Publication: Histone modifications in status epilepticus induced by Kainate
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Date
2006
Authors
Taniura, H. ; Sng, J.C.G. ; Yoneda, Y.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
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 aminoterminal
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 spatiotemporal
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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