title: Quercetin reverses hypobaric hypoxia-induced hippocampal neurodegeneration and improves memory function in the rat.
abstract: Inadequate oxygen availability at high altitude causes elevated oxidative stress, resulting in hippocampal neurodegeneration and memory impairment. Though oxidative stress is known to be a major cause of neurodegeneration in hypobaric hypoxia, neuroprotective and ameliorative potential of quercetin, a flavonoid with strong antioxidant properties in reversing hypobaric hypoxia-induced memory impairment has not been studied. Four groups of male adult Sprague Dawley rats were exposed to hypobaric hypoxia for 7 days in an animal decompression chamber at an altitude of 7600 meters. Rats were supplemented with quercetin orally by gavage during 7 days of hypoxic exposure. Spatial working memory was assessed by a Morris Water Maze before and after exposure to hypobaric hypoxia. Changes in oxidative stress markers and apoptotic marker caspase 3 expression in hippocampus were assessed. Histological assessment of neurodegeneration was performed by cresyl violet and fluoro Jade B staining. Our results showed that quercetin supplementation during exposure to hypobaric hypoxia decreased reactive oxygen species levels and consequent lipid peroxidation in the hippocampus by elevating antioxidant status and free radical scavenging enzyme system. There was reduction in caspase 3 expression, and decrease in the number of pyknotic and fluoro Jade B-positive neurons in hippocampus after quercetin supplementation during hypoxic exposure. Behavioral studies showed that quercetin reversed the hypobaric hypoxia-induced memory impairment. These findings suggest that quercetin provides neuroprotection to hippocampal neurons during exposure to hypobaric hypoxia through antioxidative and anti-apoptotic mechanisms, and possesses promising therapeutic potential to ameliorate hypoxia-induced memory dysfunction.
authors.affiliation: 1 Defense Institute of Physiology and Allied Sciences , Defense Research Development Organization, Ministry of Defense, Timarpur, Delhi, India .
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Prasad
authors.forename: Iswar
authors.initials: I
authors.lastname: Baitharu
authors.forename: Alpesh Kumar
authors.initials: AK
authors.lastname: Sharma
authors.forename: Ruma
authors.initials: R
authors.lastname: Dutta
authors.forename: Dipti
authors.initials: D
authors.lastname: Prasad
authors.forename: Shashi Bala
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000531:Altitude; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001274:Atmospheric Pressure; D053148:Caspase 3 / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008570:Memory, Short-Term; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000209:etiology; D009474:Neurons / Q000473:pathology; D018384:Oxidative Stress; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D011794:Quercetin; D053148:Caspase 3