About this item:

566 Views | 139 Downloads

Author Notes:

Gary W. Miller: gwmille@emory.edu

Academic Editor: Huaibin Cai

Subject:

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

Tools:

Journal Title:

Parkinson's Disease

Volume:

Volume 2011

Publisher:

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2011 Tonya N. Taylor et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

Creative Commons License

Export to EndNote