Effects of Dietary Sphingomyelin on Central Nervous System Myelination in Developing Rats

Abstract

Human milk contains sphingomyelin (SM) as a major component of the phospholipid fraction. Galactosylceramide (cerebroside), a metabolite of sphingolipids, increases along with CNS myelination, and is generally considered a universal marker of myelination in all vertebrates. L-Cycloserine (LCS) is an inhibitor of serine palmitoyltransferase (SPT), a rate-limiting enzyme for sphingolipid biosynthesis that is reported to show increased activity with development of the rat CNS. The present study examined the effects of dietary SM on CNS myelination during development in LCS-treated rats. From 8 d after birth, Wistar rat pups received a daily s.c. injection (100 mg/kg) of LCS. From 17 d after birth, the animals were fed an 810 mg/100g of bovine SM-supplemented diet (SM-LCS group) or a nonsupplemented diet (LCS group). At 28 d after birth, the animals were killed and subjected to biochemical and morphometric analyses. The myelin dry weight, myelin total lipid content, and cerebroside content were significantly lower in the SM-LCS and LCS groups than in a group not treated with LCS (the non-LCS group). However, these levels were significantly higher in the SM-LCS group than in the LCS group. Morphometric analysis of the optic nerve revealed that the axon diameter, nerve fiber diameter, myelin thickness, and g value (used to compare the relative thickness of myelin sheaths around fibers of different diameter) were significantly lower in the LCS group than in the other groups, but were similar in the SM-LCS and non-LCS groups. These findings suggest that dietary SM contributes to CNS myelination in developing rats with experimental inhibition of activity. Abbreviations SM, sphingomyelin LCS, L-cycloserine PC, phosphatidylcholine PE, phosphatidylethanolamine PI, phosphatidylinositol PS, phosphatidylserine SPT, serine palmitoyltransferase TLC, thin-layer chromatography SM is composed of phosphocholine as the polar head group and sphingosine as the backbone of the molecule, and it is therefore classified as one of the sphingolipids. Recent studies have demonstrated that sphingolipids are found in all eukaryotic and some prokaryotic organisms (1). These molecules are involved in the regulation of cell growth (2), cell differentiation, and diverse other functions, including cell-substratum interactions and intracellular signal transduction (3, 4). Human milk has a lower content of phospholipids compared with triglycerides. Bitman et al. (5) reported that human milk has a total phospholipid content of approximately 15 to 20 mg/dL, with SM accounting for approximately 37% of the phospholipid fraction. Although many foods contain a small amount of SM (6), its nutritional and physiologic roles have not been fully examined.CNS myelin has a higher lipid content (65-80%) than that of general cell membranes. SM and sphingolipid metabolites, such as cerebroside and sulfatide, are prominent components of the myelin sheath that surrounds the axons of some neurons. This sheath acts as an insulator for nerve impulses and controls the sal...

Effect of Hypoxic-Ischemic Injury on Serine Palmitoyltransferase Activity in the Developing Rat Brain

“…We have reported that dietary sphingomyelin contributes to CNS myelination in developing rats [6] . De novo synthesis of sphingolipids is initiated by serine palmitoyltransferase (SPT), which is the rate-limiting enzyme for the reaction by which serine and palmitoyl-ConA form 3-ketosphinganine ( fig.…”

“…De novo synthesis of sphingolipids is initiated by serine palmitoyltransferase (SPT), which is the rate-limiting enzyme for the reaction by which serine and palmitoyl-ConA form 3-ketosphinganine ( fig. 3 ) [6][7][8] . SPT is located in the endoplasmic reticulum and the Golgi apparatus [6] .…”

Composition, Properties and Nutritional Aspects of Milk Fat Globule Membrane – A Review

“…Sphingolipids and metabolites Reduction of the number of aberrant crypt foci and adenocarcinomas Dillehay et al [1994] Shift in tumor type (malignant → benign) Schmelz et al [1996; Symolon et al [2004]; Spitsberg [2005] Anticholesterolemic Noh & Koo [2003; Nyberg et al [2000]; Eckhardt et al [2002] Protection of the liver from fat-and cholesterolinduced steatosis Duivenvoorden et al 2006 Suppression of gastrointestinal pathogens Sprong et al [2002]; Vesper et al [1999]; Pfeuffer & Schrezenmeir [2001] Neonatal gut maturation Oshida et al [2003] Myelination of the developing central nervous system Oshida et al [2003] Endogenous modulators of vascular function Michel et al [2007] Associated with age-related diseases and the development of Alzheimer Parodi [2001]; Spitsberg [2005] Sphingosine 1-phosphate Mitogenic Zhang et al [1990Zhang et al [ , 1991 Phosphatidyl-serine (PS) Restore normal memory on a variety of tasks McDaniel et al [2003] Positive effects on alzheimer patients Crook et al [1992]; Heiss et al [1994]; Pepeu et al [1996]; Gindin et al [1998]; Hashioka et al [2004] Improve exercise capacity of exercising humans Kingsley [2006] Phosphatidylcholine (PC) Support liver recovery from toxic chemical attack or viral damage Kidd [2002] Protects the human GI mucosa against toxic attack Anand et al [1999] Reduction of necrotising enterocolitis Carlson et al [1998] Lysophosphat-idylcholine (lyso PC) Bacteriostatic and bactericidal capacity van Rensburg et al [1992] Strong gastroprotective role in the duodenal mucosa ; ; Kivinen et al [1995] Other components Vitamin E and carotenoids Antioxidants Spitsberg [2005] as a mediator of senescence in a cell culture...…”

Rapid Quantitative Analysis of Sphingolipids in Seafood Using HPLC with Evaporative Light-Scattering Detection: Its Application in Tissue Distribution of Sphingolipids in Fish

“…Despite of relatively small amounts, sphingolipids are signifi cant components in foods and highly essential for human health 8 . Dietary sphingolipids have benefi cial effects such as preventing cancer 9-14 , improving skin barrier 15 and contributing to central nervous system myelination 16 .…”