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?-Synuclein overexpressing transgenic mice show internal organ pathology and autonomic deficits.

ABSTRACT: While studying transgenic mice that overexpress human wildtype alpha-synuclein (Thy1-ASO, ASO) for typical brain alpha-synucleinopathy and central nervous system neuropathology, we observed progressive functional changes in the gastrointestinal and other peripheral organs. A more systematic study revealed that the gastrointestinal tract in ASO mice showed severe distension and blockage of the large intestine by 9-12 months of age. Functional assessments demonstrated a reduction in fecal water content and fecal pellet output, and increased whole gut transit time, in ASO mice compared to wildtype littermates, indicative of constipation, a symptom commonly reported by Parkinson's disease (PD) patients. Food intake was increased and body weight was decreased in 12 month old ASO mice, suggestive of metabolic abnormalities. Post-mortem histological analyses showed that human alpha-synuclein protein was robustly expressed in axonal fibers and in occasional cell bodies of the enteric nervous system, and in the heart of ASO mice. Accumulation of proteinase-K insoluble alpha-synuclein, reminiscent of neurodegenerative processes in PD was also observed. The functional and pathological changes we document here in ASO mice could relate to the autonomic deficits also seen in idiopathic and alpha-synuclein-mediated genetic forms of PD. These experimental data provide a foundation for therapeutic modeling of autonomic changes in PD and related alpha-synucleinopathies.

SUBMITTER: Hallett PJ

PROVIDER: S-EPMC3376017 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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α-Synuclein overexpressing transgenic mice show internal organ pathology and autonomic deficits.

Hallett Penelope J PJ McLean Jesse R JR Kartunen Andrew A Langston J William JW Isacson Ole O

Neurobiology of disease 20120419 2

While studying transgenic mice that overexpress human wildtype alpha-synuclein (Thy1-ASO, ASO) for typical brain alpha-synucleinopathy and central nervous system neuropathology, we observed progressive functional changes in the gastrointestinal and other peripheral organs. A more systematic study revealed that the gastrointestinal tract in ASO mice showed severe distension and blockage of the large intestine by 9-12 months of age. Functional assessments demonstrated a reduction in fecal water co ...[more]

PMID: 22549133

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?-Synuclein overexpressing transgenic mice show internal organ pathology and autonomic deficits.

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α-Synuclein overexpressing transgenic mice show internal organ pathology and autonomic deficits.

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