title: Neurite outgrowth stimulation by n-3 and n-6 PUFAs of phospholipids in apoE-containing lipoproteins secreted from glial cells.
abstract: PUFAs, which account for 25-30% of the total fatty acids in the human brain, are important for normal brain development and cognitive function. However, it remains unclear how PUFAs are delivered to neurons and exert their effects. In this study, we demonstrated that n-3 and n-6 PUFAs added to the medium are incorporated into membrane phospholipids of primary glial cells from rat cortices, and then secreted as the fatty acid moiety of phospholipids in apoE-containing lipoproteins (LpEs). Tandem mass spectrometry analysis further showed that LpEs secreted from glial cells contain a variety of metabolites of PUFAs produced in glial cells by elongation and unsaturation. LpEs are absorbed by endocytosis into neurons via LDL receptor-related protein 1. LpE-containing n-3 and n-6 PUFAs exhibit a strong effect on neurite outgrowth of hippocampal neurons by increasing the number of branches. This study sheds light on the novel role of LpEs in the central nervous system and also a novel pathway in which PUFAs act on neurons.
authors.affiliation: Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto 606-8502, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakato
authors.affiliation: Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University, Kyoto 605-8501, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Matsuo
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.affiliation: Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa 230-0045, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.affiliation: Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto 606-8502, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ogawa
authors.affiliation: Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto 606-8502, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kioka
authors.affiliation: Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto 606-8502, Japan Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D003470:Culture Media; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000494:pharmacology; D043371:Fatty Acids, Omega-6 / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001057:Apolipoproteins E; D003470:Culture Media; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D008074:Lipoproteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010743:Phospholipids
keywords: apolipoprotein E; apolipoprotein E-containing lipoprotein; low density lipoprotein receptor-related protein 1; neuron; polyunsaturated fatty acid