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

Abstract

Yingjuan Xu,1 Zeman Fang,1 Cairu Wu,1 Haiyun Xu,1,2 Jiming Kong,3 Qingjun Huang,1 Handi Zhang1 1Shantou University Mental Health Center, Shantou, Guangdong, People’s Republic of China; 2Affiliated Kangning Hospital, School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, CanadaCorrespondence: Handi ZhangShantou University Mental Health Center, Shantou, Guangdong 515065, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: 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: social defeat stress, adolescence, myelin, oligodendrocyte lineage cells, interleukin-1β

Keywords

• social defeat stress
• adolescence
• myelin
• oligodendrocyte lineage cells
• interleulin-1β