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Dietary Restriction Does Not Protect the Nigrostriatal Dopaminergic Pathway of Older Animals From Low-Dose MPTP-Induced Neurotoxicity

Departments of ¹ Cellular and Structural Biology
² Physiology, The University of Texas Health Science Center, San Antonio.
³ The Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio.

To determine whether reduced caloric intake affects the susceptibility of nigrostriatal dopamine (DA) neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, 1-year-old male C57BL6 mice were offered food ad libitum or were given only 60% of the normal dietary intake. After 3 months, both groups were treated with low cumulative doses of 0, 10, 15, or 20 mg/kg MPTP. One week later, the striata were collected and DA, dihydroxyphenylalanine (DOPAC), and norepinephrine (NE) were measured. Treatment with MPTP had no effect on striatal NE but produced a dose-related depletion of DA and DOPAC in both the ad libitum-fed and the dietary-restricted mice. The MPTP-induced depletions of DA and DOPAC were not ameliorated in the dietary-restricted versus the ad libitum-fed mice. Baseline DA levels and those observed after treatment with the 15-mg/kg dose of MPTP were lower in the dietary-restricted mice compared with the ad libitum-fed mice. Overall, these results suggest that, at least in 1-year-old mice, dietary restriction for 3 months does not protect nigral DA nerve terminals from low toxic dosages of MPTP.

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				N. Maswood, J. Young, E. Tilmont, Z. Zhang, D. M. Gash, G. A. Gerhardt, R. Grondin, G. S. Roth, J. Mattison, M. A. Lane, R. E. Carson, R. M. Cohen, P. R. Mouton, C. Quigley, M. P. Mattson, and D. K. Ingram Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease PNAS, December 28, 2004; 101(52): 18171 - 18176. [Abstract] [Full Text] [PDF]