Dipeptidyl peptidase-4 inhibitors and sulfonylureas prevent the progressive impairment of the nigrostriatal dopaminergic system induced by diabetes during aging.

Dipeptidyl peptidase-4 inhibitors and sulfonylureas prevent the progressive impairment of the nigrostriatal dopaminergic system induced by diabetes during aging. Neurobiol Aging. 2020 Feb 04;: Authors: Lietzau G, Magni G, Kehr J, Yoshitake T, Candeias E, Duarte AI, Pettersson H, Skogsberg J, Abbracchio MP, Klein T, Nyström T, Ceruti S, Darsalia V, Patrone C Abstract The nigrostriatal dopaminergic system (NDS) controls motor activity, and its impairment during type 2 diabetes (T2D) progression could increase Parkinson's disease risk in diabetics. If so, whether glycemia regulation prevents this impairment needs to be addressed. We investigated whether T2D impairs the NDS and whether dipeptidyl peptidase-4 inhibition (DPP-4i; a clinical strategy against T2D but also neuroprotective in animal models) prevents this effect, in middle-aged mice. Neither T2D (induced by 12 months of high-fat diet) nor aging (14 months) changed striatal dopamine content assessed by high-performance liquid chromatography. However, T2D reduced basal and amphetamine-stimulated striatal extracellular dopamine, assessed by microdialysis. Both the DPP-4i linagliptin and the sulfonylurea glimepiride (an antidiabetic comparator unrelated to DPP-4i) counteracted these effects. The functional T2D-induced effects did not correlate with NDS neuronal/glial alterations. However, aging itself affected striatal neurons/glia, and the glia effects were counteracted mainly ...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research