Adolescent social isolation affects parvalbumin expression in the medial prefrontal cortex in the MAM-E17 model of schizophrenia
Altered parvalbumin (PV) expression is observed in the prefrontal cortex of subjects with schizophrenia. Environmental context, particularly during adolescence, might regulate PV expression. In the present study, we investigated the effect of adolescent social isolation (SI) on PV expression in the medial prefrontal cortex in a neurodevelopmental model (MAM-E17) of schizophrenia. SI exposure occurred from postnatal day 30 to 40, followed by resocialization until late adolescence or early adulthood. PV mRNA and protein levels, as well as the number of PV cells, were analysed at these ages. Moreover, epigenetic regulation of PV expression by histone methylation was examined by measuring the total and PV gene-bound H3K4me3 levels. MAM only decreased levels of the PV mRNA and protein in adulthood. Decreases in total H3K4me3 levels and its level at the PV gene were also observed at this age. In contrast, in late adolescence, SI induced a decrease in the expression of the PV mRNA in the MAM group that was related to the reduction in total and PV gene-bound H3K4me3 levels. However, at this age, SI increased the levels of the PV protein in both the control and MAM groups. In adulthood, SI did not affect PV mRNA or H3K4me3 levels but decreased levels of the PV protein in both groups. Both MAM and SI failed to change the number of PV cells at any age. The results indicate that adolescent SI accelerated epigenetic impairments of PV expression in MAM-E17 rats; however, subsequent resocialization abolished this dysfunction, but failed to prevent alterations in PV protein.
KeywordsEnvironment Risk factor Schizophrenia Epigenetics Neurodevelopment
The study was supported by grant 2014/13/B/NZ4/00218 funded by the National Science Centre, Poland and statutory activity of Institute of Pharmacology, Polish Academy of Sciences.
The study was supported by grant 2014/13/B/NZ4/00218 from the National Science Center, Poland and statutory activity of Institute of Pharmacology, Polish Academy of Sciences.
Compliance with ethical standards
All applicable international, national and institutional guidelines for the care and use of animals were followed. All procedures performed in the studies involving animals were conducted in accordance with the ethical standards of the institution or practice at which the studies were conducted. The study was performed in strict accordance with the recommendations of the European Council Guide for the Care and Use of Laboratory Animals (86/609/EEC), as adopted and promulgated by the European Communities Council Directive (2010/63/EU). The protocols were approved by the Committee for Laboratory Animal Welfare and the Ethics of the Institute of Pharmacology, Polish Academy of Sciences in Kraków. All efforts were made to minimize animal suffering and to reduce the number of animals used.
Conflict of interest
The authors have no conflicts of interest to declare.
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