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Expression of class II histone deacetylases in two mouse models of temporal lobe epilepsy
Author(s) -
Jagirdar Rohan,
Drexel Meinrad,
Bukovac Anneliese,
Tasan Ramon O.,
Sperk Günther
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13440
Subject(s) - epileptogenesis , granule cell , status epilepticus , epilepsy , neuroscience , histone , biology , microbiology and biotechnology , chemistry , hippocampus , biochemistry , dentate gyrus , gene
Abstract Epigenetic mechanisms like altered histone acetylation may have a crucial role in epileptogenesis. In two mouse models of temporal lobe epilepsy, we investigated changes in the expression of class II histone deacetylases ( HDAC ), a group of signal transducers that shuttle between nucleus and cytoplasm. Intrahippocampal injection of kainic acid ( KA ) induced a status epilepticus, development of spontaneous seizures (after 3 days), and finally chronic epilepsy and granule cell dispersion. Expression of class II HDAC m RNA s was investigated at different time intervals after KA injection in the granule cell layers and in sectors CA 1 and CA 3 contralateral to the site of KA injection lacking neurodegeneration. Increased expression of HDAC 5 and 9 m RNA s coincided with pronounced granule cell dispersion in the KA ‐injected hippocampus at late intervals (14–28 days after KA ) and equally affected both HDAC 9 splice variants. In contrast, in the pilocarpine model (showing no granule cell dispersion), we observed decreases in the expression of HDAC 5 and 9 at the same time intervals. Beyond this, striking similarities between both temporal lobe epilepsy models such as fast decreases in HDAC 7 and 10 m RNA s during the acute status epilepticus were observed, notably also in the contralateral hippocampus not affected by neurodegeneration. The particular patterns of HDAC m RNA expression suggest a role in epileptogenesis and granule cell dispersion. Reduced expression of HDAC s may result in increased expression of pro‐ and anticonvulsive proteins. On the other hand, export of HDAC s from the nucleus into the cytoplasm could allow for deacetylation of cytoplasmatic proteins involved in axonal and dendritic remodeling, like granule cell dispersion.HDAC 5 and HDAC 9 expression is highly increased in granule cells of the KA ‐injected hippocampus and parallels granule cell dispersion. Both HDAC s are thought to be targeted to the cytoplasm and to act there by deacetylating cytoplasmatic (e.g. cytosceleton‐related) proteins.