Insulin resistance impairs nigrostriatal dopamine function

• Published in: Experimental neurology Vol. 231; no. 1; pp. 171 - 180
• Main Authors: Morris, J.K., Bomhoff, G.L., Gorres, B.K., Davis, V.A., Kim, J., Lee, P.-P., Brooks, W.M., Gerhardt, G.A., Geiger, P.C., Stanford, J.A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-09-2011; Elsevier
• Subjects: Animals; Biological and medical sciences; Corpus Striatum - metabolism; Corpus Striatum - physiopathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Diabetes; Diabetes Complications - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Dietary Fats - adverse effects; Dietary Fats - metabolism; Disease Models, Animal; Dopamine - physiology; Dopamine - secretion; Glucose; High fat diet; Insulin; Insulin Resistance - physiology; Iron; Iron - metabolism; Iron Metabolism Disorders - complications; Iron Metabolism Disorders - metabolism; Male; Medical sciences; Neural Pathways - metabolism; Neurology; Parkinson Disease - etiology; Parkinson Disease - metabolism; Parkinson's disease; Rats; Rats, Inbred F344; Substantia Nigra - metabolism; Substantia Nigra - pathology; Parkinson's disease; MRI; DMT1; IPGTT; Iron; Glucose; Insulin; AUC; High fat diet; PI3-K; Tf; UTR; PD; TfR2; TfR1; UCP2; Diabetes; HF; Endocrinopathy; Pancreatic hormone; Nervous system diseases; Dopamine; Diabetes mellitus; Parkinson disease; Metabolic diseases; Catecholamine; Cerebral disorder; Target tissue resistance; Central nervous system disease; Neurotransmitter; Insulin resistance; Degenerative disease; Extrapyramidal syndrome
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2011.06.005

Clinical studies have indicated a link between Parkinson's disease (PD) and Type 2 Diabetes. Although preclinical studies have examined the effect of high-fat feeding on dopamine function in brain reward pathways, the effect of diet on neurotransmission in the nigrostriatal pathway, which is affected in PD and parkinsonism, is less clear. We hypothesized that a high-fat diet, which models early-stage Type 2 Diabetes, would disrupt nigrostriatal dopamine function in young adult Fischer 344 rats. Rats were fed a high fat diet (60% calories from fat) or a normal chow diet for 12
weeks. High fat-fed animals were insulin resistant compared to chow-fed controls. Potassium-evoked dopamine release and dopamine clearance were measured in the striatum using
in vivo electrochemistry. Dopamine release was attenuated and dopamine clearance was diminished in the high-fat diet group compared to chow-fed rats. Magnetic resonance imaging indicated increased iron deposition in the substantia nigra of the high fat group. This finding was supported by alterations in the expression of several proteins involved in iron metabolism in the substantia nigra in this group compared to chow-fed animals. The diet-induced systemic and basal ganglia-specific changes may play a role in the observed impairment of nigrostriatal dopamine function.
► High fat-fed animals exhibit attenuated nigrostriatal DA release
in vivo. ► Nigrostriatal DA release is correlated with the degree of insulin resistance. ► Striatal DA uptake and turnover are decreased with high fat feeding. ► High fat feeding increases measures of iron deposition in the substantia nigra.