The Effects of Early Life Social Isolation Are Sex-Specific

Early life social isolation (ESI) is a severe stress that disrupts brain development, contributing to susceptibility to various stressors and predisposition to neurological and other diseases in later life. In rats, ESI can be modeled by maternal separation of pups, allowing for the study of its after-effects at different stages of animal development. This editorial highlights an article in the current issue of the Journal of Neurochemistry that reports the long-lasting behavioral effects of mild ESI (brief repetitive episodes of pup separation during the third week of postnatal development of rats) and the changes in the BDNF system of the nucleus accumbens. In particular, this study focused on ESI effects dependent on animal sex. This allowed the authors to show that mild ESI impaired social reward processing only in male rats and that this effect was accompanied by persistent downregulation of BDNF/TrkB signaling in the nucleus accumbens. In contrast, ESI in females had no behavioral consequences in the studied paradigm, although it led to increased BDNF/TrkB signaling. These findings indicate that male rats are more susceptible to maternal separation stress than females and highlight the important role of the BDNF system in the formation of this vulnerability.