High-fat diet exacerbates MPTP-induced dopaminergic degeneration in mice.

Abstract

The identification of modifiable nutritional risk factors is highly relevant to the development of preventive strategies for neurodegenerative disorders including Parkinson's disease (PD). In this study, adult C57BL/6 mice were fed either a control (CD-12%kcal) or a high-fat diet (HFD-60%kcal) for 8 weeks prior to MPTP exposure, a toxin which recreates a number of pathological features of PD. HFD-fed mice significantly gained weight (+41%), developed insulin resistance and a systemic immune response characterized by an increase in circulating leukocytes and plasmatic cytokines/chemokines (interleukin-1α, MCP-1, MIP-1α). As expected, the MPTP treatment produced nigral dopaminergic degeneration as evidenced by the loss of striatal dopamine and the decreased number of nigral tyrosine hydroxylase (TH)- and dopamine transporter-expressing neurons (23% and 25%, respectively). However, exposure to HFD exacerbated the effects of MPTP on striatal TH (23%) and dopamine levels (32%), indicating that diet-induced obesity is associated with a reduced capacity of nigral dopaminergic terminals to cope with MPTP-induced neurotoxicity. Since high-fat consumption is commonplace in our modern society, dietary fat intake may represent an important modifiable risk factor for PD.

• Authors: M Bousquet, I St-Amour, M Vandal, P Julien, F Cicchetti, F Calon
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 45 Issue 1 Pg. 529-38 (Jan 2012) ISSN: 1095-953X [Electronic] United States
• PMID: 21971528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Ccl2 protein, mouse
• Chemokine CCL2
• Chemokine CCL3
• Insulin
• Interleukin-1alpha
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Dopamine

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)
• Animals
• Chemokine CCL2 (blood)
• Chemokine CCL3 (blood)
• Corpus Striatum (metabolism, pathology)
• Diet, High-Fat
• Dopamine (metabolism)
• Dopaminergic Neurons (drug effects, pathology)
• Insulin (blood)
• Insulin Resistance
• Interleukin-1alpha (blood)
• Mice
• Nerve Degeneration (chemically induced, pathology)
• Substantia Nigra (metabolism, pathology)