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

Animal models of epilepsy have allowed the determination of the basic molecular and cellular mechanisms of epileptogenesis. Generalized limbic seizures and subsequent status epilepticus can be induced by either pilocarpine, the muscarinic acetylcholine receptor agonist or kainate, the glutamate receptor agonist. There has been increasing interest that chromatin remodeling might play a critical role in gene regulation even in non-dividing cells such as neurons. One form of chromatin remodeling is histone amino-terminal modification that can generate synergistic or antagonistic affinities for the interactions of transcriptional factors, in turn causing changes in gene activity. Two widely studied histone modification processes are histone acetylation and phosphorylation. While histone hyperacetylation indicates an increase in gene activity, its hypoacetylation marks gene repression. Both states are controlled by a dynamic interplay of histone acetyltransferase (HAT) and histone deacetylase (HDAC). We have found the upregulation of acetylation and phosphorylation of histones, coupled with status epilepticus after kainate administration. c-fos and c-jun mRNA have been sequentially induced in response to kainate, in different hippocampal subpopulations starting from the dentate gyrus and spreading to the cornus ammonis regions well correlated with the spatio-temporal distribution of histone H4 hyperacetylation. Both histone modifications are associated with the c-fos gene promoter after kainate stimulation, while only histone acetylation with the c-jun gene. Pretreatment with curcumin, which has a HAT inhibitory activity specific for CBP/p300, attenuates histone modifications, IEGs expression and also the severity of status epilepticus after kainate treatment. Histone modifications may have a crucial role in the development of epilepsy induced by kainate.
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PMID:Histone modifications in status epilepticus induced by kainate. 1659 77

The development of inhibitory circuits depends on the action of a network of transcription factors and epigenetic regulators that are critical for interneuron specification and differentiation. Although the identity of many of these transcription factors is well established, much less is known about the specific contribution of the chromatin-modifying enzymes that sculpt the interneuron epigenome. Here, we generated a mouse model in which the lysine acetyltransferase CBP is specifically removed from neural progenitors at the median ganglionic eminence (MGE), the structure where the most abundant types of cortical interneurons are born. Ablation of CBP interfered with the development of MGE-derived interneurons in both sexes, causing a reduction in the number of functionally mature interneurons in the adult forebrain. Genetic fate mapping experiments not only demonstrated that CBP ablation impacts on different interneuron classes, but also unveiled a compensatory increment of interneurons that escaped recombination and cushion the excitatory-inhibitory imbalance. Consistent with having a reduced number of interneurons, CBP-deficient mice exhibited a high incidence of spontaneous epileptic seizures, and alterations in brain rhythms and enhanced low gamma activity during status epilepticus. These perturbations led to abnormal behavior including hyperlocomotion, increased anxiety and cognitive impairments. Overall, our study demonstrates that CBP is essential for interneuron development and the proper functioning of inhibitory circuitry in vivo.
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PMID:The Epigenetic Factor CBP Is Required for the Differentiation and Function of Medial Ganglionic Eminence-Derived Interneurons. 3033 86