title: Insulin resistance impairs nigrostriatal dopamine function.
abstract: 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.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Morris
authors.forename: G L
authors.initials: GL
authors.lastname: Bomhoff
authors.forename: B K
authors.initials: BK
authors.lastname: Gorres
authors.forename: V A
authors.initials: VA
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: P-P
authors.initials: PP
authors.lastname: Lee
authors.forename: W M
authors.initials: WM
authors.lastname: Brooks
authors.forename: G A
authors.initials: GA
authors.lastname: Gerhardt
authors.forename: P C
authors.initials: PC
authors.lastname: Geiger
authors.forename: J A
authors.initials: JA
authors.lastname: Stanford
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology*; D048909:Diabetes Complications / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D007501:Iron / Q000378:metabolism; D019189:Iron Metabolism Disorders / Q000150:complications / Q000378:metabolism; D008297:Male; D009434:Neural Pathways / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology
chemical_list: D004041:Dietary Fats; D007501:Iron; D004298:Dopamine