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Hyperbaric oxygen alleviates selective domains of cognitive and motor deficits in female 5xFAD mice

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Abstract

Treatment of Alzheimer’s disease (AD) has been limited to managing of symptoms or anti-amyloid therapy with limited results and uncertainty. Seeking out new therapies that can reverse the effects of this devastating disease is important. Hyperbaric oxygen (HBO) therapy could be such a candidate as it has been shown to improve brain function in certain neurological conditions. Furthermore, the role sex plays in the vulnerability/resilience to AD remains equivocal. An understanding of what makes one sex more vulnerable to AD could unveil new pathways for therapy development. In this study, we investigated the effects of HBO on cognitive, motor, and affective function in a mouse model of AD (5xFAD) and assessed protein oxidation in peripheral tissues as a safety indicator. The motor and cognitive abilities of 5xFAD mice were significantly impaired. HBO therapy improved cognitive flexibility and associative learning of 5xFAD females but not males, but HBO had no effect other aspects of cognition. HBO also reversed AD-related declines in balance but had no impact on gait and anxiety-like behavior. HBO did not affect body weights or oxidative stress in peripheral tissues. Our study provides further support for HBO therapy as a potential treatment for AD and emphasizes the importance of considering sex as a biological variable in therapeutic development. Further investigations into the underlying mechanisms of HBO’s sex-specific responses are warranted, as well as optimizing treatment protocols for maximum benefits.

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Funding

This research was supported by BvB Foundation Dallas, Office of Vice President for Research and Innovation, the Institute for Healthy Aging, and National Institutes of Health/National Institute on Aging (T32 AG020494), School of Biomedical Sciences seed grant, a grant in Aid of Research from the National Academy of Sciences, administered by Sigma Xi, The Scientific Research Society.

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  1. Department of Pharmacology & Neuroscience, School of Biomedical Sciences, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie, Fort Worth, TX, 76107, USA

    Paapa Mensah-Kane, Delaney L. Davis, Helen S. Shi, Oanh T. Trinh, Philip H. Vann, Ladislav Dory & Nathalie Sumien

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  1. Paapa Mensah-Kane
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  2. Delaney L. Davis
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  3. Helen S. Shi
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Correspondence to Nathalie Sumien.

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Mensah-Kane, P., Davis, D.L., Shi, H.S. et al. Hyperbaric oxygen alleviates selective domains of cognitive and motor deficits in female 5xFAD mice. GeroScience 46, 517–530 (2024). https://doi.org/10.1007/s11357-023-01047-2

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