title: Enriched endogenous omega-3 fatty acids in mice protect against global ischemia injury.
abstract: Transient global cerebral ischemia, one of the consequences of cardiac arrest and cardiovascular surgery, usually leads to delayed death of hippocampal cornu Ammonis1 (CA1) neurons and cognitive deficits. Currently, there are no effective preventions or treatments for this condition. Omega-3 (ω-3) PUFAs have been shown to have therapeutic potential in a variety of neurological disorders. Here, we report that the transgenic mice that express the fat-1 gene encoding for ω-3 fatty acid desaturase, which leads to an increase in endogenous ω-3 PUFAs and a concomitant decrease in ω-6 PUFAs, were protected from global cerebral ischemia injury. The results of the study show that the hippocampal CA1 neuronal loss and cognitive deficits induced by global ischemia insult were significantly less severe in fat-1 mice than in WT mice controls. The protection against global cerebral ischemia injury was closely correlated with increased production of resolvin D1, suppressed nuclear factor-kappa B activation, and reduced generation of pro-inflammatory mediators in the hippocampus of fat-1 mice compared with WT mice controls. Our study demonstrates that fat-1 mice with high endogenous ω-3 PUFAs exhibit protective effects on hippocampal CA1 neurons and cognitive functions in a global ischemia injury model.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Chuanming
authors.initials: C
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wan
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Chengwei
authors.initials: C
authors.lastname: He
authors.affiliation: Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, PR China.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.affiliation: Laboratory for Lipid Medicine and Technology, the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Su
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: D015820:Cadherins; C502406:fat1 protein, mouse; C518399:resolvin D1; D004281:Docosahexaenoic Acids