title: Chronic dietary intake of α-linolenic acid does not replicate the effects of DHA on passive properties of entorhinal cortex neurons.
abstract: n-3 PUFA are receiving growing attention for their therapeutic potential in central nervous system (CNS) disorders. We have recently shown that long-term treatment with DHA alters the physiology of entorhinal cortex (EC) neurons. In the present study, we investigated by patch-clamp the effect of another major dietary n-3 PUFA, α-linolenic acid (LNA), on the intrinsic properties of EC neurons. Mice were chronically exposed to isoenergetic diets deficient in n-3 PUFA or enriched in either DHA or LNA on an equimolar basis. GC analyses revealed an increase in DHA (34%) and a decrease in arachidonic acid (AA, - 23%) in brain fatty acid concentrations after consumption of the DHA-enriched diet. Dietary intake of LNA similarly affected brain fatty acid profiles, but at a lower magnitude (DHA: 23%, AA: - 13%). Compared to the n-3 PUFA-deficient diet, consumption of DHA, but not LNA, induced membrane hyperpolarisation ( -60 to -70 mV), increased cellular capacitance (32%) and spontaneous excitatory postsynaptic current frequency (50%). We propose that the inefficiency of LNA to modulate cellular capacitance was related to its inability to increase the brain DHA:AA ratio over the threshold necessary to up-regulate syntaxin-3 (46%) and translocate drebrin (40% membrane:cytosol ratio). In summary, our present study shows that the increase in brain DHA content following chronic administration of LNA was not sufficient to alter the passive and synaptic properties of EC neurons, compared to direct dietary intake of DHA. These diverging results have important implications for the therapeutic use of n-3 PUFA in CNS disease, favouring the use of preformed DHA.
authors.affiliation: Faculté de pharmacie, Université Laval, Québec, QC, Canada.
authors.forename: Dany
authors.initials: D
authors.lastname: Arsenault
authors.forename: Carl
authors.initials: C
authors.lastname: Julien
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage; D004032:Diet; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000378:metabolism; D025802:Electric Capacitance; D055724:Electrophysiological Phenomena; D018728:Entorhinal Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D009747:Nutritional Physiological Phenomena; D018408:Patch-Clamp Techniques; D050765:Qa-SNARE Proteins / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D009479:Neuropeptides; D050765:Qa-SNARE Proteins; C053386:drebrins; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids