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

Clusterin is a protein that has been implicated in cell death and remodelling in a number of different tissues. To further investigate the role of clusterin in nerve cell death its expression was measured in the rat brain at various times after status epilepticus (SE) induced by 1 h of hippocampal stimulation, by using in situ hybridization, immunocytochemistry, and immunoblotting. SE lead to a dramatic time-dependent increase in clusterin mRNA in non-nerve cells resembling astrocytes in the hippocampus beginning after 24 h. There was also an earlier induction of clusterin mRNA in dentate granule cells, that survive SE. Only a low mRNA signal was observed over the CA1 pyramidal cells, which die after SE. In contrast to these mRNA results, massive clusterin-like immunoreactivity was observed in CA1 pyramidal cells and dentate hilar neurons (and both of these neuronal populations die after SE), but not in dentate granule cells. We speculate that astrocytes produce clusterin after SE and that the clusterin is then secreted and taken up by hippocampal neurons destined to die. Thus, the role of clusterin in nerve cell death/ regeneration warrants further investigation.
Brain Res Mol Brain Res 1995 Sep
PMID:Clusterin accumulates in dying neurons following status epilepticus. 750 Aug 39

Glial cell-line derived neurotrophic factor (GDNF) has recently been cloned and shown to have trophic effects on dopaminergic nigral neurons. However, GDNF mRNA has not been detected in striatum or other forebrain areas of adult rat. Using limbic motor status epilepticus induced by pilocarpine to activate neurons in motor and limbic areas, we now demonstrate GDNF mRNA signals in the striatum, hippocampus and cortex using in situ hybridisation. The finding of GDNF mRNA in the stimulated striatum opens the possibility that GDNF may be a target-derived, trophic factor in the nigro-striatal system. This expression of GDNF mRNA may be linked to excitatory cortical input. Increases in GDNF mRNA after status epilepticus in hippocampus and neocortex indicate additional roles for GDNF.
Brain Res Mol Brain Res 1994 Oct
PMID:Glial cell-line derived neurotrophic factor (GDNF) mRNA upregulation in striatum and cortical areas after pilocarpine-induced status epilepticus in rats. 785 63

The mRNA levels of four immediate early genes (IEG) were measured in rat brain regions 60 min after administration of pilocarpine (30 mg/kg) to lithium-treated (3 mmol/kg) rats, during generalized convulsive status epilepticus. Northern blots demonstrated induction of the genes in the order of c-fos = jun-B > c-jun > jun-D with large increases in the cerebral cortex, hippocampus, and striatum, a smaller increase in the cerebellum, and less in the brainstem. The mRNA levels of these four IEG were measured in rat cerebral cortex and hippocampus at several times after administration of the cholinergic agonist pilocarpine (5 or 30 mg/kg) with or without lithium pretreatment (3 mmol/kg, 16 h prior, or chronic 4 week dietary administration). Treatment with pilocarpine (30 mg/kg) alone increased mRNA levels in the order of c-fos > jun-B > c-jun but did not change the jun-D mRNA level, and maximal c-fos and jun-B mRNA levels occurred earlier (30 min) in the cortex than in the hippocampus. Treatment with the lower dose of pilocarpine (5 mg/kg) alone caused only small increases in c-fos and jun-B mRNA levels and these responses were unaffected by lithium pretreatment. Lithium pretreatment potentiated IEG expression induced by 30 mg/kg pilocarpine, likely as a result of the seizures caused by this combination of drugs because pretreatment with anticonvulsants (diazepam or MK-801) blocked seizures and the enhanced IEG mRNA levels. The mRNA levels were increased during seizures in the order of c-fos > jun-B > c-jun > jun-D in the hippocampus and jun-B > c-fos > c-jun > jun-D in the cortex, and were increased for a longer duration as well as to a greater extent than after administration of pilocarpine alone. Administration of pilocarpine (30 mg/kg) to rats treated chronically with lithium caused increases similar to those measured with acute lithium pretreatment. Thus the induction of IEG by cholinergic stimulation varied with dose, time, and brain region, and unique responses were observed for each of the IEG. Lithium pretreatment did not impair IEG expression induced by the lower dose of pilocarpine and greatly enhanced expression of IEG after administration of the higher dose of pilocarpine concomitant with seizure activity.
Brain Res Mol Brain Res 1994 Aug
PMID:Distinctive rat brain immediate early gene responses to seizures induced by lithium plus pilocarpine. 798 56

Neurons undergoing delayed neuronal death produced by hypoxia-ischaemia (HI) or status epilepticus (SE) showed a massive expression of c-Jun in their nuclei 24 h after the insult. With SE there was also a weaker induction of c-Fos and Jun B in dying neurons. SE induced in the presence of the NMDA antagonist MK-801 produced no delayed c-Jun expression in the hippocampus and nerve cell death did not occur in this region, although there was a delayed c-jun expression in the amygdala/piriform region, and cell death occurred in this area. Activation of central muscarinic receptors with pilocarpine, or block of D2 dopamine receptors with haloperidol, treatments which do not cause neuronal damage, strongly induced Fos and Jun B in hippocampal and striatal neurons, but only induced c-Jun very weakly. Thus, c-Jun may participate in the genetic cascade of events that produce programmed cell death in neurons.
Brain Res Mol Brain Res 1993 Jun
PMID:Is c-Jun involved in nerve cell death following status epilepticus and hypoxic-ischaemic brain injury? 832 31

The influence of kainic acid (KA), which induces acute seizures, on expression of mRNA for the calcium-binding protein, calbindin-D28k, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and early-response genes [c-fos, zif268 (NGFI-A), nur77 (NGFI-B)] was examined in rat hippocampus by Northern blot analysis. A significant increase (3.2-fold) in BDNF mRNA was observed 1 h after KA injection (12 mg/kg i.p.) and peak expression (9.4-fold) occurred 3 h after KA. The induction of BDNF mRNA was preceded by the induction of c-fos, mRNA (30 min after KA) and was followed by the induction of calbindin-D28k mRNA (3.5-fold 3 h after KA; a maximal response was at 3-6 h after KA). Region-specific changes, analyzed by immunocytochemistry and in situ hybridization, indicated that the most dramatic increases in calbindin protein and mRNA after KA treatment were in the dentate gyrus. Although calbindin-D28k and BDNF mRNAs were induced, a 3.4-3.8-fold decrease in NT-3 mRNA was observed by Northern analysis 3-24 h after KA treatment. Calbindin-D28k gene expression was also examined in rats with a chronic epileptic state characterized by recurrent seizures established with an episode of electrical stimulation-induced status epilepticus (SE). When these animals were examined 30 days post-SE, no changes in hippocampal calbindin-D28k mRNA were observed. Our findings suggest that the induction of calbindin-D28k mRNA (which may be interrelated to the induction of BDNF mRNA) is an early response which may not be related to enhanced neuronal activity or seizures per se, but rather to maintaining neuronal viability.
Brain Res Mol Brain Res 1997 Jul
PMID:Early induction of mRNA for calbindin-D28k and BDNF but not NT-3 in rat hippocampus after kainic acid treatment. 922 16

Considerable evidence indicates that ATP, acting intracellularly of as a neurotransmitter, can influence nerve cell physiology in a variety of ways. Defects in the functioning of ATP-metabolizing enzymes could therefore lead to disturbances in neurotransmission and creation of sustained neuronal discharges characteristic of status epilepticus. In this study we investigated synaptosomal ATPase changes in rat brains during lithium/pilocarpine-induced status epilepticus. After 2 h of continuous electroencephalographic spiking, both Mg(2+)- and Ca(2+)-dependent ecto-ATPases were significantly decreased in freshly prepared synaptosomal preparations from the status rats. The intracellularly acting Ca2+Mg(2+)-ATPase (Ca-pump) was also decreased, but no changes occurred in synaptosomal Na+K(+)-ATPase activity. The difference between ecto-ATPase activities of the control and status rat brains was not affected by repeated freezing-thawing and lengthy storage. Possible involvement of reduced synaptosomal divalent cation-dependent ATPases in the pathophysiology of status epilepticus is discussed.
Mol Chem Neuropathol 1997 Jun
PMID:Reduced cortical ecto-ATPase activity in rat brains during prolonged status epilepticus induced by sequential administration of lithium and pilocarpine. 937 20

Pentylenetetrazol (PTZ)-induced status epilepticus (SE) leads to acute and long-term metabolic decreases in specific brain regions of rats at 10 (P10) or 21 days after birth (P21). These decreases are not related to apparent neuronal damage. Therefore, to better understand the neuronal activation and stress response to PTZ in immature rats, we mapped the expression of c-Fos and of the 72 kDa heat-shock protein (HSP72) in the same model of severe SE induced by the repetitive i.p. injections of subconvulsive doses of PTZ. Rats were sacrificed either at 2 or 24 h after the onset of SE in order to reveal c-Fos immunoreactivity, and at 24 and 72 h for HSP72 expression. Hematoxylin-eosin staining was performed at 24, 72 and 144 h after SE. The expression of c-Fos at 2 h after SE was more marked at P21 than at P10 and was prominent at both ages in the hippocampal dentate gyrus, cerebral cortex and amygdala. Some immunoreactivity was also present in the hypothalamus, thalamus and a few brainstem and cerebellar regions at both ages. There was a good relation between the regions expressing c-Fos and those exhibiting acute metabolic decreases at P21. Conversely, PTZ seizures did not lead to any expression of c-Fos at 24 h after SE or of HSP72 at 24 or 72 h at any age. Cell density was not affected by PTZ-induced SE at any age and at any time. These results suggest that c-Fos is a useful marker of neuronal activation induced by severe and prolonged seizures in the immature brain. The lack of HSP72 and of late c-Fos expression likely reflect the absence of neuronal damage in this model of PTZ-induced SE in the immature rat.
Brain Res Mol Brain Res 1997 Oct 15
PMID:Effects of pentylenetetrazol-induced status epilepticus on c-Fos and HSP72 immunoreactivity in the immature rat brain. 940 20

The effects of GM1 monosialoganglioside pretreatment on brain damage resulting from soman-induced seizure activity were examined in this study. Male Sprague-Dawley rats were infused with GM1 via an osmotic minipump connected through a permanent cannula implanted intracerebroventricularly and challenged with soman (83 micrograms/kg, i.e., 1.25 x LD50) 4 d after initiation of GM1 infusion. Electrocorticographic recordings were monitored via indwelling cortical electrodes. Twenty-seven hours after soman administration, anesthetized rats were euthanized via transcardial perfusion with buffered paraformaldehyde. Brains were processed for hematoxylin and eosin (H&E), cresyl violet (CV), and acetylcholinesterase (AChE) histochemistry, and glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) immunohistochemistry. All soman-challenged rats not infused with GM1 (n = 14) developed status epilepticus (SE).
Mol Chem Neuropathol 1998 May
PMID:GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage. 977 43

In adult rats, kainic acid-induced status epilepticus reduces GluR2 subunit expression prior to neurodegeneration of hippocampal CA3 neurons. Increased formation of Ca2+ permeable AMPA receptors may contribute to the delayed neurodegenerative process. In rat pups, highly prone to seizures but resistant to seizure-induced hippocampal damage, GluR2 mRNA and protein expression remain constant in CA3 neurons possibly contributing to their survival. To investigate whether reduced GluR2 expression in hippocampus may lead to enhanced hippocampal vulnerability in an age-dependent manner and whether changes correspond to altered electroencephalography (EEG) patterns, unilateral microinfusion of GluR2 antisense oligodeoxynucleotides (AS-ODNs) into hippocampus was performed at three ages (postnatal (P8), P13, and adult). At P13, GluR2 knockdown resulted in spontaneous seizure-like behavioral manifestations and neurodegeneration of CA3 neurons lateral and distal from the cannula infusion site. EEG recordings revealed high rhythmic activity associated with seizure-like behavior. In P8 pups and adult rats, there were no behavioral manifestations; distant hippocampal damage of the CA3 was not observed. Results indicate that unilateral knockdown of hippocampal GluR2 subunit expression induces age-dependent seizure-like behavioral manifestations, altered EEG recording patterns, and reduces the survival of CA3 neurons in the hippocampus of young rats during a specific postnatal period (3rd week), when GluR2 expression peaks in development and glutamatergic inputs are maturing.
Brain Res Mol Brain Res 1998 Oct 30
PMID:GluR2 hippocampal knockdown reveals developmental regulation of epileptogenicity and neurodegeneration. 979 29

Animals exposed to kainic acid (KA) induced status epilepticus display a striking pattern of selective neuronal vulnerability in the hippocampus. Neurons in the hilus/CA3 and CA1 subfields appear particularly sensitive whereas dentate gyrus (DG) granule cells are resistant. The molecular basis for this differential susceptibility remains largely unknown. Recently, an involvement of nitric oxide, c-Jun amino-terminal kinases (JNK) and interleukin-1 beta converting enzyme (ICE)-related proteases has been proposed in KA induced neuronal cell death. In the present study, we have determined the regional expression of transcripts for two modulating genes operating in these pathways, i.e., the endogenous protein inhibitor of neuronal nitric oxide synthase (PIN), and a cytoplasmic inhibitor of the JNK signal transduction pathway, designated JNK interacting protein-1 (JIP-1) and of the gene for the apoptosis-executing protease Caspase-3 in KA-treated animals. The expression of PIN and JIP-1 was found significantly upregulated in granule cells of the resistant DG. In contrast, an induction of the ICE-related protease Caspase-3 was observed in vulnerable hippocampal regions, i.e. CA1, CA3 and hilus. These results point towards PIN and JIP-1 as antiapoptotic factors contributing to selective resistance of granule cells, whereas Caspase-3 may be involved in cell death of hippocampal CA1, CA3 and hilar neurons in the kainate epilepsy model.
Brain Res Mol Brain Res 1999 Apr 06
PMID:Differential regulation of apoptosis-related genes in resistant and vulnerable subfields of the rat epileptic hippocampus. 1010 Dec 44


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