Transplantation of medial ganglionic eminence cells rescues early-life stress-induced social and cognitive impairments in postnatal mice

Abstract

During the critical window of early development, exposure to stress has been demonstrated to impair brain function, thereby elevating the likelihood of subsequent social and cognitive impairments. In our study, we have developed a reliable mouse model of early life stress that emulates prevalent stressors in the human population, utilizing early maternal-infant separation coupled with a four-week chronic unpredictable mild stress (CUMS). Subsequent to this intervention, we transplanted GABAergic progenitor cells into the hippocampus with the aim of mitigating the social and cognitive deficits observed in postnatal mice. Our findings reveal that mice subjected to early stress display significant social and cognitive impairments, characterized by deficits in communication, cognitive developmental delays, repetitive behaviors, and anxiety-related affective disorders. The transplantation of GABAergic progenitor cells into the hippocampus of these stressed mice has been shown to enhance neurogenesis, increasing the population of GABAergic neurons and augmenting the expression of key synaptic proteins, including Reelin, Fyn, PSD95, and SYN.Our results highlight the potential of medial ganglion cell transplantation into the hippocampus to ameliorate the social and cognitive deficits triggered by early life stress. This approach holds significant promise for the therapeutic intervention of psychobehavioral disturbances stemming from early stress exposure.