Polyunsaturated fatty acids are potent neuroprotectors.
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.
Lauritzen
I
I
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Blondeau
N
N
Heurteaux
C
C
Widmann
C
C
Romey
G
G
Lazdunski
M
M
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016704:Synapsins / Q000378:metabolism; D013997:Time Factors; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; C503433:Kcnk4 protein, mouse; D015221:Potassium Channels; D016704:Synapsins; D017962:alpha-Linolenic Acid; D019308:Palmitic Acid; D008274:Magnesium; D007608:Kainic Acid; D002118:Calcium