MICROGLIAL PROPERTIES IN STRESS MODELS: A MISSING LINK UNDERLYING HETEROGENEOUS OLIGODENDROCYTE ALTERATIONS?

Social stress is a key trigger for disorders of increased aversion responsiveness, such as major depression (MDD), anxiety (ADs), and is linked to functional changes in the anterior cingulate cortex (ACC)-amygdala (AMY) – medial prefrontal cortex (mPFC)-AMY circuits in rodents. These alterations might implicate within- and between-regional changes in the oligodendrocyte lineage and myelination.
In adult male mice, we previously demonstrated that heightened aversion responsiveness due to social stress alters myelination patterns and oligodendrocyte proliferation-maturation dynamics. However, key features of these (mal)adaptive responses remain inconsistently reported across studies. Intriguingly, in a pilot analysis, we observed that the extent of the oligodendrocyte precursor cells (OPCs) and myelin response to social stress correlated with the density of microglia cells.
Under physiological conditions, microglia – the immune cells of the CNS – continuously monitor the CNS microenvironment and play a key role in maintaining oligodendrocyte lineage and myelin homeostasis. We therefore hypothesised that microglia sense, decode, and respond to the social stress signals, thereby tailoring the oligodendrocyte lineage adaptive response.
To begin addressing this hypothesis, we employed histological and semi-automated image analyses to comprehensively characterized microglia properties following aversive experiences. Specifically, we assessed: (1) the density and proliferation rate of microglia; (2) the spatial relationship between microglia and OPCs; and (3) microglia morphological complexity (as an indication of their activity/status). By gathering this preliminary yet integrative histological evidence, we aim to establish a foundation for investigating pathophysiological mechanisms that may underlie the clinical and neurobiological heterogeneity of neuropsychiatric disorders.