The Long-Term Effects of Adolescent Social Defeat Stress on Oligodendrocyte Lineage Cells and Neuroinflammatory Mediators in Mice

Objective: Adverse childhood and adolescent experiences are associated with the emergences of psychopathology later in life and have negative consequences on white matter integrity. However, this adversity-induced white matter impairment remains not fully investigated. Methods: Adolescent Balb/c mice were subjected to intermittent social defeat stress once a day during postnatal days 25 to 40. Then, the subjects were allowed to recover for three weeks before sacrifice. At the end, oligodendrocyte (OL) lineage cells, cell proliferation, and microglia activation, as well as myelin basic protein (MBP) levels in frontal cortex and hippocampus were evaluated. The levels of interleukin (IL)-1 beta and IL-6 in the brain regions were assessed. Results: MBP protein level in frontal cortex, but not in the hippocampus of defeated mice, decreased significantly compared to controls. The numeral densities of mature OLs, oligodendrocyte progenitor cells, and proliferating cells in medial prefrontal cortex were comparable between the defeated mice and controls. The defeated mice, however, showed significantly higher IL-1 beta level, although IL-6 level and numeral density of microglia in frontal cortex did not change relative to controls. Conclusion: These results indicate that effects of intermittent social defeat stress on the white matter integrity and OL lineage cells in mouse brain are region- and developmental stage-specific. Upregulated IL-1 beta may contribute to this negative consequence though the underlying mechanism remains to be investigated.