Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enriched environments (EEs) during development have been shown to influence adult behaviour. Environmental conditions during childhood may contribute to the onset and/or pathology of schizophrenia; however, it remains unclear whether EE might prevent the development of schizophrenia. Herein, we investigated the effects of EE during adolescence on phencyclidine (PCP)-induced abnormal behaviour, a proposed schizophrenic endophenotype. Male ICR mice (3 wk old) were exposed to an EE for 4 wk and then treated with PCP for 2 wk. The EE potentiated the acute PCP treatment-induced hyperlocomotion in the locomotor test and prevented chronic PCP treatment-induced impairments of social behaviour and recognition memory in the social interaction and novel object recognition tests. It also prevented the PCP-induced decrease of acetylated Lys9 in histone H3-positive cells and increase of the histone deacetylase (HDAC)5 level in the prefrontal cortex. To investigate whether the histone modification during adolescence might be critical for the effect of EE, 3-wk-old mice were first treated with sodium butyrate (SB; an HDAC inhibitor) for 4 wk and then treated with PCP for 2 wk. Chronic SB treatment during adolescence mimicked the effects of EE, including potentiation of hyperlocomotion induced by acute PCP treatment and prevention of social and cognitive impairments, decrease of acetylated Lys9 in histone H3-positive cells and increase of the HDAC5 level in the prefrontal cortex associated with chronic PCP treatment. Our results suggest that EEs prevent PCP-induced abnormal behaviour associated with histone deacetylation. EEs during childhood might prove to be a novel strategy for prophylaxis against schizophrenia.
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PMID:Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice. 2209 54

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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PMID:Molecular mechanism of action of valproate acid alone or in combination with chlorpromazine in the epigenetic regulation of schizophrenia. 3057 48