Subtle microglia and oligodendrocyte precursor cell histological changes across social stress paradigms

Social stress is a key risk factor for disorders of increased aversion responsiveness, and changes in cortico-limbic oligodendrocyte lineage and myelination may contribute to this pathological process. In adult male mice, we demonstrated previously that social stress-induced aversion hyper-responsiveness co-occurs with altered oligodendrocyte proliferation-maturation dynamics and myelin content. Overall, however, findings on these inter-relationships are inconsistent across studies using various stress paradigms, suggesting that there is not a simple relationship between social stress and the extent and direction (i.e., loss vs. gain) of changes in the oligodendrocyte lineage and myelin. Under physiological conditions, the immune cells of the CNS, microglia, monitor the CNS microenvironment and contribute to oligodendrocyte lineage and myelin homeostasis. Also, recent reports suggest that microglia state might influence oligodendrocyte lineage changes in response to certain social stress paradigms. Here, we begin to address the hypothesis that social stress induced changes in microglia and oligodendrocyte lineage are inter-related in mice. We employed histological and semi-automated image analyses to characterize a subset of microglia and OPC histological properties in medial prefrontal cortex (mPFC) and basal amygdala (BA) following aversive social experiences, including chronic social stress (CSS), CSS followed by aversion learning (excessive aversive stimulation), and social isolation (as the absence of sociopositive stimulation). Specifically, we assessed: (1) the density and proliferation rate of microglia and OPCs; (2) the spatial relationship between microglia and OPCs; and (3) microglia morphological complexity as a proxy for their activity/state. The preliminary integrative histological evidence is for subtle stress paradigm-associated alterations in microglia- and OPC-related features, and limited correlative histological associations between these cell populations.