The neurotoxicity of valine deficiency in rats

When valine, an essential amino acid, was withdrawn from the diet of weanling rats, the animals rapidly developed a unique pattern of neurological symptoms characterized by head retraction, staggering and aimless circling. At necropsy degenerative changes were most prominent in the neurons of the red nuclei, brain stem structures which modulate motor function. To explore the pathogenesis of the neurotoxicity associated with valine deficiency, we fed rats purified diets deficient in valine alone or in valine plus other branched chain and neutral amino acids, and we examined brain tissues by light microscopy. Motor disfunction and red nuclei damage occurred only in rats fed diets lacking valine alone and not in rats fed diets lacking all three branched chain amino acids. These results suggest that the neurotoxicity of valine deficiency results from amino acid imbalance rather than from lack of dietary valine per se.