Assessment of mitochondrial and non‐mitochondrial O2 consumption using in hippocampal tissue exposed to intermittent hypoxia.

R4831 --> Intermittent Hypoxia (IH) is a well‐recognized trait of untreated sleep apnea. We have recently demonstrated that mitigating oxidative stress induced by IH prevents impairments to hippocampal NMDAr‐dependent LTP, hippocampal adult neurogenesis, spatial learning and memory. As these processes are also dependent on metabolic activity, the changes of metabolism caused by IH could also contribute to the impairment of synaptic plasticity and adult neurogenesis. The objective of this on‐going study is to assess mitochondrial respiration in hippocampal tissue after ten days of IH (IH10). We assessed hippocampal mitochondrial respiration using Seahorse XF24 Extracellular Flux Analyzer technology. The tissue biopsies (Diameter: 1mm, thickness: 350 μm) were prepared from hippocampal brain slices originating from control mice or mice exposed to IH10. Preliminary experiments indicate that the basal O2 consumption rate (OCR) tended to decrease in IH10 (control: 202 ± 15 pmol/min, n=8 vs. IH: 126 ± 39 pmol/min n=4, P=0.05) and maximal OCR induced by FCCP was decreased in IH10 (control: 278 ± 29 pmol/min vs. IH10: 126 ± 39 pmol/min, P<0.05). These findings suggest IH impaired mitochondrial function in the hippocampus. ATP‐linked OCR induced by oligomycin and proton leak were not altered by IH10. Interestingly, the proportion of non‑mitochondrial OCR in control was smaller than IH10 (control: 13 ± 1 % vs. IH10: 20 ± 5 %, P<0.05). Such a difference in non‐mitochondrial OCR may reflect a state favoring enhanced reactive oxygen species production independent of mitochondrial origin. In conclusion, our study provides greater insights into the molecular basis by which untreated sleep apnea accelerates neurodegeneration in conditions such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]