Polyunsaturated fatty acids are potent neuroprotectors

被引:393
作者
Lauritzen, I [1 ]
Blondeau, N [1 ]
Heurteaux, C [1 ]
Widmann, C [1 ]
Romey, G [1 ]
Lazdunski, M [1 ]
机构
[1] CNRS, Inst Pharmacol Mol & Cellulaire, UPR 411, F-06560 Valbonne, France
关键词
background K+ channels; epilepsy; excitotoxicity; ischemia; polyunsaturated fatty acids;
D O I
10.1093/emboj/19.8.1784
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Results reported in this work suggest a potential therapeutic value of polyunsaturated fatty acids for cerebral pathologies as previously proposed by others for cardiac diseases. We show that the polyunsaturated fatty acid linolenic acid prevents neuronal death in an animal model of transient global ischemia even when administered after the insult. Linolenic acid also protects animals treated with kainate against seizures and hippocampal lesions. The same effects have been observed in an in vitro model of seizure-like activity using glutamatergic neurons and they have been shown to be associated with blockade of glutamatergic transmission by low concentrations of distinct polyunsaturated fatty acids. Our data suggest that the opening of background K+ channels, like TREK-1 and TRAAK, which are activated by arachidonic acid and other polyunsaturated fatty acids such as docosahexaenoic acid and linolenic acid, is a significant factor in this neuroprotective effect. These channels are abundant in the brain where they are located both pre- and post-synaptically, and are insensitive to saturated fatty acids, which offer no neuroprotection.
引用
收藏
页码:1784 / 1793
页数:10
相关论文
共 53 条
  • [1] POTASSIUM CHANNEL ACTIVATORS ABOLISH EXCITOTOXICITY IN CULTURED HIPPOCAMPAL PYRAMIDAL NEURONS
    ABELE, AE
    MILLER, RJ
    [J]. NEUROSCIENCE LETTERS, 1990, 115 (2-3) : 195 - 200
  • [2] EXCITOTOXICITY INDUCED BY ENHANCED EXCITATORY NEUROTRANSMISSION IN CULTURED HIPPOCAMPAL PYRAMIDAL NEURONS
    ABELE, AE
    SCHOLZ, KP
    SCHOLZ, WK
    MILLER, RJ
    [J]. NEURON, 1990, 4 (03) : 413 - 419
  • [3] Fish consumption and risk of sudden cardiac death
    Albert, CM
    Hennekens, CH
    O'Donnell, CJ
    Ajani, UA
    Carey, VJ
    Willett, WC
    Ruskin, JN
    Manson, JE
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1998, 279 (01): : 23 - 28
  • [4] Ionotropic glutamate receptors: New types and new concepts
    Barnard, EA
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 1997, 18 (05) : 141 - 148
  • [5] CHOI DW, 1994, PROG BRAIN RES, V100, P47
  • [6] Colbert CM, 1999, J NEUROSCI, V19, P8163
  • [7] DUPRAT F, 2000, IN PRESS MOL PHARM
  • [8] Ettaiche M, 1999, INVEST OPHTH VIS SCI, V40, P729
  • [9] EXCITATORY AMINO-ACID RECEPTORS, NEURAL MEMBRANE PHOSPHOLIPID-METABOLISM AND NEUROLOGICAL DISORDERS
    FAROOQUI, AA
    HORROCKS, LA
    [J]. BRAIN RESEARCH REVIEWS, 1991, 16 (02) : 171 - 191
  • [10] A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids
    Fink, M
    Lesage, F
    Duprat, F
    Heurteaux, C
    Reyes, R
    Fosset, M
    Lazdunski, M
    [J]. EMBO JOURNAL, 1998, 17 (12) : 3297 - 3308