Ovarian hormone loss decreases astroglial expression of mitochondrial-encoded rat Humanin in the CA1 region of the hippocampus.

MERINO F; SEILICOVICH A; ZARATE S; REINES A; DENING MARIA BELEN

Copenhague

Congreso; 10º FENS Forum of Neuroscience; 2016

Rat Humanin (HNr) is a secreted peptide encoded in the mitochondrial genome with neuroprotective actions. HNr is localized in tissues with high metabolic rates and its expression decreases with age. Previously, we showed that chronic ovariectomy (OVX) induces mitochondrial dysfunction associated with a membrane lipid profile comparable to an aging phenotype in the hippocampus, a highly hormone-responsive area primarily affected during aging. Aims: to study HNr localization in different cell types in the hippocampus. Also, to assess the effect of OVX upon HNr expression and its putative relationship with the expression of astroglial marker GFAP in all hippocampal regions.Methods: Adult rats were ovariectomized or sham-operated. After 12 weeks the co-expression of HNr with GFAP, S100B, NF-200 or Olig2 was evaluated in brain sections by immunohistochemistry. Positive structures were quantified as relative immunoreactive area by Image J software. Results: HNr co-localized with astroglial but not neuronal or oligodendroglial markers. OVX decreased HNr expression in CA1 without changing its levels in the dentate gyrus. Also, GFAP expression was lower in all hippocampal regions in OVX rats and there was a positive correlation between HNr and GFAP levels in both SHAM and OVX rats.Conclusions: Astrocytes are the main source of neuroprotective HNr in the hippocampus and OVX-induced HNr lower expression is associated with decreased expression of GFAP. Our results suggest that OVX promotes functional and morphological changes in astrocyes, reducing their complexity and/or number. This could affect astroglial support to neuronal function and may represent an underlying mechanism for synaptic dysfunction after menopause.