Role of the Oxytocinergic System in Correcting Neurogenic Impairments Induced by Early Life Stress: an in vitro Study

Early life stress (ELS) induces long-term changes in neuroplasticity, which are associated with oxytocinergic system dysfunction. However, the molecular mechanisms of these impairments and the possibilities for their correction remain insufficiently studied. This work investigated the influence of ELS, exogenous oxytocin (OXT), and the oxytocin receptor antagonist atosiban on cellular processes related to homeostasis and neurogenesis in neurospheres in vitro. Neurospheres were isolated from the subventricular zone and piriform cortex of CD1 mouse brains (age P60) from control and ELS groups, followed by oxytocin (1 µM) or atosiban (1 µM) treatment. The levels of apoptosis, the degree of DNA damage (γH2AX), and the expression of neurogenesis marker genes PSA-NCAM, Dcx, Tbr1, Gad67, and Vglut1 were quantified using qRT-PCR. It was found that ELS increased the level of cell apoptosis and decreased the expression of PSA-NCAM, Dcx, and Gad67 genes, while oxytocin led to a decrease in the number of apoptotic cells but did not affect the expression of the studied genes, except for the suppression of Tbr1. In control cultures, oxytocin increased the expression of PSA-NCAM and Tbr1, while simultaneously reducing the level of Gad67, which may reflect a regulatory influence of this gene on the balance of excitatory and inhibitory transmission in the developing neuronal network. Atosiban-induced stimulation, in turn, led to increased apoptosis in control samples, emphasizing the role of oxytocinergic activity in maintaining neuronal viability even in the absence of stress factors. The obtained data indicate that ELS causes long-term impairments in neurogenesis and cellular homeostasis, while the modulating effect of OXT relies on the initial state of cells. These results highlight the potential role of the oxytocinergic system in correcting the consequences of ELS.