Undernutrition in the developing rat: effect upon myelination

Abstract

Long-Evans rats were undernourished from birth by removing the mother from the sucling rats for part of each day; the undernutrition was continued after weaning till 60 days of age by restricting the daily food intake. Brain development was monitored by histologic and selected biochemical analyses coordinated with an ultrastructural morphometric analysis of the pyramidal tract of 30-day-old rats. Brain and body growth were already reduced after 10 days of undernutrition. At 20 days of age, the peak of myelination in the controls, the body and brain weights of the undernourished rats, compared to the controls, were reduced by 25 and 60%, respectively, and by the end of the study (60 days), the brain and body weights were reduced by 30 and 70%, respectively. Morphometric analysis indicated that the proportion of myelinated axons was significantly reduced in starved (34%) relative to control (43%) animals. Fiber analysis revealed that not only were the myelin sheaths thinner in the undernourished rats, but that the sheath was disproportionately reduced relative to the axon diameter. Chemical analysis on a whole brain basis demonstrated a greater than 60% deficit in the relatively myelin-specific galactolipids. (Whole brain analysis included regions more severely affected than the morphometrically analyzed pyramidal tract.) We also obtained evidence for both a delay in the initiation and a general retardation of myelinogenesis. The promyelinating fibers (axons with one or two non-compacted myelin lamellae) still constituted 4.5% of the myelinated fibers in the undernourished animals at 30 days but had declined to 0.3% in the controls. Analysis of the fabtty acids of cerebroside and sulfatide (lipids enriched in myelin) demonstrated in the undernourished group a pattern characteristic of a younger animal. Thus, the effect of undernutrition on the developing rat appears to be one of inhibited and somewhat retarded myelination. These effects were most likely due to a reduction in the number of myelinating glia formed and the restricted capacity of those which form to generate myeline lamellae.