title: Quercetin ameliorates hypobaric hypoxia-induced memory impairment through mitochondrial and neuron function adaptation via the PGC-1α pathway.
abstract: OBJECTIVE
  Acute hypobaric hypoxia (HH) causes persistent cognitive impairment, affecting memory function specifically. Mitochondrial dysfunction and synaptic morphological change were the prominent pathological features of HH exposure on brain. Quercetin, a flavonoid found in fruits, vegetables, leaves and grains, is reported to prevent ischemia induced by neuronal injury. This study investigated the efficacy of quercetin to ameliorate HH-induced memory deficit.
  
  
  METHODS
  Rats were exposed to HH equivalent to 5000 m for 7 days in a decompression chamber and received quercetin daily (50, 75 or 100 mg/kg·bw) via gavage during the period of exposure. Cognitive performance was assessed by the Morris water maze test. In vitro, the effect of quercetin was tested in hippocampus tissue.
  
  
  RESULTS
  Quercetin, especially at 100 mg/kg·bw, significantly reduced HH-induced memory decline. Meanwhile, HH-induced hippocampus mitochondrial and synaptic lesions were ameliorated by quercetin. Furthermore, quercetin regulated the expression of sirtuin 1(Sirt1), PGC-1α, and the proteins related with mitochondrial biogenesis and dynamics. Moreover, quercetin increased expression of fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF), showing the PGC-1α/FNDC5/BNDF pathways might be involved in neuronal adaptation.
  
  
  CONCLUSIONS
  The results suggest quercetin has prophylactic potential for amelioration of HH-induced memory impairment, which is associated with the mitochondrial and neuronal adaptation in hippocampus.
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zou
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Chen
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Yanxiang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Qianyong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Ka
authors.initials: K
authors.lastname: Chen
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
authors.forename: Mantian
authors.initials: M
authors.lastname: Mi
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011312:Pressure / Q000009:adverse effects; D011794:Quercetin / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C583676:FNDC5 protein, rat; D005353:Fibronectins; D018697:Nootropic Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D011794:Quercetin; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: Hypobaric hypoxia; PGC-1α; memory impairment; mitochondria; neuroprotection; quercetin