Valproate administration to mice increases histone acetylation and 5-lipoxygenase content in the hippocampus

Gene expression can be regulated by chromatin remodeling induced by the opposing actions of histone acetyltransferases and histone deacetylases (HDAC). HDAC inhibitors are considered putative anti-cancer drugs, but may also alter gene expression in the brain. Valproic acid (valproate; VPA), a drug u...

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Bibliographic Details
Published in:Neuroscience letters 2003-07, Vol.345 (2), p.141-143
Main Authors: Yildirim, Emre, Zhang, Zhijing, Uz, Tolga, Chen, Chang-qing, Manev, Radmila, Manev, Hari
Format: Article
Language:English
Subjects:
5-Lipoxygenase
Acetylation - drug effects
Animals
Anticonvulsants. Antiepileptics. Antiparkinson agents
Arachidonate 5-Lipoxygenase - metabolism
Arachidonic acid
Biological and medical sciences
Chromatin remodeling
Enzyme Inhibitors - pharmacology
Epigenetic
Hippocampus - drug effects
Hippocampus - enzymology
Hippocampus - metabolism
Histone deacetylase
Histones - metabolism
Immunoblotting
Leukotriene
Male
Medical sciences
Mice
Mice, Inbred Strains
Neuropharmacology
Pharmacology. Drug treatments
Time Factors
Valproic acid
Valproic Acid - pharmacology
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Summary:Gene expression can be regulated by chromatin remodeling induced by the opposing actions of histone acetyltransferases and histone deacetylases (HDAC). HDAC inhibitors are considered putative anti-cancer drugs, but may also alter gene expression in the brain. Valproic acid (valproate; VPA), a drug used for treatment of bipolar disorder, has been characterized as a HDAC inhibitor. In neuronal cultures, VPA increases the expression of 5-lipoxygenase (5-LOX). Here we show that in vivo treatment of mice with intraperitoneal VPA injections increases the acetylation of histone H3 and the content of 5-LOX immunoreactive protein in the hippocampus. Since the extent of 5-LOX expression may alter mouse behavior, we suggest that VPA-altered chromatin remodeling and 5-LOX expression in the brain may be functionally important.
ISSN:0304-3940
1872-7972
DOI:10.1016/S0304-3940(03)00490-7