Ovarian hormones induce the expression and release of astroglial mitochondrial-encoded rat Humanin in vitro

DENING MARÍA BELÉN; CODAGNONE MARTIN; TRAETTA MARIANELA; SEILICOVICH ADRIANA; REINÉS ANALÍA; ZÁRATE SANDRA

Congreso; 26th ISN-ESN Biennial Meeting; 2017

Ovarian hormones exert neuroprotective actions in part by direct effects on neurons but also indirectly by regulating the release of neurotrophic factors by astrocytes. Ovarian hormone loss during menopause is associated with brain hypometabolism, synaptic failure and increased risk of neurodegeneration. Humanin (HN) is a mitochondrial-derived peptide with cytoprotective, metabolic, and anti-inflammatory effects in multiple cell types and animal models; it is localized in tissues with high metabolic rates and its expression decreases with age. Our previous studies in vivo show that HN colocalizes with astrocyte markers and its expression decreases in the hippocampus of hormone-deprived female rats. Still, little is known about ovarian hormone regulation of HN expression and secretion by astrocytes and the effects of this peptide on neuronal function.The aim of this work was to study the direct actions of estradiol and progesterone on the expression and release of HN by hippocampal astrocytes in vitro. To this aim, cultured astrocytes were incubated with estradiol (E, 1 nM), progesterone (P, 1 uM), E+P or vehicle for 24 h. Intracellular HNr expression was evaluated by immunocytochemistry and secreted HNr was determined by ELISA in the conditioned media. Our results show that HNr is expressed in astrocytes in vitro and that ovarian hormones increased its levels. The incubation with E+P was the most effective treatment to induce HNr secretion by astrocytes.Our results indicate that ovarian hormones positively regulate HN expression and release by astrocytes. Further experiments will assess the effect of astrocyte HN on neuronal function. The knowledge of HN effects in brain cells and its regulation by ovarian hormones could help find new therapeutic targets for interventions that may promote a healthier lifespan for post-menopausal women.