Caloric Restriction Increases Neurotrophic Factor Levels and Attenuates Neurochemical and Behavioral Deficits in a Primate Model of Parkinson's Disease

We report that a low-calorie diet can lessen the severity of neurochemical deficits and motor dysfunction in a primate model of Parkinson's disease. Adult male rhesus monkeys were maintained for 6 months on a reduced-calorie diet [30% caloric restriction (CR)] or an ad libitum control diet afte...

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Published in:	Proceedings of the National Academy of Sciences - PNAS 2004-12, Vol.101 (52), p.18171-18176
Main Authors:	Maswood, Navin, Young, Jennifer, Tilmont, Edward, Zhang, Zhiming, Gash, Don M, Gerhardt, Greg A, Grondin, Richard, Roth, George S, Mattison, Julie, Lane, Mark A, Carson, Richard E, Cohen, Robert M, Mouton, Peter R, Quigley, Christopher, Mattson, Mark P, Ingram, Donald K
Format:	Article
Language:	eng
Subjects:	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology Animals Behavior, Animal Biological Sciences Body weight Brain - anatomy & histology Brain - pathology Brain-Derived Neurotrophic Factor - biosynthesis Caloric Restriction Corpus Striatum - pathology Diet Disease Models, Animal Dopamine - pharmacology Enzyme-Linked Immunosorbent Assay Glial Cell Line-Derived Neurotrophic Factor Haplorhini Low calorie diets Macaca mulatta Male Monkeys Nerve Growth Factors - biosynthesis Neurochemistry - methods Neuroglia - metabolism Neurology Neurons Neuroscience Neurotoxins Neurotoxins - metabolism Neurotrophin 3 - metabolism Parkinson disease Parkinson Disease - pathology Parkinsons disease Positron emission tomography Primates Statistical significance Substantia Nigra - pathology Time Factors
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Summary:	We report that a low-calorie diet can lessen the severity of neurochemical deficits and motor dysfunction in a primate model of Parkinson's disease. Adult male rhesus monkeys were maintained for 6 months on a reduced-calorie diet [30% caloric restriction (CR)] or an ad libitum control diet after which they were subjected to treatment with a neurotoxin to produce a hemiparkinson condition. After neurotoxin treatment, CR monkeys exhibited significantly higher levels of locomotor activity compared with control monkeys as well as higher levels of dopamine (DA) and DA metabolites in the striatal region. Increased survival of DA neurons in the substantia nigra and improved manual dexterity were noted but did not reach statistical significance. Levels of glial cell line-derived neurotrophic factor, which is known to promote the survival of DA neurons, were increased significantly in the caudate nucleus of CR monkeys, suggesting a role for glial cell line-derived neurotrophic factor in the anti-Parkinson's disease effect of the low-calorie diet.
ISSN:	0027-8424 1091-6490