjacent to large vessels from where they practically disappeared. The number of amoeboid microglial cells in this area has recovered rather quickly (in 3 hrs). The population densify of microglial cells, especially of amoeboid forms, sharply increased with the augmentation of cell death and remained unchanged for about 5 days.

  16. Effect of Prolonged Simulated Microgravity on Metabolic Proteins in Rat Hippocampus: Steps toward Safe Space Travel.

    Science.gov (United States)

    Wang, Yun; Javed, Iqbal; Liu, Yahui; Lu, Song; Peng, Guang; Zhang, Yongqian; Qing, Hong; Deng, Yulin

    2016-01-04

    Mitochondria are not only the main source of energy in cells but also produce reactive oxygen species (ROS), which result in oxidative stress when in space. This oxidative stress is responsible for energy imbalances and cellular damage. In this study, a rat tail suspension model was used in individual experiments for 7 and 21 days to explore the effect of simulated microgravity (SM) on metabolic proteins in the hippocampus, a vital brain region involved in learning, memory, and navigation. A comparative (18)O-labeled quantitative proteomic strategy was used to observe the differential expression of metabolic proteins. Forty-two and sixty-seven mitochondrial metabolic proteins were differentially expressed after 21 and 7 days of SM, respectively. Mitochondrial Complex I, III, and IV, isocitrate dehydrogenase and malate dehydrogenase were down-regulated. Moreover, DJ-1 and peroxiredoxin 6, which defend against oxidative damage, were up-regulated in the hippocampus. Western blot analysis of proteins DJ-1 and COX 5A confirmed the mass spectrometry results. Despite these changes in mitochondrial protein expression, no obvious cell apoptosis was observed after 21 days of SM. The results of this study indicate that the oxidative stress induced by SM has profound effects on metabolic proteins.

  17. 伽玛刀照射对癫痫大鼠海马氨基酸递质及超微结构的影响%Effect of gamma knife surgery on amino acid transmitters and ultramicrostructure of epileptic rats' hippocampus

    Institute of Scientific and Technical Information of China (English)

    王俊华; 高德智; 刘阿力; 万虹; 孟凡刚; 孙异临

    2012-01-01

    Objective To analyze the radiobiological effect of gamma knife surgery (GKS) on epileptic rat and the treatment mechanism of GKS for epilepsy. Methods Kainic acid was used in 50 rats to develop epilepsy model which were randomly divided into two groups (1st group of epileptic model under observation, n=25; 2nd group of epileptic model for GKS treatment,n= 25) and another 25 rats were injected with physiological saline in hippocampus as a control group (3rd group) to study the behavior changes of the three groups. Extracellular fluid of rat hippocampus was extracted at 1 day, 1 week, 2 weeks, 4 weeks and 8weeks after GKS by brain micro-dialysis. Reversed-phase high performance liquid chromatography analysis was performed to determine the changes of glutamic acid (Glu) and gamma-aminobutyric acid (GABA) in rat hippocampus of different groups. Ultramicrostructure changes of hippocampus were observed with e-lectric microscopy. Results At 1 week, GABA content of rats' hippocampus of 1st and 2nd groups was lower than that of 3rd group; at 2 weeks, Glu content of 1st and 2nd groups was higher than that of 3rd group; at 4 weeks, Glu and GABA content of 2nd group were lower and higher respectively than that of 1st group, and all the differences were statistically significant (P <0. 05). Observation of ultramicrostructure of hippocampus showed that the changes of 1st and 2nd groups at early and mid stages were accordant, however, the ultramicrostructure of 2nd group recovered partially at later period with obvious repair of mitochondria. Conclusion GKS can regulate the content of Glu and GABA of hippocampus to achieve a new balance of the two transmitters and inhibition of epileptic episode, meanwhile, substantially contribute to the pathological repair of damage resulting from epileptic episode.%目的 研究伽玛刀照射对癫痫大鼠的放射生物学作用,探讨伽玛刀治疗癫痫的作用机制.方法 利用海人酸制备癫痫大鼠模型50只(癫痫组25

  18. Effects of tanshinone on neuropathological changes induced by amyloid β-peptide1-40 injection in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Long-xuan LI; Jia-pei DAI; Li-qiang RU; Guang-fu YIN; Bin ZHAO

    2004-01-01

    AIM: To investigate the effect of tanshinone (Tan) on the neuropathological changes induced by amyloid β-peptide1-40 (Aβ-40) injection in hippocampus in rats. METHODS: Aβ1-40 10 μg was injected bilaterally into the dorsal blade of the dentate gyrus in the hippocampus. The level of acetylcholinesterase (AChE) in hippocampus was evaluated by histochemistry. The expressions of neuronal nitric oxide synthase (nNOS) and inducible form of NOS (iNOS) were detected by immunohistochemistry and Western blot. Aβ-40-injected rats were treated ig with Tan, the major active ingredient from Salvia miltiorrhiza of Chinese herb extract. RESULTS: The level of AChE positive fibers of each subfield in Aβ1-40-injected hippocampus decreased significantly compared with those of control (P<0.01). The expression of nNOS was down-regulated whereas the iNOS was up-regulated. After treatment with Tan (50 mg/kg, ig), the changes mentioned above were significantly improved. Moreover, the correlation analysis revealed a significant negative correlation between the area percentage of AChE positive fibers and the number of iNOS positive neural cells in CA 1, CA2 to CA3 (CA2-3), and dentate gyrus (DG) subfields (P<0.01). CONCLUSION:Tan can protect the neuropathological changes induced by Aβ-40 injection in hippocampus.

  19. Histamine H3 receptor activation counteracts adenosine A2A receptor-mediated enhancement of depolarization-evoked [3H]-GABA release from rat globus pallidus synaptosomes.

    Science.gov (United States)

    Morales-Figueroa, Guadalupe-Elide; Márquez-Gómez, Ricardo; González-Pantoja, Raúl; Escamilla-Sánchez, Juan; Arias-Montaño, José-Antonio

    2014-08-20

    High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus (GP), a neuronal nucleus in the basal ganglia involved in the control of motor behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied whether H3R activation modified the previously reported enhancing action of adenosine A2A receptor (A2AR) stimulation on depolarization-evoked [(3)H]-GABA release. At 3 and 10 nM, the A2AR agonist CGS-21680 enhanced [(3)H]-GABA release induced by high K(+) (20 mM) and the effect of 3 nM CGS-21680 was prevented by the A2AR antagonist ZM-241385 (100 nM). The presence of presynaptic H3Rs was confirmed by the specific binding of N-α-[methyl-(3)H]-histamine to membranes from GP synaptosomes (maximum binding, Bmax, 1327 ± 79 fmol/mg protein; dissociation constant, Kd, 0.74 nM), which was inhibited by the H3R ligands immepip, clobenpropit, and A-331440 (inhibition constants, Ki, 0.28, 8.53, and 316 nM, respectively). Perfusion of synaptosomes with the H3R agonist immepip (100 nM) had no effect on K(+)-evoked [(3)H]-GABA release, but inhibited the stimulatory action of A2AR activation. In turn, the effect of immepip was blocked by the H3R antagonist clobenpropit, which had no significant effect of its own on K(+)-induced [(3)H]-GABA release. These data indicate that H3R activation selectively counteracts the facilitatory action of A2AR stimulation on GABA release from striato-pallidal projections.

  20. Effects of subconvulsive electrical stimulation to the hippocampus on emotionality and spatial learning and memory in rats

    Institute of Scientific and Technical Information of China (English)

    王庆松; 王正国; 朱佩芳; 蒋建新

    2003-01-01

    Objective To observe the effects of repeated subconvulsive electrical stimuli to the hippocampus on the emotional behavior and spatial learning and memory ability in rats.Methods One hundred and eight male Wistar rats were randomized into 3 groups. Animals in group SE (n=42) were given subconvulsive electrical stimulation to the hippocampus through a constant pulsating current of 100 μA with an intratrain frequency of 25 Hz, pulse duration of 1 millisecond, train duration of 10 seconds and interstimulus interval of 7 minutes, 8 times a day, for 5 days. In the electrode control group or CE group (n=33), animals were implanted with an electrode in the hippocampus, but were not stimulated. Group NC (n=33) animals received no electrode or any stimulation. The emotional behavior of experimental rats was examined by activity in an unfamiliar open field and resistance to capture from the open field, while the spatial learning and memory ability was measured during training in a Morris water maze.Results The stimulated rats tested 1 month after the last round of stimulation displayed substantial decreases in open field activity (scale: 10.4±2.3, P<0.05) and increases in resistance to capture (scale: 2.85±0.56, P<0.01). The amount of time for rats in group SE to find the platform (latency) as a measurement for spatial bias was prolonged (29±7) seconds after 15 trials in the water maze, P<0.05). The experimental rats swam aimlessly in all four pool quadrants during the probe trial in the Morris water maze.Conclusions Following repeated subconvulsive electrical stimuli to the hippocampus, rats displayed long-lasting significant abnormalities in emotional behavior, increased anxiety and defensiveness, enhanced ease to and delayed habituation to startlement, transitory spatial learning and memory disorder, which parallels many of the symptoms in posttraumatic stress disorder patients.

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

    Science.gov (United States)

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

    1999-12-03

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

  2. Carbamazepine suppresses synchronized afterdischarging in disinhibited immature rat hippocampus in vitro.

    Science.gov (United States)

    Smith, K L; Swann, J W

    1987-01-06

    Bath application of therapeutic concentrations of the anticonvulsant carbamazepine suppressed penicillin-induced synchronized afterdischarging in immature rat CA3 hippocampal pyramidal cells. Afterdischarging was completely abolished in all preparations at a concentration of 30 microM (IC50 = 8.5 +/- 1.4 microM; mean +/- S.E.M.). The duration of the preceding epileptiform burst was not altered at this concentration and was diminished by only 24.4 +/- 1.2% at a supratherapeutic concentration of 100 microM. These results suggest that a carbamazepine-sensitive neurophysiological mechanism distinct from those responsible for epileptiform burst generation plays a key role in the generation of afterdischarges in developing hippocampus.

  3. Electroconvulsive Stimulation, but not Chronic Restraint Stress, Causes Structural Alterations in Adult Rat Hippocampus

    DEFF Research Database (Denmark)

    Olesen, Mikkel V.; Wörtwein, Gitta; Pakkenberg, Bente

    2015-01-01

    The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible...... changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number...... induces depression-like behavior, without significantly changing neurogenesis, the total number of neurons or the volume of the hippocampus. Further, electroconvulsive stimulation prevents stress-induced depression-like behavior and increases neurogenesis. The total number of neurons and the granule cell...

  4. High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats

    Directory of Open Access Journals (Sweden)

    Hai-Quyen Tran

    2016-10-01

    Full Text Available Dextromethorphan (DM administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens. However, neither MK-801 nor naloxone affected DM-induced mitochondrial dysfunction and formation of myelinoid bodies, indicating that the neurotoxic mechanism needs to be further elucidated. Therefore, the spectrum of toxicological effects associated with DM need to be reassessed.

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

    Science.gov (United States)

    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 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 ayahuasca doses: 250 mg/kg (1.29 ± 0.19 vs 0.84 ± 0.21, P ayahuasca administration in doses: 250 mg/kg (noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P ayahuasca ingestion.

  6. Circadian variations in expression of the trkB receptor in adult rat hippocampus.

    Science.gov (United States)

    Dolci, Claudia; Montaruli, Angela; Roveda, Eliana; Barajon, Isabella; Vizzotto, Laura; Grassi Zucconi, Gigliola; Carandente, Franca

    2003-12-19

    The expression of brain-derived neurotrophic factor (BDNF) in the central nervous system (CNS) and the expression of its high-affinity trkB receptor on neuron surfaces are known to depend on neuron activity. The expression of BDNF (mRNA and protein) and trkB mRNA shows circadian oscillations in rat hippocampal homogenates. We investigated circadian variations in trkB expression in specific areas of the adult rat hippocampal formation by immunohistochemistry. In sets of two experiments performed in the spring, 39 2-month-old male Wistar rats were accustomed to a 12-h light-12-h dark cycle for 2 weeks. Three animals were then sacrificed every 4 h. Forty-micrometer-thick coronal sections of hippocampal formation were obtained and processed for trkB immunohistochemistry. Cell staining intensity was assessed by image analysis of different hippocampal areas on five sections per animal. Circadian rhythmicity was evaluated by the cosinor method. Statistically significant circadian variations in trkB expression were found in dentate gyrus, entorhinal cortex, and the CA3 and hilar regions of the hippocampus, with highest expression during the first half of the dark (activity) period. These findings suggest a relationship between trkB expression and the physiological neuronal activation of wakefulness. TrkB receptor expression in the hippocampal regions studied was continuous and changes were gradual over the 24-h cycle, suggesting that more complex regulatory mechanisms also intervened.

  7. Sound sensitivity of neurons in rat hippocampus during performance of a sound-guided task

    Science.gov (United States)

    Vinnik, Ekaterina; Honey, Christian; Schnupp, Jan; Diamond, Mathew E.

    2012-01-01

    To investigate how hippocampal neurons encode sound stimuli, and the conjunction of sound stimuli with the animal's position in space, we recorded from neurons in the CA1 region of hippocampus in rats while they performed a sound discrimination task. Four different sounds were used, two associated with water reward on the right side of the animal and the other two with water reward on the left side. This allowed us to separate neuronal activity related to sound identity from activity related to response direction. To test the effect of spatial context on sound coding, we trained rats to carry out the task on two identical testing platforms at different locations in the same room. Twenty-one percent of the recorded neurons exhibited sensitivity to sound identity, as quantified by the difference in firing rate for the two sounds associated with the same response direction. Sensitivity to sound identity was often observed on only one of the two testing platforms, indicating an effect of spatial context on sensory responses. Forty-three percent of the neurons were sensitive to response direction, and the probability that any one neuron was sensitive to response direction was statistically independent from its sensitivity to sound identity. There was no significant coding for sound identity when the rats heard the same sounds outside the behavioral task. These results suggest that CA1 neurons encode sound stimuli, but only when those sounds are associated with actions. PMID:22219030

  8. Apigenin, a natural flavonoid, inhibits glutamate release in the rat hippocampus.

    Science.gov (United States)

    Chang, Chia Ying; Lin, Tzu Yu; Lu, Cheng Wei; Wang, Chia Chuan; Wang, Ying Chou; Chou, Shang Shing Peter; Wang, Su Jane

    2015-09-05

    The purpose of this study was to examine the effect and mechanism of apigenin, a natural flavonoid, on glutamate release in the rat hippocampus. In rat hippocampal nerve terminals (synaptosomes), apigenin inhibited glutamate release and the elevation of the cytosolic free Ca(2+) concentration evoked by 4-aminopyridine, whereas it had no effect on 4-aminopyridine-mediated depolarization and Na(+) influx. The apigenin-mediated inhibition of evoked glutamate release was prevented by chelating the extracellular Ca(2+) ions and blocking Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel activity. Furthermore, we determined that gamma-aminobutyric acid type A (GABAA) receptors are present in the hippocampal nerve terminals because they are colocalized with the presynaptic marker synaptophysin. However, the effect of apigenin on 4-aminopyridine-evoked glutamate release from synaptosomes was unaffected by the GABAA receptor antagonists SR95531 and bicuculline. Furthermore, in slice preparations, whole-cell patch-clamp experiments showed that apigenin reduced the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, suggesting a presynaptic mechanism. On the basis of these results, we suggested that apigenin exerts its presynaptic inhibition probably by reducing Ca(2+) entry mediated by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, thereby inhibiting glutamate release from the rat hippocampal nerve terminals.

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

    Science.gov (United States)

    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.

  10. Proteomic analysis of rat cerebral cortex, hippocampus and striatum after exposure to morphine.

    Science.gov (United States)

    Bierczynska-Krzysik, Anna; Pradeep John, Julius Paul; Silberring, Jerzy; Kotlinska, Jolanta; Dylag, Tomasz; Cabatic, Maureen; Lubec, Gert

    2006-10-01

    Although a series of proteins in the brain have been shown to be qualitatively or quantitatively dysregulated following morphine administration, a systematic proteomic study has not been carried out so far. We therefore aimed to show the effect of morphine on protein levels in the rat brain. For this purpose rats were given a morphine base in subcutaneously placed pellets and subsequently the cerebral cortex, hippocampus and striatum were taken for proteomic studies after three days. Extracted proteins were run on two-dimensional gel electrophoresis, scanned and quantified by specific software. Proteins with significantly different levels were analysed by mass spectrometry (MALDI-TOF-TOF). Twenty-six proteins were found to be differentially expressed and were unambiguously identified. Dysregulated proteins were from several protein pathways and cascades including signaling, metabolic, protein handling, antioxidant and miscellaneous classes. These findings represent an initial approach to the generation of a 'morphinome' and may form the basis for further protein chemical studies as a valuable analytical tool. Moreover, the study reveals morphine-regulated proteins in different brain areas and indicates the pathways involved following morphine administration in the rat, the main species for pharmacological studies in the field.

  11. Ketamine induces tau hyperphosphorylation at serine 404 in the hippocampus of neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Haiyan Jin; Zhiyong Hu; Mengjie Dong; Yidong Wu; Zhirui Zhu; Lili Xu

    2013-01-01

    Male Wistar 7-day-old rats were injected with 40 mg/kg ketamine intraperitoneally, followed by three additional injections of 20 mg/kg ketamine each upon restoration of the righting reflex. Neonatal rats injected with equivalent volumes of saline served as controls. Hippocampal samples were collected at 1, 7 or 14 days following administration. Electron microscopy showed that neuronal structure changed noticeably following ketamine treatment. Specifically, microtubular structure became irregular and disorganized. Quantitative real time-PCR revealed that phosphorylated tau mRNA was upregulated after ketamine. Western blot analysis demonstrated that phosphorylated tau levels at serine 396 initially decreased at 1 day after ketamine injection, and then gradually returned to control values. At 14 days after injection, levels of phosphorylated tau were higher in the ketamine group than in the control group. Tau protein phosphorylated at serine 404 significantly increased after ketamine injection, and then gradually decreased with time. However, the levels of tau protein at serine 404 were significantly greater in the ketamine group than in the control group until 14 days. The present results indicate that ketamine induces an increase of phosphorylated tau mRNA and excessive phosphorylation of tau protein at serine 404, causing disruption of microtubules in the neonatal rat hippocampus and potentially resulting in damage to hippocampal neurons.

  12. Medium-intensity acute exhaustive exercise induces neural cell apoptosis in the rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Shanni Li; Jin Liu; Hengmei Yan

    2013-01-01

    The present study assessed the influence of medium-intensity (treadmill at a speed of 19.3 m/min until exhaustion) and high-intensity (treadmill at a speed of 26.8 m/min until exhaustion) acute exhaustive exercise on rat hippocampal neural cell apoptosis. TUNEL staining showed significantly increased neural cell apoptosis in the hippocampal CA1 region of rats after medium- and high-intensity acute exhaustive exercise, particularly the medium-intensity acute exhaustive exercise, when compared with the control. Immunohistochemistry showed significantly increased expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax in the hippocampal CA1 region of rats after medium- and high-intensity acute exhaustive exercise. Additionally, the ratio of Bax to Bcl-2 increased in both exercise groups. In particular, the medium-intensity acute exhaustive exercise group had significantly higher Bax and Bcl-2 protein expression and a higher Bax/Bcl-2 ratio. These findings indicate that acute exhaustive exercise of different intensities can induce neural cell apoptosis in the hippocampus, and that medium-intensity acute exhaustive exercise results in greater damage when compared with high-intensity exercise.

  13. Evaluation of Bcl-2 Family Gene Expression in Hippocampus of 3, 4-methylenedioxymethamphetamine Treated Rats

    Directory of Open Access Journals (Sweden)

    Hamed Hashemi-Nasl

    2012-01-01

    Full Text Available Objective: 3,4-methylenedioxymethamphetamine (MDMA is an illicit, recreational drugthat causes cellular death and neurotoxicity. This study evaluates the effects of differentdoses of MDMA on the expression of apoptosis–related proteins and genes in the hippocampusof adult rats.Materials and Methods: In this expremental study,a total of 20 male Sprague Dawley rats(200-250 g were treated with MDMA (0, 5, 10, 20 mg/kg i.p. twice daily for 7 days. Sevendays after the last administration of MDMA, the rats were killed. Bax and Bcl-2 genesin addition to protein expressions were detected by western blot and reverse transcriptionpolymerasechain reaction (RT-PCR.Results were analyzed using one-way ANOVA andp≤0.05 was considered statistically significant.Results: Our results showed that MDMA caused dose dependent up-regulation of Baxand down-regulation of Bcl-2 in the hippocampus. There was a significant alteration inbcl-2 and bax genes density.Conclusion: Changes in apoptosis-related proteins and respective genes relating to Baxand Bcl-2 might be involved in the molecular mechanism of MDMA-induced apoptosis.

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

    Science.gov (United States)

    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. Gene Expression Profile of Calcium/Calmodulin-Dependent Protein Kinase IIα in Rat's Hippocampus during Morphine Withdrawal

    OpenAIRE

    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 o...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  18. Study on cognition disorder and morphologic change of neurons in hippocampus area following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    洪军; 崔建忠; 周云涛; 高俊玲

    2002-01-01

    Objective: To explore the correlation between cognition disorder and morphologic change of hippocampal neurons after traumatic brain injury (TBI).   Methods: Wistar rat models with severe TBI were made by Marmarous method. The histopathological change of the neurons in the hippocampus area were studied with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated X-dUPT nick end labeling (TUNEL), respectively. The cognitive function was evaluated with the Morris water maze test.   Results: The comprehensive neuronal degeneration and necrosis could be observed in CA2-3 regions of hippocampus at 3 days after injury. Apoptotic positive neurons in CA2-4 regions of hippocampus and dentate gyrus increased in the injured group at 24 hours following TBI. They peaked at 7 days and then declined. Significant impairment of spatial learning and memory was observed after injury in the rats.   Conclusions: The rats have obvious disorders in spatial learning and memory after severe TBI. Meanwhile, delayed neuronal necrosis and apoptosis can be observed in the neurons in the hippocampus area. It suggests that delayed hippocampal cell death may contribute to the functional deficit.

  19. GABA-agonists induce the formation of low-affinity GABA-receptors on cultured cerebellar granule cells via preexisting high affinity GABA receptors

    DEFF Research Database (Denmark)

    Belhage, B; Meier, E; Schousboe, A

    1986-01-01

    The kinetics of specific GABA-binding to membranes isolated from cerebellar granule cells, cultured for 12 days from dissociated cerebella of 7-day-old rats was studied using [3H]GABA as the ligand. The granule cells were cultured in the presence of the specific GABA receptor agonist 4, 5, 6, 7-t...

  20. The β-amyloid protein induces S100β expression in rat hippocampus through a mechanism that involves IL-1

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To explore the effect of β-amyloid protein (Aβ) on S100β expression in rat hippocampus and its mechanisms. Methods At 7 days after bilateral stereotaxis injection of different dose of fibrillar Aβ 25-35 and interluekin-1 receptor antagonist (IL-1ra) into the rat CA1 region, the learning and memory abilities of rats were tested with passive avoidance task. Amyloid deposition was detected by using Congo red staining technique. Nissl staining and immunohistochemical techniques were used to analyze th...

  1. Effect of two GABA-ergic drugs on the cognitive functions of rapid eye movement in sleep-deprived and recovered rats.

    Science.gov (United States)

    Bao, Lidao; Si, Lengge; Wang, Yuehong; Wuyun, Gerile; Bo, Agula

    2016-08-01

    Rapid eye movement (REM) sleep is closely associated with nervous functions. The present study aimed to evaluate the effects of gabazine and tiagabine on the cognitive functions (CF) of REM sleep-deprived and sleep recovered rats. Rats were divided into REM sleep deprivation, blank control (CC) and environmental groups. The REM sleep deprivation group was further divided into non-operation (nonOP), sham-operated (Sham), gabazine (SR) and tiagabine groups. Each group was evaluated over five time points: Sleep deprived for 1 day (SD 1 day), SD 3 day, SD 5 day, sleep recovery 6 h (RS 6 h) and RS 12 h. A rat model of REM sleep deprivation was established by a modified multi-platform water method, with CF assessed by Morris water maze. Hypothalamic γ-aminobutyric acid (GABA) and glutamic acid contents were measured via high performance liquid chromatography. The number and morphology of hypocretin (Hcrt) neurons and Fos in the hypothalamus, and GABAARα1-induced integral optical density were detected by immunofluorescence. Compared to the CC group, the nonOP and Sham group rats CF were significantly diminished, Fos-positive and Fos-Hcrt double positive cells were significantly increased, and GABA content and GABAARα1 expression levels were significantly elevated (Psleep deprivation diminished CF, increased the number of Hcrt neurons, GABA content and GABAARα1 expression. Furthermore, all alterations were positively correlated with deprivation time and corrected by sleep recovery, as demonstrated by single-factor multi-level variance analysis at the various time points in each group. Therefore, the Hcrt nervous system may be an eligible therapeutic target for the treatment of insomnia.

  2. The role of basolateral amygdala adrenergic receptors in hippocampus dependent spatial memory in rat

    Directory of Open Access Journals (Sweden)

    Vafaei A.L.

    2008-03-01

    Full Text Available Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs in hippocampus dependent spatial memory in place avoidance task in male rat. Material and Methods: Long Evans rats (n=150 were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter arena. The rats were injected bilaterally in the BLA specific ARS (Adrenergic receptors agonist norepinephrine (NE, 0.5 and 1 µg/µl and specific β-ARs antagonist propranolol (PRO, 0.5 and 1 µg/µl before acquisition, after training or before retrieval of the place avoidance task. Control rats received vehicle at the same volume. The learning in a single 30-min session was assessed 24h later by a 30-min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Results: Acquisition and consolidation were enhanced and impaired significantly by NE and PRO when the drugs were injected 10 min before or immediately after training, respectively. In contrast, neither NE nor PRO influenced animal performances when injected before retention testing. Conclusion: Findings of this study indicates that adrenergic system of the BLA plays an important role in regulation of memory storage and show further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.

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

    Science.gov (United States)

    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.

  4. Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4-8)

    NARCIS (Netherlands)

    Gispen, W.H.; Chepkova, A.N.; French, P.; Wied, D. de; Ontskul, A.H.; Ramakers, G.M.J.; Skrebitski, V.G.; Urban, I.J.A.

    1995-01-01

    Vasopressin (VP) is axonally distributed in many brain structures, including the ventral hippocampus. Picogram quantities of VP injected into the hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into

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

    Science.gov (United States)

    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. Sleep and movement differentiates actions of two types of somatostatin-expressing GABAergic interneuron in rat hippocampus.

    Science.gov (United States)

    Katona, Linda; Lapray, Damien; Viney, Tim J; Oulhaj, Abderrahim; Borhegyi, Zsolt; Micklem, Benjamin R; Klausberger, Thomas; Somogyi, Peter

    2014-05-21

    Neuropeptides acting on pre- and postsynaptic receptors are coreleased with GABA by interneurons including bistratified and O-LM cells, both expressing somatostatin but innervating segregated dendritic domains of pyramidal cells. Neuropeptide release requires high-frequency action potentials, but the firing patterns of most peptide/GABA-releasing interneurons during behavior are unknown. We show that behavioral and network states differentiate the activities of bistratified and O-LM cells in freely moving rats. Bistratified cells fire at higher rates during sleep than O-LM cells and, unlike O-LM cells, strongly increase spiking during sharp wave-associated ripples (SWRs). In contrast, O-LM interneurons decrease firing during sleep relative to awake states and are mostly inhibited during SWRs. During movement, both cell types fire cooperatively at the troughs of theta oscillations but with different frequencies. Somatostatin and GABA are differentially released to distinct dendritic zones of CA1 pyramidal cells during sleep and wakefulness to coordinate segregated glutamatergic inputs from entorhinal cortex and CA3.

  7. Xanthohumol-induced presynaptic reduction of glutamate release in the rat hippocampus.

    Science.gov (United States)

    Chang, Yi; Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu Kuei; Wang, Ying Chou; Wang, Su Jane

    2016-01-01

    This study examined whether xanthohumol, a hop-derived prenylated flavonoid present in beer, affects glutamate release in the rat hippocampus. In the rat hippocampal nerve terminals (synaptosomes), xanthohumol inhibited the release of 4-aminopyridine (4-AP)-evoked glutamate and the elevation of cytosolic Ca(2+) concentration, whereas it had no effect on 4-AP-mediated depolarization. The inhibitory effect of xanthohumol on the evoked glutamate release was prevented by removing extracellular Ca(2+), using the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-CgTX MVIIC, the calmodulin antagonists W7 and calmidazolium, and the protein kinase A inhibitor H89; however, no such effect was observed when the G-protein inhibitor N-ethylmaleimide was used. In addition, immunocytochemical data demonstrated that GABAA receptors are present in the hippocampal synaptosomes and that the xanthohumol effect on evoked glutamate release was antagonized by the GABAA receptor antagonist SR95531. Furthermore, in slice preparations, xanthohumol reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude. We conclude that xanthohumol acts at GABAA receptors present in the hippocampal nerve terminals to decrease the Ca(2+) influx through N- and P/Q-type Ca(2+) channels, which subsequently suppresses the Ca(2+)-calmodulin/PKA cascade to decrease the evoked glutamate release.

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

    Science.gov (United States)

    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.

  9. Neonatal exposure to novelty enhances long-term potentiation in CA1 of the rat hippocampus.

    Science.gov (United States)

    Tang, Akaysha C; Zou, Bende

    2002-01-01

    Exposing rats to an enriched environment over an extended period of time has been shown to enhance hippocampal long-term potentiation (LTP). Whether such prolonged exposure to environmental manipulation is necessary for LTP enhancement and whether the environmentally induced enhancement can persist long after the cessation of the environmental manipulation remain unknown. Using a novelty exposure procedure modified from the method of neonatal handling, we exposed neonatal rats to a non-home environment for 3 min/day during the first 3 weeks of life. We examined the LTP of both population spikes and excitatory postsynaptic potentials (EPSPs), in vitro, in the CA1 of the hippocampus during adulthood (7-8 and 13-14 months of age). We found that both the LTP of population spikes and the LTP of EPSPs were enhanced among animals who experienced neonatal novelty exposure. These results demonstrate that effective environmental enhancement of LTP can be achieved by as brief and as transient a manipulation as a 3-min/day exposure over the first 3 weeks of life. The resulting enhancement can outlast the environmental manipulation by at least 1 year.

  10. Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning

    Directory of Open Access Journals (Sweden)

    Hai-feng Li

    2015-01-01

    Full Text Available Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had disappeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraquat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

  11. EFFECTS OF KAINIC ACID ON GLUTATIONE AND NITRITE IN RAT HIPPOCAMPUS

    Directory of Open Access Journals (Sweden)

    Nadka I. Boyadjieva

    2011-09-01

    Full Text Available Epileptiformic activity could result in apoptotic neuronal death, in which oxidative stress could play an important role. In case of decreased antioxidant brain status cellular death could be facilitated. Kainic acid is often used in a model of epilepsy in rats. Up to now there is not enough data evaluating levels of glutathione and nitric oxide in kainic acid-induced epilepsy acutely and several days after the kainic acid exposure. This information will be useful for assessing long term prognosis on a risk of further brain damage.We studied hippocampal levels of glutathione and nitric oxide at the 3th hour (acute group and after 7 days of kainic (chronic group acid exposure. We found that glutathione level is statistically significantly lower in the hippocampus 7 days after kainic acid exposure, as compared with values measured in the acute group. For both kainic acid treated groups glutathione levels were significantly lower than controls.Levels of nitric oxide were found to be significantly higher 7 days after kainic acid exposure as compared with acute group. For both kainic acid treated groups nitric oxyde levels were significantly lower than controls.We conclude that in kainic acid treated rats oxidative stress could be present even after a single treatment. This could be a potentially pathogenic factor for further brain damages.

  12. Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning

    Institute of Scientific and Technical Information of China (English)

    Hai-feng Li; Shi-xing Zhao; Bao-peng Xing; Ming-li Sun

    2015-01-01

    Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had dis-appeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were signiifcantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical ifndings showed that CHOP immunoreactivity was signiifcantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-medi-ated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data conifrmed that endoplasmic reticular stress can be induced by acute paraquat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

  13. Anticonvulsant and neuroprotective effects of Rosa damascena hydro-alcoholic extract on rat hippocampus

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    Mansour Homayoun

    2015-04-01

    Full Text Available Objective: Previously, analgesic, hypnotic, and anticonvulsant effects have been suggested for Rosa damascena (R. damascena. In the present study, possible anti-seizure and neuro-protective effects of hydro-alcoholic extract of R. damascena has been investigated after inducing seizures in rats by pentylenetetrazole (PTZ. Materials and Methods: The rats were divided to five groups: (1 Control: received saline, (2 PTZ: 100 mg/kg, i.p., (3 PTZ-Extract 50 mg/kg(PTZ-Ext 50, (4 PTZ- Extract 100 mg/kg(PTZ-Ext 100, and (5 PTZ- Extract 200 mg/kg(PTZ-Ext 200 groups which were treated with 50, 100, and 200 mg/kg respectively of hydro-alcoholic extract of R. damascena for one week before PTZ injection. The animals were examined for electrocorticography (ECoG recording and finally, the brains were removed for histological study. Results: The hydro-alcoholic extract of R. damascena significantly prolonged the latency of seizure attacks and reduced the frequency and amplitude of epileptiform burst discharges induced by PTZ injection. Moreover, all three doses of the extract significantly inhibited production of dark neurons in different regions of the hippocampus in the mentioned animal model. Conclusion: The present study showed that the hydro-alcoholic extract of R. damascena has anticonvulsant and neuroprotective effects. More investigations are needed to be done in order to better understand the responsible compound(s as well as the possible mechanism(s.

  14. Effects of sericin on heme oxygenase-1 expression in the hippocampus and cerebral cortex of type 2 diabetes mellitus rats

    Institute of Scientific and Technical Information of China (English)

    Zhihona Chen; Yaqiang He; Wenliang Fu; Jingfeng Xue

    2011-01-01

    Previous studies have demonstrated that sericin effectively reduces blood glucose, and protects islet cells, as well as the gonads and kidneys. However, whether sericin improves diabetes mellitus-induced structural and functional problems in the central nervous system remains poorly understood. Rat models of type 2 diabetes mellitus were established by intraperitoneal injection of streptozotocin. The present study observed histological changes in the hippocampus and cerebral cortex, as well as heme oxygenase-1 expression, and explored sericin effects on the central nervous system in diabetic rats. Pathological damage to neural cells in the rat hippocampus and cerebral cortex was relieved following intragastric administration of sericin at a dose of 2.4 g/kg for 35 consecutive days. Heme oxygenase-1 protein and mRNA expressions were decreased in the hippocampus and cerebral cortex of diabetes mellitus rats after sericin treatment. The results suggest that sericin plays a protective effect on the nervous system by decreasing the high expression of heme oxygenase-1 following diabetes mellitus.

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

    Science.gov (United States)

    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.

  16. Involvement of brain-derived neurotrophic factor and neurogenesis in oestradiol neuroprotection of the hippocampus of hypertensive rats.

    Science.gov (United States)

    Pietranera, L; Lima, A; Roig, P; De Nicola, A F

    2010-10-01

    The hippocampus of spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats shows decreased cell proliferation and astrogliosis as well as a reduced number of hilar cells. These defects are corrected after administration of 17β-oestradiol (E(2) ) for 2 weeks. The present work investigated whether E(2) treatment of SHR and of hypertensive DOCA-salt male rats modulated the expression of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in hippocampal neurogenesis. The neurogenic response to E(2) was simultaneously determined by counting the number of doublecortin-immunopositive immature neurones in the subgranular zone of the dentate gyrus. Both hypertensive models showed decreased expression of BDNF mRNA in the granular zone of the dentate gyrus, without changes in CA1 or CA3 pyramidal cell layers, decreased BDNF protein levels in whole hippocampal tissue, low density of doublecortin (DCX)-positive immature neurones in the subgranule zone and decreased length of DCX+ neurites in the dentate gyrus. After s.c. implantation of a single E(2) pellet for 2 weeks, BDNF mRNA in the dentate gyrus, BDNF protein in whole hippocampus, DCX immunopositive cells and the length of DCX+ neurites were significantly raised in both SHR and DOCA-salt-treated rats. These results indicate that: (i) low BDNF expression and deficient neurogenesis distinguished the hippocampus of SHR and DOCA-salt hypertensive rats and (ii) E(2) was able to normalise these biologically important functions in the hippocampus of hypertensive animals.

  17. Involvement of GABA and opioid peptide receptors in sevoflurane-induced antinociception in rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    Ying-wei WANG; Xiao-ming DENG; Xin-min YOU; Shu-xiao LIU; Zhi-qi ZHAO

    2005-01-01

    Aim: The spinal cord is pivotal in immobility induced by volatile anesthetics because the anesthetics depress the activity of motor neurons in the spinal cord.The aim of this study was to observe the effects of sevoflurane on pain processing at the spinal level. Methods: The firing of the gastrocnemius muscle was evoked by electrical stimulation to the ipsilateral hindpaw in rats. The nociceptive C response of electromyography (EMG)was selected to study. The GABAA receptor antagonist bicuculline (0.1 mg/kg) and opioid receptor antagonist naloxone (0.4 mg/kg) were administered intravenously, either in the presence or in the absence of 1.0% sevoflurane. Results: In rats with transected spinal cord,sevoflurane produced a profound reduction in the C response in a dose- and timedependent manner. In the presence of 1.0% sevoflurane, the C responses were increased after injections of bicuculline and naloxone. Conclusion: Sevoflurane is a volatile anesthetic that acts directly on the spinal cord to suppress the nociceptive reflex. The sevoflurane-induced suppression of the C response is antagonized by either bicuculline or naloxone. The results suggest that spinal GABAA receptors and opioid peptide receptors are involved in the sevoflurane-induced suppression of spinal nociception.

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

    Science.gov (United States)

    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.

  19. ESTIMATION OF THE NUMBER OF NEURONS IN THE HIPPOCAMPUS OF RATS WITH PENICILLIN INDUCED EPILEPSY

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    Ilgaz Akdogan

    2011-05-01

    Full Text Available Epilepsy is a neurological disease arising from strong and uncontrollable electrical firings of a group of neurons in the central nervous system. Experimental epileptic models have been developed to assess the physiopathology of epileptic seizures. This study was undertaken to estimate the number of neurons in the rat hippocampus with penicillin induced epilepsy, using a stereological method, "the optical fractionator". In the experimental group, 500 IU penicillin-G was injected intra-cortically, and in the control group, the same volume of saline was administered. A week later, the animals were decapitated and their brains were removed by craniatomy. Frozen brains were cut with a thickness of 150 ěm in a cryostat. Sections were collected by systematic random sampling and stained with hematoxylen-eosin. Microscopic images of pyramidal cell layers from hippocampus CA1, CA2 and CA3 subfields were then transferred to a monitor, using a 100x objective (N.A. = 1.25. Using the optical disector method, the neurons were counted in the frames and determined with a fractionator sampling scheme. The total pyramidal neuron number was then estimated using the optical fractionator method. The total pyramidal neuron number was found to be statistically lower in the experimental group (mean = 142,888 ± 11,745 than in the control group (mean = 177,953 ± 10,907 (p < 0.05. The results suggest that a decrease in the hippocampal neuronal number in a penicillin model of epilepsy can be determined objectively and efficiently using the optical fractionator method.

  20. Suppression of synaptic plasticity by fullerenol in rat hippocampus in vitro

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    Wang XX

    2016-09-01

    Full Text Available Xin-Xing Wang,1,2,* Ying-Ying Zha,3,* Bo Yang,1 Lin Chen,1,2 Ming Wang1,2 1CAS Key Laboratory of Brain Function and Diseases, 2Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 3Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Fullerenol, a water-soluble fullerene derivative, has attracted much attention due to its bioactive properties, including the antioxidative properties and free radical scavenging ability. Due to its superior nature, fullerenol represents a promising diagnostic, therapeutic, and protective agent. Therefore, elucidation of the possible side effects of fullerenol is important in determining its potential role. In the present study, we investigated the acute effects of 5 µM fullerenol on synaptic plasticity in hippocampal brain slices of rats. Incubation with fullerenol for 20 minutes significantly decreased the peak of paired-pulse facilitation and long-term potentiation, indicating that fullerenol suppresses the short- and long-term synaptic plasticity of region I of hippocampus. We found that fullerenol depressed the activity and the expression of nitric oxide (NO synthase in hippocampus. In view of the important role of NO in synaptic plasticity, the inhibition of fullerenol on NO synthase may contribute to the suppression of synaptic plasticity. These findings may facilitate the evaluation of the side effects of fullerenol. Keywords: fullerenol, hippocampal slice, nitric oxide synthase, synaptic plasticity, oxidative stress

  1. Glucocorticoid ultradian rhythmicity directs cyclical gene pulsing of the clock gene period 1 in rat hippocampus.

    Science.gov (United States)

    Conway-Campbell, B L; Sarabdjitsingh, R A; McKenna, M A; Pooley, J R; Kershaw, Y M; Meijer, O C; De Kloet, E R; Lightman, S L

    2010-10-01

    In vivo glucocorticoid (GC) secretion exhibits a distinctive ultradian rhythmicity. The lipophilic hormone can rapidly diffuse into cells, although only the pulse peak is of sufficient amplitude to activate the low affinity glucocorticoid receptor (GR). Discrete pulses readily access brain regions such as the hippocampus where GR expression is enriched and known to regulate neuronal function, including memory and learning processes. In the present study, we have tested the hypothesis that GR brain targets are responsive to ultradian GC rhythmicity. We have used adrenalectomised rats replaced with pulses of corticosterone to determine the transcriptional effects of ultradian pulses in the hippocampus. Confocal microscopy confirmed that each GC pulse results in transient GR nuclear localisation in hippocampal CA1 neurones. Concomitant GR activation and DNA binding was demonstrated by synthetic glucocorticoid response element oligonucleotide binding, and verified for the Clock gene Period 1 promoter region by chromatin immunoprecipitation assays. Strikingly each GC pulse induced a 'burst' of transcription of Period 1 measured by heterogeneous nuclear RNA quantitative polymerase chain reaction. The net effect of pulsatile GC exposure on accumulation of the mature transcript was also assessed, revealing a plateau of mRNA levels throughout the time course of pulsatile exposure, indicating the pulse timing works optimally for steady state Per1 expression. The plateau dropped to baseline within 120 min of the final pulse, indicating a relatively short half-life for hippocampal Per1. The significance of this strict temporal control is that any perturbation to the pulse frequency or duration would have rapid quantitative effects on the levels of Per1. This in turn could affect hippocampal function, especially circadian related memory and learning processes.

  2. Differential presynaptic actions of pyrethroid insecticides on glutamatergic and GABAergic neurons in the hippocampus.

    Science.gov (United States)

    Hossain, Muhammad Mubarak; Suzuki, Tadahiko; Unno, Toshihiro; Komori, Seiichi; Kobayashi, Haruo

    2008-01-14

    This study was designed to investigate the effects of several pyrethroids on the extracellular level of glutamate and gamma-aminobutyric acid (GABA) in the hippocampus of rats measured using microdialysis following systemic (i.p.) administration. Pyrethroids, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II), were found to have differential effects on glutamatergic and GABAergic neurons in the hippocampus. Allethrin had an interesting dual effect, increasing glutamate release with low doses (10 and 20mg/kg) to about 175-150% and decreasing glutamate release with high dose (60 mg/kg) to about 50% of baseline. Cyhalothrin (10, 20 and 60 mg/kg) inhibited the release of glutamate dose-dependently to about 60-30% of baseline. The extracellular level of GABA was decreased to about 50% of baseline by 10 and 20mg/kg allethrin. The high dose of allethrin (60 mg/kg) and all doses of cyhalothrin (10, 20 and 60 mg/kg) increased the extracellular level of GABA while decreasing the level of glutamate. Deltamethrin dose-dependently increased extracellular glutamate levels to about 190-275% of baseline while decreasing the level of GABA. Local infusion of TTX (1 microM), a Na(+) channel blocker, completely prevented the effect of allethrin (10, 20 and 60 mg/kg), cyhalothrin (20 and 60 mg/kg) and deltamethrin (20mg/kg) on glutamate and GABA release, but only partially blocked the effects of 60 mg/kg deltamethrin. The effect of deltamethrin (60 mg/kg) on glutamate release was completely prevented by local infusion of nimodipine (10 microM), an L-type Ca(2+) channel blocker. Collectively, results from this study suggest that the excitatory glutamatergic neurons in the hippocampus are modulated by inhibitory GABA-releasing interneurons and that other mechanisms, beside sodium channels, may be involved with the neurotoxic action of pyrethroids.

  3. Transient changes in the localization and activity of ecto-nucleotidases in rat hippocampus following lipopolysaccharide treatment

    Science.gov (United States)

    Kittel, Ágnes; Sperlágh, Beata; Pelletier, Julie; Sévigny, Jean; Kirley, Terence L.

    2016-01-01

    The concentrations of extracellularly released nucleotides are controlled by metabolism via ecto-nucleotidases, but the precise physiological roles of the ecto-nucleoside triphosphate diphosphohydrolases in the modulation of purinergic receptor signalling are still unclear. Bacterial endotoxin lipopolysaccharide (LPS) treatment (administered intraperitoneally, 2 mg/kg body weight) of rats resulted in no significant changes in the overall ecto-nucleotidase activities of the hippocampus, however, LPS treatment did cause transient changes in the morphology of endothelial cells and pericytes and in the localization pattern of ecto-ATPase activity in rat hippocampus. The transient decrease in NTPDase1 (ecto-nucleoside triphosphate diphosphohydrolase1) activity, located on the luminal side of the endothelial cells, was balanced by increases in ecto-nucleotidase activities in pericytes and at other sites, consistent with an unchanged overall ecto-ATPase activity of the hippocampus. Since the transient loss of NTPDase1 activity was not accompanied by a loss of NTPDase1 protein, we hypothesize that LPS caused transient alterations in the lipid membranes, since NTPDase1 activity is known to be sensitive to changes in membrane structure via its transmembrane domains. After 2–3 days, the LPS-induced changes in cell morphology and ecto-nucleotidase localization disappeared. We conclude that a low dose of LPS causes transient changes in the localization pattern of ecto-nucleotidases in endothelial cells and pericytes, which, coupled with the observed cellular morphological changes, may indicate modified cellular signalling in the hippocampus. PMID:17576046

  4. Phenotype-dependent Ca(2+) dynamics in single boutons of various anatomically identified GABAergic interneurons in the rat hippocampus.

    Science.gov (United States)

    Lőrincz, Tibor; Kisfali, Máté; Lendvai, Balázs; Sylvester Vizi, Elek

    2016-02-01

    Interneurons (INs) of the hippocampus exert versatile inhibition on pyramidal cells by silencing the network at different oscillation frequencies. Although IN discharge can phase-lock to various rhythms in the hippocampus, under high-frequency axon firing, the boutons may not be able to follow the fast activity. Here, we studied Ca(2+) responses to action potentials (APs) in single boutons using combined two-photon microscopy and patch clamp electrophysiology in three types of INs: non-fast-spiking (NFS) neurons showing cannabinoid 1 receptor labelling and dendrite targeting, fast-spiking partially parvalbumin-positive cells synapsing with dendrites (DFS), and parvalbumin-positive cells with perisomatic innervation (PFS). The increase in [Ca(2+) ]i from AP trains was substantially higher in NFS boutons than in DFS or PFS boutons. The decay of bouton Ca(2+) responses was markedly faster in DFS and PFS cells compared with NFS neurons. The bouton-to-bouton variability of AP-evoked Ca(2+) transients in the same axon was surprisingly low in each cell type. Importantly, local responses were saturated after shorter trains of APs in NFS cells than in PFS cells. This feature of fast-spiking neurons might allow them to follow higher-frequency gamma oscillations for a longer time than NFS cells. The function of NFS boutons may better support asynchronous GABA release. In conclusion, we demonstrate several neuron-specific Ca(2+) transients in boutons of NFS, PFS and DFS neurons, which may serve differential functions in hippocampal networks.

  5. Impairment of long-term potentiation in the hippocampus of alcohol-treated OLETF rats.

    Science.gov (United States)

    Min, Jung-Ah; Lee, Hye-Ryeon; Kim, Jae-Ick; Ju, Anes; Kim, Dai-Jin; Kaang, Bong-Kiun

    2011-08-01

    Type 2 diabetes and chronic heavy alcohol consumption each have been known to be associated with the impairment of hippocampus-dependent cognitive functions. Although both conditions often coexist clinically and there is accumulated evidence of a relationship between the two, the combined effect on hippocampal long-term potentiation (LTP) has not yet been investigated. We compared the effect of type 2 diabetes itself with that of type 2 diabetes with chronic heavy alcohol consumption on the hippocampal LTP using Otsuka Long-Evans Tokushima Fatty (OLETF) rat model, which resembles the characteristics of human type 2 diabetes. Ten of 16-week-old male OLETF rats were randomized into two treatment groups according to weight: the OLETF-Alcohol (O-A, n=5) and the OLETF-Control (O-C, n=5). The rats in the O-A group were fed Lieber-DeCarli Regular EtOH over a 10-week period and the amount of alcohol consumption was 8.42±2.52g/kg/day. To ensure the effect of poor glycemic control on LTP, intraperitoneal glucose tolerance test was performed after a 10-week treatment. The hippocampal LTP was measured by extracellular field excitatory post-synaptic potentials at Shaffer collateral (SC) synapses in the CA1 region. Although the O-A group showed significantly lower fasting and postprandial glucose (Palcohol consumption could potentiate the impairment of hippocampal LTP in individuals with impaired glucose tolerance or early type 2 diabetes, even though it did not aggravate, but did improve glycemic control. Clinical attention to chronic heavy drinking will be required in preventing cognitive impairment in individuals with type 2 diabetes.

  6. Hypofractionated stereotactic radiotherapy to the rat hippocampus. Determination of dose response and tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Ernst-Stecken, A.; Roedel, F.; Grabenbauer, G.; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Radiation Therapy and Novalis Shaped Beam Surgery Center; Jeske, I.; Bluemcke, I. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Neuropathology; Hess, A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Experimental and Clinical Pharmacology and Toxicology; Ganslandt, O. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Neurosurgery; Brune, K. [Erlangen-Nuernberg Univ., Erlangen (Germany). Doerenkamp Professor for Innovations in Animal and Consumer Protection

    2007-08-15

    Purpose: To determine the effect of hypofractionated stereotactic radiotherapy (hfSRT) on adult rat brain tissue (necrosis, impact on blood-brain barrier, signal changes on high-field magnetic resonance imaging [MRI]). Material and Methods: Adult male Wistar rats underwent MRI and CT scanning of the brain and respective images were introduced into the Novalis trademark radiosurgery device (BrainLab, Feldkirchen, Germany). All animals (body weight 350 g) were irradiated weekly with doses of 2 x 10 Gy (n = 3 animals), 3 x 10 Gy (n = 3 animals) and 4 x 10 Gy (n = 3 animals), targeted to the left hippocampus after image-guided positioning. 4.7-T T2-weighted MRI scanning was performed in each animal. Animals were sacrificed 8, 12, and 16 weeks after hfSRT and brains were immersion-fixed in 4% paraformaldehyde for subsequent histopathologic analysis. Results: In concordance with isodose distributions, pathologic signal hyperintensities in MRI were recorded from 4 x 10 Gy after 8 weeks, 3 x 10 Gy after 12 weeks, while 2 x 10 Gy induced slight detectable alterations only after 16 weeks. Subsequent histopathologic analysis revealed hippocampal cell necrosis with significantly earlier and stronger occurrence for higher doses (40 Gy > 30 Gy > 20 Gy). Pial microvessel permeability also increased after 40 Gy, whereas 30 Gy induced moderate changes. Conclusion: Conclusion: Partial-brain irradiation with hfSRT (Novalis trademark System) was successfully adopted for small animals and histopathologic analysis confirmed its repositioning accuracy. The neuropathologic effects correlated with dose and observation time. The approach will be further developed for quality assurance in hfSRT of normal brain tissue, as well as novel treatment modalities in epileptic rats and orthotopic tumor models. (orig.)

  7. Mitochondrial dynamics in the hippocampus is influenced by antidepressant treatment in a genetic rat model of depression

    DEFF Research Database (Denmark)

    Chen, F.; Wegener, Gregers; Madsen, T. M.;

    2013-01-01

    number in hippocampus. All rats were injected imipramine (a classic tricyclic antidepressant) or saline (i.p) once daily for 14 days on normal rats (10 mg/kg) and for 25 days on the Flinders Sensitive Lines (FSL) rats and their controls the Flinders Resistant Line (FRL) rats (15 mg/kg), a genetic rat...... of mitochondria in CA1SR displayed significantly smaller in the FSL-saline group compared to FRL-saline group and SD-saline group. But the mean volume of mitochondria showed significantly bigger in the FSL-saline group compared to FRL-saline group and SD-saline group. Following treatment, the FSL-imipramine group...... and SD-saline group. Impramine treatment can significantly increase the mitochondria numerical density and the number of mitochondria in FSL-imipramine group. Our results support the mitochondria plasticity hypothesis that depressive disorders may be related to impairments of mitochondria plasticity...

  8. Brain-derived neurotrophic factor (BDNF) enhances GABA transport by modulating the trafficking of GABA transporter-1 (GAT-1) from the plasma membrane of rat cortical astrocytes

    DEFF Research Database (Denmark)

    Vaz, Sandra H; Jørgensen, Trine Nygaard; Cristóvão-Ferreira, Sofia

    2011-01-01

    /MAPK pathway and requires active adenosine A(2A) receptors. Transport through GAT-3 is not affected by BDNF. To elucidate if BDNF affects trafficking of GAT-1 in astrocytes, we generated and infected astrocytes with a functional mutant of the rat GAT-1 (rGAT-1) in which the hemagglutinin (HA) epitope...

  9. βCCT, an antagonist selective for α(1)GABA(A) receptors, reverses diazepam withdrawal-induced anxiety in rats.

    Science.gov (United States)

    Divljaković, Jovana; Milić, Marija; Namjoshi, Ojas A; Tiruveedhula, Veera V; Timić, Tamara; Cook, James M; Savić, Miroslav M

    2013-02-01

    The abrupt discontinuation of prolonged benzodiazepine treatment elicits a withdrawal syndrome with increased anxiety as a major symptom. The neural mechanisms underlying benzodiazepine physical dependence are still insufficiently understood. Flumazenil, the non-selective antagonist of the benzodiazepine binding site of GABA(A) receptors was capable of preventing and reversing the increased anxiety during benzodiazepine withdrawal in animals and humans in some, but not all studies. On the other hand, a number of data suggest that GABA(A) receptors containing α(1) subunits are critically involved in processes developing during prolonged use of benzodiazepines, such are tolerance to sedative effects, liability to physical dependence and addiction. Hence, we investigated in the elevated plus maze the level of anxiety 24 h following 21 days of diazepam treatment and the influence of flumazenil or a preferential α(1)-subunit selective antagonist βCCt on diazepam withdrawal syndrome in rats. Abrupt cessation of protracted once-daily intraperitoneal administration of 2 mg/kg diazepam induced a withdrawal syndrome, measured by increased anxiety-like behavior in the elevated plus maze 24 h after treatment cessation. Acute challenge with either flumazenil (10mg/kg) or βCCt (1.25, 5 and 20 mg/kg) alleviated the diazepam withdrawal-induced anxiety. Moreover, both antagonists induced an anxiolytic-like response close, though not identical, to that seen with acute administration of diazepam. These findings imply that the mechanism by which antagonism at GABA(A) receptors may reverse the withdrawal-induced anxiety involves the α(1) subunit and prompt further studies aimed at linking the changes in behavior with possible adaptive changes in subunit expression and function of GABA(A) receptors.

  10. Indomethacin can downregulate the levels of inflammatory mediators in the hippocampus of rats submitted to pilocarpine-induced status epilepticus

    Directory of Open Access Journals (Sweden)

    Michele Juliane Vieira

    2014-09-01

    Full Text Available OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus.

  11. MicroRNA-mediated GABA Aα-1 receptor subunit down-regulation in adult spinal cord following neonatal cystitis-induced chronic visceral pain in rats.

    Science.gov (United States)

    Sengupta, Jyoti N; Pochiraju, Soumya; Pochiraju, Soumiya; Kannampalli, Pradeep; Bruckert, Mitchell; Addya, Sankar; Yadav, Priyanka; Miranda, Adrian; Shaker, Reza; Banerjee, Banani

    2013-01-01

    The nociceptive transmission under pathological chronic pain conditions involves transcriptional and/or translational alteration in spinal neurotransmitters, receptor expressions, and modification of neuronal functions. Studies indicate the involvement of microRNA (miRNA) - mediated transcriptional deregulation in the pathophysiology of acute and chronic pain. In the present study, we tested the hypothesis that long-term cross-organ colonic hypersensitivity in neonatal zymosan-induced cystitis is due to miRNA-mediated posttranscriptional suppression of the developing spinal GABAergic system. Cystitis was produced by intravesicular injection of zymosan (1% in saline) into the bladder during postnatal (P) days P14 through P16 and spinal dorsal horns (L6-S1) were collected either on P60 (unchallenged groups) or on P30 after a zymosan re-challenge on P29 (re-challenged groups). miRNA arrays and real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed significant, but differential, up-regulation of mature miR-181a in the L6-S1 spinal dorsal horns from zymosan-treated rats compared with saline-treated controls in both the unchallenged and re-challenged groups. The target gene analysis demonstrated multiple complementary binding sites in miR-181a for GABA(A) receptor subunit GABA(Aα-1) gene with a miRSVR score of -1.83. An increase in miR-181a concomitantly resulted in significant down-regulation of GABA(Aα-1) receptor subunit gene and protein expression in adult spinal cords from rats with neonatal cystitis. Intrathecal administration of the GABA(A) receptor agonist muscimol failed to attenuate the viscero-motor response (VMR) to colon distension in rats with neonatal cystitis, whereas in adult zymosan-treated rats the drug produced significant decrease in VMR. These results support an integral role for miRNA-mediated transcriptional deregulation of the GABAergic system in neonatal cystitis-induced chronic pelvic pain. Copyright © 2012 International

  12. The peculiarities of the ultrastructure of frontal cortex and hippocampus of rats in conditions of experimental allergic encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Nefodov A.A.

    2016-03-01

    Full Text Available Background. Multiple sclerosis refers to the demyelinating diseases of the nervous system, in which the main pathological changes develop in the white matter and are characterized by disintegration of myelin sheaths of conductive systems in different parts of the brain and spinal cord. Objective. To assess the degree of ultrastructural changes of frontal cortex and hippocampus of rats in conditions of experimental allergic encephalomyelitis. Methods. The research was conducted on 14 white rats divided randomly in 2 groups: group 1 – intact animals; group 2 – rats with experimental allergic encephalomyelitis. Experimental allergic encephalomyelitis was induced in 8 animals of the experimental group single subcutaneous inoculation encephalitogenic mixture in full adjuvant of Freynd at the rate of 100 mg homogenate of homologous spinal cord, 0.2 ml puff (the content of killed mycobacteria 5 mg/ml and 0.2 ml of physiological solution on the animal. Transmission electron microscopy was performed on the 14th day of encephalitogenic mixture administration. Results. In the frontal cortex and hippocampus experimental allergic encephalomyelitis induces apoptosis of the neurocytes with disruption of the structure of mitochondria (increase in size, the fragmentation of the outer membrane, destruction of cristae, disseminated perineuronal edema of the brain substance, violation of the structure of most axo-somatic synapses, the demyelination of nerve conductors with signs of fragmentation of neurofibril. Conclusion. The single subcutaneous inoculation of encephalitogenic mixture in full adjuvant of Freynd leads to the development of multifocal demyelination and axonal degeneration in the hippocampus and frontal cortex of experimental animals. Citation: Nefodov AA, Mamchur VI, Tverdokhleb IV. [The peculiarities of the ultrastructure of frontal cortex and hippocampus of rats in conditions of experimental allergic encephalomyelitis]. Morphologia. 2016

  13. Mixed electrical-chemical synapses in adult rat hippocampus are primarily glutamatergic and coupled by connexin-36

    OpenAIRE

    Farid eHamzei-Sichani; Davidson, Kimberly G. V.; Thomas eYasumura; William G M Janssen; Wearne, Susan L.; Patrick R. Hof; Traub, Roger D.; Rafael eGutierrez; Ole Petter Ottersen; Rash, John E.

    2012-01-01

    Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neuronal communication in the mammalian brain, whereas axodendritic and axosomatic gap junctions have rarely been described. We present ultrastructural, immunocytochemical, and dye-coupling evidence for mixed (electrical/chemical) synapses in adult rat hippocampus on both principal cells and interneurons. Thin-section electron microscopic images of small gap junction-like appositions were found at mossy fiber...

  14. Mixed Electrical–Chemical Synapses in Adult Rat Hippocampus are Primarily Glutamatergic and Coupled by Connexin-36

    OpenAIRE

    Hamzei-Sichani, Farid; Davidson, Kimberly G. V.; Yasumura, Thomas; William G M Janssen; Wearne, Susan L.; Patrick R. Hof; Traub, Roger D.; Gutiérrez, Rafael; Ottersen, Ole P.; Rash, John E.

    2012-01-01

    Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neuronal communication in mammalian brain, whereas axodendritic and axosomatic gap junctions have rarely been described. We present ultrastructural, immunocytochemical, and dye-coupling evidence for “mixed” (electrical/chemical) synapses on both principal cells and interneurons in adult rat hippocampus. Thin-section electron microscopic images of small gap junction-like appositions were found at mossy fiber (...

  15. Development of synaptic connectivity onto interneurons in stratum radiatum in the CA1 region of the rat hippocampus

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    Riebe Ilse

    2012-01-01

    Full Text Available Abstract Background The impact of a given presynaptic neuron on the firing probability of the postsynaptic neuron critically depends on the number of functional release sites that connect the two neurons. One way of determining the average functional synaptic connectivity onto a postsynaptic neuron is to compare the amplitudes of action potential dependent spontaneous synaptic currents with the amplitude of the synaptic currents that are independent of action potentials ("minis". With this method it has been found that average synaptic connectivity between glutamatergic CA3 and CA1 pyramidal cells increases from single connections in the neonatal rat, to multiple connections in the young adult rat. On the other hand, γ-aminobutyric acid (GABAergic interneurons form multiple connections onto CA1 pyramidal cells already in the neonatal rat, and the degree of multiple GABAergic connectivity is preserved into adulthood. In the present study, we have examined the development of glutamate and GABA connectivity onto GABAergic CA1 stratum radiatum interneurons in the hippocampal slice, and compared this to the connectivity onto CA1 pyramidal neurons. Results In GABAergic interneurons in the CA1 stratum radiatum, irrespective of developmental stage, we found that the average amplitude of action potential dependent spontaneous AMPA receptor-mediated synaptic currents were of the same magnitude as the mini AMPA receptor mediated synaptic currents. This finding indicates that these GABAergic interneurons, in contrast to the CA1 pyramidal neurons, preserve single glutamate connectivity throughout development. For GABA connectivity, on the other hand, we found multiple functional synaptic connections onto the interneurons, as onto the pyramidal cells. Conclusions The results presented here confirm that glutamate and GABA synaptic connectivity develop very differently in the hippocampal CA1 region. Thus, whereas average GABA connectivity is multiple

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

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    Raggenbass, M.; Tribollet, E.; Dubois-Dauphin, M.; Dreifuss, J.J. (Univ. Medical Center, Geneva (Switzerland))

    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.

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

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    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

  18. Noninvasive focused ultrasound stimulation can modulate phase-amplitude coupling between neuronal oscillations in the rat hippocampus

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    Yi Yuan

    2016-07-01

    Full Text Available 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 W/cm2, 9.6 W/cm2, 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.

  19. Effect of 8 weeks Resistance Training on BDNF and TrkB in the Hippocampus of Adult Male Rats

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    S Mojtahedi

    2014-08-01

    Full Text Available Background & aim: Exercise enhances the synaptic plasticity and neuroprotective effects in the adult brain. However, it remains unknown that how plasticity molecules change following types of training. The purpose of this study was to determine the effect of eight weeks resistance training on protein levels of Brain Derived Neurotrophic Factor(BDNF and receptor of TrkB, in the hippocampus of adult male rats. Methods: In this experimental study, twelve adult male rats, 8 weeks of age, with an average weight of 200 to 225 grams were randomly divided into two groups, control and exercise respectively. The exercise was to increase the weight on the ladder. 24 hours after their last training session. The animals were killed and the hippocampus was removed for further testing. ELISA determined changes in protein levels. Data were analyzed by independent t test. Results: There was a significant difference between train and control groups In protein level of variables statically (p≤0.05. In addition, protein levels of BDNF and TrkB in the hippocampus of rats increased. Conclusion: Resistance training is beneficial for promoting hippocampal plasticity associated with BDNF signaling and consequently functional and cognitive benefits.

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

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    Jiahong Zhu

    Full Text Available 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

  1. GABA transmission in the ventral pallidum is not involved in the control of latent inhibition in the rat.

    Science.gov (United States)

    Lawrence, N S; Sharp, T; Peters, S P; Gray, J A; Young, A M J

    2003-01-01

    Latent inhibition describes a process of learning to ignore stimuli of no consequence, and is disrupted in acute, positive-symptomatic schizophrenia. Understanding the neural basis of latent inhibition in animals may help to elucidate the neural dysfunction underlying positive schizophrenic symptoms in man. Evidence suggests a crucial role for dopamine transmission in the nucleus accumbens in the control of latent inhibition. The present studies investigated the role of the GABA-ergic efferent from the nucleus accumbens to the ventral pallidum in latent inhibition. The GABA(A) agonist muscimol (4.56 ng/microl), and antagonist picrotoxin (0.2 microg/microl), were infused into the ventral pallidum, and effects on latent inhibition were assessed using a conditioned suppression procedure. Neither drug produced specific effects on latent inhibition when given alone and, in the case of muscimol, failed to reverse the disruption of latent inhibition induced by systemic amphetamine. In addition to significant non-specific drug effects, a positive control experiment revealed that intra-pallidal picrotoxin significantly enhanced locomotion, suggesting that our manipulations of ventral pallidal GABA function were behaviourally effective. We conclude that modulating ventral pallidal GABA transmission does not affect latent inhibition. The implications of this finding for theories of the neural circuitry mediating latent inhibition and for understanding the functional role of ventral pallidal GABA transmission are discussed.

  2. Antioxidant Activity of Oral Administration of Rosmarinus Officinalis Leaves Extract on Rat's Hippocampus which Exposed to 6-Hydroxydopamine

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    Arashpour Rasoul

    2016-01-01

    Full Text Available Carnosic acid, a diterpene of Rosemarinus officinalis leaves extract (RE, has potent antioxidant activity in vitro. The dopaminergic connection of substantia nigra pars compacta to the hippocampus might be affected by oxidative stress which caused cognitive impairment observed in the early phase of Parkinson's disease (PD. Adult male Wistar rats were lesioned bilaterally by intra-nigral injection of 6-OHDA, and divided into six groups: four groups that orally given RE containing 40% of carnosic acid, at doses of 25, 50 and 100 mg/kg (treated rats and distilled water (H2O, once daily for a period of 14 days before and after the injury. There were also two another groups as control rats which injected by normal saline and untreated lesion group. The injured animals were evaluated for their spatial memory performance by Morris Water Maze test. Lesioned rats showed significant increase in escape latency, as compared with control group. Two weeks after injury, tissue samples were collected from the hippocampus. Levels of catalase (CAT, glutathione peroxidase (GPX and superoxide dismutase (SOD, malondialdehyde (MDA and reactive oxygen species (ROS were determined. There were significant increase of SOD, GPX and CAT enzymes activities in RE50 treated group as compared to lesioned rats. We found a significant decrease of ROS in RE50 treated group as compared to Lesioned rats. These findings provide evidence that 50 mg/kg of RE decreased oxidative damage of the hippocampus induced by 6-OHDA and serve as potential candidate for the treatment of PD.

  3. Synaptic innervation to rat hippocampus by vasopressin-immuno-positive fibres from the hypothalamic supraoptic and paraventricular nuclei.

    Science.gov (United States)

    Zhang, L; Hernández, V S

    2013-01-03

    The neuropeptide arginine vasopressin (AVP) exerts a modulatory role on hippocampal excitability through vasopressin V(1A) and V(1B) receptors. However, the origin and mode of termination of the AVP innervation of the hippocampus remain unknown. We have used light and electron microscopy to trace the origin, distribution and synaptic relationships of AVP-immuno-positive fibres and nerve terminals in the rat hippocampus. Immuno-positive fibres were present in all areas (CA1-3, dentate gyrus) of the whole septo-temporal extent of the hippocampus; they had the highest density in the CA2 region, strongly increasing in density towards the ventral hippocampus. Two types of fibres were identified, both establishing synaptic junctions. Type A had large varicosities packed with immuno-positive large-granulated peptidergic vesicles and few small clear vesicles forming type I synaptic junctions with pyramidal neuron dendrites, dendritic spines and with axonal spines. Type B had smaller varicosities containing mostly small clear vesicles and only a few large-granulated vesicles and established type II synaptic junctions mainly with interneuron dendrites. The AVP-positive axons in stratum oriens appeared to follow and contact metabotropic glutamate receptor 1α (mGluR1α)-immuno-positive interneuron dendrites. Fluoro-Gold injection into the hippocampus revealed retrogradely labelled AVP-positive somata in hypothalamic supraoptic and paraventricular nuclei. Hypothalamo-hippocampal AVP-positive axons entered the hippocampus mostly through a ventral route, also innervating the amygdala and to a lesser extent through the dorsal fimbria fornix, in continuation of the septal AVP innervation. Thus, it appears the AVP-containing neurons of the magnocellular hypothalamic nuclei serve as important sources for hippocampal AVP innervation, although the AVP-expressing neurons located in amygdala and bed nucleus of the stria terminalis reported previously may also contribute.

  4. Antioxidant effects of Dendropanax morbifera Léveille extract in the hippocampus of mercury-exposed rats

    OpenAIRE

    2015-01-01

    Background Dendropanax morbifera Léveille has been employed for the treatment of infectious diseases using folk medicine. In this study, we evaluated the antioxidant effects of a leaf extract of Dendropanax morbifera Léveille in the hippocampus of mercury-exposed rats. Methods Seven-week-old Sprague–Dawley rats received a daily intraperitoneal injection of 5 μg/kg dimethylmercury and/or oral Dendropanax morbifera Léveille leaf extract (100 mg/kg) for 4 weeks. Animals were sacrificed 2 h after...

  5. Protective effects of glucose-6-phosphate dehydrogenase on neurotoxicity of aluminium applied into the CA1 sector of rat hippocampus

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    Marina D Jovanovic

    2014-01-01

    Full Text Available Background & objectives: Aluminum (Al toxicity is closely linked to the pathogenesis of Alzheimer′s disease (AD. This experimental study was aimed to investigate the active avoidance behaviour of rats after intrahippocampal injection of Al, and biochemical and immunohistochemical changes in three bilateral brain structures namely, forebrain cortex (FBCx, hippocampus and basal forebrain (BF. Methods: Seven days after intra-hippocampal (CA1 sector injection of AlCl 3 into adult male Wistar rats they were subjected to two-way active avoidance (AA tests over five consecutive days. Control rats were treated with 0.9% w/v saline. The animals were decapitated on the day 12 post-injection. The activities of acetylcholinesterase (AChE and glucose-6-phosphate dehydrogenase (G6PDH were measured in the FBCx, hippocampus and BF. Immunohistochemical staining was performed for transferrin receptors, amyloid β and tau protein. Results: The activities of both AChE and G6PDH were found to be decreased bilaterally in the FBCx, hippocampus and basal forebrain compared to those of control rats. The number of correct AA responses was reduced by AlCl 3 treatment. G6PDH administered prior to AlCl 3 resulted in a reversal of the effects of AlCl 3 on both biochemical and behavioural parameters. Strong immunohistochemical staining of transferrin receptors was found bilaterally in the FBCx and the hippocampus in all three study groups. In addition, very strong amyloid β staining was detected bilaterally in all structures in AlCl 3 -treated rats but was moderate in G6PDH/AlCl 3 -treated rats. Strong tau staining was noted bilaterally in AlCl 3 -treated rats. In contrast, tau staining was only moderate in G6PDH/AlCl 3 -treated rats. Interpretation & conclusions: Our findings indicated that the G6PDH alleviated the signs of behavioural and biochemical effects of AlCl 3 -treatment suggesting its involvement in the pathogenesis of Al neurotoxicity and its potential

  6. Effect of Alcohol and Tobacco Smoke on Long-Term Memory and Cell Proliferation in the Hippocampus of Rats.

    Science.gov (United States)

    Gomez, Rosane; Schneider, Ricardo; Quinteros, Dayane; Santos, Carolina Ferreira; Bandiera, Solange; Thiesen, Flavia Valadão; Coitinho, Adriana Simon; Fernandes, Marilda da Cruz; Wieczorek, Marina Godinho

    2015-12-01

    Alcohol is frequently used in combination with tobacco and few studies explore interactions between these two drugs of abuse. Here, we evaluated the effect of chronic alcohol administration and concomitant exposure to tobacco smoke on long-term memory and on cell proliferation in the hippocampus of rats. Forty male Wistar rats were assigned to four groups and treated with alcohol (2g/kg by gavage) and/or exposed to tobacco smoke (from six cigarettes, by inhalation) twice a day (at 9:00 AM and 2:00 PM) for 30 days. Long-term memory was evaluated in the inhibitory avoidance test and hippocampal cell proliferation was analyzed for bromodeoxyuridine immunohistochemistry. Our results showed that alcohol, tobacco smoke, or their combination improved the long-term memory evaluated by the memory index in rats. Moreover, alcohol and tobacco coadministration decreased bromodeoxyuridine-labeled cells by 60% when compared to the control group, while alcohol treatment decreased labeled cells by 40%. The tobacco group showed a nonsignificant 26% decrease in labeled cells compared to the control group. Chronic alcohol and tobacco coadministration improves the long-term memory in rats in the inhibitory avoidance test. However, coadministration decreases the cell proliferation in the hippocampus of rats, suggesting a deleterious effect by the combined use of these drugs of abuse. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Na+/Ca2+ Exchanger 3 is Downregulated in the Hippocampus and Cerebrocortex of Rats with Hyperthermia-induced Convulsion

    Institute of Scientific and Technical Information of China (English)

    Dan Sun; Jun-Hua Xiao; Yan Bai; Mo-Si Chen; Jia-Sheng Hu; Ge-Fei Wu; Bing Mao

    2015-01-01

    Background: Na+/Ca2+ exchanger (NCX) plays a crucial role in pentylenetetrazol-induced convulsion.However, it is unclear whether NCX is critically involved in hyperthermia-induced convulsion.In this study, we examined the potential changes in NCX3 in the hippocampus and cerebrocortex of rats with hyperthermia-induced convulsion.Methods: Twenty-one Sprague Dawley rats were randomly assigned to control group, convulsion-prone group and convulsion-resistant group (n =7 in each group).Whole-cell patch-clamp method was used to record NCX currents.Both the Western blotting analysis and immunofluorescence labeling techniques were used to examine the expression of NCX3.Results: NCX currents were decreased in rats after febrile convulsion.Compared to the control group, NCX3 expression was decreased by about 40% and 50% in the hippocampus and cerebrocortex of convulsion-prone rats, respectively.Furthermore, the extent of reduction in NCX3 expression seemed to correlate with the number of seizures.Conclusions: There is a significant reduction in NCX3 expression in rats with febrile convulsions.Our findings also indicate a potential link between NCX3 expression, febrile convulsion in early childhood, and adult onset of epilepsy.

  8. Reciprocal regulation of epileptiform neuronal oscillations and electrical synapses in the rat hippocampus.

    Science.gov (United States)

    Kinjo, Erika R; Higa, Guilherme S V; Morya, Edgard; Valle, Angela C; Kihara, Alexandre H; Britto, Luiz R G

    2014-01-01

    Gap junction (GJ) channels have been recognized as an important mechanism for synchronizing neuronal networks. Herein, we investigated the participation of GJ channels in the pilocarpine-induced status epilepticus (SE) by analyzing electrophysiological activity following the blockade of connexins (Cx)-mediated communication. In addition, we examined the regulation of gene expression, protein levels, phosphorylation profile and distribution of neuronal Cx36, Cx45 and glial Cx43 in the rat hippocampus during the acute and latent periods. Electrophysiological recordings revealed that the GJ blockade anticipates the occurrence of low voltage oscillations and promotes a marked reduction of power in all analyzed frequencies.Cx36 gene expression and protein levels remained stable in acute and latent periods, whereas upregulation of Cx45 gene expression and protein redistribution were detected in the latent period. We also observed upregulation of Cx43 mRNA levels followed by changes in the phosphorylation profile and protein accumulation. Taken together, our results indisputably revealed that GJ communication participates in the epileptiform activity induced by pilocarpine. Moreover, considering that specific Cxs undergo alterations through acute and latent periods, this study indicates that the control of GJ communication may represent a focus in reliable anti-epileptogenic strategies.

  9. A new pH-sensitive rectifying potassium channel in mitochondria from the embryonic rat hippocampus.

    Science.gov (United States)

    Kajma, Anna; Szewczyk, Adam

    2012-10-01

    Patch-clamp single-channel studies on mitochondria isolated from embryonic rat hippocampus revealed the presence of two different potassium ion channels: a large-conductance (288±4pS) calcium-activated potassium channel and second potassium channel with outwardly rectifying activity under symmetric conditions (150/150mM KCl). At positive voltages, this channel displayed a conductance of 67.84pS and a strong voltage dependence at holding potentials from -80mV to +80mV. The open probability was higher at positive than at negative voltages. Patch-clamp studies at the mitoplast-attached mode showed that the channel was not sensitive to activators and inhibitors of mitochondrial potassium channels but was regulated by pH. Moreover, we demonstrated that the channel activity was not affected by the application of lidocaine, an inhibitor of two-pore domain potassium channels, or by tertiapin, an inhibitor of inwardly rectifying potassium channels. In summary, based on the single-channel recordings, we characterised for the first time mitochondrial pH-sensitive ion channel that is selective for cations, permeable to potassium ions, displays voltage sensitivity and does not correspond to any previously described potassium ion channels in the inner mitochondrial membrane. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

  10. Distribution and posttranslational modification of synaptic ERα in the adult female rat hippocampus.

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    Tabatadze, Nino; Smejkalova, Tereza; Woolley, Catherine S

    2013-02-01

    Acute 17β-estradiol (E2) signaling in the brain is mediated by extranuclear estrogen receptors. Here we used biochemical methods to investigate the distribution, posttranslational modification, and E2 regulation of estrogen receptor-α (ERα) in synaptosomal fractions isolated by differential centrifugation from the adult female rat hippocampus. We find that ERα is concentrated presynaptically and is highly enriched with synaptic vesicles. Immunoisolation of vesicles using vesicle subtype-specific markers showed that ERα is associated with both glutamate and γ-aminobutyric acid-containing neurotransmitter vesicles as well as with some large dense core vesicles. Experiments using broad spectrum and residue-specific phosphatases indicated that a portion of ERα in synaptosomal fractions is phosphorylated at serine/threonine residues leading to a mobility shift in SDS-PAGE and creating a double band on Western blots. The phosphorylated form of ERα runs in the upper of the two bands and is particularly concentrated with synaptic vesicles. Finally, we used E2 with or without the acyl protein thioesterase 1 inhibitor, Palmostatin B, to show that 20 min of E2 treatment of hippocampal slices depletes ERα from the synaptosomal membrane by depalmitoylation. We found no evidence that E2 regulates phosphorylation of synaptosomal ERα on this time scale. These studies begin to fill the gap between detailed molecular characterization of extranuclear ERα in previous in vitro studies and acute E2 modulation of hippocampal synapses in the adult brain.

  11. Manipulating epileptiform bursting in the rat hippocampus using chaos control and adaptive techniques.

    Science.gov (United States)

    Slutzky, Marc W; Cvitanovic, Predrag; Mogul, David J

    2003-05-01

    Epilepsy is a relatively common disease, afflicting 1%-2% of the population, yet many epileptic patients are not sufficiently helped by current pharmacological therapies. Recent reports have suggested that chaos control techniques may be useful for electrically manipulating epileptiform bursting behavior in vitro and could possibly lead to an alternative method for preventing seizures. We implemented chaos control of spontaneous bursting in the rat hippocampal slice using robust control techniques: stable manifold placement (SMP) and an adaptive tracking (AT) algorithm designed to overcome nonstationarity. We examined the effect of several factors, including control radius size and synaptic plasticity, on control efficacy. AT improved control efficacy over basic SMP control, but relatively frequent stimulation was still necessary and very tight control was only achieved for brief stretches. A novel technique was developed for validating period-1 orbit detection in noisy systems by forcing the system directly onto the period-1 orbit. This forcing analysis suggested that period-1 orbits were indeed present but that control would be difficult because of high noise levels and nonstationarity. Noise might actually be lower in vivo, where regulatory inputs to the hippocampus are still intact. Thus, it may still be feasible to use chaos control algorithms for preventing epileptic seizures.

  12. Differential effects of benzodiazepines on phospholipid methylation in hippocampus and cerebellum of rats

    Energy Technology Data Exchange (ETDEWEB)

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

    Science.gov (United States)

    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.

  14. Vortioxetine promotes early changes in dendritic morphology compared to fluoxetine in rat hippocampus.

    Science.gov (United States)

    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.

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

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

    2015-01-01

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

  16. Investigation of Propolis’ Effect on Thiobarbituric Acid Reactive Substances and Anti-Oxidant Enzyme Levels of Hippocampus in Diabetic Rats Induced by Streptozotocin

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    Köksal, Burcu; Emre, Memet Hanifi; Polat, Alaadin

    2015-01-01

    BACKGROUND: Propolis is an organic resinous viscous substance collected from flower bud and plant sprig by bees. Propolis has a potential treatment agent for oxidative damage caused by diabetes in hippocampus due to its flavonoid and phenolic content. AIM: In this study effect of propolis on thiobarbituric acid reactive substances and anti-oxidative enzyme levels of hippocampus in diabetic rats induced by streptozotocin was investigated. MATERIALS AND METHODS: The study involved measuring levels of SOD, CAT, GSH-Px and TBARs in hippocampus tissue of STZ-induced diabetic rats (Adult Male Sprague Dawley rats) after applying propolis for one month. The subjects of the study were composed of 51 rats randomly assigned to four groups (Control, STZ, P+STZ and STZ+P). For analysis of data, Kruskal Wallis Test was utilized. RESULTS: The findings of the study showed that there were no significant difference in the levels of TBARS, SOD, CAT and GSH-Px of hippocampus across the groups. CONCLUSION: Propolis application in four-week duration does not have effect on TBARS, SOD, CAT and GSH-Px levels of hippocampus of diabetic rats. These findings mean that more time for observing oxidative harms on hippocampus is needed. PMID:27275196

  17. Choline acetyltransferase in the hippocampus is associated with learning strategy preference in adult male rats.

    Science.gov (United States)

    Hawley, Wayne R; Witty, Christine F; Daniel, Jill M; Dohanich, Gary P

    2015-08-01

    One principle of the multiple memory systems hypothesis posits that the hippocampus-based and striatum-based memory systems compete for control over learning. Consistent with this notion, previous research indicates that the cholinergic system of the hippocampus plays a role in modulating the preference for a hippocampus-based place learning strategy over a striatum-based stimulus--response learning strategy. Interestingly, in the hippocampus, greater activity and higher protein levels of choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine, are associated with better performance on hippocampus-based learning and memory tasks. With this in mind, the primary aim of the current study was to determine if higher levels of ChAT and the high-affinity choline uptake transporter (CHT) in the hippocampus were associated with a preference for a hippocampus-based place learning strategy on a task that also could be solved by relying on a striatum-based stimulus--response learning strategy. Results confirmed that levels of ChAT in the dorsal region of the hippocampus were associated with a preference for a place learning strategy on a water maze task that could also be solved by adopting a stimulus-response learning strategy. Consistent with previous studies, the current results support the hypothesis that the cholinergic system of the hippocampus plays a role in balancing competition between memory systems that modulate learning strategy preference.

  18. HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia

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    Jihong Xing

    2016-07-01

    Full Text Available Background/Aims: This study was to examine the role played by hypoxia inducible factor-1 (HIF-1α in regulating pro-inflammatory cytokines (PICs pathway in the rat hippocampus after cardiac arrest (CA induced-transient global ischemia followed by cardiopulmonary resuscitation (CPR. Those PICs include interleukin-1β (IL-1β, interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α. Methods: A rat model of CA induced by asphyxia was used in the current study. Following CPR, the hippocampus CA1 region was obtained for ELISA to determine the levels of HIF-1α and PICs; and Western Blot analysis to determine the protein levels of PIC receptors. Results: Our data show that IL-1β, IL-6 and TNF-α were significant elevated in the hippocampus after CPR as compared with control group. This was companied with increasing of HIF-1α and the time courses for HIF-1α and PICs were similar. In addition, PIC receptors, namely IL-1R, IL-6R and TNFR1 were upregulated in CA rats. Also, stimulation of HIF-1α by systemic administration of ML228, HIF-1α activator, significantly attenuated the amplified IL-6/IL-6R and TNF-α /TNFR1 pathway in the hippocampus of CA rats, but did not modify IL-1β and its receptor. Moreover, ML228 attenuated upregulated expression of Caspase-3 indicating cell apoptosis evoked by CA. Conclusion: Transient global ischemia induced by CA increases the levels of IL-1β, IL-6 and TNF-α and thereby leads to enhancement in their respective receptor in the rat hippocampus. Stabilization of HIF-1α plays a role in attenuating amplified expression IL-6R, TNFR1 and Caspase-3 in the processing of transient global ischemia. Results of our study suggest that PICs contribute to cerebral injuries evoked by transient global ischemia and in this pathophysiological process activation of HIF-1α improves tissues against ischemic injuries. Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that

  19. Protective role of melatonin in domoic acid-induced neuronal damage in the hippocampus of adult rats.

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    Ananth, C; Gopalakrishnakone, P; Kaur, C

    2003-01-01

    Domoic acid (DA), a kainite-receptor agonist and potent inducer of neurotoxicity, has been administered intravenously in adult rats in the present study (0.75 mg/kg body weight) to demonstrate neuronal degeneration followed by glial activation and their involvement with inducible nitric oxide synthase (iNOS) in the hippocampus. An equal volume of normal saline was administered in control rats. The pineal hormone melatonin, which protects the neurons efficiently against excitotoxicity mediated by sensitive glutamate receptor, was administered intraperitoneally (10 mg/kg body weight), 20 min before, immediately after, and 1 h and 2 h after the DA administration, to demonstrate its role in therapeutic strategy. Histopathological analysis (Nissl staining) demonstrated extensive neuronal damage in the pyramidal neurons of CA1, CA3 subfields and hilus of the dentate gyrus (DG) in the hippocampus at 5 days after DA administration. Sparsely distributed glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were observed in the hippocampus at 4-24 h after DA administration and in the control rats. Astrogliosis was evidenced by increased GFAP immunoreactivity in the areas of severe neuronal degeneration at 5 days after DA administration. Along with this, microglial cells exhibited an intense immunoreaction with OX-42, indicating upregulation of complement type 3 receptors (CR3). Ultrastructural study revealed swollen or shrunken degenerating neurons in the CA1, CA3 subfields and hilus of the DG and hypertrophied astrocytes showing accumulation of intermediate filament bundles in the cytoplasm were observed after administration of DA. Although no significant change could be observed in the mRNA level of iNOS expression between the DA-treated rats and controls at 4-24 h and at 5-day time intervals, double immunofluorescense revealed co-expression of induced iNOS with GFAP immunoreactive astrocytes, but not in the microglial cells, and iNOS expression in the neurons

  20. 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.

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    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.

  1. Effect of environmental enrichment exposure on neuronal morphology of streptozotocin-induced diabetic and stressed rat hippocampus

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    Narendra Pamidi

    2014-08-01

    Full Text Available Background: Environmental enrichment (EE exposure is known to influence the structural changes in the neuronal network of hippocampus. In the present study, we evaluated the effects of EE exposure on the streptozotocin (STZ-induced diabetic and stressed rat hippocampus. Methods: Male albino rats of Wistar strain (4-5 weeks old were grouped into normal control (NC, vehicle control (VC, diabetes (DI, diabetes + stress (DI + S, diabetes + EE (DI + E, and diabetes + stress + EE (DI + S + E groups (n = 8 in each group. Rats were exposed to stress and EE after inducing diabetes with STZ (40 mg/kg. Rats were sacrificed on Day 30 and brain sections were processed for cresyl violet staining to quantify the number of surviving neurons in the CA1, CA3, and dentate hilus (DH regions of hippocampus. Results: A significant (p < 0.001 decrease in the number of survived neurons was noticed in DI (CA1, 34.06 ± 3.2; CA3, 36.1 ± 3.62; DH, 9.83 ± 2.02 as well as DI + S (CA1, 14.03 ± 3.12; CA3, 20.27 ± 4.09; DH, 6.4 ± 1.21 group rats compared to NC rats (CA1, 53.64 ± 2.96; CA3, 62.1 ± 3.34; DH, 21.11 ± 1.03. A significant (p < 0.001 increase in the number of survived neurons was observed in DI + E (CA1, 42.3 ± 3.66; CA3, 46.73 ± 4.74; DH, 17.03 ± 2.19 and DI + S + E (CA1, 29.69 ± 4.47; CA3, 36.73 ± 3.89; DH, 12.23 ± 2.36 group rats compared to DI and DI + S groups, respectively. Conclusions: EE exposure significantly reduced the amount of neuronal damage caused by complications of diabetes and stress to the neurons of hippocampus.

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

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    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. Pharmacokinetics and dopamine/acetylcholine releasing effects of ginsenoside Re in hippocampus and mPFC of freely moving rats

    Institute of Scientific and Technical Information of China (English)

    Jing SHI; Wei XUE; Wen-jie ZHAO; Ke-xin LI

    2013-01-01

    Aim: To investigate the pharmacokinetics and dopamine/acetylcholine-releasing effects of ginsenoside Re (Re) in brain regions related to learning and memory,and to clarify the neurochemical mechanisms underlying its anti-dementia activity.Methods: Microdialysis was conducted on awake,freely moving adult male SD rats with dialysis probes implanted into the hippocampus,medial prefrontal cortex (mPFC) or the third ventricle.The concentrations of Re,dopamine (DA) and acetylcholine (ACh) in dialysates were determined using LC-MS/MS.Results: Subcutaneous administration of a single dose of Re (12.5,25 or 50 mg/kg) rapidly distributed to the cerebrospinal fluid and exhibited linear pharmacokinetics.The peak concentration (Cmax) occurred at 60 min for all doses.Re was not detectable after 240 min in the dialysates for the low dose of 12.5 mg/kg.At the same time,Re dose-dependently increased extracellular levels of DA and ACh in the hippocampus and mPFC,and more prominent effects were observed in the hippocampus.Conclusion: The combined study of the pharmacokinetics and pharmacodynamics of Re demonstrate that increase of extracellular levels of DA and ACh,particularly in the hippocampus,may contribute,at least in part,to the anti-dementia activity of Re.

  4. Neuroprotective effect of sodium ferulate and signal transduction mechanisms in the aged rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Ying JIN; En-zhi YAN; Xiao-ming LI; Ying FAN; Yan-jie ZHAO; Zhuo LIU; Wan-zhu LIU

    2008-01-01

    Aim: To investigate whether the age-related increase in interleukin-1β (IL-1β) and c-Jun N-terminal kinases (JNK) pathway was coupled with a decrease in cell survival signaling pathways and whether sodium ferulate (SF) treatment was ef-fective in preventing these age-associated changes. Methods: Groups of young and aged rats were fed for 4 weeks on a diet enriched in SF (100 mg/kg and 200 mg/kg per day). At the end of the period of dietary manipulation, Western blot-ting analysis was used to determine the expressions of IL-1β, phosphorylated mitogen-activated protein kinase kinase (MKK)4, phospho-JNK, phospho-c-Jun, phosphorylated extracellular signal-regulated kinase (ERK 1/2), phospho-MEK, phospho-Akt, phosphorylated ribosomal protein S6 protein kinase (p70S6K), and activated caspase-3 and caspase-7. Nissl staining was used to observe the morphological change in hippocampal CAI regions. Immunohistochemical techniques for glial fibrillary acidic protein (GFAP) and integrin αM (OX-42) were used to determine the astrocyte and microglia activation. Results: IL-1β protein levels, and phospho-MKK4, phospho-JNK1/2, and phospho-c-Jun were significantly enhanced in hippocampus prepared from age-matched control rats. Increased IL-1β production and JNKI/2 activation was accompanied by down-regulation of MEK/ERK1/2 pathway and Akt/p7OS6K pathway, leading to cell apoptosis assessed by activation of caspase-3. Significantly, treatment of aged rats with SF (100 mg/kg and 200 mg/kg per day) for 4 weeks prevented the age-related increase in IL-1β and IL-1β-induced JNK signaling pathway and also the age-related changes in ERK and Akt kinase. Conclusion: SF plays neuroprotec-tire roles through suppression of IL-1β and IL-1β-induced JNK signaling and upregulation of MEK/ERK1/2 and Akt/p70S6K survival pathways.

  5. Dynamic changes of glial fibrillary acidic protein and nestin in the hippocampus of adult rat brain following ischemic vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Tianping Yu; Peng Zhang; Xiong Zhang; Linhui Wang; Mingyuan Tian; Yu Li

    2011-01-01

    Vascular dementia produced by permanent ligation of bilateral common carotid arteries involves progressive deterioration of intellectual and cognitive function in rats, which are closely associated with the hippocampus. This study used immunohistochemical analysis to detect the expression of glial fibrillary acidic protein and nestin in the hippocampus in a vascular dementia model. The results revealed that both glial fibrillary acidic protein and nestin expression were increased 1 day after permanent ligation of the bilateral common carotid arteries, compared with a sham-operated group. The expression of glial fibrillary acidic protein peaked at 7 days post-surgery. The expression of nestin was a little weaker than that of glial fibrillary acidic protein, and peaked at 14 days (P<0.01). The expression of both proteins slightly decreased at 21 and 28 days, accompanied by recovery of cerebral blood flow. In conclusion, this study demonstrated that glial fibrillary acidic protein and nestin exhibited dynamic expression in the rat hippocampus after permanent ligation of bilateral common carotid arteries. This finding suggests that dynamic alterations in protein expression play an important role in the pathogenesis of vascular dementia.

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

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    Lidiane Dal Bosco

    2015-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  9. Analysis of morphometric and ultrastructural characteristics of blood microcirculation in hippocampus of rats with alloxan diabetes under administration of citicoline

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    Владимир Иванович Жилюк

    2015-07-01

    Full Text Available Aim: determine morphometric and ultrastructural features of blood microcirculation in hippocampus of rats with alloxan diabetes under experimental therapy with citicoline.Materials and methods. The research was carried out on 48 white male Wistar rats (250-300 g randomized in 3 groups by 16 animals: I – intact (distilled water, intragastrically; II – animals with diabetes (distilled water, intragastrically; III – animals with diabetes + citicoline (500 mg/kg, intragastrically. Diabetes was reproduced by single subcutaneous injection of alloxan monohydrate (150 mg/kg. Blood glucose level was determined on the 11th day after administration of alloxan using a glucometer. Citicoline and distilled water were introduced once a day during 20 days starting from the 11th day after administration of alloxan. In morpho-functional study of hippocampal CA1-zone neurons the histological sections were deparaffinized and dyed with gallocyanin-chrome alum by Einarson for specific detection of RNA. Pictures were received with a microscope Axioskop (Zeiss, Germany. Using a computer-based picture analysis system VIDAS-386 (Kontron Elektronik, Germany the density of endothelial nuclei, the nucleus area and the concentration of RNA in the nucleus were determined. The study of ultrastructural changes of blood microcirculation in hippocampus was carried out using transmission electron microscope PEM-100-01 («SELMI», Ukraine by standard procedure and in accordance with common standards. Statistical difference between the groups were assessed by non-parametric Mann-Whitney U-test.Results. It has been established that citicoline contributed to recovery of proliferative activity of endothelium in vascular bed of hippocampus manifested with increase of endothelial nuclei density, their area and levels of nuclear RNA by 19,4% (p < 0,001, 17,2% (p < 0,05 and 25,8% (p < 0,01. Simultaneously it has been determined that hematoencephalic barrier damage in hippocampus of

  10. Effects of long-term infusion of sedatives on the cognitive function and expression level of RAGE in hippocampus of rats.

    Science.gov (United States)

    Wang, Junyan; Niu, Mengxuan; Bai, Shuancheng

    2016-08-01

    This study aims to investigate the effects of long-term infusion of midazolam, propofol, and lytic cocktail on the rat cognitive ability and expression of receptor for advanced glycation end products (RAGE) in the hippocampus. The correlation between cognitive function and RAGE protein expression level could provide basis for clinical application. Adult male Wistar rats were first treated with midazolam, propofol, lytic cocktail, and saline solution for 5 consecutive days, respectively, and then their behavioral performance in a Morris water maze was monitored to determine the effects of these sedatives on the cognition of spatial learning and memory. After the behavioral tests, the expression level of RAGE protein in the hippocampus of each rat was determined by ELISA and immunohistochemistry. Compared with the control rats, the sedative-treated rats showed impaired performance in the Morris water maze. These three sedatives rendered similar extents of impairment of learning and memory at the first day after the treatment (p  0.05). In addition, midazolam and propofol, but not lytic cocktail, caused significant upregulation of RAGE expression in the hippocampus. The upregulation of RAGE protein was further corroborated by the increment of RAGE-positive cells in the CA1 region of hippocampus from midazolam- and propofol-treated rats. The long-term treatment of propofol, midazolam, and lytic cocktail could impair cognition. The upregulation of RAGE protein in hippocampus might play a role in the midazolam- and propofol-caused cognitive dysfunction.

  11. Exposure to diphenyl ditelluride, via maternal milk, causes oxidative stress in cerebral cortex, hippocampus and striatum of young rats

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    Stangherlin, Eluza Curte; Ardais, Ana Paula; Rocha, Joao Batista Teixeira; Nogueira, Cristina Wayne [Universidade Federal de Santa Maria, Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Santa Maria, RS (Brazil)

    2009-05-15

    The present study evaluated the effect of diphenyl ditelluride [(PhTe){sub 2}] exposure to mothers on the cerebral oxidative status of their offspring. The dams received (PhTe){sub 2} or canola oil via subcutaneous injection once daily during the first 14 days of lactational period. At post natal day 28, biochemical parameters of oxidative stress were evaluated in cerebral structures - cortex, hippocampus and striatum - of young rats. Exposure to (PhTe){sub 2} increased lipid peroxidation levels and inhibited {delta}-ALA-D, catalase and SOD activities in hippocampus and striatum of young rats. (PhTe){sub 2} induced changes in the levels of non-enzymatic antioxidant defenses in cortex and striatum of young rats. The exposure to (PhTe){sub 2}, via maternal milk, caused oxidative stress in cerebral structures of young rats. Thus, the possible role of disrupted prooxidant/antioxidant balance in (PhTe){sub 2} toxicity was demonstrated. These results highlighted a possible molecular mechanism involved in toxicity caused by (PhTe){sub 2}. (orig.)

  12. Inhibition of GABA release by presynaptic ionotropic GABA receptors in hippocampal CA3.

    Science.gov (United States)

    Axmacher, Nikolai; Draguhn, Andreas

    2004-02-09

    Vesicular transmitter release can be regulated by transmitter-gated ion channels at presynaptic axon terminals. The central inhibitory transmitter GABA acts on such presynaptic ionotropic receptors in various cells, including inhibitory interneurons. Here we report that GABA-mediated postsynaptic inhibitory currents in CA3 pyramidal cells of rat hippocampal slices are suppressed by agonists of GABAA receptors. The effect is present for both stimulus-induced and miniature IPSCs, indicating a reduction in the probability of vesicular release by presynaptic, action-potential-independent mechanisms. We conclude that the release of GABA from hippocampal CA3 interneurons is regulated by a negative feedback via presynaptic ionotropic GABA autoreceptors.

  13. Enriched environment induces beneficial effects on memory deficits and microglial activation in the hippocampus of type 1 diabetic rats.

    Science.gov (United States)

    Piazza, Francele Valente; Segabinazi, Ethiane; Centenaro, Lígia Aline; do Nascimento, Patrícia Severo; Achaval, Matilde; Marcuzzo, Simone

    2014-03-01

    Type 1 diabetes mellitus (T1DM) has been associated with long-term complications in the central nervous system, causing brain cellular dysfunctions and cognitive deficits. On the other hand, enriched environment (EE) induces experience-dependent plasticity, especially in the hippocampus, improving the performance of animals in learning and memory tasks. Thus, our objective was to investigate the influence of the EE on memory deficits, locomotion, corticosterone levels, synaptophysin (SYP) protein immunoreactivity, cell survival and microglial activation in the dentate gyrus (DG) of T1DM rat hippocampus. Male Wistar rats (21-day-old) were exposed to EE or maintained in standard housing (controls, C) for 3 months. At adulthood, the C and EE animals were randomly divided and diabetes was induced in half of them. All the animals received 4 doses of BrdU, 24 h apart. Hippocampus-dependent spatial memory, general locomotion and serum corticosterone levels were evaluated at the end of the experiment. The animals were transcardially perfused 30 days post-BrdU administration. Our results showed that EE was able to prevent/delay the development of memory deficits caused by diabetes in rats, however it did not revert the motor impairment observed in the diabetic group. SYP immunoreactivity was increased in the enriched healthy group. The EE decreased the serum corticosterone levels in diabetic adult rats and attenuated the injurious microglial activation, though without altering the decrease of the survival cell. Thus, EE was shown to help to ameliorate cognitive comorbidities associated with T1DM, possibly by reducing hyperactivity in the hypothalamic-pituitary-adrenal axis and microglial activation in diabetic animals.

  14. Parvalbumin-containing interneurons in rat hippocampus have an AMPA receptor profile suggestive of vulnerability to excitotoxicity.

    Science.gov (United States)

    Moga, Diana; Hof, Patrick R; Vissavajjhala, Prabhakar; Moran, Thomas M; Morrison, John H

    2002-05-01

    alpha-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors mediate excitatory neurotransmission in the central nervous system, and contain combinations of four subunits (GluR1-4). We developed a GluR3-specific monoclonal antibody and quantified the cellular distribution of GluR3 in rat hippocampus. GluR3 immunoreactivity was detected in all pyramidal neurons and most interneurons. In addition, we found a subset of parvalbumin (PV)-containing interneurons in the hippocampus and neocortex that was notable for its intense GluR3 immunoreactivity and lack of GluR2 immunoreactivity. Such an expression pattern of AMPA receptor subunits is likely to make these interneurons selectively vulnerable to excitotoxicity.

  15. Physiological properties of anatomically identified axo-axonic cells in the rat hippocampus.

    Science.gov (United States)

    Buhl, E H; Han, Z S; Lörinczi, Z; Stezhka, V V; Karnup, S V; Somogyi, P

    1994-04-01

    1. The properties of a well-defined type of GABAergic local circuit neuron, the axo-axonic cell (n = 17), were investigated in rat hippocampal slice preparations. During intracellular recording we injected axo-axonic cells with biocytin and subsequently identified them with correlated light and electron microscopy. Employing an immunogold-silver intensification technique we showed that one of the physiologically characterized cells was immunoreactive for gamma-aminobutyric acid (GABA). 2. Axo-axonic cells were encountered in the dentate gyrus (n = 5) as well as subfields CA3 (n = 2) and CA1 (n = 10). They generally had smooth, beaded dendrites that extended throughout all hippocampal layers. Their axons ramified densely in the cell body layers and in the subjacent stratum oriens or hilus, respectively. Tested with electron microscopy, labeled terminals (n = 53) established synapses exclusively with the axon initial segment of principal cells in strata oriens and pyramidale and rarely in lower radiatum. Within a 400-microns slice a single CA1 axo-axonic cell was estimated to be in synaptic contact with 686 pyramidal cells. 3. Axo-axonic cells (n = 14) had a mean resting membrane potential of -65.1 mV, an average input resistance of 73.9 M omega, and a mean time constant of 7.7 ms. Action potentials were of short duration (389-microseconds width at half-amplitude) and had a mean amplitude of 64.1 mV. 4. Nine of 10 tested cells showed a varying degree of spike frequency adaptation in response to depolarizing current injection. Current-evoked action potentials were usually curtailed by a deep (10.2 mV) short-latency afterhyperpolarization (AHP) with a mean duration of 28.1 ms. 5. Cells with strong spike frequency accommodation (n = 5) had a characteristic firing pattern with numerous spike doublets. These appeared to be triggered by an underlying depolarizing afterpotential. In the same cells, prolonged bursts of action potentials were followed by a prominent long

  16. Hormonal regulation of delta opioid receptor immunoreactivity in interneurons and pyramidal cells in the rat hippocampus.

    Science.gov (United States)

    Williams, Tanya J; Torres-Reveron, Annelyn; Chapleau, Jeanette D; Milner, Teresa A

    2011-02-01

    Clinical and preclinical studies indicate that women and men differ in relapse vulnerability to drug-seeking behavior during abstinence periods. As relapse is frequently triggered by exposure of the recovered addict to objects previously associated with drug use and the formation of these associations requires memory systems engaged by the hippocampal formation (HF), studies exploring ovarian hormone modulation of hippocampal function are warranted. Previous studies revealed that ovarian steroids alter endogenous opioid peptide levels and trafficking of mu opioid receptors in the HF, suggesting cooperative interaction between opioids and estrogens in modulating hippocampal excitability. However, whether ovarian steroids affect the levels or trafficking of delta opioid receptors (DORs) in the HF is unknown. Here, hippocampal sections of adult male and normal cycling female Sprague-Dawley rats were processed for quantitative immunoperoxidase light microscopy and dual label fluorescence or immunoelectron microscopy using antisera directed against the DOR and neuropeptide Y (NPY). Consistent with previous studies in males, DOR-immunoreactivity (-ir) localized to select interneurons and principal cells in the female HF. In comparison to males, females, regardless of estrous cycle phase, show reduced DOR-ir in the granule cell layer of the dentate gyrus and proestrus (high estrogen) females, in particular, display reduced DOR-ir in the CA1 pyramidal cell layer. Ultrastructural analysis of DOR-labeled profiles in CA1 revealed that while females generally show fewer DORs in the distal apical dendrites of pyramidal cells, proestrus females, in particular, exhibit DOR internalization and trafficking towards the soma. Dual label studies revealed that DORs are found in NPY-labeled interneurons in the hilus, CA3, and CA1. While DOR colocalization frequency in NPY-labeled neuron somata was similar between animals in the hilus, proestrus females had fewer NPY-labeled neurons that

  17. Effect of Propofol on Glutamate and γ-aminobutyric Acid Release from Rat Hippocampal Synaptosomes

    Institute of Scientific and Technical Information of China (English)

    SHANG You; YAO Shanglong; ZENG Yinming; LIU Hongliang; CAO Junli

    2005-01-01

    To investigate the effect of propofol on the release of glutamate and γ-aminobutyric acid (GABA) from rat hippocampal synatosomes, synaptosomes was made from hippocampus and incubated with artificial cerebrospinal fluid (aCSF). With the experiment of Ca2+-dependent release of glutamate and GABA, dihydrokainic acid (DHK) and nipectic acid were added into aCSF. For the observation of Ca2+-independent release of glutamate and GABA, no DHK, nipectic acid and Ca2+were added from aCSF. The release of glutamate and GABA were evoked by 20μmol/L veratridine or 30 mmol/L KCl. The concentration of glutamate and GABA in aCSF was measured by using high-performance liquid chromatography (HPLC). 30, 100 and 300 μmol/L propofol significantly inhibited veratridine-evoked Ca2+-dependent release of glutamate and GABA (P<0.01 or P<0.05). However, propofol showed no effect on elevated KCl-evoked Ca2+-dependent release of glutamate and GABA (P>0.05). Veratridine or elevated KCl evoked Ca2+ -independent release of glutamate and GABA was not affected significantly by propofol (P>0.05). Propofol could inhibit Ca2+-dependent release of glutamate and GABA. However, it has no effect on the Ca2+-independent release ofglutamate and GABA.

  18. CX3CL1 is up-regulated in the rat hippocampus during memory-associated synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Graham K Sheridan

    2014-08-01

    Full Text Available Several cytokines and chemokines are now known to play normal physiological roles in the brain where they act as key regulators of communication between neurons, glia and microglia. In particular, cytokines and chemokines can affect cardinal cellular and molecular processes of hippocampal-dependent long-term memory consolidation including synaptic plasticity, synaptic scaling and neurogenesis. The chemokine, CX3CL1 (fractalkine, has been shown to modulate synaptic transmission and long-term potentiation (LTP in the CA1 pyramidal cell layer of the hippocampus. Here, we confirm widespread expression of CX3CL1 on mature neurons in the adult rat hippocampus. We report an up-regulation in CX3CL1 protein expression in the CA1, CA3 and dentate gyrus of the rat hippocampus 2 h after spatial learning in the water maze task. Moreover, the same temporal increase in CX3CL1 was evident following long-term potentiation-inducing theta-burst stimulation in the dentate gyrus. At physiologically relevant concentrations, CX3CL1 inhibited LTP maintenance in the dentate gyrus. This attenuation in dentate LTP was lost in the presence of GABAA receptor/chloride channel antagonism. CX3CL1 also had opposing actions on glutamate-mediated rise in intracellular calcium in hippocampal organotypic slice cultures in the presence and absence of GABAA receptor/chloride channel blockade. Using primary dissociated hippocampal cultures, we established that CX3CL1 reduces glutamate-mediated intracellular calcium rises in both neurons and glia in a dose dependent manner. In conclusion, CX3CL1 is up-regulated in the hippocampus during a brief temporal window following spatial learning the purpose of which may be to regulate glutamate-mediated neurotransmission tone. Our data supports a possible role for this chemokine in the protective plasticity process of synaptic scaling.

  19. Galvanic vestibular stimulation impairs cell proliferation and neurogenesis in the rat hippocampus but not spatial memory.

    Science.gov (United States)

    Zheng, Yiwen; Geddes, Lisa; Sato, Go; Stiles, Lucy; Darlington, Cynthia L; Smith, Paul F

    2014-05-01

    Galvanic vestibular stimulation (GVS) is a method of activating the peripheral vestibular system using direct current that is widely employed in clinical neurological testing. Since movement is recognized to stimulate hippocampal neurogenesis and movement is impossible without activation of the vestibular system, we speculated that activating the vestibular system in rats while minimizing movement, by delivering GVS under anesthesia, would affect hippocampal cell proliferation and neurogenesis, and spatial memory. Compared with the sham control group, the number of cells incorporating the DNA replication marker, bromodeoxyuridine (BrdU), was significantly reduced in the bilateral hippocampi in both the cathode left-anode right and cathode right-anode left stimulation groups (P ≤ 0.0001). The majority of the BrdU(+ve) cells co-expressed Ki-67, a marker for the S phase of the cell cycle, suggesting that these BrdU(+ve) cells were still in the cell cycle; however, there was no significant difference in the degree of co-labeling between the two stimulation groups. Single labeling for doublecortin (DCX), a marker of immature neurons, showed that while there was no significant difference between the different groups in the number of DCX(+ve) cells in the right dentate gryus, in the left dentate gyrus there was a significant decrease in the cathode left-anode right group compared with the sham controls (P ≤ 0.03). Nonetheless, when animals were tested in place recognition, object exploration and Morris water maze tasks, there were no significant differences between the GVS groups and the sham controls. These results suggest that GVS can have striking effects on cell proliferation and possibly neurogenesis in the hippocampus, without affecting spatial memory.

  20. Suppression of axonal conduction by sinusoidal stimulation in rat hippocampus in vitro

    Science.gov (United States)

    Jensen, A. L.; Durand, D. M.

    2007-06-01

    Deep brain stimulation (DBS), also known as high frequency stimulation (HFS), is a well-established therapy for Parkinson's disease and essential tremor, and shows promise for the therapeutic control of epilepsy. However, the direct effect of DBS on neural elements close to the stimulating electrode remains an important unanswered question. Computational studies have suggested that HFS has a dual effect on neural elements inhibiting cell bodies, while exciting axons. Prior experiments have shown that sinusoidal HFS (50 Hz) can suppress synaptic and non-synaptic cellular activity in several in vitro epilepsy models, in all layers of the hippocampus. However, the effects of HFS on axons near the electrode are still unclear. In the present study, we tested the hypothesis that HFS suppresses axonal conduction in vitro. Sinusoidal HFS was applied to the alvear axon field of transverse rat hippocampal slices. The results show that HFS suppresses the alvear compound action potential (CAP) as well as the CA1 antidromic evoked potential (AEP). Complete suppression was observed as a 100% reduction in the amplitude of the evoked field potential for the duration of the stimulus. Evoked potential width and latency were not significantly affected by sinusoidal HFS. Suppression was dependent on HFS amplitude and frequency, but independent of stimulus duration and synaptic transmission. The frequency dependence of sinusoidal HFS is similar to that observed in clinical DBS, with maximal suppression between 50 and 200 Hz. HFS produced not only suppression of axonal conduction but also a correlated rise in extracellular potassium. These data provide new insights into the effects of HFS on neuronal elements, and show that HFS can block axonal activity through non-synaptic mechanisms.

  1. Sprouty2 in the dorsal hippocampus regulates neurogenesis and stress responsiveness in rats.

    Directory of Open Access Journals (Sweden)

    Antonia L Dow

    Full Text Available Both the development and relief of stress-related psychiatric conditions such as major depression (MD and post-traumatic stress disorder (PTSD have been linked to neuroplastic changes in the brain. One such change involves the birth of new neurons (neurogenesis, which occurs throughout adulthood within discrete areas of the mammalian brain, including the dorsal hippocampus (HIP. Stress can trigger MD and PTSD in humans, and there is considerable evidence that it can decrease HIP neurogenesis in laboratory animals. In contrast, antidepressant treatments increase HIP neurogenesis, and their efficacy is eliminated by ablation of this process. These findings have led to the working hypothesis that HIP neurogenesis serves as a biomarker of neuroplasticity and stress resistance. Here we report that local alterations in the expression of Sprouty2 (SPRY2, an intracellular inhibitor of growth factor function, produces profound effects on both HIP neurogenesis and behaviors that reflect sensitivity to stressors. Viral vector-mediated disruption of endogenous Sprouty2 function (via a dominant negative construct within the dorsal HIP of adult rats stimulates neurogenesis and produces signs of stress resilience including enhanced extinction of conditioned fear. Conversely, viral vector-mediated elevation of SPRY2 expression intensifies the behavioral consequences of stress. Studies of these manipulations in HIP primary cultures indicate that SPRY2 negatively regulates fibroblast growth factor-2 (FGF2, which has been previously shown to produce antidepressant- and anxiolytic-like effects via actions in the HIP. Our findings strengthen the relationship between HIP plasticity and stress responsiveness, and identify a specific intracellular pathway that could be targeted to study and treat stress-related disorders.

  2. Expression of S100A6 in Rat Hippocampus after Traumatic Brain Injury Due to Lateral Head Acceleration

    Directory of Open Access Journals (Sweden)

    Bo Fang

    2014-04-01

    Full Text Available In a rat model of traumatic brain injury (TBI, we investigated changes in cognitive function and S100A6 expression in the hippocampus. TBI-associated changes in this protein have not previously been reported. Rat S100A6 was studied via immunohistochemical staining, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR after either lateral head acceleration or sham. Reduced levels of S100A6 protein and mRNA were observed 1 h after TBI, followed by gradual increases over 6, 12, 24, and 72 h, and then a return to sham level at 14 day. Morris water maze (MWM test was used to evaluate animal spatial cognition. TBI- and sham-rats showed an apparent learning curve, expressed as escape latency. Although TBI-rats displayed a relatively poorer cognitive ability than sham-rats, the disparity was not significant early post-injury. Marked cognitive deficits in TBI-rats were observed at 72 h post-injury compared with sham animals. TBI-rats showed decreased times in platform crossing in the daily MWM test; the performance at 72 h post-injury was the worst. In conclusion, a reduction in S100A6 may be one of the early events that lead to secondary cognitive decline after TBI, and its subsequent elevation is tightly linked with cognitive improvement. S100A6 may play important roles in neuronal degeneration and regeneration in TBI.

  3. General, kappa, delta and mu opioid receptor antagonists mediate feeding elicited by the GABA-B agonist baclofen in the ventral tegmental area and nucleus accumbens shell in rats: reciprocal and regional interactions.

    Science.gov (United States)

    Miner, Patricia; Shimonova, Lyudmila; Khaimov, Arthur; Borukhova, Yaffa; Ilyayeva, Ester; Ranaldi, Robert; Bodnar, Richard J

    2012-03-14

    Food intake is significantly increased following administration of agonists of GABA and opioid receptors into the nucleus accumbens shell (NACs) and ventral tegmental area (VTA). GABA-A or GABA-B receptor antagonist pretreatment within the VTA or NACs differentially affects mu-opioid agonist-induced feeding elicited from the same site. Correspondingly, general or selective opioid receptor antagonist pretreatment within the VTA or NACs differentially affects GABA agonist-induced feeding elicited from the same site. Regional interactions have been evaluated in feeding studies by administering antagonists in one site prior to agonist administration in a second site. Thus, opioid antagonist-opioid agonist and GABA antagonist-GABA agonist feeding interactions have been identified between the VTA and NACs. However, pretreatment with GABA-A or GABA-B receptor antagonists in the VTA failed to affect mu opioid agonist-induced feeding elicited from the NACs, and correspondingly, these antagonists administered in the NACs failed to affect mu opioid-induced feeding elicited from the VTA. To evaluate whether regional and reciprocal VTA and NACs feeding interactions occur for opioid receptor modulation of GABA agonist-mediated feeding, the present study examined whether feeding elicited by the GABA-B agonist, baclofen microinjected into the NACs was dose-dependently blocked by pretreatment with general (naltrexone: NTX), mu (beta-funaltrexamine: BFNA), kappa (nor-binaltorphamine: NBNI) or delta (naltrindole: NTI) opioid antagonists in the VTA, and correspondingly, whether VTA baclofen-induced feeding was dose-dependently blocked by NACs pretreatment with NTX, BFNA, NBNI or NTI in rats. Bilateral pairs of cannulae aimed at the VTA and NACs were stereotaxically implanted in rats, and their food intakes were assessed following vehicle and baclofen (200 ng) in each site. Baclofen produced similar magnitudes of increased food intake following VTA and NACs treatment. Baclofen

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Jun WANG; Yu-hua WANG; Yuan-yuan HOU; Tao XI; Yao LIU; Jing-gen LIU

    2013-01-01

    Aim: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.Methods: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.Results: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.Conclusion: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.

  6. Protective effects of ascorbic acid and garlic extract against lead-induced apoptosis in developing rat hippocampus.

    Science.gov (United States)

    Ebrahimzadeh-Bideskan, Ali-Reza; Hami, Javad; Alipour, Fatemeh; Haghir, Hossein; Fazel, Ali-Reza; Sadeghi, Akram

    2016-10-01

    Lead exposure has negative effects on developing nervous system and induces apoptosis in newly generated neurons. Natural antioxidants (i.e. Ascorbic acid and Garlic) might protect against lead-induced neuronal cell damage. The aim of the present study was to investigate the protective effects of Ascorbic acid and Garlic administration during pregnancy and lactation on lead-induced apoptosis in rat developing hippocampus. Timed pregnant Wistar rats were administrated with Lead (1500 ppm) via drinking water (Pb group) or lead plus Ascorbic acid (Pb + AA Group, 500 mg/kg, IP), or lead plus Garlic Extract (Pb + G Group, 1 ml garlic juice/100 g BW, via Gavage) from early gestation (GD 0) until postnatal day 50 (PN 50). At the end of experiments, the pups' brains were carefully dissected. To identify neuronal death, the brain sections were stained with TUNEL assay. Mean of blood and brain lead levels increased significantly in Pb group comparing to other studied groups (P Ascorbic acid or Garlic (P Ascorbic acid and Garlic during pregnancy and lactation protect against lead-induced neuronal cell apoptosis in the hippocampus of rat pups partially via the reduction of Pb concentration in the blood and in the brain.

  7. Expression of apoptosis-Related genes bcl-2 and bax in rat brain hippocampus, followed by intraperitoneal injection of nanosilver

    Directory of Open Access Journals (Sweden)

    Maryam Ghoshcian

    2016-05-01

    Full Text Available Background: Silver nanoparticles are small scale substance (<100 nm used in food technology and medical industry. The data suggest that nanosilver may produce neurotoxicity by generating free radical-induced oxidative stress and by altering gene expression producing apoptosis and neurotoxicity. In this study, the apoptotic effects of Nano silver on apoptosis- related genes expression bcl-2 and bax on rat hippocampus, which is involved in memory and learning, was investigated. Materials & Methods: 28 male Wistar rats were divided into four groups of control and three groups of the treatment. The control group received saline and the treatment groups received intraperitoneal injections of silver nanoparticles at doses of 100, 200 and 400ppm. Ten days after the last injection, the hippocampal region was dissected and removed and then the expression of bcl-2 and bax genes was evaluated using semi-qualitative RT-PCR and Densitometry assay. Results: The expression of anti- apoptotic b-cl2 gene was reduced in the treatment groups compared to the control group. In comparison, the expression of pro- apoptotic bax gene was increased in the treatment groups compared to the control group. This apoptotic affects was increased at higher doses. Conclusion: The data suggest that silver nanoparticles may produce apoptosis by altering apoptosis- related genes expression, in rat brain hippocampus cells.

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

    Science.gov (United States)

    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...

  9. Building models for postmortem abnormalities in hippocampus of schizophrenics.

    Science.gov (United States)

    Benes, Francine M

    2015-09-01

    Postmortem studies have suggested that there is abnormal GABAergic activity in the hippocampus in schizophrenia (SZ). In micro-dissected human hippocampal slices, a loss of interneurons and a compensatory upregulation of GABAA receptor binding activity on interneurons, but not PNs, has suggested that disinhibitory GABA-to-GABA connections are abnormal in stratum oriens (SO) of CA3/2, but not CA1, in schizophrenia. Abnormal expression changes in the expression of kainate receptor (KAR) subunits 5, 6 and 7, as well as an inwardly-rectifying hyperpolarization-activated cationic channel (Ih3; HCN3) may play important roles in regulating GABA cell activity at the SO CA3/2 locus. The exclusive neurons at this site are GABAergic interneurons; these cells also receive direct projections from the basolateral amygdala (BLA). When the BLA is stimulated by stereotaxic infusion of picrotoxin in rats, KARs influence axodendritic and presynaptic inhibitory mechanisms that regulate both inhibitory and disinhibitory interneurons in the SO-CA3/2 locus. The rat model described here was specifically developed to extend our understanding of these and other postmortem findings and has suggested that GABAergic abnormalities and possible disturbances in oscillatory rhythms may be related to a dysfunction of disinhibitory interneurons at the SO-CA3/2 site of schizophrenics.

  10. Correlation between IL-10 and microRNA-187 expression in epileptic rat hippocampus and patients with temporal lobe epilepsy

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    Walid A. Alsharafi

    2015-12-01

    Full Text Available Accumulating evidence is emerging that microRNAs (miRs are key regulators controlling neuroinflammatory processes, which are known to play a potential role in the pathogenesis of temporal lobe epilepsy (TLE. The aim of the present study was to investigate the dynamic expression pattern of interleukin (IL–10 as an anti-inflammatory cytokine and miR-187 and post-transcriptional inflammation-related miRNA in the hippocampus of a rat model of status epilepticus (SE and patients with TLE. We performed a real-time quantitative PCR and western blot on rat hippocampus (2 hours, 7 days, 21 days and 60 days following pilocarpine-induced SE, and on hippocampus obtained from TLE patients and normal controls. To detect the relationship between IL-10 and miR-187 on neurons, lipopolysaccharide (LPS and IL-10-stimulated neurons were prepared. Furthermore, we identified the effect of antagonizing of miR-187 by its antagomir on IL-10 secretion. Here we reported that that IL-10 secretion and miR-187 expression levels are inversely correlated after SE.. In patients with TLE, the expression levels of IL-10 was also significantly upregulated, whereas miR-187 expression was significantly downregulated. Moreover, miR-187 expression was significantly reduced following IL-10 stimulation in an IL-10–dependent manner. On the other hand, antagonizing miR-187 reduced the production of IL-10 in hippocampal tissues of rat model of SE. Our findings demonstrate a critical role of miR-187 in the physiological regulation of IL-10 anti-inflammatory responses and elucidate the role of neuro-inflammation in the pathogenesis of TLE. Therefore, modulation of the IL-10 / miR-187 axis may be a new therapeutic approach for TLE.

  11. Regulation by divalent cations of /sup 3/H-baclofen binding to GABA/sub B/ sites in rat cerebellar membranes

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K.; Goto, M.; Fukuda, H.

    1983-02-21

    When investigating the effects of divalent cations (Mg/sup 2 +/, Ca/sup 2 +/, Sr/sup 2 +/, Ba/sup 2 +/, Mn/sup 2 +/ and Ni/sup 2 +/) on /sup 3/H-baclofen binding to rat cerebellar synaptic membranes, we found that the specific binding of /sup 3/H-baclofen was not only dependent on divalent cations, but was increased dose-dependently in the presence of these cations. The effects were in the following order of potency: Mn/sup 2 +/ approx. = Ni/sup 2 +/ > Mg/sup 2 +/ > Ca/sup 2 +/ > Sr/sup 2 +/ > Ba/sup 2 +/. Scatchard analysis of the binding data revealed a single component of the binding sites in the presence of 2.5 mM MgCl/sub 2/, 2.5 mM CaCl/sub 2/ or 0.3 mM MnCl/sub 2/ whereas two components appeared in the presence of 2.5 mM MnCl/sub 2/ or 1 mM NiCl/sub 2/. In the former, divalent cations altered the apparent affinity (K/sub d/) without affecting density of the binding sites (B/sub max/). In the latter, the high-affinity sites showed a higher affinity and lower density of the binding sites than did the single component of the former. As the maximal effects of four cations (Mg/sup 2 +/, Ca/sup 2 +/, Mn/sup 2 +/, and Ni/sup 2 +/) were not additive, there are probably common sites of action of these divalent cations. Among the ligands for GABA/sub B/ sites, the affinity for (-), (+) and (+/-)baclofen, GABA and ..beta..-phenyl GABA increased 2 - 6 fold in the presence of 2.5 mM MnCl/sub 2/, in comparison with that in HEPES-buffered Krebs solution (containing 2.5 mM CaCl/sub 2/ and 1.2 mM MgSO/sub 4/), whereas that for muscimol was decreased to one-fifth. Thus, the affinity of GABA/sub B/ sites for its ligands is probably regulated by divalent cations, through common sites of action.

  12. Modulatory effects of gonadorelin on GABA-induced depolarization and GABA-activated current in rat spinal ganglion neurons%戈那瑞林对大鼠脊神经节细胞GABA引起的去极化及GABA激活电流的调制作用

    Institute of Scientific and Technical Information of China (English)

    周小萍; 吴晓平; 关兵才; 李之望

    1996-01-01

    目的:探索戈那瑞林对大鼠初级感觉神经元膜GABA引起的去极化和GABA激活电流的调制作用.方法:应用细胞内记录和全细胞膜片钳技术分别在大鼠脊神经节(SG)标本和新鲜分离神经元进行实验.结果:GABA(10μmol·L-1-1mmol·L-1)在大多数神经元引起可为荷包牡丹碱(100 μmol·L-1)所阻断的膜去极化.预加戈那瑞林(50 μmol·L-1)可减少GABA引起的去极化,抑制率为79±22%(n=29),而戈那瑞林本身不产生膜反应或只引起轻微去极化.在11个细胞中有6个细胞GABA激活电流也为戈那瑞林的预处理所抑制,另5个细胞无改变或反应稍有增加.结论:戈那瑞林对初级感觉神经元GABA介导的去极化和GABA激活电流具有抑制作用.%AIM: To explore the modulatory effects of gonadorelin on GABA-induced depolarization and GABA-activated current in membrane of rat primary sensory neurons. METHODS: Intracellular recordings and whole-cell patch clamp techniques were performed on neurons in rat spinal ganglia (SG) preparation and neurons freshly isolated from rat SG, respectively. Drugs were applied by superfusion and/or by bath application.RESULTS: In the majority of neurons GABA (10tion, which was blocked by bicucullin (100 μmol tion by 79±22 % (n=29), while gonadorelin elicited no effect or slight depolarization alone.In 6 of 11 cells, GABA-activated currents were also inhibited by pretreatment with gonadorelin no change or a slight potentiation. CONCLUSION: Gonadorelin exerts an inhibitory effect on GABA-induced depolarization and GABA-activated current in the primary sensory neurons.

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

    OpenAIRE

    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 p...

  14. Study on the effects of acupuncture combined with music therapy on the balance excitatory and inhibitory of hippocampal Glu/GABA in anxiety model rats%针刺结合音乐疗法对焦虑模型大鼠海马 Glu/GABA兴奋/抑制平衡系统的影响

    Institute of Scientific and Technical Information of China (English)

    郑蔚; 赵日霞; 刘海静

    2016-01-01

    Objective It is to observe the influence of acupuncture combined with music therapy on the content and ration of Glu/GABA in hippocampus in anxiety model rats, and approach the anti-anxiety mechanism.Methods 50 cases of male SD rats were randomly divided into blank group, model group, acupuncture group, music group and acupuncture combined with music group with 10 rats in each group.Except the blank group, the other animals were used in unpredictable chronic emo-tional stress method ( Chronic Emotional Stress, CES) for 21 days to make anxiety model; at the same time, the animals of music group, acupuncture group, acupuncture combined with music group in 1 hours before each stimulus were gave the corre-sponding acupuncture or music therapy.After experiment, the hippocampi of rats in each group were extracted to detect the Glu and GABA contents by using high efficiency liquid chromatography.Results Compared with the blank group, the concen-tration of Glu and the value of Glu/GATA were significantly increased and the concentration of GABA was significantly reduced in the model group ( all P0.05).Conclusion Anti-anxiety mechanism of acupuncture combined with music therapy is related to the function of regulating the concentration of Glu/GABA in hippocampus.%目的:通过观察针刺结合音乐疗法对焦虑模型大鼠海马谷氨酸( Glu)、γ-氨基丁酸( GABA)含量和二者比值的影响,探讨此方法的部分抗焦虑机制。方法将50只雄性SD大鼠随机分为空白组、模型组、针刺组、音乐组和针刺音乐组,每组10只。除空白组外,其余组大鼠均给予连续21 d不可预见性的刺激,同时针刺组、音乐组及针刺音乐组在每次刺激前1h给予相应的针灸及音乐干预。实验结束后取各组大鼠的海马,采用高效液相色谱检测法分析各组样本中Glu和GABA含量。结果模型组大鼠海马Glu含量及Glu/GABA比值均明显高于空白组(P均<0.05),GABA含

  15. Osthole improves synaptic plasticity in the hippocampus and cognitive function of Alzheimer's disease rats via regulating glutamate

    Institute of Scientific and Technical Information of China (English)

    Xiaohua Dong; Danshen Zhang; Li Zhang; Wei Li; Xianyong Meng

    2012-01-01

    Osthole,an effective monomer in Chinese medicinal herbs,can cross the blood-brain barrier and protect against brain injury,with few toxic effects.In this study,a rat model of Alzheimer's disease was established after intracerebroventricular injection of β-amyloid peptide (25-35).Subsequently,the rats were intraperitoneally treated with osthole (12.5 or 25.0 mg/kg) for 14 successive days.Results showed that osthole treatment significantly improved cognitive impairment and protected hippocampal neurons of Alzheimer's disease rats.Also,osthole treatment alleviated suppressed long-term potentiation in the hippocampus of Alzheimer's disease rats.In these osthole-treated Alzheimer's disease rats,the level of glutamate decreased,but there was no significant change in Y-amino-butyric acid.These experimental findings suggest that osthole can improve learning and memory impairment,and increase synaptic plasticity in Alzheimer's disease rats.These effects of osthole may be because of its regulation of central glutamate and Y-amino-butyric acid levels.

  16. Selective pharmacological modulation of pyramidal neurons and interneurons in the CA1 region of the rat hippocampus

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    Marzia eMartina

    2013-03-01

    Full Text Available The hippocampus is a complex network tightly regulated by interactions between excitatory and inhibitory neurons. In neurodegenerative disorders where cognitive functions such as learning and memory are impaired this excitation-inhibition balance may be altered. Interestingly, the uncompetitive NMDAR antagonist memantine, currently in clinical use for the treatment of Alzheimer’s disease (AD, may alter the excitation-inhibition balance in the hippocampus. However, the specific mechanism by which memantine exerts this action is not clear. To better elucidate the effect of memantine on hippocampal circuitry, we studied its pharmacology on NMDAR currents in both pyramidal cells (PCs and interneurons (Ints in the CA1 region of the hippocampus. Applying whole-cell patch-clamp methodology to acute rat hippocampal slices, we report that memantine antagonism is more robust in PCs than in Ints. Using specific NMDAR subunit antagonists, we determined that this selective antagonism of memantine is attributable to specific differences in the molecular make up of the NMDARs in excitatory and inhibitory neurons. These findings offer new insight into the mechanism of action and therapeutic potential of NMDA receptor pharmacology in modulating hippocampal excitability.

  17. Glutamate binding is altered in hippocampus and cortex of Wistar rats after pilocarpine-induced Status Epilepticus.

    Science.gov (United States)

    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.

  18. Glucocorticoids and the expression of mRNAs for neurotrophins, their receptors and GAP-43 in the rat hippocampus.

    Science.gov (United States)

    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.

  19. Distinct Localization of SNAP47 Protein in GABAergic and Glutamatergic Neurons in the Mouse and the Rat Hippocampus.

    Science.gov (United States)

    Münster-Wandowski, Agnieszka; Heilmann, Heike; Bolduan, Felix; Trimbuch, Thorsten; Yanagawa, Yuchio; Vida, Imre

    2017-01-01

    Synaptosomal-associated protein of 47 kDa (SNAP47) isoform is an atypical member of the SNAP family, which does not contribute directly to exocytosis and synaptic vesicle (SV) recycling. Initial characterization of SNAP47 revealed a widespread expression in nervous tissue, but little is known about its cellular and subcellular localization in hippocampal neurons. Therefore, in the present study we applied multiple-immunofluorescence labeling, immuno-electron microscopy and in situ hybridization (ISH) and analyzed the localization of SNAP47 in pre- and postsynaptic compartments of glutamatergic and GABAergic neurons in the mouse and rat hippocampus. While the immunofluorescence signal for SNAP47 showed a widespread distribution in both mouse and rat, the labeling pattern was complementary in the two species: in the mouse the immunolabeling was higher over the CA3 stratum radiatum, oriens and cell body layer. In contrast, in the rat the labeling was stronger over the CA1 neuropil and in the CA3 stratum lucidum. Furthermore, in the mouse high somatic labeling for SNAP47 was observed in GABAergic interneurons (INs). On the contrary, in the rat, while most INs were positive, they blended in with the high neuropil labeling. ISH confirmed the high expression of SNAP47 RNA in INs in the mouse. Co-staining for SNAP47 and pre- and postsynaptic markers in the rat revealed a strong co-localization postsynaptically with PSD95 in dendritic spines of pyramidal cells and, to a lesser extent, presynaptically, with ZnT3 and vesicular glutamate transporter 1 (VGLUT1) in glutamatergic terminals such as mossy fiber (MF) boutons. Ultrastructural analysis confirmed the pre- and postsynaptic localization at glutamatergic synapses. Furthermore, in the mouse hippocampus SNAP47 was found to be localized at low levels to dendritic shafts and axon terminals of putative INs forming symmetric synapses, indicating that this protein could be trafficked to both post- and presynaptic sites in both

  20. The effects of doxepin on stress-induced learning, memory impairments, and TNF-α level in the rat hippocampus.

    Science.gov (United States)

    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 (PStress-doxepin groups did not reveal any differences compared to control group at any given doses. TNF-α level was increased significantly (Pstress 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.

  1. Biphasic functional regulation in hippocampus of rat with chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid artery.

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    Jihye Bang

    Full Text Available BACKGROUND: Chronic cerebral hypoperfusion induced by permanent occlusion of the bilateral common carotid artery (BCCAO in rats has been commonly used for the study of Alzheimer's disease and vascular dementia. Despite the apparent cognitive dysfunction in rats with BCCAO, the molecular markers or pathways involved in the pathological alternation have not been clearly identified. METHODS: Temporal changes (sham, 21, 35, 45, 55 and 70 days in gene expression in the hippocampus of rats after BCCAO were measured using time-course microarray analysis. Gene Ontology (GO and pathway analyses were performed to identify the functional involvement of temporally regulated genes in BCCAO. RESULTS: Two major gene expression patterns were observed in the hippocampus of rats after BCCAO. One pattern, which was composed of 341 early up-regulated genes after the surgical procedure, was dominantly involved in immune-related biological functions (false discovery rate [FDR]<0.01. Another pattern composed of 182 temporally delayed down-regulated genes was involved in sensory perception such as olfactory and cognition functions (FDR<0.01. In addition to the two gene expression patterns, the temporal change of GO and the pathway activities using all differentially expressed genes also confirmed that an immune response was the main early change, whereas sensory functions were delayed responses. Moreover, we identified FADD and SOCS3 as possible core genes in the sensory function loss process using text-based mining and interaction network analysis. CONCLUSIONS: The biphasic regulatory mechanism first reported here could provide molecular evidence of BCCAO-induced impaired memory in rats as well as mechanism of the development of vascular dementia.

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