CHRONIC ADMINISTRATION OF PROPIONIC-ACID REDUCES GANGLIOSIDE N-ACETYLNEURAMINIC ACID CONCENTRATION IN CEREBELLUM OF YOUNG-RATS

Elevated levels of propionate comparable to those of human propionic a cidaemia were achieved in the blood of young rats by injecting subcuta neously buffered propionic acid (PPA) twice a day at 8-h intervals fro m the 6th to the 28th day of life. A matched group of animals (control s) was treated with the same volumes of saline. The animals were weigh ed and sacrificed by decapitation at 28, 35 or 60 days of age. Cerebel lum and cerebrum were weighed and their protein and ganglioside N-acet ylneuraminic acid (G-NeuAc) contents determined. Body, cerebral and ce rebellar weights were similar in both groups, suggesting that PPA per se neither alters the appetite of the rats nor causes malnutrition. Br ain protein concentration was also not affected by chronic administrat ion of PPA, in contrast to G-NeuAc concentration which was significant ly reduced in the cerebellum. Since ganglioside concentration is close ly related to the dendritic surface and indirectly reflects synaptogen esis, our results of an important ganglioside deficit in the brain of PPA-treated animals may be related to the neurologic dysfunction chara cteristic of propionic acidaemic patients. (C) 1998 Elsevier Science B .V. All rights reserved.