Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of inducible heat shock protein-70 mRNA (hsp-70 mRNA) was studied in the rat brain following systemic administration of different convulsant agents: an L-type voltage-dependent calcium channel agonist, (+/-)-BAY K 8644 (BAY-K); the excitotoxic glutamate agonists kainic acid and N-methyl-D-aspartic acid (NMDA); and the GABAA receptor complex antagonists pentylenetetrazole (PTZ) and lindane (gamma-hexaclorocyclohexane). BAY-K induced minimal hsp-70 mRNA expression in the hippocampus of convulsant rats, localized in the dentate gyrus and the pyramidal cell layer of Ammon's horn. Kainic acid treatment in rats, showing severe limbic convulsions, caused intense expression of hsp-70 mRNA and protein (HSP-70). Expression was localized in select cerebral regions, notably the pyramidal cell layer of the hippocampal CA3 field of Ammon's horn and the piriform cortex, and also the subicular complex and the amygdala, and, to a lesser extent, the entorhinal cortex, the pyramidal cell layer of CA1, several thalamic nuclei, and the parietal cortex. In contrast, systemic administration of NMDA, PTZ or lindane led to no detectable induction of hsp-70 mRNA in the rat brain, despite producing convulsions. Histological examination revealed cell injury only following kainic acid treatment. Damage was most apparent in the piriform and entorhinal cortices, pyramidal cell layer of the CA1 field, and cortical amygdaloid nuclei. BAY-K, NMDA, PTZ and lindane did not lead to any observable histopathological changes. These results show that convulsions of different aetiology do not inevitably induce hsp-70 mRNA expression or cell damage. Intense expression of hsp-70 mRNA was generally associated with regions that later showed variable degrees of nerve cell damage, although hsp-70 mRNA expression was not always predictive of subsequent cell death or survival.
Brain Res Mol Brain Res 1994 Nov
PMID:Regional expression of inducible heat shock protein-70 mRNA in the rat brain following administration of convulsant drugs. 753 33

Schizophrenia is associated with a complex pattern of alterations in the glutamatergic system of the brain. Previous studies have shown a reduced density of some hippocampal non-N-methyl-D-aspartate (non-NMDA) receptors which is accompanied by a loss of encoding receptor mRNA. We have extended this work using in situ hybridization histochemistry with oligonucleotide probes specific for two non-NMDA receptor transcripts, GluR1 and GluR2, in right and left medial temporal lobe sections from 9 schizophrenics and 14 matched normal controls. Both mRNAs were found to be decreased bilaterally and to a similar degree in the hippocampal formation in schizophrenia. Analysis of autoradiograms showed a regional loss of GluR1 and GluR2 mRNAs in dentate gyrus, CA4, CA3 and subiculum. GluR2 mRNA was also reduced in parahippocampal gyrus. These reductions ranged from 25% to 70% in terms of 35S nCi/g tissue equivalents. Additionally we measured grain density for the mRNAs over individual pyramidal neurons in each area. GluR1 and GluR2 mRNAs were less abundant per neuron in CA4 and CA3 in schizophrenia than in controls. GluR2 mRNA was also reduced significantly in parahippocampal gyrus neurons, with an increase in the proportion of GluR1 mRNA to GluR2 mRNA in this cell population. No asymmetries in expression of GluR1 and GluR2 were found in normal or schizophrenic brains. These data further the evidence for reduced non-NMDA receptor expression in the medial temporal lobe in schizophrenia. They confirm the decrease in GluR1 mRNA and show that there are similar losses of GluR2 mRNA in the hippocampal formation. The pattern of changes in the two mRNAs suggests a common mechanism which is unknown but which may be a correlate of the neurodevelopmental abnormalities postulated to underlie the disease. The reduction of GluR2 mRNA but not GluR1 mRNA in parahippocampal gyrus neurons in schizophrenia may have functional consequences given the calcium permeability of non-NMDA receptors lacking the GluR2 subunit.
Brain Res Mol Brain Res 1995 Apr
PMID:Decreased expression of mRNAs encoding non-NMDA glutamate receptors GluR1 and GluR2 in medial temporal lobe neurons in schizophrenia. 760 9

We previously reported transiently elevated ER protein levels in the postnatal rat hippocampus suggesting that this brain region may be sensitive to estrogenic trophic and organizational influences during a 'critical period' of sexual differentiation. In order to examine whether alterations in ER gene expression underlie the ontogenetic pattern of the hippocampal ER, we examined ER mRNA levels over the early postnatal period and in adult rats. This was accomplished by both a highly quantitative RNase protection assay and in situ hybridization histochemistry. Hippocampal ER mRNA levels increased significantly (P < 0.005) between birth and postnatal day (PDN) 4 when peak concentrations were found and then declined by PND-10. Adult male hippocampal ER mRNA values were similar to those found in newborn and PND-10 animals but were significantly less (P < 0.05) than those observed on PND-4. Results from the in situ hybridization experiments correlated well with those from the RNase protection analysis. High levels of ER mRNA were present in the CA3 pyramidal layer with somewhat lower labeling intensities present in CA1 and the dentate gyrus of the PND-4 animal. In contrast, adult male animals demonstrated little hybridization throughout the hippocampus. Thus, the temporal pattern in ER mRNA levels in the hippocampus found in the present study correlates well with our previous developmental profile of the ER protein. These findings suggest that the ontogeny of ER in the hippocampus is regulated by alterations in ER gene expression in specific neuronal populations.
Brain Res Mol Brain Res 1995 May
PMID:Estrogen receptor mRNA alterations in the developing rat hippocampus. 760 32

The chicken ovalbumin upstream promoter transcription factor, COUP-TF I, and the protein ARP-1 (COUP-TF II) are two highly homologous orphan receptors of the nuclear hormone receptor family. In this study we investigated their expression patterns in the adult nervous system of the mouse. In situ hybridizations were performed on brain sections with 35S-labeled cRNA probes derived from the 3'-non-coding regions of the mARP-1 and mCOUP-TF I mRNAs. Both COUP-TF I and ARP-1 were shown to be expressed in the adult brain and they displayed restricted and distinct expression patterns. COUP-TF I transcripts were predominantly found in the rostral and caudal parts of the adult mouse brain, whereas ARP-1 transcripts prevaled in the middle part of the brain. High expression of COUP-TF I was detected in the olfactory nucleus, in neocortex layers I/II and V/VL, in the dentate gyrus and in areas CA1/CA3/CA4 of the hippocampus, and in the granular layer of the cerebellum. Only low amounts of COUP-TF I mRNA were detected in the ventral, the laterodorsal and in the interanteromedial thalamic nuclei. Small amounts of COUP-TF I transcripts were also found in the epithelial layer of the ventricle and in arachnoid membranes. High expression of ARP-I was detected in the reticular, the ventral lateral and the gelatinosus thalamic nuclei. Other hot spots of ARP-1 mRNA expression were the amygdaloid nucleus and the arachnoid membranes. Lower amounts of ARP-1 transcripts were found in the anterior and lateral hypothalamic areas, in the suprachiasmatic nucleus, and in the choroid plexus.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1995 May
PMID:Localization of transcripts of the related nuclear orphan receptors COUP-TF I and ARP-1 in the adult mouse brain. 760 34

We have previously shown that somatostatin (SS) immunoreactive (-i) neurons, located in the rat dentate hilus, are vulnerable to cerebral ischemia (Johansen et al., 1987). Within 40 h after ischemia, the cells show clear signs of cell death. At the same time, we observed that dying cells, located in the projection field of the mossy fibers (dentate hilus and CA3 mossy fiber layer), accumulate free zinc. We now demonstrate that the hilar cells, accumulating zinc after ischemia, are SS-i cells. Since it is known that hypothermia can ameliorate ischemic brain damage, we furthermore studied whether hypothermia (29 degrees C) protects the vulnerable SS-i neurons in hilus from zinc accumulation and ischemic cell death. We found that hypothermia both prevented ischemia-induced neuronal zinc accumulation and cell death. We speculate that hilar SS-i cells are highly vulnerable to ischemia, and develop rapid ischemic cell death, because they accumulate zinc shortly after ischemia.
Mol Chem Neuropathol
PMID:Hypothermia protects somatostatinergic neurons in rat dentate hilus from zinc accumulation and cell death after cerebral ischemia. 768 76

We have used nonisotopic in situ hybridization techniques with biotinylated junctional oligonucleotide probes to study expression of amyloid precursor protein (APP) 695 and 751 mRNA in the hippocampal formation of Alzheimer's disease. Both mRNAs are strongly expressed in neurons of the hippocampal formation, particularly in the dentate gyrus granule cells and the pyramidal neurons of CA3. The patterns of expression of neither APP695 nor APP751 mRNA correlate well with the stereotyped topography of neurofibrillary tangles or senile plaques, which occur primarily in CA1 and subiculum. We double-labeled in situ sections with immunohistochemical reagents for neurofibrillary tangles or senile plaques. Neurons that contain neurofibrillary tangles continue to express APP mRNA. The level of APP695 and APP751 was measured semiquantitatively by optical density measurements in neurons that were close to (within 25 microns) or father from a senile plaque (more than 100 microns). There was no increase in expression in neurons in the immediate microenvironment of senile plaques. Our results suggest that no major change in distribution or type of APP mRNA accompanies neurofibrillary tangle or senile plaque development.
Brain Res Mol Brain Res 1993 May
PMID:Nonisotopic in situ hybridization of amyloid beta protein precursor in Alzheimer's disease: expression in neurofibrillary tangle bearing neurons and in the microenvironment surrounding senile plaques. 768 84

1. This study was conducted to determine whether chronic psychosocial conflict alters the expression of glucocorticoid receptor (GR) mRNA in the hippocampus of male tree shrews (Tupaia belangeri). 2. To generate probes for the in situ hybridization, the tree shrew GR gene was partly cloned. There was a 90% homology between the deduced amino acid sequence of the cloned tree shrew GR and that of the corresponding human GR sequence. 35S-Labeled riboprobes which had been transcribed from the tree shrew GR clone hybridized to pyramidal neurons in all subregions of the tree shrew hippocampal formation and to granule neurons in the dentate gyrus. 3. After in situ hybridization, the expression of GR mRNA was semiquantitatively determined by counting silver grains over single neurons of the hippocampal formation of psychosocially stressed tree shrews and control animals. After 12 days of social conflict, the number of silver grains in the CA1 and CA3 pyramidal neurons of stressed animals was significantly lower than in controls. No statistically significant differences in mRNA expression were observed in the pyramidal neurons of the subiculum and in the granule neurons of the dentate gyrus. 4. The present results suggest that psychosocial stress leads to a site-specific down-regulation of hippocampal GR via modification of mRNA expression.
Cell Mol Neurobiol 1994 Jun
PMID:Hippocampal glucocorticoid receptor expression in the tree shrew: regulation by psychosocial conflict. 771 16

Glucocorticoids and serotonin (5-HT) modulate behaviour and hypothalamic-pituitary-adrenal (HPA) axis responses. The two systems interact prominently in the hippocampus, where these effects may occur. We have previously shown that hippocampal 5-HT2C receptor mRNA expression is increased by adrenalectomy or central 5-HT lesions. We have now determined expression of corticosteroid and 5-HT receptor subtype genes in the hippocampus across the diurnal cycle, when there are changes both in plasma corticosterone and hippocampal 5-HT levels, as well as the responses of these transcripts to acute and chronic stress, using in situ hybridisation histochemistry. Expression of both glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNAs was significantly higher (131-153%) in the hippocampus at 08.00 h (corticosterone nadir) than at 20.00 h (corticosterone peak). 5-HT2C receptor mRNA expression also showed circadian variation (106-184% higher in CA1-CA3 in the morning). Hippocampal 5-HT1A and 5-HT2A receptor mRNA expression had no diurnal variation. Chronic (15 day) adjuvant arthritis stress, abolished the circadian corticosterone nadir, maintaining plasma corticosterone around diurnal peak values. Chronic arthritis stress suppressed hippocampal 5-HT2C receptor mRNA expression at 08.00 h to levels comparable to 20.00 h controls. By contrast to chronic stress, 6 h after acute laparotomy stress, plasma corticosterone was elevated above control (20.00 h) and 5-HT2C receptor mRNA expression was increased (CA2). Neither acute nor chronic stress altered MR, GR, 5-HT1A or 5-HT2A receptor mRNA expression in any hippocampal subfield. These results show that hippocampal expression of the 5-HT2C receptor gene, but not other subtypes, is sensitive to a variety of manipulations.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1995 Feb
PMID:Modulation of serotonin and corticosteroid receptor gene expression in the rat hippocampus with circadian rhythm and stress. 772 17

We isolated a cDNA clone, named BSPL, that encodes a brain-specific dipeptidyl peptidase-like protein with 30% identity and 50% similarity to CD26, a lymphocyte membrane antigen involved in T-cell activation. BSPL lacks, however, the catalytic residue responsible for peptidase activity. The expression of BSPL is widespread throughout the CNS but restricted to neurons under normal conditions. Twenty-four hours after injection of kainic acid into the hippocampus, a dramatic increase in the concentration of BSPL mRNA was detected by in situ hybridization in the CA3 region of the injected hemisphere as compared with the contralateral hemisphere or sham-injected animals. An increase in the steady-state level of BSPL mRNA concentration was also found following tetanic stimulation of the perforant path to produce LTP in granule cells of the dentate gyrus. Hybridization signals could be detected in dendritic processes of pyramidal neurons and in some glial cells upon either type of stimulation. These data suggest that BSPL may be involved in synaptic plasticity.
Brain Res Mol Brain Res 1994 Sep
PMID:Transcripts encoding a neural membrane CD26 peptidase-like protein are stimulated by synaptic activity. 780 28

Hippocampal function is modulated by adrenal corticosteroids released in a diurnal rhythm or in response to stress. Hippocampal excitability is also modulated by the activity of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain. One mechanism of corticosteroid action in the hippocampus is likely to be via regulation of the GABA system, including corticosteroid regulation of GABAA receptor expression. The GABAA receptor is a heterooligomeric complex composed of subunits derived from a number of distinct genes. We examined the effects of short-term adrenalectomy and low-level corticosterone replacement on mRNA levels for 5 GABAA receptor subunits. In situ hybridization studies demonstrated that mRNA levels for GABAA receptor alpha 1, alpha 2, beta 2, and gamma 2 subunits were altered in the hippocampus of female rats by adrenalectomy. Levels of alpha 1 and gamma 2 mRNA increased in CA3, alpha 2 mRNA increased in the dentate gyrus, while beta 2 mRNA decreased in the dentate gyrus and CA2 relative to sham-operated animals following adrenalectomy. These effects were reversed by the addition of 100 micrograms/ml corticosterone to the drinking water. Adrenalectomy had no effect on the levels of beta 1 mRNA and no effect on any subunit examined in CA1 or the cingulate cortex. These data support the conclusion that corticosteroids can modulate hippocampal excitability through the site-specific regulation of the expression of specific GABAA receptor subunits. Corticosterone-induced changes in subunit expression might alter GABAergic synaptic inhibition by altering the density of GABAA receptors or altering the subunit composition and thereby the pharmacological properties of the receptors.
Mol Cell Neurosci 1994 Oct
PMID:Adrenalectomy selectively regulates GABAA receptor subunit expression in the hippocampus. 782 Mar 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>