Dehydroepiandrosterone alleviates hypoxia‐induced learning and memory dysfunction by maintaining synaptic homeostasis

Abstract

Aims: Hypoxia causes plenty of pathologies in the central nervous system (CNS) including impairment of cognitive and memory function. Dehydroepiandrosterone (DHEA) has been proved to have therapeutic effects on CNS injuries by maintaining the homeostasis of synapses, yet its effect on hypoxia-induced CNS damage remains unknown. Methods: In vivo and in vitro models were established. Concentrations of glutamate and γ GABA were tested by ELISA. Levels of synapse-associated proteins were measured by western blotting. Density of dendritic protrusions of hippocampal neurons was assessed by Golgi staining. Immunofluorescence was adopted to observe the morphology of primary neurons. The novel object recognition test (NORT) and shuttle box test were used to evaluate cognition. Results: Dehydroepiandrosterone reversed abnormal elevation of glutamate levels, shortenings of neuronal processes, decreases in the density of dendritic protrusions, downregulation of synaptosome-associated protein (SNAP25), and impaired cognition caused by hypoxia. Hypoxia also resulted in notably downregulation of syntaxin 1A (Stx-1A). Overexpression of Stx-1A dramatically attenuated hypoxia-induced elevation of glutamate. Treatment with DHEA reversed the Stx-1A downregulation caused by hypoxic exposure. Conclusion: Dehydroepiandrosterone may exert a protective effect on hypoxiainduced memory impairment by maintaining synaptic homeostasis. These findings offer a novel understanding of the therapeutic effect of DHEA on hypoxia-induced cognitive dysfunction.

A longitudinal study on the impact of high‐altitude hypoxia on perceptual processes

“…The plateau environment is known for its low oxygen availability, low pressure, low temperature, low humidity, and high solar radiation. Among them, hypoxia is a major factor affecting human life activities in plateau environments (Guan et al., 2022). Despite several years of research, hypoxia remains a significant public health problem that has a direct and vital impact on human cognitive ability (Liu et al., 2022) and leads to several behavioral and physiological changes (Zhao et al., 2016).…”