IGF1 gene therapy delays reproductive senescence

HERRERA, MACARENA LORENA; DOLCETTI, FRANCO JUAN CRUZ; ARÉVALO ARÉVALO, MARÍA ÁNGELES; HEREÑÚ, CLAUDIA BEATRIZ; BELLINI, MARIA JOSE; FALOMIR-LOCKHART, EUGENIA; GARCÍA-SEGURA, LUIS MIGUEL

Córdoba

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Sociedad Argentina de Investigación en Neurociencias

The hypothalamus, a region known to regulate many basic functions such as growth, development, reproduction and metabolism, is thought to be a regulatory center of aging. Evidence demonstrates that the inhibition or activation of the transcription factor NF-κB in microglia or in neurons of the basal hypothalamus (HMB) affects the life expectancy and the "beginning" of aging, as well as the release of GnRH. There is solid evidence that middle age (MA) rats have reduced activation of GnRH neurons, GnRH release, and an abnormal LH surge. These findings provide a link between inflammation, response to stress and systemic and cerebral aging.In this project, we implemented long-term anti-inflammatory gene therapy for IGF-I in the HMB of MA female rats (8 months) up to 12 months, in order to modulate the inflammatory response mediated by NFkB and delay the appearance of reproductive cessation.Our results show that, at the end of the experiment, rats treated with IGF1 presen a higher proportion of cycling rats compared to the control group. We also observed that IGF1 group has a higher number of axonal projections of the GnRH+ neurons. These results suggest that IGF1 prolongs the reproductive life of MA rats, maintaining GnRH+ neurons functionality.