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The Journal of Neuroscience, June 24, 2009, 29(25):8103-8113; doi:10.1523/JNEUROSCI.1495-09.2009

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Behavioral/Systems/Cognitive
Nonmotor Symptoms of Parkinson's Disease Revealed in an Animal Model with Reduced Monoamine Storage Capacity

Tonya N. Taylor,^1,2 W. Michael Caudle,⁷ Kennie R. Shepherd,^1,2 AliReza Noorian,^1,3 Chad R. Jackson,⁴ P. Michael Iuvone,^4,5 David Weinshenker,⁶ James G. Greene,^1,3,4 and Gary W. Miller^1,2,3,4

¹Center for Neurodegenerative Disease and ²Department of Environmental and Occupational Health, Rollins School of Public Health, and ³Departments of Neurology, ⁴Pharmacology, ⁵Ophthalmology, and ⁶Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30322, and ⁷Department of Pathology, University of Washington, Seattle, Washington 98104

Correspondence should be addressed to Gary W. Miller, Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building, Room 505K, Atlanta, GA 30322. Email: gary.miller{at}emory.edu

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the loss of dopamine neurons in the substantia nigra pars compacta, culminating in severe motor symptoms, including resting tremor, rigidity, bradykinesia, and postural instability. In addition to motor deficits, there are a variety of nonmotor symptoms associated with PD. These symptoms generally precede the onset of motor symptoms, sometimes by years, and include anosmia, problems with gastrointestinal motility, sleep disturbances, sympathetic denervation, anxiety, and depression. Previously, we have shown that mice with a 95% genetic reduction in vesicular monoamine transporter expression (VMAT2-deficient, VMAT2 LO) display progressive loss of striatal dopamine, L-DOPA-responsive motor deficits, -synuclein accumulation, and nigral dopaminergic cell loss. We hypothesized that since these animals exhibit deficits in other monoamine systems (norepinephrine and serotonin), which are known to regulate some of these behaviors, the VMAT2-deficient mice may display some of the nonmotor symptoms associated with PD. Here we report that the VMAT2-deficient mice demonstrate progressive deficits in olfactory discrimination, delayed gastric emptying, altered sleep latency, anxiety-like behavior, and age-dependent depressive behavior. These results suggest that the VMAT2-deficient mice may be a useful model of the nonmotor symptoms of PD. Furthermore, monoamine dysfunction may contribute to many of the nonmotor symptoms of PD, and interventions aimed at restoring monoamine function may be beneficial in treating the disease.

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Received March 26, 2009; revised May 9, 2009; accepted May 21, 2009.

Correspondence should be addressed to Gary W. Miller, Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building, Room 505K, Atlanta, GA 30322. Email: gary.miller{at}emory.edu

Related articles in J. Neurosci.:

Mice with Reduced Vesicular Monoamine Storage Content Display Nonmotor Features of Parkinson's Disease

Anthony C. Vernon
J. Neurosci. 2009 29: 12842-12844. [Full Text]  

This article has been cited by other articles:

				A. C. Vernon Mice with Reduced Vesicular Monoamine Storage Content Display Nonmotor Features of Parkinson's Disease J. Neurosci., October 14, 2009; 29(41): 12842 - 12844. [Full Text] [PDF]

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