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.
Highlights
Childhood and adolescent adversities are associated with the increased risk of developing later psychopathology[1,2,3], including major depressive disorder[4], anxiety disorders, impaired social behavior[5,6] and cognitive functions[6,7]
Metabolite changes in prefrontal cortex measured by Magnetic resonance spectroscopy (MRS) have been reported in stress-related disorders including depression[12], anxiety disorders[13,14], obsessive-compulsive disorder[15], post-traumatic stress disorder (PTSD)[16] and bipolar disorder[17]
Repeated measures two-way ANOVA indicated that a significant interaction of stress and time on total distance travelled in open-field test (F 1, 34 = 5.68; P < 0.05)
Summary
The intermittent social defeat stress-induced hypoactivity, but not social avoidance, recovered in three weeks after the stress. The MBP immunoreactivity in mPFC was decreased by adolescent exposure to adverse social experience, but no oligodendrocyte loss, indicating that the myelination process was impeded in this brain region This result is consistent with a previous study showing that social isolation during early adolescence did not change the number of mature oligodendrocyte but reduced the expression of MBP25. Adolescent social stress caused both a temporary and a delayed neurochemical changes in mPFC, which are concurrent with an abnormal development in myelination in this brain region These results suggest that social adversity experience during adolescence exerts immediate and long-lasting influences on behaviors, neurochemistry and myelination, which are relevant to the symptoms and pathophysiology of stress-related psychiatric disorders
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