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

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Abstract

Early life stress (ELS) induces long-term changes in neuroplasticity which are associated with dysfunction of the oxytocinergic system. However, the molecular mechanisms of such impairments as well as the possibilities of their correction remain poorly understood. In this study, we investigated the effects of ELS, exogenous oxytocin (OXT), and an oxytocin receptor antagonist (atosiban) on cellular processes associated with homeostasis and neurogenesis in neurospheres in vitro. Neurospheres were isolated from the subventricular zone and pyriform cortex of CD1 mice (age P60) in the control and ELS groups, followed by exposure to oxytocin (OXT, 1 μM) or atosiban (1 μM). The level of apoptosis, the DNA damage (H2AX) and the expression of neurogenesis associated genes PSA-NCAM, Dcx, Tbr1, Gad67 and Vglut1 (qRT-PCR) were then quantitatively assessed. The data obtained showed that ELS increased the number of apoptotic cells and decreased the expression of PSA-NCAM, Dcx and Gad67 genes, while OXT improved apoptotic indices, but had no effect on the expression of the studied genes, with the exception of a decrease in Tbr1. In control group, OXT increased the expression of PSA-NCAM and Tbr1, while simultaneously decreasing the level of Gad67, which may reflect its regulatory effect on the balance of excitatory and inhibitory transmission in the developing neuronal network. Atosiban stimulation, however, resulted in increased apoptosis in control samples, highlighting the role of oxytocinergic activity in maintaining neuronal viability even in the absence of stress. These data indicate that ELS causes long-term impairments of neurogenesis and cellular homeostasis, and the modulating effect of OXT depends on the initial state of the cells. These results highlight the potential role of the oxytocinergic system in correcting the consequences of early life stress.

About the authors

E. D Khilazheva

V.F. Yoino-Yasenetsky Krasnoyarsk State Medical University

Krasnoyarsk, Russia

A. N Lukyanchuk

V.F. Yoino-Yasenetsky Krasnoyarsk State Medical University; Russian Center of Neurology and Neurosciences

Krasnoyarsk, Russia; Moscow, Russia

Yu. A Panina

V.F. Yoino-Yasenetsky Krasnoyarsk State Medical University

Krasnoyarsk, Russia

O. L Lopatina

V.F. Yoino-Yasenetsky Krasnoyarsk State Medical University

Krasnoyarsk, Russia

N. A Malinovskaya

V.F. Yoino-Yasenetsky Krasnoyarsk State Medical University

Krasnoyarsk, Russia

A. V Blagova

Russian Center of Neurology and Neurosciences

Moscow, Russia

A. B Salmina

V.F. Yoino-Yasenetsky Krasnoyarsk State Medical University; Russian Center of Neurology and Neurosciences

Krasnoyarsk, Russia; Moscow, Russia

Yu. K Komleva

Russian Center of Neurology and Neurosciences

Email: yuliakomleva@mail.ru
Moscow, Russia

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