title: Quercetin attenuates domoic acid-induced cognitive deficits in mice.
abstract: Domoic acid (DA) is one of the best known marine toxins, causative of important neurotoxic alterations. DA effects are documented both in wildlife and experimental assays, showing that this toxin causes severe injuries principally in the hippocampal area. Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress are involved in DA-induced cognitive functional impairment. Therefore, therapeutics targeted to improve mitochondrial function and increase oxidative stress defence could be beneﬁcial. Quercetin, a bioﬂavanoid, has been reported to have potent neuroprotective effects and anti-oxidative ability, but its preventive effects on DA-induced mitochondrial dysfunction and cognitive impairment have not been well characterised. In this study, we evaluated the effects of quercetin on DA-induced cognitive deficits in mice and explored its potential mechanism. Our results showed that the oral administration of quercetin to DA-treated mice significantly improved their behavioural performance in a novel objective recognition task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of PPARγ coactivator 1α-mediated mitochondrial biogenesis signalling and an amelioration of mitochondrial dysfunction. Moreover, quercetin activated nuclear factorerythroid-2-related factor-2 (Nrf2)-mediated phase II enzymes and decreased reactive oxygen species and protein carbonylation. Furthermore, the AMP-activated protein kinase (AMPK) activity significantly increased in the quercetin-treated group. Taken together, these findings suggest that a reduction in mitochondrial dysfunction through the increase of AMPK activity, coupled with an increase in Nrf2 pathway mediated oxidative defence, may be one of the mechanisms by which quercetin improves cognitive impairment induced by DA in mice.
authors.affiliation: a Department of Pathogen Biology, Medical College , Henan University of Science and Technology , Luoyang , China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: b Department of Pathology, Medical College , Henan University of Science and Technology , Luoyang , China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: c Department of Biochemistry and Molecular Biology, Medical College , Henan University of Science and Technology , Luoyang , China.
authors.forename: Sanqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: c Department of Biochemistry and Molecular Biology, Medical College , Henan University of Science and Technology , Luoyang , China.
authors.forename: Guomin
authors.initials: G
authors.lastname: Shen
authors.affiliation: c Department of Biochemistry and Molecular Biology, Medical College , Henan University of Science and Technology , Luoyang , China.
authors.forename: Shu
authors.initials: S
authors.lastname: Hu
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000031:analogs & derivatives; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D011794:Quercetin; C012301:domoic acid; D007608:Kainic Acid
keywords: AMPK; Cognitive deficits; Domoic acid; Mitochondrial dysfunction; Oxidative stress; Quercetin