Sex differences in brain mitochondrial metabolism: influence of endogenous steroids and stroke

Abstract

Steroids are neuroprotective and growing body of evidence indicates that mitochondria are a potential target of their effects. The mitochondria are the site of cellular energy synthesis, regulate oxidative stress and play a key role in cell death after brain injury and neurodegenerative diseases. After a summary of the literature on the general functions of mitochondria and the effects of sex steroid administrations on mitochondrial metabolism, we will summarize and discuss our recent findings concerning sex differences in brain mitochondrial function in physiological and pathological conditions. To analyze the influence of endogenous sex steroids, oxidative phosphorylation system, mitochondrial oxidative stress and brain steroid levels were compared between male and female mice, either intact or gonadectomized. Our results show that females have higher mitochondrial respiration and lower oxidative stress as compared to males and these differences were suppressed by ovariectomy but not orchidectomy. We have also shown that the decrease in brain mitochondrial respiration induced by ischaemia/reperfusion is different according to sex. In both sexes, treatment with progesterone reduced the ischaemia/reperfusion-induced mitochondrial alterations. Our findings point to sex differences in brain mitochondrial function under physiological conditions, and after stroke, and identify mitochondria as a target of the neuroprotective properties of progesterone. Thus, it is necessary to investigate sex specificity in brain physio-pathological mechanisms, especially when mitochondria impairment is involved.

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