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Parkinson’s Disease
Volume 2011, Article ID 124165, 9 pages
http://dx.doi.org/10.4061/2011/124165
Review Article

VMAT2-Deficient Mice Display Nigral and Extranigral Pathology and Motor and Nonmotor Symptoms of Parkinson's Disease

1Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA
2Center for Neurodegenerative Disease, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA
3Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK
4Department of Neurology, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA
5Department of Pharmacology, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA

Received 27 October 2010; Accepted 3 January 2011

Academic Editor: Huaibin Cai

Copyright © 2011 Tonya N. Taylor et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dopamine is transported into synaptic vesicles by the vesicular monoamine transporter (VMAT2; SLC18A2). Disruption of dopamine storage has been hypothesized to damage the dopamine neurons that are lost in Parkinson's disease. By disrupting vesicular storage of dopamine and other monoamines, we have created a progressive mouse model of PD that exhibits catecholamine neuron loss in the substantia nigra pars compacta and locus coeruleus and motor and nonmotor symptoms. With a 95% reduction in VMAT2 expression, VMAT2-deficient animals have decreased motor function, progressive deficits in olfactory discrimination, shorter latency to behavioral signs of sleep, delayed gastric emptying, anxiety-like behaviors at younger ages, and a progressive depressive-like phenotype. Pathologically, the VMAT2-deficient mice display progressive neurodegeneration in the substantia nigra (SNpc), locus coeruleus (LC), and dorsal raphe (DR) coupled with α-synuclein accumulation. Taken together, these studies demonstrate that reduced vesicular storage of monoamines and the resulting disruption of the cytosolic environment may play a role in the pathogenesis of parkinsonian symptoms and neurodegeneration. The multisystem nature of the VMAT2-deficient mice may be useful in developing therapeutic strategies that go beyond the dopamine system.