ROLE OF ESTRADIOL RECEPTOR BETA (ERβ) ON BRAIN MITOCHONDRIAL FUNCTIONS AND CARDIO‐RESPIRATORY CONTROL IN AGED FEMALE MICE

Abstract

We tested the hypothesis that ERβ is involved in brain mitochondrial function and cardio‐respiratory control in aged female mice. We used aged (17–18 months‐old) ERβKO and wild‐type controls (WT) female mice to assess arterial blood pressure (via a tail‐cuff sensor) and indices of respiratory pattern (sighs and apneas – recorded by whole body plethysmography at rest). We also measured respiratory parameters at rest and in response to brief (<10 minutes) exposure to hypoxia (12% O2) or hypercapnia (5% CO2). Because ERβ is localized in mitochondria, and because estradiol and ERβ agonist increase mitochondrial O2 consumption, we used fresh brain cortex tissue (~2 mg) permeabilized with saponin to assess mitochondrial respiration with high‐resolution respirometry (O2k‐ Oroboros) and in‐vitro activity of the complex I of the electron transport chain. In ERβKO female mice, mean arterial blood pressure was lower than in old WT mice (88±4 vs 110±3 mmHg, P<0.05), the frequency of sighs was similar in ERβKO than in WT micez (26±3 vs 19±2 sighs/h P=ns) and the frequency of apneas much lower (4±2 vs 26±9 apnea/h, P=0.01). In ERβKO mice, minute ventilation is reduced in response to hypoxia (−50%, P<0.01) and hypercapnia (−39%, P<0.01) compared to WT mice. Concerning mitochondrial function, with substrates of complex I (Pyruvate/Glutamate/Malate) and in presence of ADP, ERβKO mice have a reduced O2 consumption compared to WT mice (60±7 vs 98±4 pmol O2/s/mg tissue, p<0.05). With the substrate of complex II (succinate) and ADP, there was no difference between ERβKO and WT mice. In vitro activity of complex I is 70% lower in ERβKO mice compared to WT (P<0.01). We conclude that the deletion of ERβ reduces chemoreflex functions and reduces mitochondrial function in the central nervous system. This role ERβ may be relevant in pathological or physiological conditions in which O2 homeostasis is compromised (sleep apnea, altitude, lung diseases).Support or Funding InformationCIHR, Région Rhône Alpes and consulat de France in QuébecThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.