Nonmotor symptoms of Parkinson's disease revealed in an animal model with reduced monoamine storage capacity.
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, alpha-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.
Taylor
Tonya N
TN
Center for Neurodegenerative Disease and Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA.
Caudle
W Michael
WM
Shepherd
Kennie R
KR
Noorian
AliReza
A
Jackson
Chad R
CR
Iuvone
P Michael
PM
Weinshenker
David
D
Greene
James G
JG
Miller
Gary W
GW
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000209:etiology / Q000378:metabolism / Q000523:psychology; D004192:Discrimination, Psychological; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D005746:Gastric Emptying; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D020919:Sleep Disorders, Intrinsic / Q000209:etiology / Q000378:metabolism / Q000523:psychology; D013550:Swimming; D050493:Vesicular Monoamine Transport Proteins / Q000172:deficiency* / Q000235:genetics; D014796:Visual Perception
D002395:Catecholamines; D050493:Vesicular Monoamine Transport Proteins