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

Levels of messenger RNAs for brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3, and their high-affinity receptors, TrkB and TrkC, were analysed in the brains of genetically fast and slow kindling rats using in situ hybridization. Basal expression of neurotrophins and Trk messenger RNAs in the hippocampal formation, amygdala, frontoparietal and piriform cortices did not differ between the two strains. At 2 h after the third generalized grade 5 seizure, induced by kindling stimulations in the amygdala, increased expression of brain-derived neurotrophic factor messenger RNA was detected in the dentate gyrus granule cell layer, amygdala, frontoparietal and piriform cortices of the fast kindlers. Similar seizure-evoked increases of brain-derived neurotrophic factor messenger RNA levels were also observed in the amygdala and piriform cortex of slow kindlers. However, in these animals, brain-derived neurotrophic factor messenger RNA expression was not significantly altered by the seizures in the dentate gyrus granule cell layer and frontoparietal cortex. Furthermore, the seizure-induced increase of nerve growth factor, TrkB and TrkC messenger RNAs and decrease of neurotrophin-3 messenger RNA levels in the dentate gyrus granule cell layer was only observed in fast, but not in slow, kindlers. The neurotrophins are believed to regulate synaptic plasticity and efficacy and to facilitate long-term potentiation and kindling epileptogenesis. The present data suggest that the slow and fast kindling rates in the two strains studied here might partly be due to differences in seizure-evoked neurotrophin and Trk synthesis.
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PMID:Seizure-induced differential expression of messenger RNAs for neurotrophins and their receptors in genetically fast and slow kindling rats. 892 34

We have examined the role of metabotropic glutamate receptor activation in regulating neurotrophin messenger RNA levels in the brain with the use of the selective agonist (1S,3R)-1-aminocy-clopentane-1,3-dicarboxylic acid. Intracerebroventricular injection of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid into adult adult rats resulted in increased expression of nerve growth factor and brain-derived neurotrophic factor messenger RNA in the hippocampal and pyriform cortex and decreased levels of neurotrophin-3 messenger RNA in the hippocampal dentate gyrus granule cell layer. C-fos messenger RNA levels were also increased throughout hippocampal and cortical subfields following (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid administration. (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid-induced changes in messenger RNA levels occurred without behavioral seizures, yet these changes were similar in magnitude and time course to early changes in neurotrophin and c-fos messenger RNA levels observed following recurrent limbic seizures. In contrast quisqualate, a potent agonist of metabotropic as well as ionotropic kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors, was only capable of inducing increased expression of brain-derived neurotrophic factor messenger RNA at doses which produced recurrent motor seizures, and both effects were completely inhibited by the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Neurotrophin messenger RNA changes induced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid were also partially susceptible to 6-cyano-7-nitroquinoxaline-2,3-dione antagonism, as well as the specific N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)-cyclohepten-5,10- iminedizoleipine. These results suggest that (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive metabotropic glutamate receptors can dramatically increase the expression of neurotrophin and c-fos messenger RNAs in rat forebrain without producing significant behavioral trauma and that these influences may involve ionotropic glutamate receptors in certain brain regions.
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PMID:A metabotropic glutamate receptor agonist regulates neurotrophin messenger RNA in rat forebrain. 904 76

Seizures have been shown to regulate neurotrophin expression in adult mammalian brain. However, there has been some controversy as to whether seizures affect neurotrophin expression in very immature brain. In the present study, we have examined the effects of seizures induced by pilocarpine following lithium pretreatment or by kainic acid on the expression of brain derived neurotrophic factor (BDNF) mRNA in developing rat brain by in situ hybridization. In adult brain, lithium/pilocarpine treatment resulted in dramatic elevations of hybridization to BDNF cRNA in neocortical and limbic brain structures. In developing brain, lithium/pilocarpine induced elevations of BDNF mRNA in the hippocampus, piriform and entorhinal cortex as early as postnatal day 7 (P7). By P12, the pattern of enhanced expression was similar to that of the adult. Maximal elevations of hybridization were present 2 to 4 h following pilocarpine injection. Electrophysiological recording demonstrated that lithium/pilocarpine treatment resulted in electrographic seizures. Pretreatment with diazepam blocked the seizures as well as the elevation of BDNF mRNA. Kainic acid induced elevations of BDNF mRNA in the CA3 subfield of the hippocampal pyramidal cell layer, but not in other brain areas in pups as young as P7. These data indicate that seizures during the neonatal and early juvenile period of brain development induce elevated BDNF mRNA expression, and that different methods of seizure induction yield different patterns of elevations in hybridization. Furthermore, BDNF may be capable of playing a role in the development of seizure susceptibility in the immature brain.
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PMID:Induction of brain derived neurotrophic factor mRNA by seizures in neonatal and juvenile rat brain. 907 63

Intraventricular 192 IgG-saporin was used to induce a selective lesion of basal forebrain cholinergic neurons in rats. When subjected to 40 rapid hippocampal kindling stimulations with 5-min intervals, these animals exhibited increased number of generalized seizures and a higher mean seizure grade in response to the first five stimulations, and required fewer stimuli to develop focal behavioural seizures, as compared to non-lesioned rats. In contrast, both groups showed similarly enhanced responsiveness when test stimulated four weeks later. Using in situ hybridization, cholinergic denervation was found to cause a significant decrease of basal brain-derived neurotrophic factor messenger RNA levels in the hippocampal formation and piriform cortex, whereas gene expression for nerve growth factor, neurotrophin-3, and TrkB and TrkC was unchanged. Four weeks after rapid kindling stimulations, basal levels of brain-derived neurotrophic factor messenger RNA in the dentate granule cells were restored to normal in the lesioned rats, whereas neurotrophin-3 messenger RNA levels were decreased. No differences in the seizure-evoked levels of neurotrophin and Trk messenger RNAs were detected, except in the dentate granule cell layer, which had significantly higher brain-derived neurotrophic factor messenger RNA expression in the lesioned animals at 2 h. In conclusion, the basal forebrain cholinergic system (i) dampens the severity of recurring seizures induced by rapid hippocampal kindling stimulations, but has no effect on the subsequent delayed phase of epileptogenesis; and (ii) exerts a tonic stimulation of basal brain-derived neurotrophic factor messenger RNA levels in the hippocampal formation and piriform cortex. The findings also indicate that the cholinergic lesion does not affect neurotrophin and Trk gene expression after recurring seizures, and that the kindling process leads to long-term changes in basal brain-derived neurotrophic factor and neurotrophin-3 messenger RNA levels in the denervated animals.
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PMID:Effects of cholinergic denervation on seizure development and neurotrophin messenger RNA regulation in rapid hippocampal kindling. 928 42

Approximately 30% of a breeding colony of Sprague-Dawley rats homozygous for an autosomal recessive mutation mf ("mutilated foot") associated with a peripheral sensory neuropathy have been found unexpectedly to suffer spontaneous epileptiform attacks. Seizures ranged from brief episodes of compulsive running to tonic-clonic convulsions lasting for up to 30 s, recurring at intervals of hours or days. EEG recordings during seizures showed high-voltage 8-10 Hz spike trains that abated over the ensuing 1-2 min. Interictal records were usually normal. Twice-daily kindling of the amygdala (200 microA sinewave for 1.0 s) was unexpectedly ineffective. Most of the rats that had suffered spontaneous seizures failed to develop kindled afterdischarges, even after 30 kindling stimulations. Other mf rats developed prolonged high-amplitude kindled afterdischarges that were arrested at stage 2 and failed to evolve into convulsive seizures. Hippocampal dentate granule cells of kindled mf rats, stained for zinc by Timm's method, showed significantly less mossy fibre sprouting than wild-type Sprague-Dawley rats after the same number of kindled afterdischarges. A minority of the mf rats tested (2 of 14) kindled normally. Auditory stimulation (n = 23) or stroboscopic flicker (n = 14) failed to elicit seizures or running fits in any mf rat. Peripheral neuropathy corresponding to that in the mf rat, with resistance to kindling and diminished mossy fibre sprouting, have also been reported in transgenic mice with defective p75NGFR neurotrophin receptors. A homologous genetic defect in the rat could account for most of the features of the mf phenotype.
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PMID:Spontaneous epileptiform seizures but increased resistance to kindled seizures in a mutant Sprague-Dawley rat (mf/mf). 940 5

The VGF gene encodes a neuronal secretory-peptide precursor that is rapidly induced by neurotrophic growth factors and by depolarization in vitro. VGF expression in the animal peaks during critical periods in the developing peripheral and central nervous systems. To gain insight into the possible functions and regulation of VGF in vivo, we have used in situ hybridization to examine the regulation of VGF messenger RNA by experimental manipulations, and have found it to be regulated in the CNS by paradigms that affect electrical activity and by lesion. Inhibition of retinal electrical activity during the critical period of visual development rapidly repressed VGF messenger RNA in the dorsal lateral geniculate nucleus of the thalamus. In the adult, kainate-induced seizures transiently induced VGF messenger RNA in neurons of the dentate gyrus, hippocampus, and cerebral cortex within hours. Cortical lesion strongly induced VGF messenger RNA in ipsilateral cortex within hours, and strongly repressed expression in ipsilateral striatum. Ten days postlesion there was a delayed induction of VGF messenger RNA in a portion of deafferented striatum where compensatory cortical sprouting has been detected. Expression of the neuronal secretory-peptide precursor VGF is therefore modulated in vivo by monocular deprivation, seizure, and cortical lesion, paradigms which lead to neurotrophin induction, synaptic remodeling and axonal sprouting.
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PMID:The messenger RNA encoding VGF, a neuronal peptide precursor, is rapidly regulated in the rat central nervous system by neuronal activity, seizure and lesion. 948 99

The expression of neurotrophins is altered by amygdala kindled seizures. Because thyroid hormone can regulate the transcription of neurotrophins, we asked whether thyroid hormone regulates neurotrophin mRNA expression following amygdala kindling. Rats with electrodes implanted in the basolateral nucleus of the amygdala were either depleted of thyroid hormone or given excess thyroid hormone. The rats were then kindled daily until they had one generalized seizure. The brains were removed 4 h after the seizure and processed for in situ hybridization of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) mRNAs. In non-kindled rats, thyroid hormone depletion increased the levels of BDNF mRNA in the paraventricular nucleus of the hypothalamus and the pituitary gland. NGF and NT-3 mRNA expression was not altered. In addition, thyroid hormone manipulations had no effect on kindling or on kindling-induced BDNF and NGF mRNA. However, the kindling-induced decrease in NT-3 mRNA expression in the dentate gyrus granule cell layer was significantly attenuated by thyroid hormone depletion. These effects were reversed by thyroid hormone replacement. The results indicate that thyroid hormone plays a modulatory role in the seizure-induced changes of NT-3 mRNA expression found in the dentate gyrus.
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PMID:Attenuation of kindling-induced decreases in NT-3 mRNA by thyroid hormone depletion. 955 83

Previous results from our laboratory indicate that two nights of voluntary wheel running upregulates brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. In order to investigate the time-course of the BDNF response and to examine how physical activity preferentially activates particular transcriptional pathways, the effects of 6 and 12 h of voluntary wheel running on BDNF and exons I-IV mRNA expression were investigated in rats. Hippocampal full-length BDNF mRNA expression was rapidly influenced by physical activity, showing significant increases in expression levels as soon as 6 h of voluntary wheel running. Moreover, there was a strong positive correlation between distance run and BDNF mRNA expression. Exon I mRNA expression was significantly upregulated after 6 h of running and was maintained or enhanced by 12 h of voluntary running. Exon II had a slower time-course and was significantly upregulated after 12 h, selectively in the CA1 hippocampal region. Exon III and Exon IV showed no significant increase in expression level after 6 or 12 h of running in the paradigm studied. It is significant that the rapid neurotrophin response is demonstrated for a physiologically relevant stimulus, as opposed to the extreme conditions of seizure paradigms. Furthermore, exercise-induced upregulation of BDNF may help increase the brain's resistance to damage and neurodegeneration that occurs with aging.
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PMID:Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus. 979 93

Systemic administration of pilocarpine, which results in status epilepticus followed by recurrent seizures in rats, is a widely used experimental model of chronic limbic epilepsy. Marked structural alterations have been documented in pilocarpine-induced epilepsy, and these include cell loss in the hippocampus and other brain areas, and sprouting of mossy and cholinergic fibers in the hippocampus. Evidence is accumulating that neurotrophins and neurotrophin receptors are involved in the cascade of these events. Two and 4 months after pilocarpine-induced epilepsy, neurons containing the 75-kDa low affinity neurotrophin receptor (p75NTR) were investigated with immunohistochemistry in the medial septal and diagonal band nuclei. No significant differences in the distribution and number of immunoreactive neurons were found in the epileptic rats compared to control saline-treated animals. However, in the epileptic animals, a significant decrease in the perikaryal size of p75NTR-immunoreactive neurons of the septal/diagonal band region was found by 60 days, and such atrophic changes were more marked in the diagonal band nuclei by 120 days. These findings indicate that the p75NTR-containing cell bodies, which include the neurons projecting to the hippocampal formation and are cholinergic in the normal brain, survive after months of spontaneous recurrent seizures, during which, therefore, a supply of p75NTR to target regions is maintained in the chronic epileptic brain. However, the present data point out that these p75NTR-containing neurons undergo a significant shrinkage in pilocarpine-induced chronic epilepsy, thus indicating that they are involved in the brain pathology of temporal lobe epilepsy.
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PMID:Persistence and atrophy of septal/diagonal band neurons expressing the p75 neurotrophin receptor in pilocarpine-induced chronic epilepsy in the rat. 985 21

Recent work has shown that neurotrophin gene expression is increased after seizures evoked in the kindling model of epilepsy, but whether neurotrophins regulate kindling development is as yet unclear. In this study, we attempted to block selectively the activation of distinct neurotrophin receptors throughout kindling development in the rat via chronic intracerebroventricular administration of trk receptor bodies. The efficacy and selectivity of the trk receptor bodies were established by inhibition of neurotrophin-induced trk receptor phosphorylation in pheochromocytoma (PC12) cells and primary cultures of cortical neurons. The intracerebroventricular infusion of trkB receptor body (trkB-Fc) inhibited development of kindling in comparison with that seen with saline or human IgG controls, trkA-Fc, or trkC-Fc. These results imply that activation of trkB receptors contributes to the development of kindling, a form of activity-dependent behavioral plasticity in the adult mammalian brain.
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PMID:Selective inhibition of kindling development by intraventricular administration of TrkB receptor body. 995 19


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