In vivo incorporation ofN-acetyl-d-[U-14C]mannosamine into brain gangliosides of rats with quinolinic acid-induced lesions of the forebrain nucleus basalis magnocellularis

Abstract

Quinolinic acid, an excitotoxic agent, was applied unilaterally to the nucleus basalis magnocellularis of the rat forebrain, which resulted in neuronal destructions and consequently, loss of cholinergic projections to the cortex. The effects on ganglioside metabolism in brain cortical matter were studied. Total ganglioside contents in lesioned brains (n = 8) were found to be significantly decreased (range, 20-60%) but changes in brain ganglioside patterns on thin layer chromatograms were not apparent. On the other hand, in vivo incorporation of N-acetyl-D-[U-14C]mannosamine into brain gangliosides ranged from 19 to 36% (mean, 26%) of radiolabel in controls, and 5 to 21% (mean, 13%), a significant reduction in lesioned brains. Labeling of brain glycoproteins or of nonganglioside lipids was not affected. Since central cholinergic hypofunctions are also important neurochemical characteristics of Alzheimer's disease, abnormal ganglioside metabolism found in the lesioned rats may be of significance in the human disorder, where reduced brain ganglioside contents have also been reported.