MALNUTRITION AND BRAIN DEVELOPMENT: CEREBELLAR WEIGHT, DNA, RNA, PROTEIN AND HISTOLOGICAL CORRELATIONS

Abstract— Rat pups were reared in litters of 20 and litters of 6 to study effects of malnutrition on cerebellar development. Cell production and cell content were determined by assaying for DNA, as a measure of cell number, and RNA and protein, as indicators of cell constituents. By comparing DNA contents at 3, 4, 8, 11, 14, 17, 21, and 28 days after birth, we concluded that (a) there is little nutritional reserve at birth since significant differences appear by day 4, (b) most relative differences between groups appeared by day 8, with absolute differences increasing to day 21, and (c) there is partial recovery of cell number and cell constituents in the malnourished rats between 21 and 28 days.
Areal measurements of histological preparations showed that malnutrition resulted in less total area in cerebellar midsagittal sections at days 8, 11. and 14. In malnourished animals, the germinal matrix area of the cerebellum, the external granular layer, was smaller on the 8th postnatal day, the same on the eleventh day, and larger on the fourteenth day when compared with that of well fed animals. At all three ages alterations could be discerned in the distribution of cells between the mitotic external mantle and nonmitotic internal matrix portions of the external granular layer.
Further studies involving exchanging animals between large and small litters at various ages indicated that the time around days 4 to 8 is most sensitive to malnutrition. The results suggest a process in which malnutrition exerts its maximum effect by a slowing of cell production in the external granular layer in the initial exponential growth phase. It is likely that an adaptation occurs immediately in the external granular layer which subsequently permits a partial recovery of cerebellar growth between days 21 and 28.