Sex differences in the mitochondrial bioenergetics of astrocytes but not microglia at a physiologically relevant brain oxygen tension

摘要

Biological sex is thought to influence mitochondrial bioenergetic function. Previous respiration measurements examining brain mitochondrial sex differences were made at atmospheric oxygen using isolated brain mitochondria. Oxygen is 160 mm Hg (21%) in the atmosphere, while the oxygen tension in the brain generally ranges from similar to 5 to 45 mm Hg (similar to 1-6% O-2). This study tested the hypothesis that sex and/or brain physiological oxygen tension influence the mitochondrial bioenergetic properties of primary rat cortical astrocytes and microglia. Oxygen consumption was measured with a Seahorse XF24 cell respirometer in an oxygen-controlled environmental chamber. Strikingly, male astrocytes had a higher maximal respiration than female astrocytes when cultured and assayed at 3% O-2. Three percent O-2 yielded a low physiological dissolved O-2 level of similar to 1.2% (9.1 mm Hg) at the cell monolayer during culture and 1.2-3.0%O-2 during assays. No differences in bioenergetic parameters were observed between male and female astrocytes at 21% O-2 (dissolved O-2 of similar to 19.7%, 150 mm Hg during culture) or between either of these cell populations and female astrocytes at 3% O-2. In contrast to astrocytes, microglia showed no sex differences in mitochondrial bioenergetic parameters at either oxygen level, regardless of whether they were non-stimulated or activated to a proinflammatory state. There were also no O-2- or sex-dependent differences in proinflammatory TNF-alpha or IL-1 beta cytokine secretion measured at 18 h activation. Overall, results reveal an intriguing sex variance in astrocytic maximal respiration that requires additional investigation. Findings also demonstrate that sex differences can be masked by conducting experiments at non-physiological O-2. (C) 2017 Elsevier Ltd. All rights reserved.