Effect of an intra hypothalamic gene therapy with IGF 1 on behavioral parameters.

JERONIMO PENINNI; MACARENA LORENA HERRERA; FRANCO JUAN CRUZ DOLCETTI; MARIA JOSÉ BELLINI; EUGENIA FALOMIR-LOCKHART

virtual

Congreso; The Virtual Congress on Brain Health, Innovation & Technologies; 2020

Bioevents Ltd.

BACKGROUNDAging is characterized by a coordinated organs and tissues functional impairment. The hypothalamus, a region known to regulate many basic functions such as growth, development, reproduction and metabolism, is proposed as a regulatory center of aging. Evidence demonstrates that the inhibition or activation of microglial or neural transcription factor NF-κB of the basal hypothalamus (BH) 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 do not respond to estradiol positive feedback with an appropriate modulation of excitatory and inhibitory hypothalamic neurotransmitter release. This imbalance could cause reduced activation of GnRH neurons, reduced GnRH release, and an abnormal LH surge. OBJECTIVEIt is well known that IGF-1 plays a physiological role in neuroprotection and neuroinflammation. We decided to investigate the effects of intrahypothalamic gene therapy for IGF-1 in MA rats .We propose that transgenic IGF-1 will modulate neuroinflammation and delay reproductive senescence.METHODSWe employed recombinant adenovirus RAds as a carrier to deliver either a therapeutic (IGF-1) or control gene (DsRed) and performed intra-hypothalamic stereotactic injections with Rad-IGF-1, Rad-DsRed or PBS.CONCLUSIONThe MA rat brain reduction of factors like IGF-1 could be the reason of the affected modulation on excitatory and inhibitory hypothalamic release. These findings provide a link between inflammation, response to stress and systemic and cerebral aging.