Insulin resistance impairs nigrostriatal dopamine function

J. K. Morris, G. L. Bomhoff, B. K. Gorres, V. A. Davis, J. Kim, P. P. Lee, W. M. Brooks, G. A. Gerhardt, P. C. Geiger, J. A. Stanford

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

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.

Original languageEnglish
Pages (from-to)171-180
Number of pages10
JournalExperimental Neurology
Volume231
Issue number1
DOIs
StatePublished - Sep 2011

Bibliographical note

Funding Information:
We thank Susan Smittkamp and George Quintero for technical assistance. This work was supported by NIH grant AG026491 and P20 RR016475 , Kansas Intellectual and Developmental Disabilities Research Center grant HD02528 , the Kansas City Area Life Sciences Institute , and predoctoral National Research Service Award NS063492 awarded to J. K. Morris, with core support from MRRC and Hoglund Brain Imaging Center .

Keywords

  • Diabetes
  • Glucose
  • High fat diet
  • Insulin
  • Iron
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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