The response of the hypothalamus to high doses of monosodium glutamate in mice and monkeys: Cytochemistry and ultrastructural study of lysosomal changes

Abstract

Administration of high doses (4 or 1 gm/kg) of monosodium- l-glutamate (MSG) in aqueous solution subcutaneously in 100 mice 5–7 days old produced changes in the arcuate nuclei and median eminence of the hypothalamus in 60% of treated mice given 4 gm/kg and in 42% of those receiving 1 gm/kg. The remaining mice appeared to be unaffected. The action of MSG was directed against both neuronal and glial cells. Corresponding doses of MSG given orally to 95 mice elicited a predominantly glial reaction in 28%. When four monkeys were given MSG (4 gm/kg) at 4 days of age, no distinction could be drawn between the appearance of the arcuate nuclei, median eminence, or ependymal cells in treated animals and the same structures in untreated controls. This species difference in susceptibility, as well as individual disparities among the mice, is probably attributable to the dissimilar degree of myelination of the central nervous system present at birth. Cytochemical and ultrastructural studies on the hypothalamus of the affected mice demonstrated a significant increase in the number of lysosomes, with appearance of numerous myeloid bodies. The presumptive intermediate stage of autophagic vacuole formation was not seen. The lysosomal effects observed have served to delineate hitherto unsuspected changes in the cell cytoplasm in affected animals.