IGF1 Gene Therapy Delays Reproductive Senescence

DOLCETTI, FRANCO JUAN CRUZ; FALOMIR-LOCKHART, EUGENIA; HERRERA MACARENA LORENA; HEREÑU, CLAUDIA B.; GARCIA-SEGURA, LUIS M.; AREVALO, MA; BELLINI , MARÍA J

Cordoba

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Sociedad RAgentin de Neurocinecias

The hypothalamus, a region known to regulate many basicfunctions such as growth, development, reproduction, andmetabolism, is thought to be a regulatory center of aging.Evidence demonstrates that the inhibition or activation ofthe transcription factor NF-jB in microglia or in neurons ofthe basal hypothalamus (HMB) affects the life expectancyand the ?beginning? of aging as well as the release ofGnRH. There is solid evidence that middle-aged (MA) ratshave reduced activation of GnRH neurons, GnRH release,and an abnormal LH surge. These findings provide a linkbetween inflammation, response to stress, and systemicand cerebral aging. In this project, we implemented longtermanti-inflammatory gene therapy for IGF1 in the HMBof MA female rats (8 months) up to 12 months, in order tomodulate the inflammatory response mediated by NFkB anddelay the appearance of reproductive cessation. Our resultsshow that, at the end of the experiment, rats treated withIGF1 present a higher proportion of cycling rats comparedto the control group. We also observed that IGF1 group hasa higher number of axonal projections of the GnRHþ neurons.These results suggest that IGF1 prolongs the reproductivelife of MA rats, maintaining GnRHþ neuronsfunctionality.