Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease.

Abstract

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.

• Authors: Navin Maswood, Jennifer Young, Edward Tilmont, Zhiming Zhang, Don M Gash, Greg A Gerhardt, Richard Grondin, George S Roth, Julie Mattison, Mark A Lane, Richard E Carson, Robert M Cohen, Peter R Mouton, Christopher Quigley, Mark P Mattson, Donald K Ingram
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Issue 52 Pg. 18171-6 (Dec 28 2004) ISSN: 0027-8424 [Print] United States
• PMID: 15604149 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Brain-Derived Neurotrophic Factor
• Glial Cell Line-Derived Neurotrophic Factor
• Nerve Growth Factors
• Neurotoxins
• Neurotrophin 3
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Dopamine

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)
• Animals
• Behavior, Animal
• Brain (anatomy & histology, pathology)
• Brain-Derived Neurotrophic Factor (biosynthesis)
• Caloric Restriction
• Corpus Striatum (pathology)
• Disease Models, Animal
• Dopamine (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Glial Cell Line-Derived Neurotrophic Factor
• Haplorhini
• Macaca mulatta
• Male
• Nerve Growth Factors (biosynthesis)
• Neurochemistry (methods)
• Neuroglia (metabolism)
• Neurotoxins (metabolism)
• Neurotrophin 3 (metabolism)
• Parkinson Disease (pathology)
• Positron-Emission Tomography
• Substantia Nigra (pathology)
• Time Factors