Abstract
Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms. We showed that the KD recipe used was ketogenic and increased plasma levels of ketone bodies, especially β-hydroxybutyrate. The results of the behavior tests showed that the KD did not affect general locomotor activity but obviously promoted spatial learning. Moreover, the KD significantly improved the spatial memory impairment caused by hypobaric hypoxia (simulated altitude of 6000 m, 24 h). In addition, the improving-effect of KD was mimicked by intraperitoneal injection of BHB. The western blot and immunohistochemistry results showed that KD treatment not only increased the acetylated levels of histone H3 and histone H4 compared to that of the control group but also antagonized the decrease in the acetylated histone H3 and H4 when exposed to hypobaric hypoxia. Furthermore, KD-hypoxia treatment also promoted PKA/CREB activation and BDNF protein expression compared to the effects of hypoxia alone. These results demonstrated that KD is a promising strategy to improve spatial memory impairment caused by hypobaric hypoxia, in which increased modification of histone acetylation plays an important role.
Highlights
Hypobaric hypoxia is defined as a condition caused by the decreased partial pressure of oxygen in the atmosphere at high altitude, leading to reduced oxygen delivery to tissues
We found that acetylated levels of histones, such as acetyl-histone H3 (K9/K14), acetyl-histone H3 (K14), and acetyl-histone H4 (K12), were increased by Ketogenic diet (KD) treatment
KD treatment reversed the decrease in histone acetylation caused by hypobaric hypoxia
Summary
Hypobaric hypoxia is defined as a condition caused by the decreased partial pressure of oxygen in the atmosphere at high altitude, leading to reduced oxygen delivery to tissues. Ketogenic diet improves spatial memory funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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