文章基本信息

标题：Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson's disease
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作者：Melanie Bousquet ; Karl Gue ; Vincent Emond 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2011
卷号：52
期号：2
页码：263-271
DOI：10.1194/jlr.M011692
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：We have recently identified a neuroprotective role for omega-3 polyunsaturated fatty acids (n-3 PUFAs) in a toxin-induced mouse model of Parkinson's disease (PD). Combined with epidemiological data, these observations suggest that low n-3 PUFA intake is a modifiable environmental risk factor for PD. In order to strengthen these preclinical findings as prerequisite to clinical trials, we further investigated the neuroprotective role of n - 3 PUFAs in Fat-1 mice, a transgenic model expressing an n - 3 fatty acid desaturase converting n - 6 PUFAs into n - 3 PUFAs. Here, we report that the expression of the fat-1 transgene increased cortical n - 3:n - 6 PUFA ratio (+28%), but to a lesser extent than dietary supplementation (92%). Such a limited endogenous production of n - 3 PUFAs in the Fat-1 mouse was insufficient to confer neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity as assessed by dopamine levels, tyrosine hydroxylase (TH)-positive neurons and fibers, as well as nigral Nurr1 and dopamine transporter (DAT) mRNA expression. Nevertheless, higher cortical docosahexaenoic acid (DHA) concentrations were positively correlated with markers of nigral dopaminergic neurons such as the number of TH-positive cells, in addition to Nurr1 and DAT mRNA levels. These associations are consistent with the protective role of DHA in a mouse model of PD. Taken together, these data suggest that dietary intake of a preformed DHA supplement is more effective in reaching the brain and achieving neuroprotection in an animal model of PD.
关键词：docosahexaenoic acid ; dopamine ; fatty acids ; dopaminergic neurons ; catecholamines ; brain lipids