Effects of donepezil treatment on plasma and urine metabolites in amyloid beta-induced Alzheimer's disease rats.

ABSTRACT

Accumulated clinical and biomedical evidence suggests that abnormalities in systemic metabolic processes such as fatty acid and amino acid metabolism can affect the brain function and behavior of various central nervous system diseases such as Alzheimer's disease (AD). In this study, metabolic profiling was used to investigate changes in plasma and urine metabolites following stereotactic injection of amyloid ß (Aß) and treatment with donepezil in rats. Aß causes cognitive impairment, while donepezil treatment successfully improves memory impairment. Donepezil improves Aß-induced plasma fatty acid and bile acid metabolism disorders, as well as Aß-induced urine phenylalanine and tryptophan metabolism disorders in rats. More specifically, the plasma fatty acids improved by donepezil include alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid, docosahexaenoic acid, linoleic acid, arachidonic acid, oleic acid, and palmitic acid, among others. Additionally, donepezil significantly restored the downregulation of bile acids such as ursodeoxycholic acid, cholic acid, and glycocholic acid caused by Aß. As for urine metabolites, phenylacetylglycine, epinephrine, and other phenylalanine metabolites, as well as kynurenic acid, xanthurenic acid, and other tryptophan metabolites, were worsened by Aß and improved by donepezil. These findings suggest that the cognitive impairment induced by Aß and the improvement by donepezil are associated with changes in metabolic disorders in rats. This study provides basic data for the effects of Aß and donepezil on plasma and urine metabolites in Aß-induced AD rat models.