Alpha-synuclein transgenic mice display age-related slowing of gastrointestinal motility associated with transgene expression in the vagal system

作者：Noorian Ali Reza; Rha Jennifer; Annerino Dana M; Bernhard Douglas; Taylor Georgia M; Greene James G^*

来源：Neurobiology of Disease, 2012, 48(1): 9-19.

DOI：10.1016/j.nbd.2012.06.005

• Parkinson's disease
• Synuclein
• Gastrointestinal
• Gastric emptying
• Constipation
• Vagus
• DMV
• Colon
• Stomach

Gastrointestinal (GI) dysfunction is the one of the most common non-motor symptoms of Parkinson's disease (PD) and occurs in nearly every patient afflicted with this common neurodegenerative disorder. While parkinsonian motor symptoms are caused by degeneration of dopamine neurons in the midbrain substantia nigra, the neurological localization of non-motor symptoms in PD is not known. In this study, we examined a transgenic mouse model of PD in which mutant (A53T) human alpha-synuclein was expressed under control of the prion promoter (AS mice). We found that gastrointestinal expression of human alpha-synuclein in this transgenic line was limited to efferent fibers projecting from the dorsal motor nucleus of the vagus nerve (DMV) to the enteric nervous system (ENS). Older transgenic mice had a lower density of human alpha-synuclein expression in the GI tract, suggesting an age-related disruption of efferent vagal fibers in this model. At the same time, mice developed age-related declines in stool frequency and gastric emptying consistent with those seen in human PD. These behavioral and neuropathological patterns parallel those seen in PD patients and suggest the DMV as a target for further investigation into causes for Cl neuropathology and symptomatology in parkinsonism.

• 出版日期2012-10