Neonatal hypothyroidism and early undernutrition affect myelin and myelin precursor membranes in a different way

The lipid and protein composition as well as the activity of 2'3' cyclic nucleotide 3' phosphohydrolase (CNPH) and the distribution of individual proteins separated by SDS-PAGE were studied in myelin and in a fraction closely related to myelin or assumed to be a precursor membrane of mature myelin (fraction SN4) isolated from 20-day-old rats made hypothyroid at birth or submitted to early malnutrition. In both experimental conditions lipid and protein components were found to be reduced in myelin when data were expressed as mg/g fresh tissue, but the results were close to those obtained in normal controls when data were expressed as mg/mg total protein of each fraction. CNPH activity was normal in myelin but markedly reduced in fraction SN4. Although the results appear to suggest that both experimental conditions produce a reduction in the amount of myelin but no qualitative changes, the data obtained with SDS-PAGE show that the distribution of the various types of proteins present in this fraction and fraction SN4 was abnormal. Myelin and fraction SN4 isolated from malnourished animals displayed a protein profile which was quite similar to that found in fraction SN4 isolated from normal rats, indicating a delay in the process of myelin maturation. The changes in protein composition of myelin and fraction SN4 produced by neonatal hypothyroidism on the other hand differed clearly from those produced by early malnutrition; the ratio small basic protein: large basic protein (SBP:LBP) was found to be reduced in both membrane fractions in the former condition and the protein patterns of myelin and that of fraction SN4 were different, at variance with what was found in the case of malnourished animals. Our findings appear to suggest that the effects of early malnutrition and neonatal hypothyroidism upon myelin and myelin-related membranes are different, and that myelination is more affected in the latter condition.