Neurite outgrowth stimulation by n-3 and n-6 PUFAs of phospholipids in apoE-containing lipoproteins secreted from glial cells

Mitsuhiro Nakato, Michinori Matsuo, Nozomu Kono, Makoto Arita, Hiroyuki Arai, Jun Ogawa, Noriyuki Kioka, Kazumitsu Ueda

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 receptorrelated 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.

Original languageEnglish
Pages (from-to)1880-1890
Number of pages11
JournalJournal of lipid research
Volume56
Issue number10
DOIs
Publication statusPublished - 2015 Oct 1

Keywords

  • Apolipoprotein E
  • Apolipoprotein E-containing lipoprotein
  • Low density lipoprotein receptor-related protein 1
  • Neuron
  • Polyunsaturated fatty acid

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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