IGF1 GENE THERAPY DELAYS REPRODUCTIVE SENESCENCE

HERRERA, MACARENA LORENA; DOLCETTI, FRANCO JUAN CRUZ; AREVALO, MA; FALOMIR-LOCKHART , E; BELLINI , MARÍA J

Santiago de Compostela

Encuentro; 18th National Meeting of the Spanish Society of Neuroscience; 2019

SENC

Background: 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 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.Material and methods: We performed intrahypothalamic stereotactic injection to implement long-term anti-inflammatory gene therapy for IGF1 in the HMB of MA female rats (8 months) up to 12 months, in order to modulate the inflammatory response mediated by NF-kB and delay the appearance of reproductive cessation. The cyclicity of the animals was monitored daily by colpocytologyFor immunohistochemical analysis, non-contiguous brain slides were selected and processed with anti-GnRH, anti-Iba1 or anti-Kisspeptin antibodies.Results: Our results show that, at the end of the experiment, rats treated with IGF1 present a higher proportion of cycling rats compared to control group. We also observed that IGF1 group has a higher number of axonal projections of the GnRH+ neurons and a higher number of Kisppeptin+ neurons in the hypothalamic anteroventral periventricular nucleus. Conclusions: These results suggest that IGF1 prolongs the reproductive life of MA rats, maintaining GnRH+ and Kisppeptin+ neurons functionality.