Rosalind Franklin Society Proudly Announces the 2022 Award Recipient for Antioxidants & Redox Signaling

Brief episodes of sublethal hypoxia reprogram the brain response to face pos si ble subsequent lethal stimuli by triggering adaptive and prosurvival events, a phenomenon denominated hypoxic preconditioning (HP). The potential therapeutic implications of HP to forestall sporadic Alzheimer's disease (sAD) pathology remain unexplored. This study was undertaken to investigate the potential protective effects of HP in a sAD rat model and to uncover the mitochondrial adaptations under lying this nonpharmacological strategy. HP prevented the memory and learning deficits and tau pathology. More, HP attenuated reactive astrogliosis and abrogated altered energy metabolism and oxidative damage. Particularly, HP averted the increased lactate, glutamate, and succinate levels, and mitochondrial respiratory chain dysfunction. Mitochondrial biogenesis was stimulated immediately after HP, whereas in a latter phase mitochondrial fusion-fission events were modulated favoring the generation of elongated mitochondria. These results demonstrate that HP prevents sAD- like phenotype, in part by targeting mitochondria, emerging as a preventive strategy in the context of AD.