Huperzine A ameliorates cognitive deficits and oxidative stress in the hippocampus of rats exposed to acute hypobaric hypoxia.
Acute exposure to high altitudes can cause neurological dysfunction due to decreased oxygen availability to the brain. In this study, the protective effects of Huperzine A on cognitive deficits along with oxidative and apoptotic damage, due to acute hypobaric hypoxia, were investigated in male Sprague-Dawley rats. Rats were exposed to simulated hypobaric hypoxia at 6,000 m in a specially fabricated animal decompression chamber while receiving daily Huperzine A orally at the dose of 0.05 or 0.1 mg/kg body weight. After exposure to hypobaric hypoxia for 5 days, rats were trained in a Morris Water Maze for 5 consecutive days. Subsequent trials revealed Huperzine A supplementation at a dose of 0.1 mg/kg body weight restored spatial memory significantly, as evident from decreased escape latency and path length to reach the hidden platform, and the increase in number of times of crossing the former platform location and time spent in the former platform quadrant. In addition, after exposure to hypobaric hypoxia, animals were sacrificed and biomarkers of oxidative damage, such as reactive oxygen species, lipid peroxidation, lactate dehydrogenase activity, reduced glutathione, oxidized glutathione and superoxide dismutase were studied in the hippocampus. Expression levels of pro-apoptotic proteins (Bax, caspase-3) and anti-apoptotic protein (Bcl-2) of hippocampal tissues were evaluated by Western blotting. There was a significant increase in oxidative stress along with increased expression of apoptotic proteins in hypoxia exposed rats, which was significantly improved by oral Huperzine A at 0.1 mg/kg body weight. These results suggest that supplementation with Huperzine A improves cognitive deficits, reduces oxidative stress and inhibits the apoptotic cascade induced by acute hypobaric hypoxia.
Clinical Laboratory Diagnostic Center, Urumqi General Hospital of PLA, Urumqi 830000, Xinjiang, China. qinghaishi@gmail.com
Qinghai
Q
Shi
Jianfeng
J
Fu
Di
D
Ge
Yan
Y
He
Jihua
J
Ran
Zhengxiang
Z
Liu
Jing
J
Wei
Tong
T
Diao
Youfang
Y
Lu
D000399:Air Pressure; D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers; D015153:Blotting, Western; D003072:Cognition Disorders / Q000188:drug therapy* / Q000523:psychology*; D003665:Decompression Sickness / Q000523:psychology; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism
D000470:Alkaloids; D015415:Biomarkers; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C050426:huperzine A; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D005978:Glutathione