Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease.
Gastrointestinal (GI) dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Symptoms of GI dysmotility include early satiety and nausea from delayed gastric emptying, bloating from poor small bowel coordination, and constipation and defecatory dysfunction from impaired colonic transit. Understanding the pathophysiology and treatment of these symptoms in PD patients has been hampered by the lack of investigation into GI symptoms and pathology in PD animal models. We report that the prototypical parkinsonian neurotoxin, MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine), is a selective dopamine neuron toxin in the enteric nervous system (ENS). When examined 10 days after treatment, there was a 40% reduction of dopamine neurons in the ENS of C57Bl/6 mice administered MPTP (60 mg/kg). There were no differences in the density of cholinergic or nitric oxide neurons. Electrophysiological recording of neural-mediated muscle contraction in isolated colon from MPTP-treated animals confirmed a relaxation defect associated with dopaminergic degeneration. Behaviorally, MPTP induced a transient increase in colon motility, but no changes in gastric emptying or small intestine transit. These results provide the first comprehensive assessment of gastrointestinal pathophysiology in an animal model of PD. They provide insight into the impact of dopaminergic dysfunction on gastrointestinal motility and a benchmark for assessment of other PD model systems.
Anderson
Grant
G
Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Noorian
Ali Reza
AR
Taylor
Georgia
G
Anitha
Mallappa
M
Bernhard
Doug
D
Srinivasan
Shanthi
S
Greene
James G
JG
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002452:Cell Count; D003106:Colon / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents; D017615:Enteric Nervous System / Q000378:metabolism / Q000473:pathology*; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility; D005772:Gastrointestinal Transit / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*
D002395:Catecholamines; D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine