The recovery trajectory of adolescent social defeat stress-induced behavioral, 1H-MRS metabolites and myelin changes in Balb/c mice

Abstract

Adolescent exposure to social stress precipitates emotion-related disorders and affects the development and function of medial prefrontal cortex (mPFC). However, this adversity-induced behavioral and neurological changes remain not fully explored. Adolescent Balb/c mice were subjected to intermittent social defeat stress during postnatal days 28 to 42. Proton magnetic resonance spectroscopy (1H-MRS) measurements, behavioral tests and immunohistochemistry were performed one day or 3 weeks after the last stress episode. Defeated mice exhibited hypoactivity and social avoidance with the latter lasting into the early adulthood, while the anxiety level was unchanged. Social defeat experience lead to temporary decreases in the levels of total creatines (Cr + pCr) and Glx (Glu + Gln), but a delayed increase of N- acetylaspartate (NAA) levels. These alternations were accompanied with a persistent reduction of myelin basic protein expression although the number of mature oligodendrocyte did not change. These findings provide evidence that adolescent adverse social experience permanently impairs the emotion-related behavioral performance and induces biochemical and molecular changes in the brain which at least lasts into early adulthood, thus enhancing our understanding of the neurobiology of social defeat stress. Our finding also implicates that NAA signals on MRS may reflect myelin status.