Dietary restriction does not protect the nigrostriatal dopaminergic pathway of older animals from low-dose MPTP-induced neurotoxicity.
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.
Morgan
William W
WW
Departments of Cellular and Structural Biology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. morgan@uthscsa.edu
Richardson
Arlan G
AG
Nelson
James F
JF
D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry / Q000502:physiology*; D004038:Diet, Reducing; D004295:Dihydroxyphenylalanine / Q000032:analysis; D004298:Dopamine / Q000032:analysis; D020267:MPTP Poisoning / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009411:Nerve Endings / Q000737:chemistry; D009434:Neural Pathways / Q000737:chemistry; D009638:Norepinephrine / Q000032:analysis
D004295:Dihydroxyphenylalanine; D004298:Dopamine; D009638:Norepinephrine