Effects of chronic social stress on oligodendrocyte proliferation-maturation and myelin status in prefrontal cortex and amygdala in adult mice

Abstract

Stress-related neuropsychiatric disorders present with excessive processing of aversive stimuli. Whilst underlying pathophysiology remains poorly understood, within- and between-regional changes in oligodendrocyte (OL)-myelination status in anterior cingulate cortex and amygdala (ACC-AMY network) could be important. In adult mice, a 15-day chronic social stress (CSS) protocol leads to increased aversion responsiveness, accompanied by increased resting-state functional connectivity between, and reduced oligodendrocyte- and myelin-related transcript expression within, medial prefrontal cortex and amygdala (mPFC-AMY network), the analog of the human ACC-AMY network. In the current study, young-adult male C57BL/6 mice underwent CSS or control handling (CON). To assess OL proliferation-maturation, mice received 5-ethynyl-2′-deoxyuridine via drinking water across CSS/CON and brains were collected on day 16 or 31. In mPFC, CSS decreased the density of proliferative OL precursor cells (OPCs) at days 16 and 31. CSS increased mPFC myelin basic protein (MBP) integrated density at day 31, as well as increasing myelin thickness as determined using transmission electron microscopy, at day 16. In AMY, CSS increased the densities of total CC1+ OLs (day 31) and CC1+/ASPA+ OLs (days 16 and 31), whilst decreasing the density of proliferative OPCs at days 16 and 31. CSS was without effect on AMY MBP content and myelin thickness, at days 16 and 31. Therefore, CSS impacts on the OL lineage in mPFC and AMY and to an extent that, in mPFC at least, leads to increased myelination. This increased myelination could contribute to the excessive aversion learning and memory that occur in CSS mice and, indeed, human stress-related neuropsychiatric disorders.