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Author Notes:
Corresponding author: Gunasingh Masilamoni, Yerkes National Primate Research Center, 954, Gatewood Rd NE, Atlanta, GA 30322, USA, gjeyara@emory.edu, Ph: 404-727-7235.
The authors acknowledge Mrs. Susan Jenkins and Jean-Francois Pare for their technical support.
No conflicts of interest, financial or otherwise, are declared by the authors.
Subjects:
Research Funding:
This work was supported by NIH/ORIP grant P51-OD011132 to the Yerkes National Primate Research Center, grants from P50NS098685-NINDS (UDALL PD Center) and R01NS083386-NINDS.
Keywords:
- Science & Technology
- Life Sciences & Biomedicine
- Clinical Neurology
- Neurosciences
- Neurosciences & Neurology
- Parkinson's disease
- MPTP monkey
- Nigrostriatal dopamine
- Extra-striatal dopamine
- Norepinephrine
- Serotonin
- Acetylcholine
- alpha-Synuclein
- LOW-DOSE MPTP
- EYE-MOVEMENT SLEEP
- PEDUNCULOPONTINE TEGMENTAL NUCLEUS
- HYDROXYLASE-IMMUNOREACTIVE FIBERS
- PROGRESSIVE SUPRANUCLEAR PALSY
- NIGRA PARS RETICULATA
- P-CONTAINING NEURONS
- ALPHA-SYNUCLEIN
- SUBSTANTIA-NIGRA
- BASAL-GANGLIA
Chronic MPTP administration regimen in monkeys: a model of dopaminergic and non-dopaminergic cell loss in Parkinson's disease
Abstract:
Parkinson’s disease (PD) is a progressive neurodegenerative disorder clinically characterized by cardinal motor deficits including bradykinesia, tremor, rigidity and postural instability. Over the past decades, it has become clear that PD symptoms extend far beyond motor signs to include cognitive, autonomic and psychiatric impairments, most likely resulting from cortical and subcortical lesions of non-dopaminergic systems. In addition to nigrostriatal dopaminergic degeneration, pathological examination of PD brains, indeed, reveals widespread distribution of intracytoplasmic inclusions (Lewy bodies) and death of non-dopaminergic neurons in the brainstem and thalamus. For that past three decades, the MPTP-treated monkey has been recognized as the gold standard PD model because it displays some of the key behavioral and pathophysiological changes seen in PD patients. However, a common criticism raised by some authors about this model, and other neurotoxin-based models of PD, is the lack of neuronal loss beyond the nigrostriatal dopaminergic system. In this review, we argue that this assumption is largely incorrect and solely based on data from monkeys intoxicated with acute administration of MPTP. Work achieved in our laboratory and others strongly suggest that long-term chronic administration of MPTP leads to brain pathology beyond the dopaminergic system that displays close similarities to that seen in PD patients. This review critically examines these data and suggests that the chronically MPTP-treated nonhuman primate model may be suitable to study the pathophysiology and therapeutics of some non-motor features of PD.
Copyright information:
© 2017, Springer-Verlag GmbH Austria.
This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).
