The Effects of Early Life Stress on Behavior and Hippocampal Neuroplasticity

Abstract

Early life stress (ELS) can predispose individuals to develop psychopathologies, such as anxiety and depression later in life. The mechanisms underlying the relationship between ELS and mental illness still requires further elucidation and are essential for the advancement of therapies to help people with ELS related psychopathologies. Animal models of early life stress are essential for investigating the interplay between ELS induced abnormal behaviors characteristic of psychopathologies and changes in neurobiology and stress response. Research has implicated the hippocampus in ELS consequences given the synaptic plasticity of the region due to adult neurogenesis as well as its association with anxiety and depression. Moreover, changes have been observed within the hippocampus because of ELS, such as alterations in interneurons. We investigated the effects of maternal separation with early weaning (MSEW) on behavior as related to changes in hippocampal neuroplasticity in C57BL/6J during development and in adulthood. Testing mice on the elevated plus maze (EPM) and open field test (OF), we found in adulthood, MSEW mice exhibited behavior suggestive of increased anxiety and hyperactivity, respectively. Measuring behavioral inhibition and ultrasonic vocalizations when mice were isolated and when exposed to a threat, an unfamiliar male adult mouse, we found no clear, robust differences between MSEW and control mice during development. In terms of alterations in neuroplasticity, we found that compared to controls, adult MSEW mice exhibited significantly lower cell density of parvalbumin (PV) and somatostatin (SST) interneurons within the ventral hippocampus as well as a greater percentage of PV colocalization with c-Fos, an immediate early gene marker of neuronal activity. MSEW mice in development exhibited no significant alterations in hippocampal neuroplasticity.