Brain development is a sequential anatomical process characterised by specific well-defined stages of growth and maturation. One of the fundamental and necessary events in the normal development of the central nervous system in vertebrates is the formation of a myelin sheath. It is becoming more evident that this process is influenced by dietary lipids. A number of findings have indicated that the administration of a diet deficient in essential fatty acids during development causes hypomyelination in the rat brain. Our studies have shown that lipids can also play a role in accelerating myelinogenesis in the brain of rats whose mothers had been fed, during pregnancy and lactation, a lipid fraction extracted from yeast grown on n-alkanes. Further studies have shown that accelerated myelinogenesis is connected to a precocious appearance of behavioural reflexes. Thus, the use of particular lipids in human nutrition must be carefully screened for possible effects on brain development.

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In this paper we report Italian data on X-linked adrenoleukodystrophy (ALD) collected from 1985 to 1997. This disease appears to be the most common of the peroxisomal disorders and is associated with a functional defect of the peroxisomal very long chain fatty acid (VLCFA) oxidation. In Italy 117 cases have been recognized, but many cases may be unrecognized due to the heterogeneous clinical manifestations that vary from mild to very severe forms. To control the devastating course of this disease two therapeutic approaches are under evaluation: bone marrow transplantation (BMT) and dietary treatment based on a mixture of glyceroyl trioleate (GTO) and glyceroyl trierucate (GTE). Our experience of 68 subjects submitted to dietary treatment shows that almost all patients with signs of cerebral involvement at the beginning of treatment worsened or died, patients with the milder form, adrenomyeloneuropathy (AMN), remained stable, while 4 of the 15 presymptomatic subjects developed neurological signs of the disease. In recent years a more accurate selection of patients and donors for BMT has given favourable results, but some strict criteria should be respected.

The effects on myelin gene expression of prenatal diets with a different lipid content and fatty acid composition were investigated in undernourished pups. Three groups of rats were fed ad libitum during gestation diets containing either 10% of margarine or 10% of microbial lipids or a standard diet containing 3.5% of lipids. After birth, all groups were switched to a reduced intake (60%) of the standard diet. A control group received ad libitum, the standard diet during pregnancy and throughout lactation. At birth no difference in body and brain weight was observed among the groups and the only significant difference in the brain fatty acid composition was the presence of odd-chain fatty acids in the group fed microbial lipids. Milk was removed from the stomach of pups at 1, 5 and 9 days of lactation for fatty acid analysis. During undernourishment, the monoenoic fatty acid and polyenoic fatty acid percentage was always higher and lower, respectively, in the groups fed 10% than in the group fed 3.5% of lipids during pregnancy. The expression of myelin genes at 11 days of undernutrition was determined in different brain regions by Northern analysis. In the standard group, the proteolipid protein and myelin oligodendrocyte glycoprotein transcripts were well detected only in the medulla whereas in groups fed 10% of lipids the transcripts were also visible in the cerebellum. These data suggest that the high lipid content of the prenatal diet independently from its fatty acid composition affects the myelin gene expression decreasing myelin susceptibility to postnatal undernutrition.

Our previous work has shown an early development of behavioral reflexes in the offspring of rats maintained on diets containing a lipid fraction extracted from yeast (Candida lypolitica) grown on n-alkanes during pregnancy and throughout lactation. Since some of these changes could be linked to an early myelination, in this study we investigated myelin maturation in the rat brain by immunohistochemistry. At 7 days the test groups showed considerable immunopositivity to myelin basic protein and proteolipid protein at a more rostral level, such as the corpus callosum where immunopositivity is usually detected later in brain development. At 7 days in controls, staining fibers were detected only in the lower brainstem and in the cerebellum. Immunopositivity in the same regions was more intense in the test groups. Some litters were fostered at birth to produce 2 groups of animals: pups whose mothers were fed a control diet prenatally and the test diet postnatally, and vice versa. Positive fibers are already present at 7 days in the telencephalon area in both groups. These data indicate that dietary lipids can interfere with brain development by accelerating myelinogenesis.