INV SUPERIOR JUBILADO
SEILICOVICH Adriana
congresos y reuniones científicas
Título:
Humanin, a mitochondrial-derived peptide released by astrocytes, prevents synapse loss in hippocampal neurons
Autor/es:
S. ZARATE; M.TRAETTA; M.CODAGNONE; A.REINES; A. SEILICOVICH
Reunión:
Congreso; LXIII Reunión de la Sociedad Argentina de Investigación Clínica; 2018
Resumen:
Ovarian hormones are neuroprotective, in part by activating neural steroid receptors but also by regulating the release of neurotrophic factors by glial cells. After menopause, loss of ovarian hormones is often associated brain hypometabolism, synaptic failure and mitochondrial dysfunction.Humanin (HN) is a mitochondrial-derived peptide with cytoprotective, metabolic, and anti-inflammatory effects in tissues with high metabolic rates and whose expression decreases with age. Our previous data 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 release by astrocytes and the effects of this peptide on neuronal function. The aim of this study was to evaluate the effects of ovarian hormones in the expression and release of HN by astrocytes and HN action on synaptic parameters in hippocampal neurons in vitro.To this aim, cultured astrocytes were incubated with estradiol (E, 1 nM), progesterone (P, 1 uM), E+P or vehicle and intracellular HN expression was evaluated by FACS. In parallel, cultured hippocampal neurons were exposed to glutamate in a condition that induces dendritic atrophy and reduces synapse number in the presence or absence of HN (0,01 uM) and the expression pattern of the pre-synaptic marker synaptophysin (SYN) was evaluated by immunocytochemsitry and ImageJ software.Our results show that E+P increased HN expression per cell and HN levels in astrocyte conditioned media (p˂0.05; Student?s t test). Also, HN prevented glutamate-induced reduction in puncta number and total puncta area for SYN (p˂0.05, ANOVA). Our results indicate that ovarian hormones positively regulate the expression and release of an astroglial peptide likely involved in synapse maintenance. Our study could help find new therapeutic targets for interventions that may promote a healthier lifespan for post-menopausal women.