INV SUPERIOR JUBILADO
SEILICOVICH Adriana
congresos y reuniones científicas
Título:
Mitochondrial DNA repair activities in hormone-responsive brain regions in ovariectomized and estradiol-treated adult rats
Autor/es:
R.GREDILLA; F.MERINO; M. IMSEN; A. SEILICOVICH; A.REINES; T.STEVNSNER; S.ZÁRATE
Reunión:
Congreso; 2º Congreso de FALAN; 2016
Resumen:
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. Due to the proximity of mtDNA to the main sites of mitochondrial free radical generation, oxidative stress is a major source of DNA mutations in mitochondria. The base excision repair (BER) pathway removes oxidative lesions from mtDNA, thereby constituting an important mechanism to avoid accumulation of mtDNA mutations. The complexity of the brain implies that exposure and defense against oxidative stress varies among brain regions and hence some regions may be particularly prone to accumulation of mtDNA damages. Little is known about how hormonal status affect mtDNA repair mechanisms in the brain cortex and hippocampus, areas primarily affected in aging and highly responsive to ovarian hormones. In this work we evaluate the efficiency of the BER pathway in mitochondria from cortex and hippocampus of adult long-term ovariectomized rats as well as the effect of early estradiol replacement treatment in this repair pathway. Our data suggest regional specific regulation of mitochondrial BER regarding hormonal status. This study could help find new therapeutic targets for interventions in early menopause.