title: Docosahexaenoic Acid Promotes Axon Outgrowth by Translational Regulation of Tau and Collapsin Response Mediator Protein 2 Expression.
abstract: n-3 PUFAs are essential for neuronal development and brain function. However, the molecular mechanisms underlying their biological effects remain unclear. Here we examined the mechanistic action of docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acids in the brain. We found that DHA treatment of cortical neurons resulted in enhanced axon outgrowth that was due to increased axon elongation rates. DHA-mediated axon outgrowth was accompanied by the translational up-regulation of Tau and collapsin response mediator protein 2 (CRMP2), two important axon-related proteins, and the activation of Akt and p70 S6 kinase. Consistent with these findings, rapamycin, a potent inhibitor of mammalian target of rapamycin (mTOR), prevented DHA-mediated axon outgrowth and up-regulation of Tau and CRMP2. In addition, DHA-dependent activation of the Akt-mTOR-S6K pathway enhanced 5'-terminal oligopyrimidine tract-dependent translation of Tau and CRMP2. Therefore, our results revealed an important role for the Akt-mTOR-S6K pathway in DHA-mediated neuronal development.
authors.affiliation: From the Department of Neuroscience, Institute of Biomedical Sciences, Iwate Medical University, Yahaba 028-3694, Japan and the Department of Neuropsychiatry, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Mita
authors.affiliation: From the Department of Neuroscience, Institute of Biomedical Sciences, Iwate Medical University, Yahaba 028-3694, Japan and.
authors.forename: Taira
authors.initials: T
authors.lastname: Mayanagi
authors.affiliation: From the Department of Neuroscience, Institute of Biomedical Sciences, Iwate Medical University, Yahaba 028-3694, Japan and.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichijo
authors.affiliation: From the Department of Neuroscience, Institute of Biomedical Sciences, Iwate Medical University, Yahaba 028-3694, Japan and the Department of Neuropsychiatry, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Fukumoto
authors.affiliation: the Department of Neuropsychiatry, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Otsuka
authors.affiliation: the Department of Neuropsychiatry, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Sakai
authors.affiliation: From the Department of Neuroscience, Institute of Biomedical Sciences, Iwate Medical University, Yahaba 028-3694, Japan and ksobue@iwate-med.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sobue
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015290:Second Messenger Systems; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; D016875:tau Proteins; D004281:Docosahexaenoic Acids; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases
keywords: PUFA; S6 kinase; neurite outgrowth; neurodevelopment; neuron; translation control