EFFECT OF DIHYDROMYRICETIN ON MEMORY IMPAIRMENT INDUCED BY HYPOBARIC HYPOXIA IN RATS AND ITS MECHANISM

LIU Peng; SANG Yuan; LI Feng; JING Hong-jiang; MU Hui-ling; WANG Ruo-yong

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Acta Nutrimenta Sinica ›› 2025, Vol. 47 ›› Issue (2) : 177-184.

ORIGINAL ARTICLES

EFFECT OF DIHYDROMYRICETIN ON MEMORY IMPAIRMENT INDUCED BY HYPOBARIC HYPOXIA IN RATS AND ITS MECHANISM

LIU Peng, SANG Yuan, LI Feng, JING Hong-jiang, MU Hui-ling, WANG Ruo-yong

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Abstract

Objective To study the effect of dihydromyricetin (DHM) on memory impairment induced by hypobaric hypoxia and its mechanism. Methods Fourty-eight male Sprague Dawley rats were randomly divided into normoxia group (NOR), normoxia plus dihydromyricetin group (NOR+DHM), hypoxia group (HYP) and hypoxia dihydromyricetin group (HYP+DHM), with 12 rats in each group. A hypobaric oxygen chamber was used to simulate hypobaric hypoxia environment equivalent to altitude 6000 m. The rats in the HYP group and HYP+DHM group were exposed to hypobaric hypoxia environment for 23 hours every day. The NOR+DHM and HYP+DHM groups were given 100mg/(kg·d) DHM by gavage, and the NOR group and HYP group were given the same volume of distilled water as the control group. All rats were tested for their memory ability after hypobaric hypoxia using the Morris water maze probe test. After the second probe test, the brains of the rats were further analyzed. The ultrastructure changes of synapse in the hippocampus were observed by transmission electron microscopy. The expressions of synaptic structure-related proteins and BDNF signaling pathway proteins were detected and analyzed by Western blots. Results The rats in the HYP group spent significantly less time and path length in the target quadrant than those in the NOR group (P<0.05), while the rats in the HYP+DHM group spent significantly more time and path length in the target quadrant than those in the HYP group. The observation by transmission electron microscope showed that the postsynaptic density of neurons in hippocampal CA1 region in the HYP group was thinner and less, and the mitochondria of the neurons were larger and swollen with vacuolar structure and partial loss of ridge structure was observed. The postsynaptic density was thicker in the HYP+DHM group than that in the HYP group, and the mitochondrial ridge structure was clearer than that in in the HYP group. Western blots analysis showed that compared with the NOR group, the expressions of PSD95 and SYP in the HYP group were decreased (P<0.05), while the expressions of PSD95 and SYP in the HYP+DHM group were significantly increased (P<0.05). Compared with the NOR group, the protein expression levels of BDNF and TrkB in the HYP group were significantly decreased (P<0.05), and the phosphorylation levels of PI3K and Akt in the HYP group were significantly decreased (P<0.05). After DHM intervention, the protein expression levels of BDNF and TrkB and the phosphorylation levels of PI3K and Akt in the HYP+DHM group were significantly increased (P<0.05). Conclusion Acute exposure to hypobaric hypoxia can impair memory ability. DHM can protect the synaptic structure and morphology of hippocampal neurons via the BDNF signaling pathway, and effectively alleviate memory impairment induced by hypobaric hypoxia exposure.

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dihydromyricetin / hypobaric hypoxia / rat / memory impairment / brain-derived neurotrophic factor / synaptic plasticity

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LIU Peng, SANG Yuan, LI Feng, JING Hong-jiang, MU Hui-ling, WANG Ruo-yong. EFFECT OF DIHYDROMYRICETIN ON MEMORY IMPAIRMENT INDUCED BY HYPOBARIC HYPOXIA IN RATS AND ITS MECHANISM[J]. Acta Nutrimenta Sinica. 2025, 47(2): 177-184

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