Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the molecular actions of status epilepticus at the chromatin level, we studied the effects of kainate-induced status epilepticus on two different histone modifications at amino terminal tails: histone H3 phosphorylation at serine 10 and histone H4 acetylation. In addition to induction of c-fos and c-jun immediate early genes (IEGs) expression in mouse hippocampus, we also found the upregulation of acetylation and phosphorylation of histones, coupled with status epilepticus after kainate administration. c-fos and c-jun mRNA were sequentially induced in response to kainate, in different hippocampal subpopulations, starting from the dentate gyrus (DG) and spreading to the cornus ammonis regions. Immunohistochemical analysis showed that the spatio-temporal distribution of histone H4 hyperacetylation after kainate treatment was well correlated with the expression of c-fos and c-jun genes. Additionally, there was a transient appearance of phosphorylated histone H3 specifically in the DG region. CREB-binding protein or CBP, a well-known transcriptional co-activator with histone acetyltransferase (HAT) activity, was also induced by kainate and its expression pattern well correlated with histone H4 hyperacetylation in the hippocampus. Chromatin immunoprecipitation analysis showed that both histone modifications were associated with c-fos gene promoter after kainate stimulation, but only histone acetylation with c-jun gene. Pretreatment with curcumin, which has a HAT inhibitory activity specific for CBP/p300, attenuated histone modifications, IEGs expression and also the severity of status epilepticus after kainate treatment. Our findings suggest the involvement of histone modifications induced by kainate not only in IEGs expression but also in the development of epilepsy.
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PMID:Histone modifications in kainate-induced status epilepticus. 1655 89

A prominent role of epigenetic mechanisms in manifestation of epilepsy has been proposed. Thus altered histone H3 and H4 acetylation has been demonstrated in experimental models of temporal lobe epilepsy (TLE). We now investigated changes in the expression of the class I and class IV histone deacetylases (HDAC) in two complementary mouse TLE models. Unilateral intrahippocampal injection of kainic acid (KA) induced a status epilepticus lasting 6 to 24h, development of spontaneous limbic seizures (2 to 3 days after KA injection) and chronic epilepsy, as revealed by telemetric recordings of the EEGs. Mice were killed at different intervals after KA injection and expression of HDAC mRNAs was investigated by in situ hybridization. We observed marked decreases in the expression of HDACs 1, 2 and 11 (by up to 75%) in the granule cell and pyramidal cell layers of the hippocampus during the acute status epilepticus (2 to 6h after KA injection). This was followed by increased expression of all class I HDAC mRNAs in all principal cell layers of the hippocampus after 12 to 48 h. In the chronic phase, 14 and 28 days after KA, only modest increases in the expression of HDAC1 mRNA were observed in granule and pyramidal cells. Immunohistochemistry using an antibody detecting HDAC2 revealed results consistent with the mRNA data and indicates also expression in glial cells on the injection side. Similar changes as seen in the KA model were observed after a pilocarpine-induced status epilepticus except that decreases in HDACs 2, 3 and 8 were also seen at the chronic 28 day interval. The prominent decreases in HDAC expression during status epilepticus are consistent with the previously demonstrated increased expression of numerous proteins and with the augmented acetylation of histone H4. It is suggested that respective putative gene products could facilitate proconvulsive as well as anticonvulsive mechanisms. The increased expression of all class I HDACs during the "silent phase", on the other hand, may be related to decreased histone acetylation, which could cause a decrease in expression of certain proteins, a mechanism that could also promote epileptogenesis. Thus, addressing HDAC expression may have a therapeutic potential in interfering with a status epilepticus and with the manifestation of TLE.
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PMID:Rapid changes in expression of class I and IV histone deacetylases during epileptogenesis in mouse models of temporal lobe epilepsy. 2623 35