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Murine Model for Parkinson's Disease: from 6-OH Dopamine Lesion to Behavioral Test
Published on: January 15, 2010
Aged monkeys as a partial model for Parkinson's disease
P J Hurley1, J D Elsworth, M C Whittaker
1Department of Psychiatry, Yale University School of Medicine, 300 George Street 9th Floor, New Haven, CT 06510, USA.
Pharmacology, Biochemistry, and Behavior
|May 31, 2011
Summary
Aging in monkeys naturally induces parkinsonism, mirroring neurotoxin-induced Parkinson's disease (PD) symptoms and dopamine depletion. Aged monkeys exhibit motor and behavioral changes similar to PD, but do not respond to dopamine replacement therapies.
Area of Science:
- Neuroscience
- Primatology
- Gerontology
Background:
- Parkinson's Disease (PD) shares biochemical pathways with natural aging, particularly involving dopaminergic system decline.
- The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is used to model PD by depleting dopamine in the nigrostriatal system.
Purpose of the Study:
- To compare motor and behavioral changes in aged monkeys with MPTP-induced parkinsonism.
- To investigate the extent to which natural aging mimics Parkinson's Disease.
Main Methods:
- Aged monkeys were assessed using the Parkinson's factor score (Parkscore) and compared to young adults and MPTP-exposed monkeys.
- Post-mortem striatal dopamine (DA) concentrations were measured and correlated with behavioral scores.
- The efficacy of L-Dopa and DA-agonists was evaluated in aged monkeys.
Main Results:
- Aged monkeys exhibited higher Parkscore ratings, indicating significant motor and behavioral deficits (tremor, eating problems, delayed initiation, poverty of movement).
- Post-mortem analysis revealed a 63% reduction in ventral putamen DA in aged monkeys compared to young adults, with greater depletion in the putamen than the caudate nucleus.
- Dopamine replacement therapies did not effectively reverse the parkinsonian measures in aged monkeys.
Conclusions:
- Naturally aged monkeys display a parkinsonism profile similar to MPTP-induced PD, characterized by selective dopamine depletion in the putamen.
- This aging-related dopamine depletion pattern in monkeys mirrors that observed in human Parkinson's Disease.
- Aged monkeys, like aging humans, show limited therapeutic benefit from standard dopamine replacement treatments.
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