Non-motor symptoms of Parkinson's disease revealed in an animal model with reduced monoamine storage capacity

• Type of Material: Article
• Authors: Tonya N. Taylor, Emory University; William Michael Caudle, Emory University; Kennie R. Shepherd, Emory University; AliReza Noorian, Emory University; Chad R. Jackson, Emory University; P Michael Iuvone, Emory University; David Weinshenker, Emory University; James G Greene, Emory University; Gary W Miller, Emory University
• Language: English
• Date: 2009-06-24
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Society for Neuroscience
• Final Published Version (URL): http://www.jneurosci.org/content/29/25/8103
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 29
• Issue: 25
• Grant/Funding Information: This work was supported by NIH grants P01 ES016731 (Miller), 1F31ES017247-01 (Taylor), R01 EY004864 (Iuvone), T32 GM007092 (Jackson), NSF 0450303 (Jackson), and the Michael J. Fox Foundation (Greene).; National Institute of Environmental Health Sciences : NIEHS
• Keywords: depression; norepinephrine; olfaction; serotonin; dopamine; VMAT2
• Research Categories: Biology, Neuroscience

Abstract

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 non-motor 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, α-synuclein accumulation, and nigral dopaminergic cell loss. We hypothesized that since these animals exhibit deficits in other monoamine systems (norepinephrine, serotonin), which are known to regulate some of these behaviors that the VMAT2-deficient mice may display some of the non-motor 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 non-motor symptoms of PD. Furthermore, monoamine dysfunction may contribute to many of the non-motor symptoms of PD and interventions aimed at restoring monoamine function may be beneficial in treating the disease.