Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rat brain-derived neurotrophic factor (BDNF) gene consists of four short 5'-exons linked to separate promoters and one 3'-exon encoding the mature BDNF protein. Using in situ hybridization we demonstrate here that kindling-induced seizures, cerebral ischaemia and insulin-induced hypoglycaemic coma increase BDNF mRNA levels through insult- and region-specific usage of three promoters within the BDNF gene. Both brief (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate gyrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was markedly elevated in the dentate gyrus and, in addition, exon I mRNA showed a moderate increase. Single and recurrent (n = 40) hippocampal seizures significantly increased expression of exon I, II and III mRNAs in the dentate gyrus granule cells. After recurrent seizures, including generalized convulsions, there were also major increases of both exon I and III mRNAs in the CA3 region, amygdala, piriform cortex and neocortex, whereas in the hippocampal CA1 sector marked elevations were detected only for exon III mRNA. The insults had no effect on the level of exon IV mRNA in the brain. The region- and insult-specific pattern of promoter activation might be of importance for the effectiveness of protective responses as well as for the regulation of plastic changes following brain insults.
 ...
PMID:Brain insults in rats induce increased expression of the BDNF gene through differential use of multiple promoters. 802 13

Recent studies show that focal brain injury, cerebral ischaemia, hypoglycaemia and seizures increase the expression of c-fos and brain-derived neurotrophic factor in brain. Here we report that hippocampal focal brain injury transiently induces the immediate early genes c-fos, jun-B, c-jun and krox-24 (zif-268) messenger RNA and protein and brain-derived neurotrophic factor messenger RNA in rat dentate gyrus neurons, an effect that was blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Prior administration of the protein synthesis inhibitor cycloheximide super-induced immediate early gene messenger RNA, abolished immediate early gene protein induction, but had no effect on injury-mediated induction of brain-derived neurotrophic factor messenger RNA. Thus, while N-methyl-D-aspartate receptor activation results in the induction of both immediate early genes and brain-derived neurotrophic factor messenger RNA, de novo synthesis of immediate early gene proteins is not critical for the increased expression of brain-derived neurotrophic factor messenger RNA seen in brain after focal injury. These results suggest that brain-derived neurotrophic factor is induced after injury as an immediate early gene.
 ...
PMID:Brain-derived neurotrophic factor is induced as an immediate early gene following N-methyl-D-aspartate receptor activation. 811 41

Treatment with excitotoxin kainic acid is known to increase the level of messenger RNAs for nerve growth factor and brain-derived neurotrophic factor in the brain. In this study we have used quantitative in situ hybridization to analyse the effect of glucocorticoids on kainic acid-induced increase of nerve growth factor and brain-derived neurotrophic factor messenger RNA in the rat brain. In adrenalectomized animals, the kainic acid-mediated increase of brain-derived neurotrophic factor messenger RNA in the hippocampus and the cerebral cortex was reduced by 50% compared to sham-operated animals. The increase of nerve growth factor messenger RNA elicited by kainic acid in the dentate gyrus was almost completely abolished in adrenalectomized animals. No significant change was seen in c-fos messenger RNA in the hippocampus of adrenalectomized rat after kainic acid injection compared to sham-operated kainic acid-treated rats, while a three-fold reduction was seen in the cerebral cortex. Dexamethasone injection prior to kainic acid administration potentiated the kainic acid-induced increase of nerve growth factor messenger RNA in the dentate gyrus and the piriform cortex. In contrast, dexamethasone pretreatment did not potentiate the kainic acid-mediated increase of brain-derived neurotrophic factor messenger RNA. We also examined the effect of adrenalectomy and kainic acid injection on tropomyosin receptor kinase B and C messenger RNA, encoding essential components of high-affinity receptor for brain-derived neurotrophic factor/neurotrophin-4 and neurotrophin-3, respectively. Following adrenalectomy no change of tropomyosin receptor kinase B or C messenger RNA was detected in any of the brain regions studied compared to sham-operated animals. The injection of kainic acid caused four-fold and two-fold increases of tropomyosin receptor kinase B messenger RNA in the dentate gyrus and cerebral cortex, respectively, but no change in tropomyosin receptor kinase C messenger RNA in any of these regions. In adrenalectomized animals receiving kainic acid, the level of tropomyosin receptor kinase B messenger RNA was decreased both in the dentate gyrus and cerebral cortex as compared to sham animals treated with kainic acid. Taken together, the data suggest that excitotoxins and glucocorticoids both influence expression of brain-derived neurotrophic factor and nerve growth factor messenger RNA in the brain, but by two different mechanisms, where the effect of excitotoxin-evoked seizures is modulated by glucocorticoids.
 ...
PMID:Adrenalectomy attenuates kainic acid-elicited increases of messenger RNAs for neurotrophins and their receptors in the rat brain. 834 24

Levels of messenger RNA for nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and the tyrosine kinase receptors trkA, trkB and trkC have been studied using in situ hybridization in the rat brain 2 h and four weeks after kindling-induced seizures. Epileptiform activity evoked by hippocampal stimulation and exceeding 70 s lead to a concomitant and transient increase of brain- derived neurotrophic factor, nerve growth factor, trkB and trkC messenger RNA expression in dentate granule cells after both focal and generalized seizures. Brain-derived neurotrophic factor messenger RNA levels were also increased bilaterally in the CA1-CA3 regions, amygdala and the piriform, entorhinal, perirhinal, retrosplenial and temporal cortices after generalized seizures. The magnitude of the increases was similar throughout the development of kindling and in the fully kindled brain. No changes of trkA messenger RNA were observed. In amygdalar kindling, elevated brain-derived neurotrophic factor messenger RNA levels developed more rapidly in the amygdala-piriform cortex than after stimulation in the hippocampus but changes in the hippocampal formation were only seen in few animals. Intraventricular 6-hydroxydopamine or a bilateral fimbria-fornix lesion did not alter basal expression or seizure-evoked changes in messenger RNA levels for neurotrophins or trk receptors but increased the number of animals exhibiting elevated levels after the first stimulation, probably due to a prolongation of seizure activity. Both in sham-operated and fimbria-fornix-lesioned rats seizure activity caused a marked reduction of neurotrophin-3 messenger RNA levels in dentate granule cells. The results indicate that activation of the brain-derived neurotrophic factor gene, at least in dentate granule cells, is an "all-or-none" type of response and dependent on the duration but not the severity of seizures or the stage of kindling epileptogenesis. Changes in brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and trkB and trkC were observed concomitantly in the dentate gyrus, which suggests that seizure activity sets in motion a cascade of genomic events possibly mediated via a common mechanism. Since altered messenger RNA levels outside hippocampus were detected only for brain-derived neurotrophic factor, neurotrophin and trk gene expression in these regions seems to be regulated differently.
 ...
PMID:Regulation of neurotrophin and trkA, trkB and trkC tyrosine kinase receptor messenger RNA expression in kindling. 838 86

The protein-tyrosine kinases Trk, TrkB, and TrkC are signal-transducing receptors for a family of neurotrophic factors known as the neurotrophins. Here we show that seizures induced by hippocampal kindling lead to a rapid, transient increase of trkB mRNA and protein in the hippocampus. TrkB is a component of a high affinity receptor for brain-derived neurotrophic factor (BDNF). No change was detected in mRNAs for Trk or TrkC, components of the high affinity nerve growth factor or neurotrophin-3 receptors, respectively. trkB mRNA was also transiently increased in the dentate gyrus following cerebral ischemia and hypoglycemic coma; these treatments had no effect on trk and trkC mRNAs. The increase in trkB mRNA and protein showed the same time course and distribution as the increase in BDNF mRNA. These data suggest that BDNF and its receptor may play a local role within the hippocampus in kindling-associated neural plasticity and in neuronal protection following epileptic, ischemic, and hypoglycemic insults.
 ...
PMID:Increased production of the TrkB protein tyrosine kinase receptor after brain insults. 843 8

Neurotrophin-3 has been characterized as the product of a gene cloned by homology with nerve growth factor and brain-derived neurotrophic factor. Recombinant neurotrophin-3, like nerve growth factor and brain-derived neurotrophic factor, has been shown to enhance survival and differentiation of specific neuronal populations in vitro. However, little is known about its function and regulation in vivo. Both brain-derived neurotrophic factor and nerve growth factor messenger RNAs increased in adult rat brain, in a wide range of excitatory paradigms. In contrast, neurotrophin-3 messenger RNA decreased in some of them. Neurotrophin-3 is the most highly expressed neutrophic factor in immature areas of the central nervous system. However, no stimulation of its expression in the mature central nervous system, either in physiological or pathological conditions, has been described to date. This behaviour suggests that neurotrophin-3 could be involved in biological roles different from the prototypes nerve growth factor and brain-derived neurotrophic factor. Excitatory amino acid receptor-mediated neurotoxicity (excitotoxicity) is believed to contribute to neuronal loss in a wide range of neurodegenerative conditions (for a review, see Ref. 17). Moreover, locally increased levels of the endogenous excitotoxin quinolinic acid may be involved in the natural development of neurodegenerative diseases. The unilateral intrahippocampal injection of 120 nmol of quinolinic acid induced seizures together with local neurodegeneration in specific cell layers. In situ hybridization histochemistry was used to analyse the spatiotemporal pattern of expression of neurotrophin-3. As in other excitotoxic paradigms, neurotrophin-3 messenger RNA clearly decreased, nearly disappearing, in the contralateral hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Neuronal death and neurotrophin gene expression: long-lasting stimulation of neurotrophin-3 messenger RNA in the degenerating CA1 and CA4 pyramidal cell layers. 850 24

We have examined the effects of pentylenetetrazol-induced epileptic seizures on brain-derived neurotrophic factor messenger RNA and protein and on the messenger RNA of its receptor in the rat. Pentylenetrazol, which acts at the picrotoxin recognition site of the GABAA receptor, was injected intraperitoneally and induced seizures by decreasing the inhibitory GABAergic activity. The effects of a single acute convulsive dose (50 mg/kg) of pentylenetetrazol were analysed at different time points by in situ hybridization or immunohistochemistry. Kindling was induced by daily subconvulsive injections (30 mg/kg) of pentylenetetrazol. At different time points during the kindling process, the messenger RNAs of brain-derived neurotrophic factor and trkB and the protein levels of brain-derived neurotrophic factor were analysed. We showed that brain-derived neurotrophic factor messenger RNA dramatically increased in neurons of the granule cell layer, piriform cortex and amygdala 3 h but not 6 h after an acute high dose of pentylenetetrazol, while brain-derived neurotrophic factor-like immunoreactivity was decreased in the granule cell layer and neurons of the hilus. The trkB messenger RNA was similarly increased 3 h and 6 h after the injection and returned to control levels after 24 h. The first change during the kindling development was seen after the first severe seizure: brain-derived neurotrophic factor messenger RNA was markedly increased in the piriform cortex and amygdala but not in the hippocampus. In fully kindled rats, which had several severe seizures, brain-derived neurotrophic factor messenger RNA and trkB messenger RNA were unaffected 3 h and 24 h after the last pentylenetetrazol injection. However, brain-derived neurotrophic factor-like immunoreactivity was markedly increased in the hippocampal formation 3 h, 24 h and three days after the last pentylenetetrazol injection, and still increased after 10 days. These results suggest that brain-derived neurotrophic factor may be involved in protection mechanisms after damage during seizures and in sprouting responses. The piriform cortex/amygdala seems to be an area of origin for the kindling development.
 ...
PMID:Regulation of brain-derived neurotrophic factor messenger RNA and protein at the cellular level in pentylenetetrazol-induced epileptic seizures. 850 25

In the adult rat hippocampus mRNA of F1/GAP-43, an axonal growth-associated protein, is highly expressed in pyramidal cells, but is absent in granule cells. To determine whether granule cells can be induced to express mRNA of F1/GAP-43, transcript levels were studied after limbic seizures, which can induce sprouting of granule cell mossy fibers. Seizure-inducing electrolytic lesions were made in the dentate gyrus hilus with stainless-steel electrodes and mRNA levels were measured in contralateral hippocampus by quantitative in situ hybridization. Induction of F1/GAP-43 mRNA expression was observed in granule cells at 24 h, but not at 6 or 12 h, after the hilar lesion. When equivalent sized hilar lesions were made with platinum electrodes, which do not induce seizures, no hybridization was apparent over the granule cells. Hybridization over granule cells had declined by 48 h post-lesion, but even at 10 days it was still slightly higher than in control rats. F1/GAP-43 mRNA expression was also increased 2-fold in CA1 pyramidal cells with peak expression at 48 h post-lesion. These are the first data to our knowledge that demonstrate that F1/GAP-43 gene expression can be altered in neurons located within the adult brain. Induction of F1/GAP-43 mRNA expression in the granule cells may be important for the sprouting of mossy fibers and could be triggered by the elevated levels of brain-derived neurotrophic factor in CA3 cells which precede the increased F1/GAP-43 gene expression in granule cells.
 ...
PMID:Induction of F1/GAP-43 gene expression in hippocampal granule cells after seizures [corrected]. 851 May 1

Recent data have suggested the involvement of neurotrophins in the cascade of events occurring during seizure development. In particular, expression of both brain-derived neurotrophic factor (BDNF) and its receptor mRNAs increases in different brain structures after convulsive seizures. The physiological significance of this increase was investigated by chronic intrahippocampal perfusion of BDNF in the model of dorsal hippocampal kindling in the rat. A 7 day perfusion of BDNF, in the region of the stimulating electrode, blocked the development of kindling during the perfusion period and for the following 15 days. These results provide in vivo evidence for a protective role of BDNF in the regulation of plasticity involved in epileptogenesis in adult brain.
 ...
PMID:Protective effects of brain-derived neurotrophic factor on the development of hippocampal kindling in the rat. 854 2

We studied mRNA levels for neurotrophic factors using the amygdaloid k indling model of epilepsy. One hour after stage 5 kindled seizures, there were four-to fivefold increases in brain-derived neurotrophic factor (BDNF) mRNA in rat dentate gyrus and perirhinal cortex. Nerve growth factor (NGF) mRNA levels were increased bilaterally in some (but not all) limbic areas. There were no detectable changes in acidic fibroblast GF (aFGF) mRNA or basic fibroblast GF (bFGF) mRNA for 24 h after the kindled seizures. During kindling, levels of BDNF mRNA in the dentate gyrus correlated with projection to generalized seizures, whereas NGF mRNA in the limbic regions continued to increase during seizure development. These results indicate that the induction of mRNAs for neurotrophic factors, especially for BDNF mRNA in the dentate gyrus, corresponds to the increases in metabolic and electrical ictal discharge associated with kindled seizures. The persistent increase observed in NGF mRNA may be related to enhanced synaptic efficacy during kindling, but aFGF and bFGF are presumed to have little relation to the kindling process.
 ...
PMID:Regional increases in brain-derived neurotrophic factor and nerve growth factor mRNAs during amygdaloid kindling, but not in acidic and basist growth factor mRNAs. 860 26


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