Maternal separation disturbs postnatal development of the medial prefrontal cortex and affects the number of neurons and glial cells in adolescent rats

Abstract Adolescence is a period of extensive brain maturation. In particular, the regions of the medial prefrontal cortex (mPFC) undergo intense structural and functional refinement during adolescence. Disturbances in mPFC maturation have been implicated in the emergence of multiple psychopathologies during adolescence. One of the essential risk factors for the development of mental illness in adolescence is early-life stress (ELS), which may interfere with brain maturation. However, knowledge of the mechanisms by which ELS affects mPFC maturation and functioning in adolescents is very limited. In the present study, we applied a maternal separation (MS) procedure in rats to model ELS and studied its effect on the number of neurons and glial cells in the prelimbic region of the mPFC (PLC) of adolescent rats. Moreover, the expression of markers of cell proliferation and apoptosis was also studied. We found that MS rats had more neurons, astrocytes, and NG2-glial cells in the PLC. In contrast, the number of microglial cells was reduced in MS rats. These changes were accompanied by the decreased expression of proapoptotic genes and the increased expression of some prosurvival genes. Concurrently, MS did not affect cell proliferation in adolescents. Moreover, MS induced anxiety-like behaviors, but not anhedonic-like behavior, in adolescents. These results suggest that ELS may disturb neurodevelopmental apoptosis of neurons and early-postnatal proliferation and/or apoptosis of different populations of glial cells in the PLC. ELS-induced aberrations in the postnatal maturation of the PLC may affect cortical network organization and functioning and determine vulnerability to psychopathologies in adolescents.