Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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The effect of baclofen on bicuculline-induced epileptogenesis was investigated in the CA3 region of hippocampal slices taken from rats 9 days to 8 weeks of age. Bath application of baclofen blocked all spontaneous epileptiform activity and raised the stimulus strength required for orthodromic induction of epileptiform discharges. Baclofen was equally effective in antagonizing depolarization shift generation in mature and immature rat slices. The duration of afterdischarges recorded in immature hippocampus was unaltered, yet these events were eliminated when the proceeding depolarization shift was blocked. Baclofen hyperpolarized all CA3 pyramidal cells studied with an associated decrease in membrane resistance. These effects were produced by a direct postsynaptic action.
Cell Mol Neurobiol 1984 Dec
PMID:Postsynaptic actions of baclofen associated with its antagonism of bicuculline-induced epileptogenesis in hippocampus. 609 51

The passive electrical cable properties of CA3 pyramidal neurons from guinea pig hippocampal slices were investigated by applying current steps and recording the voltage transients from 25 CA3 neurons, using a single intracellular microelectrode and a 3-kHz time-share system. Two independent methods were used for estimating the equivalent electrotonic length of the dendrites, L, and the dendritic to somatic conductance ratio, p. The first method is similar to that used by Gorman and Mirolli (1972) and gave an average L of 0.96; the average p was 2.44. The second method is derived here for the first time and assumes a finite-length cable with lumped soma. It is an exact solution for L and p, using the slopes and intercepts of the first two peeled exponentials. The average L was 0.94; the average p was 1.51. The results, using both methods, are in close agreement. The average membrane time constant for all CA3 neurons was 23.6 ms. suggesting a large (23,600 omega cm2) average membrane resistivity. It is concluded that CA3 neurons are electronically short.
Cell Mol Neurobiol 1981 Mar
PMID:Passive cable properties of hippocampal CA3 pyramidal neurons. 734 64

To investigate the molecular changes underlying kindling epileptogenesis in the rat hippocampus, the expression levels of the genes encoding for 13 different gamma-aminobutyric acid type-A receptor (GABAAR) subunits were measured in hippocampal principal neurons using in situ hybridization techniques and semi-quantitative analysis of the autoradiograms. Schaffer collateral-commissural pathway kindled rats were investigated at three different stages of kindling acquisition, at 24 h after the last seizure and at long-term (28 days) after termination of kindling stimulations. Changes were distinct for the different subunits in the three analyzed regions (CA1, CA3, fascia dentata) and also different for the various kindling stages. In all hippocampal areas at the early phases of kindling epileptogenesis, before the appearance of generalized seizures, an increase was found of those transcripts that constituted the majority of the expressed variants in control animals (alpha 1, alpha 2, alpha 4, beta 1, beta 2, beta 3, gamma 2/gamma 2L mRNA). In these stages, the increased levels of different variants in the granular neurons of the fascia dentata were more pronounced when compared to the pattern of changes in pyramidal cells of CA1 and CA3. In fully kindled animals, the expression levels of several subunits returned to control levels, whereas beta 3 and gamma 2/gamma 2L mRNA expression was still significantly enhanced in all areas. At long-term, few changes were encountered. The long-splice variant of gamma 2 was decreased within pyramidal and granular neurons while the total level of gamma 2 mRNA was not different from controls. The increased GABAAR subunit expression in the fascia dentata may underly the reported increased GABAAR ligand binding and the increased GABA mediated inhibition. However, the decreased GABAAR binding and the attenuation of GABAergic inhibition in CA1, could not be explained by a decrement of receptor subunit expression.
Brain Res Mol Brain Res 1995 Jul
PMID:Expression of GABAA receptor subunit mRNAs in hippocampal pyramidal and granular neurons in the kindling model of epileptogenesis: an in situ hybridization study. 747 32

Three non-allelic rat calmodulin (CaM) genes CaMI, CaMII and CaMIII, which share no homology in their 5'-upstream regions, are coordinately expressed in neurons of the central nervous system (CNS). Deletion analysis of the CaMIII promoter showed that the upstream segments longer than 700 bases functioned as efficient promoters, and that the sequence from -133 to -65 was required for the activity of house-keeping type promoter in transient expression assays on a mouse glioma cell line C6. However, the transient expression seemed not to be cell type specific. To determine the temporal and spatial specificity of the promoter function, we produced transgenic mice carrying a fusion gene of the CaMIII segment from -877 to +103 and the lacZ reporter gene. In CNS of the adult transgenic mice, the localization of transgene expression was similar to that of endogenous CaMIII transcripts analyzed by in situ hybridization. The transgene was expressed prominently in pyramidal cells of the cerebral neocortex and the hippocampal regions CA1 to CA3, in Purkinje cells of the cerebellar cortex, and in neurons of the spinal cord, and moderately in granule cells of the dentate gyrus and the cerebellar cortex. In the developing CNS, the overall profiles of neuron-specific expression were also similar for both transgene and endogenous CaMIII that were expressed in the mantle layer and the dorsal root ganglia of the embryonal spinal cord. These results indicated that the neuron-specific expression of rat CaMIII was directed by this 877-base promoter sequence. The CaMIII segment used for the promoter of transgene contained a 29-bp sequence at -410, namely H3, which was conserved in the upstream regions of vertebrate CaMII and CaMIII. H3 seemed to play a pivotal role in the temporal and spatial expression of transgene in CNS, although the deletion of H3 did not decrease CAT activity in the transient expression. The transgene expression was not observed in the external granular cells of the developing cerebellum and in some neurons of the embryonic sensory ganglia in which the endogenous CaMIII was obviously expressed. Therefore, the other cis-acting element(s) located outside of this 877-bp segment seemed to be required for the temporal regulation of CaMIII in certain rudimentary neurons.
Brain Res Mol Brain Res 1995 Jul
PMID:Spatial and temporal regulation of the rat calmodulin gene III directed by a 877-base promoter and 103-base leader segment in the mature and embryonal central nervous system of transgenic mice. 747 34

The aim of this study was to determine the effect of repeated electroconvulsive stimulation (ECS) on the expression of neuropeptide Y (NPY) and somatostatin (SS) mRNA in the rat brain. For that purpose, quantitative in situ hybridization histochemistry and RNA blot analysis were used. In the hippocampal formation the prevalence of NPY mRNA positive neurons increased in the hilus of the dentate gyrus and the CA3 while a decrease was seen in layers II-III of the entorhinal cortex. In contrast, SS mRNA was increased in the granule cells of the dentate gyrus and in most neurons of the outer parts of the layer III in the entorhinal cortex with cell bodies of perforant pathway projections to the hippocampal CA1 region. Both NPY and SS mRNA expressing neurons were increased in numerical density in the prefrontal cortex with similar amounts of mRNA in individual NPY positive neurons after the stimulations while SS mRNA levels decreased in hybridization positive neurons. In the striatum the only observed significant effect was an increased prevalence of NPY mRNA positive neurons in the caudal nucleus accumbens. Our results provide an outline of a complex functional anatomy of ECS in the rat brain. This type of investigations contributes to map the neuronal systems involved in the action of ECT used in the treatment of affective and schizophrenic disorders.
Brain Res Mol Brain Res 1995 Jul
PMID:Limbic effects of repeated electroconvulsive stimulation on neuropeptide Y and somatostatin mRNA expression in the rat brain. 747 35

Regional variation in the alternative splice forms of the NMDAR1 subunit mRNA was investigated by in situ hybridization in the adult rat brain, using radiolabelled splice-specific oligonucleotide probes. Each splice variant was detected in an individual distribution. The NMDAR1-a and NMDAR1-2 forms were widely and abundantly distributed throughout the brain, except for the inferior colliculus. The NMDAR1-b and NMDAR1-4 variants were located in similar patterns in fewer areas (e.g. parietal cortex, hippocampus CA3, thalamus, inferior colliculus, cerebellar granule cells). In contrast, the NMDAR1-1 forms were distributed in a pattern approximately complementary in the forebrain to that of NMDAR1-4 (weakly expressed in thalamus and inferior colliculus). The NMDAR1-3 variants were not abundant in any structure. Considerable overlap of the in situ hybridization images was noted, so all eight splice combinations are possible in heterogenous distributions. Correlation of the distribution of NMDAR1 mRNA splice forms with functional analyses of heteromeric recombinant receptors will be necessary to ascertain if alternative splicing of the NMDAR1 subunit can account for some of the known heterogeneity of endogenous NMDA receptors.
Brain Res Mol Brain Res 1995 Aug
PMID:The distribution of splice variants of the NMDAR1 subunit mRNA in adult rat brain. 749 68

The ability of ovarian steroids to regulate the excitability of hippocampal neurons may be mediated by alterations in the inhibitory activity of GABA. We assessed the ability of estradiol, progesterone, and 3 alpha-OH-5 alpha-pregnan-20-one (3 alpha-OH-DHP; a metabolite of progesterone) to regulate gene expression of selected GABAA receptor subunits (alpha 1, alpha 2, beta 1, beta 2, and gamma 2). Using in situ hybridization, we found that progesterone, or 3 alpha-OH-DHP, suppressed mRNA levels for the alpha 1 subunit in the CA2, CA3, and the dentate gyrus subfields of the hippocampus in animals that were pretreated with estradiol. Progesterone had a more limited effect on the alpha 2 subunit, suppressing mRNA levels in estradiol-primed animals only in the CA3 region. In contrast, progesterone increased mRNA levels for the gamma 2 subunit in the CA1, CA2, and CA3 regions of the hippocampus, but only in animals that were not estradiol-primed. Estradiol alone had no significant effect on the expression of any subunit examined. Beta 1 and beta 2 subunit mRNA levels were not altered by any of the hormones tested. These data support the conclusion that progesterone and its metabolites may regulate excitability of the hippocampus by modulating the GABAA receptor gene expression; these effects of progesterone are dependent upon the circulating levels of estradiol. Alterations in the gene expression of selective subunits may lead to changes in the density of GABAA receptor protein or to changes in receptor subunit composition which might alter receptor sensitivity to activation by GABA or modulators such as the benzodiazepines and convulsants.
Brain Res Mol Brain Res 1995 Sep
PMID:Specific subunit mRNAs of the GABAA receptor are regulated by progesterone in subfields of the hippocampus. 750 Aug 38

Groups of rats were treated with buspirone (1 mg/kg/day) for 21 days using osmotic minipumps implanted subcutaneously. After buspirone treatment, the 5-HT1A receptor mRNA levels were significantly decreased in the CA1 and CA2 of the hippocampus, but were markedly increased in the dentate gyrus (DG), CA3 and CA4. The level of the 5-HT1A receptor binding sites was not significantly changed in these subhippocampal areas. Buspirone treatment markedly increased 5-HT2A receptor mRNA levels in the DG, CA2, CA3 and CA4. This was accompanied by a significant increase in the level of 5-HT2A receptor binding sites in all subhippocampal regions. These results demonstrate that chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA as well as their expressed binding sites in various regions of the hippocampus.
Brain Res Mol Brain Res 1995 Sep
PMID:Chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA and binding sites in various regions of the rat hippocampus. 750 Aug 48

Previous studies have established that the novel neuroendocrine-specific NSP gene encodes three carboxy-terminally overlapping proteins, NSP-A, NSP-B and NSP-C which are anchored to membranes of the endoplasmic reticulum. Here, we report results of studies in which expression of NSP-A in rat brain was investigated. Immunization of mice with a bacterial hybrid protein containing almost all NSP-A sequences led to the isolation of five monoclonal anti-NSP-A antibodies. The corresponding epitopes were found to be mapping to two regions unique to NSP-A. In Western blot analysis of rat cerebrum and cerebellum using these antibodies, proteins of about 145 kDa were detected. An immunohistochemical study of rat brain revealed the presence of NSP-A in many brain regions, particularly in cerebellar Purkinje cells, in neurons of the superior colliculus and of the pyriform and enthorhinal cortex, in fibers of the basal ganglia and several hippocampal regions including CA3 (stratum lucidum) and the dentate gyrus, in the induseum griseum and in the subcommissural organ, suggesting a role of NSP-A in many areas of the brain.
Brain Res Mol Brain Res 1994 Apr
PMID:Molecular analysis of expression in rat brain of NSP-A, a novel neuroendocrine-specific protein of the endoplasmic reticulum. 751 32

Stable transfer of genetic information into neurons is a powerful strategy to elucidate specific mechanisms of neurophysiology and to develop therapies for neurological disorders. To evaluate the optimal parameters for efficient gene delivery of defective herpes simplex virus type one (HSV-1) vectors into a specific brain region, an HSV-1 vector expressing E. coli beta-galactosidase was used to infect organotypic cultures of hippocampal slices. beta-Galactosidase was expressed as early as 2 h after infection in a dose-dependent manner as measured on immunoblots, and reached a maximum level after approximately 35 h. Expression of the RNA and the antigen was still evident after the longest time sampled (11-12 days), whereas no beta-galactosidase was ever detected in cultured slices infected with a control virus lacking the reporter gene. Hippocampal cells expressing the reporter gene outlined the contour of the neuronal cell body layers in fields CA3 and dentate gyrus; such correspondence was less evident in field CA1. Anatomical, morphological, and immunohistochemical criteria also confirmed that the majority of these infected cells were neurons. beta-Galactosidase was also detected in the somata and processes of infected interneurons. Tests for synaptic pathology associated with virus infection showed no changes in pre- and postsynaptic markers.
Brain Res Mol Brain Res 1994 Oct
PMID:Rapid and stable gene expression in hippocampal slice cultures from a defective HSV-1 vector. 753 3


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