Lipids were believed to be the major components of the brain structure. However, recent accumulated findings show that they can also play various roles in the brain, inducing cellular signaling, protecting neuronal cell death, preventing glial activation and even maintaining division of neural stem cells. In the present review, we first summarize physiological roles of brain lipids, then focus on ether-type glycerophospholipids, plasmalogens (Pls) showing recent evidences of how Pls can modulate the cellular signaling in the brain to maintain its integrity and to protect from the glial activation. Finally, we discuss the differential effects of other brain lipids in the glial activation.
ChrastR, SaherG, NaveKA, VerheijenMH. Lipid metabolism in myelinating glial cells: Lessons from human inherited disorders and mouse models. J Lipid Res. 2011;52(3):419–434.
2.
WangZ, KlipfellE, BennettBJ, KoethR, LevisonBS, DugarB, . Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63.
3.
HungMC, ShibasakiK, YoshidaR, SatoM, ImaizumiK.Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: Influence of a phosphatidylcholine-vitamin B12 diet. Br J Nutr. 2001;86(2):163–171.
4.
HigginsJP, FlickerL.Lecithin for dementia and cognitive impairment. Cochrane Database Syst Rev. 2003;(3):CD001015.
5.
RidgwayND. The role of phosphatidylcholine and choline metabolites to cell proliferation and survival. Crit Rev Biochem Mol Biol. 2013;48(1):20–38.
6.
VanceJE, TassevaG.Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells. Biochim Biophys Acta. 2013;1831(3):543–554.
7.
OakJH, NakagawaK, OikawaS, MiyazawaT.Amadori-glycated phosphatidylethanolamine induces angiogenic differentiations in cultured human umbilical vein endothelial cells. FEBS Lett. 2003;555(2):419–423.
8.
YaoY, HuangC, LiZF, WangAY, LiuLY, ZhaoXG, . Exogenous phosphatidylethanolamine induces apoptosis of human hepatoma HepG2 cells via the bcl-2/Bax pathway. World J Gastroenterol. 2009;15(14):1751–1758.
9.
PikeLJ. Lipid rafts: Bringing order to chaos. J Lipid Res. 2003;44(4):655–667.
10.
BrunzellJD, DavidsonM, FurbergCD, GoldbergRB, HowardBV, SteinJH, . Lipoprotein management in patients with cardiometabolic risk: Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. 2008;31(4):811–822.
11.
RizosCV, ElisafMS, LiberopoulosEN. Effects of thyroid dysfunction on lipid profile. Open Cardiovasc Med J. 2011;5:76–84.
12.
SunY, SukumaranP, VarmaA, DerryS, SahmounAE, SinghBB. Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells. Biochim Biophys Acta. 2014;1843(9):1839–1850.
13.
TestiR.Sphingomyelin breakdown and cell fate. Trends Biochem Sci. 1996;21(12):468–471.
14.
JoshiRP, KoretzkyGA. Diacylglycerol kinases: Regulated controllers of T cell activation, function, and development. Int J Mol Sci. 2013;14(4):6649–6673.
15.
VesperH, SchmelzEM, Nikolova-KarakashianMN, DillehayDL, LynchDV, MerrillAHJr. Sphingolipids in food and the emerging importance of sphingolipids to nutrition. J Nutr. 1999;129(7):1239–1250.
DuL, LiZJ, XuJ, WangJF, XueY, XueCH, . The anti-tumor activities of cerebrosides derived from sea cucumber Acaudina molpadioides and starfish Asterias amurensis in vitro and in vivo. J Oleo Sci. 2012;61(6):321–330.
20.
RahmannH.Brain gangliosides and memory formation. Behav Brain Res. 1995;66(1-2):105–116.
21.
LedeenRW, WuG.Ganglioside function in calcium homeostasis and signaling. Neurochem Res. 2002;27(7-8):637–647.
22.
WangB, Brand-MillerJ.The role and potential of sialic acid in human nutrition. Eur J Clin Nutr. 2003;57(11):1351–1369.
23.
RyanJM, RiceGE, MitchellMD. The role of gangliosides in brain development and the potential benefits of perinatal supplementation. Nutr Res. 2013;33(11):877–887.
24.
LiuH, RadlowskiEC, ConradMS, LiY, DilgerRN, JohnsonRW. Early supplementation of phospholipids and gangliosides affects brain and cognitive development in neonatal piglets. J Nutr. 2014;144(12):1903–1909.
25.
MolotkovskayaIM, KholodenkoRV, ZelenovaNA, SapozhnikovAM, MikhalevII, MolotkovskyJG. Gangliosides induce cell apoptosis in the cytotoxic line CTLL-2, but not in the promyelocyte leukemia cell line HL-60. Membr Cell Biol. 2000;13(6):811–822.
26.
NaganN, ZoellerRA. Plasmalogens: Biosynthesis and functions. Prog Lipid Res. 2001;40(3):199–229.
27.
BravermanNE, MoserAB. Functions of plasmalogen lipids in health and disease. Biochim Biophys Acta. 2012;1822(9):1442–1452.
28.
MedaL, BaronP, ScarlatoG.Glial activation in Alzheimer's disease: The role of Abeta and its associated proteins. Neurobiol Aging. 2001;22(6):885–893.
29.
IfukuM, KatafuchiT, MawatariS, NodaM, MiakeK, SugiyamaM, . Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice. J Neuroinflammation. 2012;9:197.
30.
Serrano-PozoA, FroschMP, MasliahE, HymanBT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1(1):a006189.
31.
HossainMS, IfukuM, TakeS, KawamuraJ, MiakeK, KatafuchiT.Plasmalogens rescue neuronal cell death through an activation of AKT and ERK survival signaling. PLoS One. 2013;8(12):e83508.
32.
HossainMS, MinenoK, KatafuchiT.Neuronal orphan g-protein coupled receptor proteins mediate plasmalogens-induced activation of ERK and akt signaling. PLoS One. 2016;11(3):e0150846.
33.
O'NeillLA, KaltschmidtC.NF-kappa B: A crucial transcription factor for glial and neuronal cell function. Trends Neurosci. 1997;20(6):252–258.
34.
KaltschmidtB, KaltschmidtC.NF-kappaB in the nervous system. Cold Spring Harb Perspect Biol. 2009;1(3):a001271.
35.
MattsonMP, CamandolaS.NF-kappaB in neuronal plasticity and neurodegenerative disorders. J Clin Invest. 2001;107(3):247–254.
XuD, OmuraT, MasakiN, ArimaH, BannoT, OkamotoA, . Increased arachidonic acid-containing phosphatidylcholine is associated with reactive microglia and astrocytes in the spinal cord after peripheral nerve injury. Sci Rep. 2016;6:26427.
38.
XueQS, SparksDL, StreitWJ. Microglial activation in the hippocampus of hypercholesterolemic rabbits occurs independent of increased amyloid production. J Neuroinflammation. 2007;4:20.
39.
NakajimaK, TohyamaY, KohsakaS, KuriharaT.Ceramide activates microglia to enhance the production/secretion of brain-derived neurotrophic factor (BDNF) without induction of deleterious factors in vitro. J Neurochem. 2002;80(4):697–705.
40.
JouI, LeeJH, ParkSY, YoonHJ, JoeEH, ParkEJ. Gangliosides trigger inflammatory responses via TLR4 in brain glia. Am J Pathol. 2006;168(5):1619–1630.
