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

Neuropsychiatr Dis Treat. 2020 May 22:16:1321-1330. doi: 10.2147/NDT.S247497. eCollection 2020.

Abstract

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)-1β 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-1β 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-1β may contribute to this negative consequence though the underlying mechanism remains to be investigated.

Keywords: adolescence; interleukin-1β; myelin; oligodendrocyte lineage cells; social defeat stress.

Grants and funding

This work was supported by the Grants from the Natural Science Foundation of Guangdong Province (grant number 2017A030313824) and Key Disciplinary Project of Clinical Medicine under the Guangdong High-level University Development Program (grant number 002-18119101). The sponsors had no involvement in any of the stages from study design to submission of the paper for publication.