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Query: UNIPROT:P06889 (Mol)
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We have studied the effect of intrahippocampal administration of quinolinic acid (QUIN) on the temporal expression of mRNAs encoding the immediate early genes (IEGs) c-fos and NGFI-A, by in situ hybridization histochemistry. After administration of QUIN to the left hippocampus, expression of mRNA of both IEGs was transiently stimulated. Maximal expression was found between 1 and 3 h. mRNA of both IEGs was simultaneously expressed in the ipsilateral and contralateral sides in the granule cell layer of the dentate gyrus, the pyramidal cell layer of the CA1 and CA3 fields as well as in the cortex. After pretreatment with the non-competitive NMDA antagonist MK-801 (2 mg/kg i.p. -30 min) the increased expression of both IEGs was partially prevented in the hippocampus and completely in the cortex. No inhibition was observed after treatment with the AMPA antagonist NBQX (30 mg/kg i.p. -15, -5 and +10 min). Additional delayed expression of both IEGs was observed in the ipsilateral hippocampus. This expression was related to cell damage. Twelve h after QUIN administration, c-fos and NGFI-A mRNAs were present in the dentate gyrus. After 4 days, only c-fos mRNA was observed in the dentate gyrus and CA1 field while no NGFI-A mRNA was detected. The present results show that the effect of QUIN is mediated by NMDA and not by AMPA receptors.
Brain Res Mol Brain Res 1992 Nov
PMID:Administration of quinolinic acid in the rat hippocampus induces expression of c-fos and NGFI-A. 128 Dec 56

Small unilateral electrolytic lesions placed in the hilus of the dentate gyrus produce limbic seizures. We have investigated the effects of these hilar lesions on the levels of the mRNAs encoding for 3 neurotrophic factors (NTF): nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3). 'In situ' hybridization histochemistry with synthetic oligonucleotides was used to analyze their mRNA distribution and levels. In agreement with previously published data (Science, 245 (1989) 758-761), NGF mRNA was found bilaterally, quickly and transiently increased in granule cells of the dentate gyrus. Only 2 h after the onset of limbic seizures, mRNA levels for BDNF were also found to be dramatically elevated in both sides of the hippocampus, reaching a maximum 30-fold increase in the granule cell layer of the dentate gyrus 5 h after the lesion. Moreover, increased levels of this mRNA were also been found in the pyramidal layer of the CA3 (5-fold) and CA1 (15-fold) hippocampal fields. In contrast, NT3 mRNA was found to be clearly and bilaterally decreased in dentate gyrus granule cells, reaching 5- to 6-fold decreased levels at 12 h after lesion. Taken together, these results clearly show a different regulation of neurotrophic factors genes (NGF, BDNF and NT3) expression in the different hippocampal fields, as a consequence of seizure-producing hilar lesions.
Brain Res Mol Brain Res 1992 Mar
PMID:Limbic seizures induce a differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3, in the rat hippocampus. 131 16

Gene expression of the axonal growth-associated protein, GAP-43, has been studied in the adult rat brain by in situ hybridization histochemistry. This protein is synthesized at high levels in neuronal somata in immature and regenerating neurons, but after establishment of mature synaptic relations its synthesis generally declines sharply, thus providing a marker denoting propensity for exhibiting synaptic plasticity. Detailed examination of the distribution of mRNA for GAP-43 in rat hippocampus is selectively and robustly expressed in the pyramidal neurons of field CA3 and, to a lesser extent, the polymorph neurons of the hilus of the dentate gyrus. Additional hippocampal regions of moderate expression include the tenia tecta and the subicular and entorhinal fields, but CA1 and CA2 are strikingly lower in signal. The significance of this pattern of localization is considered in the context of the phosphorylation of GAP-43 and its role in influencing synaptic events underlying the establishment and maintenance of long-term potentiation and plasticity in the hippocampus.
Brain Res Mol Brain Res 1992 Apr
PMID:GAP-43 mRNA localization in the rat hippocampus CA3 field. 131 99

In situ hybridization in conjunction with three-dimensional reconstruction was used to examine the topology of satellite DNA (sDNA) sequences in hippocampal CA1 neurons. In slices fixed immediately after preparation, 4-5 signals/nucleus were detected in CA1, CA3 and dentate neurons. 70-80% of 154 neurons examined in these 3 areas displayed all signals at the nuclear periphery. In the remaining fraction of neurons, sDNA signals were divided between the nucleolus and the nuclear periphery. sDNA signals were consistently localized to the nuclear midplane. Slices left to equilibrate in artificial cerebral spinal fluid for 1 h, in the absence of potentiation, exhibited a significant increase in the total number of signals/nucleus in CA1 and dentate neurons. This increase in the number of signals occurred in both nucleolar and peripheral compartments, with the number of the nucleolar compartment nearly doubling. The total number of signals/nucleus was found to be consistently reduced in tetanized CA1 neurons (4.89 +/- 0.09 signals/nucleus, n = 195, P less than 0.05) as compared to neurons from unpotentiated slices (5.27 +/- 0.10 signals/nucleus, n = 81). A similar decrease in the total number of signals/nucleus was also observed in CA1 neurons exposed to N-methyl-D-aspartate (NMDA), from 5.27 +/- 0.10 signals/nucleus (n = 81) to 5.00 +/- 0.08 signals/nucleus (n = 215, P less than 0.05). In contrast, dentate neurons, employed as internal controls, did not exhibit any change in number and compartmentalization of sDNA signals.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1992 Jun
PMID:Rearrangement of centromeric satellite DNA in hippocampal neurons exhibiting long-term potentiation. 132 6

The localization of gene expression of calreticulin, a calcium-binding protein in the endoplasmic reticulum, was examined throughout the entire brain of adult mice by in situ hybridization. Calreticulin mRNA is expressed widely and heterogeneously in discrete neurons throughout the brain, but the white matters expressed it weekly or faintly. In the olfactory bulb, the mRNA is expresses moderately in the mitral cells, but weakly in the periglomerular cells and internal granule cells. In the cerebrum, the gene is expressed intensely in the piriform cortex, but weakly in neocortex, the entorhinal cortex and the amygdaloid nuclei. In the hippocampal formation, calreticulin mRNA is expressed intensely in the CA1-CA3 regions but less intensely in the granule cells of the dentate gyrus. The caudate-putamen, thalamic and hypothalamic nuclei, and mammillary nuclei express the mRNA weakly or faintly. In the mesencephalon, pons and medulla, moderate expression of the mRNA is detected in the pontine nuclei and the locus ceruleus. Weak expression of the mRNA is detected in several discrete nuclei and zones such as the substantia nigra, the superior colliculus and the central gray. Expression signals of calreticulin mRNA are faint in the inferior olive. In the cerebellum, calreticulin mRNA is expressed moderately in the Purkinje cells whereas no significant expression is detected in the granule cells. The plexus choroideus of the lateral, third and fourth ventriculi express calreticulin mRNA intensely although no distinct expression of the mRNA is discerned in the ependyma.
Brain Res Mol Brain Res 1992 Aug
PMID:Localization of gene expression of calreticulin in the brain of adult mouse. 132 96

In an attempt to examine regional synthesis of the progesterone receptor (PR) in the brain, the distribution of mRNA encoding PR was investigated in the female adult rat di- and telencephalon by in situ hybridization using T7 RNA polymerase transcripts of a 320 base pair rat PR cDNA clone. The rat PR cDNA had been partially cloned and sequenced by using the reverse transcription-polymerase chain reaction (RT-PCR) method. The primer set corresponds to a part of the progesterone binding domain of human PR cDNA. Large numbers of strong labeling were observed in the arcuate nucleus, medial preoptic nucleus, and ventrolateral part of the ventromedial nucleus which are relative to sexual behavior. Moderate labeling was found in layers II and IV of the isocortex, in the pyramidal layer of the CA1 and CA3 fields of the hippocampal formation, in the cortical nucleus of the amygdala, in the nucleus of the diagonal band, and in the anterior periventricular nucleus. Weak labeling was found in many other regions. These results were largely in agreement with the distribution of PR previously reported by ligand binding assay and autoradiographic studies. This present in situ hybridization study may provide a useful tool for the analysis of the regional regulation of PR synthesis in the rat brain.
Brain Res Mol Brain Res 1992 Jul
PMID:Distribution of cells containing progesterone receptor mRNA in the female rat di- and telencephalon: an in situ hybridization study. 133 52

The GTP binding protein, Gs, activates adenyl cyclase in direct response to stimulation of several neurotransmitter receptors. In situ hybridization histochemistry (ISHH) with a 35S-labelled oligonucleotide has been used to detect the mRNA encoding the alpha subunit of Gs (Gs alpha) in human hippocampus, temporal and visual cortices and cerebellum, and its level has been compared between Alzheimer's disease (AD) and control brains. A marked regional increase was found in the hippocampus of AD cases. Analysis of levels of Gs alpha mRNA in individual constituent pyramidal cells confirmed this increase (3 to 4-fold in densitometric units) in hippocampal fields CA1, CA3 and CA4, as well as in temporal cortex. Levels of Gs alpha mRNA were also determined relative to total poly(A)+ mRNA in the same cell populations in each case. Gene-specific elevation of Gs alpha mRNA was thereby confirmed in hippocampal fields, and also in temporal cortex. No changes were seen in visual cortex. The increase in Gs alpha mRNA may represent a response by AD neurons in affected areas to receptor alterations, or to an abnormality in receptor-G protein coupling. Alternatively, altered G protein gene expression might be a pathogenic event underlying changes in linked receptor populations.
Brain Res Mol Brain Res 1991 Apr
PMID:Alzheimer's disease: specific increases in a G protein subunit (Gs alpha) mRNA in hippocampal and cortical neurons. 164 85

1. We have used in situ hybridization techniques to determine the mRNA for (Na + K)ATPase in 20 brain regions from control rats and rats treated with high doses of deoxycorticosterone (DOC). 2. DOC-treated rats developed a salt appetite following the second hormone administration on alternate days and were used after the fourth DOC administration. 3. DOC treatment did not change the number of silver grains/cell deposited in cells from Ca1, CA2, CA3, and CA4 hippocampal subfields, dentate gyrus, cerebral cortex, medial preoptic area (POA), substantia nigra, and periventricular gray matter. 4. Nonsignificant reductions were detected in lateral POA, medial and lateral septum, caudate-putamen, and three amygdaloid nuclei (cortical, basolateral, and central) from DOC-treated rats. 5. Significant reductions were obtained, after DOC administration, in arcuate and ventromedial hypothalamic nuclei and medial and lateral amygdala. 6. The results suggested that regulation of the beta-subunit mRNA of (Na + K)-ATPase may be related to the central actions of mineralocorticoids in the control of salt intake.
Cell Mol Neurobiol 1991 Jun
PMID:Effects of deoxycorticosterone treatment on beta-subunit mRNA for (Na + K)ATPase in brain regions determined by in situ hybridization. 165 Nov 64

The influence of kainic acid (KA)-induced limbic seizure activity on the expression of mRNA for nerve growth factor (NGF) in adult rat brain was studied using in situ hybridization and S1 nuclease protection techniques with RNA probes complementary to murine and rat NGF mRNA. Within hippocampus, intracerebroventricular injection of 0.5 microgram KA caused a dramatic bilateral increase in hybridization of the 35S-labeled cRNA within stratum granulosum. This increase was first evident 1 h post-KA, appeared maximal at approximately 20-fold control levels at 2-3 h post-injection, and declined to control levels by 48 h post-injection. During the period of maximal hybridization, all but the deepest cells within stratum granulosum appeared to be autoradiographically labeled. Hybridization of the NGF cRNA probe was also increased within superficial layers of piriform and entorhinal cortex and, to much lesser extent, within scattered neurons of layers II and III of neocortex in KA-treated rats. In olfactory cortical areas, hybridization was maximally elevated 15.5-24.5 h after KA injection. In contrast to these effects, KA treatment did not consistently influence the density of hybridization, or number of neurons labeled, within the dentate gyrus hilus or the hippocampus proper (CA1-CA3). In agreement with the in situ hybridization results, S1 nuclease protection assay detected KA-induced increases in hybridization within pooled dentate gyrus/CA1 samples, but not hippocampal CA3 samples. These data support the conclusion that seizure activity stimulates a transient increase in NGF expression by select populations of forebrain neurons and indicates that experimental seizure paradigms might be further exploited for analyses of the mechanisms of NGF regulation and processing in the adult brain.
Brain Res Mol Brain Res 1991 Jan
PMID:Kainic acid-induced seizures stimulate increased expression of nerve growth factor mRNA in rat hippocampus. 170 74

The effect of hyperammonemia of varying degree and duration on the gamma-glutamyl-transpeptidase (GGT) activity was studied in the homogenates and capillaries of different brain regions of the rat. "Acute" hyperammonemia (750 and 600 mg of ammonium acetate per kg b.w. were injected i.p. at 30 min interval, and the animals were decapitated immediately), in which blood ammonia was increased 14-fold, and brain ammonia six-fold above the control level, produced a 20% increase of the enzyme activity in cerebellum, and a 17% decrease in gyrus dentatus, but had no effect in the frontal cortex and the CA1 and CA3 regions of hippocampus. "Subchronic" hyperammonemia (two injections of 600 mg ammonium acetate/kg were given at 24 h intervals, and tissue samples were removed 24 h later), that was accompanied by only a 60% increase of blood or brain ammonia, increased the activity in cerebellum to 38% above control, but produced no effect in the other brain regions. "Chronic" hyperammonemia (three injections of 600 mg ammonium acetate/kg at 24 h intervals and excision of tissue samples 30 min after the last injection), in which blood and brain ammonia were, respectively, 60 and 100% higher than in control animals, elevated the GGT activity in the cerebellum by 57%, in CA1 by 15%, and in CA3 by 21%, but produced no effect in the frontal cortex or gyrus dentatus. By contrast, "chronic" hyperammonemia produced a 30% increase of GGT activity in cerebral cortical capillaries, but only a 10% increase in hippocampal capillaries, and no change in cerebellar capillaries. The results suggest that, hyperammonemia of relatively long duration may contribute to the enhancement of brain GGT activity observed in chronic forms of hepatic encephalopathy. However, ammonia does not appear to activate the enzyme directly.
Mol Chem Neuropathol
PMID:The effect of acute and repeated hyperammonemia on gamma-glutamyl transpeptidase in homogenates and capillaries of various rat brain regions. 198 79


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