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

作者：Bousquet M; St Amour I; Vandal M; Julien P; Cicchetti F^*; Calon F

来源：Neurobiology of Disease, 2012, 45(1): 529-538.

DOI：10.1016/j.nbd.2011.09.009

• Parkinson%26apos
• s disease
• Obesity
• Insulin resistance
• Dopamine
• Flow cytometry
• Cytokines
• Leukocytes
• Dopaminergic neurons
• Nutrition

The identification of modifiable nutritional risk factors is highly relevant to the development of preventive strategies for neurodegenerative disorders including Parkinson%26apos;s disease (PD). In this study, adult C57BL/6 mice were fed either a control (CD - 12%kcal) or a high-fat diet (HED - 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-1 alpha, MCP-1, MIP-1 alpha). 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 modem society, dietary fat intake may represent an important modifiable risk factor for PD.

• 出版日期2012-1