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Molecular mechanism of action of valproate acid alone or in combination with chlorpromazine in the epigenetic regulation of schizophrenia
Vol 32, Issue 6, 2018
Abstract
This study aimed to assess the molecular mechanism of the histone deacetylase inhibitor (HDACI) valproate acid (VPA) alone or in combination with the antipsychotic drug chlorpromazine in the epigenetic regulation of schizophrenia. A total of 60 perinatal CD-SD rats were divided in a control group (16 animals) and a schizophrenia model group (44 animals). For the schizophrenia model group the rats received phencyclidine (PCP) 10 mg/kg/day by intradermal injection on days 7, 9, and 11 after birth. The model was confirmed by the Morris water test in 40 rats. The control and model rats were divided into 7 groups. The Real Time PCR assay was used to detect the mRNA expression changes of GABA system gene [GABBR1 (GABA B receptor 1)], GAD1 (glutamic acid decarboxylase1), GAD2 (glutamic acid decarboxylase2), Lipase metabolic key enzyme LPL (lipoprotein lipase) gene, glutamate neurotransmitter gene GRIA2 (AMPA subtype glutamate receptors 2), inward rectifier potassium channel members KCNJ4 (potassium voltage-gated channel subfamily J member 4) and neuropeptide signal gene TAC1 (tachykinin precursor 1,TAC1) in four brain regions: the prefrontal cortex (PC), the amygdala (AM), the caudate-putamen (CPU) and the hippocampus (HIP). The platform arrival time of PMV and PMVC groups was significantly reduced compared to the PM group, the reduction being more significant in the PMV group. In the four brain regions of the epigenetic animal model of schizophrenia, the expression of GABBR1, GAD1, and GAD2 genes increased significantly. Following administration of HDACI VPA, the mRNA expression of this gene in the four brain regions decreased or approached normal levels. GABBR1 GAD1 and GAD2 are likely to be the target genes affected by the HDACI VPA.
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Copyright (c) 2018 YM. Geng, JT. Xue, JP. Su, HY. Li
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy