Abnormal upregulation of myelin genes underlies the critical period of myelination in undernourished developing rat brain.

Since myelin gene expression is suppressed during active myelination of the undernourished brain, this study was designed to determine the effects of undernourishment on the upregulation of myelin genes and the relationship between upregulation and the 'critical period' associated with permanent hypomyelination of the brain. Long-Evans rat dams were given either ad libitum or restricted access to rat chow to produce two populations of developing offsprings. The food deprivation schedule was designed to produce a degree of growth retardation comparable to our earlier studies of hypomyelination in undernourished brain. The expression of myelin genes, at various developmental ages, was determined in the forebrains from undernourished and normal, well fed controls by Northern analysis. In well nourished forebrain, proteolipid protein (PLP), myelin associated glycoprotein (MAG), and basic protein (BP) messages began to increase polynomially after day 8 post partum, leading to a rapid accumulation of message during the following several days. In undernourished forebrain, PLP, MAG, and BP messages did not show any increase until day 10, and then increased at a diminished rate as compared to well nourished forebrain. Additionally, the two PLP messages (1.6 kb and 3.2 kb) showed different vulnerabilities to protein-calorie undernourishment, which explains the abnormal ratio of the 3.2 and 1.6 kb forms we previously found in undernourished brain. This study shows a pattern of temporal specificity when the myelin PLP, MAG, and BP genes are synchronously upregulated in the normal forebrain to a high rate of transcription between day 7 to 9, which is several days before the onset of rapid myelination of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)