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)

In various chemoconvulsant models of human temporal lobe epilepsy, the induction of epileptogenesis by a prolonged period of continuous seizure activity is accompanied by significant changes in hippocampal structure. These changes include an increase in neurogenesis within the proliferative subgranular zone (SGZ) of the dentate gyrus and induction of mossy fiber sprouting in mature dentate granule cells. As dentate granule cell neurogenesis and axon outgrowth are also hallmarks of hippocampal development, we hypothesized that molecules involved in normal development may also play a role in similar changes associated with epileptogenesis. To begin to test this hypothesis, we have analyzed the expression patterns of multiple members of the basic helix-loop-helix (bHLH) family of transcription factors in both normal and epileptic adult rats. bHLH protein expression has been found recently in dentate granule cells at specific developmental stages, and analysis of developmental models suggests specific neural differentiation functions for these molecules. We show that mRNA expression of all seven bHLH family members examined in this study, as well as the divergent homeobox protein Prox1, is present in the adult. Patterns of expression varied considerably between family members, ranging from the limited expression of Mash1 in the neurogenic SGZ of the dentate gyrus to the scattered, widespread profile of Hes5 throughout the dentate gyrus and the hippocampus proper. Moreover, these varied profiles of expression were differentially regulated following status epilepticus, with some increasing (Mash1, Id2), some falling (Hes5, Prox1), and others remaining mostly unchanged (NeuroD/BETA2, NeuroD2/NDRF, Id3, Rath2/Nex1). While the function of these molecules in the adult brain remains to be characterized, our findings support the idea that molecules controlling cell-fate decisions in the developing dentate gyrus are also operative during seizure-induced neurogenesis and plasticity.
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PMID:Differential regulation of basic helix-loop-helix mRNAs in the dentate gyrus following status epilepticus. 1156 18

Various genes for transcription factors are induced in neurons involving long-lasting synaptic plasticity that is accompanied by de novo protein synthesis. In this study, we analyzed the gene expression of NeuroD-related factor (NDRF/neuroD2), a neural basic helix-loop-helix transcription factor, in the mouse hippocampus following pentylenetetrazol (PTZ)-induced seizures. Both the levels of mRNA and protein of NDRF were elevated by PTZ injection. In contrast to c-fos, a representative neuronal activation-related immediate-early gene that was induced within 1 h after PTZ administration, induction of the NDRF gene expression reached a maximum level at 7-8 h after PTZ injection and was inhibited by pretreatment with cycloheximide and MK801. In situ hybridization of the mouse hippocampus revealed that NDRF mRNA was significantly induced in the dentate gyrus. During hippocampal development, NDRF transcripts were found to be highly expressed in a juvenile period, when extensive synaptogenesis occurs. Our present results demonstrate that NDRF is a new member of the family of activation-induced transcription factors, whose expression is probably regulated by immediate-early transcription factors. NDRF is thought to be involved in long-lasting neuronal activation.
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PMID:Stimulation of gene expression of NeuroD-related factor in the mouse brain following pentylenetetrazol-induced seizures. 1175 69

The basic helix-loop-helix (bHLH) transcription factor, neuroD2, induces neuronal differentiation and promotes neuronal survival. Reduced levels of neuroD2 were previously shown to cause motor deficits, ataxia, and seizure propensity. Because neuroD2 levels may be critical for brain function, we studied the regulation of neuroD2 gene in cell culture and transgenic mouse models. In transgenic mice, a 10-kb fragment of the neuroD2 promoter fully recapitulated the endogenous neuroD2 staining pattern. A 1-kb fragment of the neuroD2 promoter drove reporter gene expression in most, but not all neuroD2-positive neuronal populations. Mutation of two critical E-boxes, E4 and E5 (E4 and E5 situated 149 and 305 bp upstream of the transcriptional start site) eliminated gene expression. NeuroD2 expression was diminished in mice lacking neurogenin1 demonstrating that neurogenin1 regulates neuroD2 during murine brain development. These studies demonstrate that neuroD2 expression is highly dependent on bHLH-responsive E-boxes in the proximal promoter region, that additional distal regulatory elements are important for neuroD2 expression in a subset of cortical neurons, and that neurogenin1 regulates neuroD2 expression during mouse brain development.
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PMID:Regulation of neuroD2 expression in mouse brain. 1469 66