Behavioral parameters of depression, anxiety and spatial memory in ovariectomized and hormone-treated adult rats and its association with mtDNA repair mechanisms in brain cortex and hippocampus

ZÁRATE SANDRA; IMSEN MERCEDES; MERINO FLORENCIA; DENING MARÍA BELÉN; REINÉS ANALÍA; STEVNSNER TINNA

Congreso; Neuroscience Day 2016 - Brain matters; 2016

Ovarian hormones exert neuroprotective actions and their loss during menopause is accompanied by synaptic and cognitive impairments and increased risk of neurodegeneration, processes that are highly associated with mitochondrial dysfunction. Accumulative damage in mitochondrial DNA (mtDNA) over time, if not properly repaired, leads to mitochondrial dysfunction and disease. Little is known about how mtDNA repair mechanisms are affected during menopause.In this work we evaluate a model of long-term ovariectomy (OVX) and early hormone replacement therapy (HRT) in rats in terms of behavioral parameters (depression, anxiety, spatial memory) and delineate further studies in brain mtDNA repair mechanisms within research collaboration with the Department of Molecular Biology in Aarhus University.Twelve-week ovarian hormone deprivation induced depressive-like behavior and impaired spatial memory in OVX rats, evaluated in the forced swimming test and the Y maze spontaneous alternation test, respectively. OVX rats also showed enhanced anxiety evaluated by the elevated plus maze test. HRT differentially impacted in these behaviors. Next, mtDNA repair mechanisms will be assessed in synaptic and non-synaptic mitochondria from rat cortex and hippocampus, areas primarily affected in aging and highly responsive to ovarian hormones.This study could help find new therapeutic targets for interventions in peri or early menopause.