Transient upregulation of immune activity induced by adolescent social stress is involved in cognitive deficit in adult male mice and early intervention with minocycline.

Increasing evidence shows that the developmental perturbation of immune activity can lead to long-lasting neurodevelopmental and behavioral abnormalities. In our previous study, we found that deficiencies of microglia and TNFα in the medial prefrontal cortex (mPFC) were involved in the impairment of cognitive flexibility induced by adolescent social stress in adult mice. It remains unclear how and when immune changes occur following adolescent stress exposure and whether it is possible to prevent the delayed occurrence of cognitive impairment through early immune intervention. Firstly, the present study investigated the time courses of microglia and TNFα changes in the mPFC following adolescent social stress. The results showed that compared to the controls, stress-exposed animals showed parallel variations in the protein expression of ionized calcium-binding adaptor molecule 1 (Iba1), a biomarker specific to microglia, and TNFα in the mPFC, with a transient increase during stress exposure, then a gradual decrease after the end of stress, leading to a significantly decreased level in adulthood. We further investigated the preventive effect of chronic treatment with the immune inhibitor minocycline during stress exposure on the cognitive and molecular alterations induced by adolescent social stress. The results showed that minocycline prevented the delayed cognitive deficit and the decreased immune changes in the mPFC of previously stressed adult mice. These results suggest that the transient upregulation of microglia and TNFα in the mPFC induced by adolescent social stress may participate in the development of cognitive flexibility deficit and that immunomodulation may act as a potential target for the early prevention of cognitive deficits in psychiatric disorders.