Mitochondrial function and nitric oxide production in hippocampus and cerebral cortex of rats exposed to enriched environment

Abstract

Male rats (21 days) were assigned to enriched environment (EE) or to standard environment (SE) for 1 year. Oxygen consumption and the sensitivity to calcium induced mitochondrial permeability transition (MPT), through mitochondrial membrane potential (ΔΨm) and swelling, were determined in isolated hippocampal and cerebral cortex mitochondria. Mitochondrial H2O2 production rate, and NOS activity and expression associated with mitochondrial membranes were also assayed. Results showed that state 3 respiratory rate was increased by 80% in cerebral cortex mitochondria from EE rats and no changes were observed in hippocampal mitochondria after EE exposure. Calcium induced-swelling was 40% and 53% lower in hippocampal and cerebral cortex mitochondria from EE rats, as compared with SE rats. Calcium loading induced membrane depolarization in cerebral cortex mitochondria from EE rats but did not affect mitochondrial ΔΨm in hippocampal mitochondria from EE animals, probably due to decreased H2O2 formation. NO production associated to mitochondrial membranes was increased by 195% in cerebral cortex mitochondria but decreased by 47% in hippocampal mitochondria from EE rats, as compared with SE rats. Western blot analysis from nNOS protein expression associated to mitochondrial samples revealed a similar pattern. Our results suggest that in hippocampus and cerebral cortex, EE exposure protects mitochondria against calcium-induced MPT maintaining a convenient membrane potential, which assures a continuous energy supply.