Adolescent social isolation affects parvalbumin expression in the medial prefrontal cortex in the MAM-E17 model of schizophrenia

Metab Brain Dis. 2019 Feb;34(1):341-352. doi: 10.1007/s11011-018-0359-3. Epub 2018 Dec 5.


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.

Keywords: Environment; Epigenetics; Neurodevelopment; Risk factor; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Epigenesis, Genetic
  • Female
  • Histones / metabolism*
  • Male
  • Methylation
  • Neurons / metabolism
  • Parvalbumins / metabolism*
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Wistar
  • Schizophrenia / metabolism*
  • Social Isolation*


  • Histones
  • Parvalbumins