IGF1 gene therapy modifies hypothalamic microglia and delays reproductive senescence

DOLCETTI, FRANCO JUAN CRUZ; FALOMIR LOCKHART, EUGENIA; HERRERA, MACARENA LORENA; GRASSI, DANIELA; ARÉVALO ARÉVALO, MARÍA ÁNGELES; BELLINI, MARIA JOSE

Congreso; XXXVI Annual Meeting of the Argentinian Society for Neuroscience Research; 2021

Sociedad argentina de investigacion en neurociencias

The process of aging affects the whole body including the central nervous system, where the hypothalamus plays a key role in the regulation of aging mechanisms. It has been described that a hypothalamic proinflammatory environment leads to reduce gonadotropin-releasing hormone (GnRH) secretion and affects Kisspeptin neurons.We postulate that reducing proinflammatory processes with neurotrophic factors, may preserve Kisspeptin system and decelerate the aging process. For this, we implemented intrahypothalamic Insulin like Growth Factor 1 (IGF1) gene therapy providing to middle-aged female rats. We evaluated therapy effects on microglial cells response, and Kisspeptin and GnRH neurons. Rats treated with IGF1 gene therapy showed higher Kisspeptin expression in the anteroventral periventricular nucleus (AVPV) and a greater immunoreactivity of GnRH in the arcuate nucleus (ARC) and medium eminence. Moreover, IGF1 treated animals displayed an increased number of Iba1 cells and double immunoreactive (MHCII/Iba1) microglial positive cells in both the AVPV and ARC. In conclusion, IGF1 gene therapy maintains Kisspeptin production in AVPV and induces GnRH release in the median eminence and modifies microglia cells number and reactivity in middle-aged female rats. Our findings lead to postulate that IGF1 gene therapy, implemented before the first signs of reproductive cessation, has a protective effect against the reproductive decline.