Kyoichi Oshida

Effects of dietary sphingomyelin on central nervous system myelination in developing rats.

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.

ω-3 fatty acids attenuate mucosal inflammation in premature rat pups.

BACKGROUNDnNecrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Although ω-3 fatty acids are known to have antiinflammatory effects, their effect against NEC remains unclear.nnnMETHODSnMother rats fed a soybean-based, docosahexaenoic acid (DHA)- or eicosapentaenoic acid (EPA)-enriched diet from days 7 to 20 of gestation were examined. On day 20, the rat pups were delivered by abdominal incision, their intestines were removed, and messenger RNA was extracted. A rat NEC model was used to confirm the effects of ω-3 fatty acids on the inflamed intestine (n = 20-28). The expression of inflammatory molecules was analyzed by real-time polymerase chain reaction (n = 11-14).nnnRESULTSnThe concentrations of DHA and EPA in the intestine were significantly increased in the DHA and EPA groups (P < .01). The expression of the antiinflammatory prostaglandin E2 receptor EP3 was increased in the DHA (P < .05) and EPA groups (P < .01). In the NEC model, the reduced incidence of colitis was confirmed in the DHA and EPA groups. The expression of peroxisome proliferator-activated receptor γ was increased (P < .05), and the inhibitor of nuclear factor-κB α/β decreased in both the DHA (P < .01) and EPA groups (P < .05).nnnCONCLUSIONnOur findings indicate that ω-3 fatty acids are beneficial for protecting the premature intestine from inflammation by regulating eicosanoid- and nuclear factor-κB-related metabolite expression.

Early dietary treatments with Lorenzo’s oil and docosahexaenoic acid for neurological development in a case with Zellweger syndrome

We treated a girl with Zellweger syndrome using a special infant formula supplemented with middle chain triglyceride (MCT) milk, docosahexaenoic acid (DHA), Lorenzos oil, and Lunaria oil, which is rich in nervonic acid (C24:1). We examined the fatty acid contents of the plasma and red blood cell (RBC) membrane. Neurological development was evaluated using Denver developmental screening test and auditory brainstem response (ABR). Her delayed neurological development, liver dysfunction, and cholestasis were all improved 2 weeks after starting the dietary treatment. DHA level in RBC membranes was increased and very long chain fatty acid (VLCFA,C26:0) levels were decreased. Our findings suggest that the dietary treatment with combination of MCT milk, DHA, Lorenzos oil, and Lunaria oil in the patients with Zellweger syndrome bring some benefits for neurological development.

Comparison of the phospholipid classes in human milk in Japanese mothers of term and preterm infants

Background: Phospholipids (PLs) play an essential role in the growth and brain development of infants. Aim: To investigate PL composition in human milk (HM), including lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine (PC) and sphingomyelin (SM), from healthy Japanese mothers. Analyses were performed on colostrum, transitional milk and mature milk from mothers of preterm and term infants. Methods: HM samples were collected from mothers of 15 term infants (term group) and of 19 preterm infants (preterm group). PL composition was determined by two‐dimensional thin‐layer chromatography in conjunction with phosphorus analysis. Results: In both groups, the PL content (% of total lipid) of mature milk was significantly lower than in colostrum. SM and PC were the main PLs in HM, but in the preterm group, the percentage of SM in mature milk was significantly higher and PC in mature milk was significantly lower than in the term group.

Effect of dietary Lorenzo's oil and docosahexaenoic acid treatment for Zellweger syndrome

ABSTRACTu2003 We investigated the possible therapeutic effect of decreasing plasma levels of very‐long‐chain fatty acids (C26:0) with a synthetic oil containing trioleate and trielucate (Lorenzos oil) as well as increasing docosahexaenoic acid (DHA) in red blood cells (RBC) with DHA ethyl ester in four patients with Zellweger syndrome. We investigated serial changes of plasma C26:0 levels and DHA levels in RBC membranes by gas‐liquid chromatography/mass spectrometry (GC/MS). After death, the fatty acid composition of each patients cerebrum and liver was studied. Dietary administration of Lorenzos oil diminished plasma C26:0 levels. Earlier administration of Lorenzos oil was more effective and the response did not depend on the duration of administration. DHA was incorporated into RBC membrane lipids when administrated orally, and its level increased for several months. The final DHA level was correlated with the duration of administration and was not related to the timing of initiation of treatment. DHA levels in the brains and livers of treated patients were higher than in untreated patients. Early initiation of Lorenzos oil and the long‐term administration of DHA may be useful for patients with Zellweger syndrome.

Effect of hypoxic-ischemic injury on serine palmitoyltransferase activity in the developing rat brain.

Background: Sphingolipid metabolism is strongly associated with central nervous system myelination. Ceramide is the most active of the sphingolipid metabolites. On the basis of ceramide biosynthesis indicated by serine palmitoyltransferase activity and cerebroside generated by ceramide, the evaluation of serine palmitoyltransferase activity in developing brains or hypoxic-ischemic damaged brains is worthwhile. Methods: Using a scintillation counter, we assessed serine palmitoyltransferase activity, a rate-limiting enzyme of sphingolipid metabolism, in the brains of developing rats and compared the activity with hypoxic-ischemic brains, using the method of Rice on postnatal day 7 (P7). Results: In the control groups, serine palmitoyltransferase activity was detected in the microsomal fraction of whole brain homogenates from P4, which was earlier than the initial expression of myelin-specific proteins such as myelin basic protein and proteolipid protein on immunochemistry. Serine palmitoyltransferase activity increased along with development on P8, P10, P14 and P21. However, hypoxic-ischemic brains showed lower serine palmitoyltransferase activity than control brains on P8, P10, P14 and P21. Conclusions: These results suggest that increase in serine palmitoyltransferase activity before myelin-specific protein expression may be an initial step in myelinogenesis and a decline in serine palmitoyltransferase activity in hypoxic-ischemic brains may be one of the major causes of delayed myelination.