Quercetin ameliorates hypobaric hypoxia-induced memory impairment through mitochondrial and neuron function adaptation via the PGC-1α pathway.

Abstract

PURPOSE:

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: Peng Liu, Dan Zou, Long Yi, Mingliang Chen, Yanxiang Gao, Rui Zhou, Qianyong Zhang, Yong Zhou, Jundong Zhu, Ka Chen, Mantian Mi
• Journal: Restorative neurology and neuroscience (Restor Neurol Neurosci) Vol. 33 Issue 2 Pg. 143-57 ( 2015) ISSN: 1878-3627 [Electronic] Netherlands
• PMID: 25588463 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• FNDC5 protein, rat
• Fibronectins
• Nootropic Agents
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, rat
• Transcription Factors
• Quercetin
• Sirt1 protein, rat
• Sirtuin 1

Topics

• Adaptation, Physiological (drug effects, physiology)
• Animals
• Brain-Derived Neurotrophic Factor (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Fibronectins (metabolism)
• Hippocampus (drug effects, pathology, physiopathology)
• Hypoxia (drug therapy, pathology, physiopathology)
• Male
• Maze Learning (drug effects, physiology)
• Memory Disorders (drug therapy, pathology, physiopathology)
• Mitochondria (drug effects, physiology)
• Neurons (drug effects, pathology, physiology)
• Nootropic Agents (pharmacology)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Pressure (adverse effects)
• Quercetin (pharmacology)
• Random Allocation
• Rats, Sprague-Dawley
• Sirtuin 1 (metabolism)
• Synapses (drug effects, pathology, physiology)
• Transcription Factors (metabolism)