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Impaired adult myelination in the prefrontal cortex of socially isolated mice.

ABSTRACT: Protracted social isolation of adult mice induced behavioral, transcriptional and ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC) and impaired adult myelination. Social re-integration was sufficient to normalize behavioral and transcriptional changes. Short periods of isolation affected chromatin and myelin, but did not induce behavioral changes. Thus, myelinating oligodendrocytes in the adult PFC respond to social interaction with chromatin changes, suggesting that myelination acts as a form of adult plasticity.

SUBMITTER: Liu J

PROVIDER: S-EPMC3729624 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Impaired adult myelination in the prefrontal cortex of socially isolated mice.

Liu Jia J Dietz Karen K DeLoyht Jacqueline M JM Pedre Xiomara X Kelkar Dipti D Kaur Jasbir J Vialou Vincent V Lobo Mary Kay MK Dietz David M DM Nestler Eric J EJ Dupree Jeffrey J Casaccia Patrizia P

Nature neuroscience 20121111 12

Protracted social isolation of adult mice induced behavioral, transcriptional and ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC) and impaired adult myelination. Social re-integration was sufficient to normalize behavioral and transcriptional changes. Short periods of isolation affected chromatin and myelin, but did not induce behavioral changes. Thus, myelinating oligodendrocytes in the adult PFC respond to social interaction with chromatin changes, suggesting that my ...[more]

PMID: 23143512

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RNA-sequencing in medial prefrontal cortex of early socially isolated mice

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Chronic fluoxetine treatment of socially isolated rats modulates prefrontal cortex proteome

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Project description:BackgroundMaternal separation models in rodents are widely used to establish molecular mechanisms underlying prolonged effects of early life adversity on neurobiological and behavioral outcomes in adulthood. However, global epigenetic signatures following early life stress in these models remain unclear.ResultsIn this study, we carried out a ChIP-seq analysis of H3K4 trimethylation profile in the prefrontal cortex of adult male mice with a history of early life stress. Two types of stress were used: prolonged separation of pups from their mothers (for 3 h once a day, maternal separation, MS) and brief separation (for 15 min once a day, handling, HD). Adult offspring in the MS group demonstrated reduced locomotor activity in the open field test accompanied by reduced exploratory activity, while the HD group showed decreased anxiety-like behavior only. In a group of maternal separation, we have found a small number (45) of slightly up-regulated peaks, corresponding to promoters of 70 genes, while no changes were observed in a group of handling. Among the genes whose promoters have differential enrichment of H3K4me3, the most relevant ones participate in gene expression regulation, modulation of chromatin structure and mRNA processing. For two genes, Ddias and Pip4k2a, increased H3K4me3 levels were associated with the increased mRNA expression in MS group.ConclusionThe distribution of H3K4me3 in prefrontal cortex showed relatively low variability across all individuals, and only some subtle changes were revealed in mice with a history of early life stress. It is possible that the observed long-lasting behavioral alterations induced by maternal separation are mediated by other epigenetic mechanisms, or other brain structures are responsible for these effects.

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