Category: Parkinson's Disease: Non-Motor Symptoms
Objective: To develop biomarkers and disease-modifying therapies for Parkinson’s disease, an animal model that recapitulates the early phase of the disease is indispensable. The aim of this study is to investigate prodromal symptoms of Parkinson’s disease in A53T-SNCA-BAC Tg mice.
Background: Parkinson’s disease is the most common neurodegenerative movement disorder and is characterized by motor symptoms, including bradykinesia, rigidity, tremor and postural instability, as well as a variety of non-motor symptoms such as constipation, olfactory disturbance and REM sleep behavioral disorder. These non-motor symptoms antedate motor symptoms by several years, and have high positive likelihood ratios for the development of Parkinson’s disease. The prodromal stage of Parkinson’s disease provides an excellent opportunity to understand the very early changes associated with the disease and to start disease-modifying therapies.
Method: We have previously reported on a prodromal Parkinson’s disease mouse model, A53T-SNCA-BAC Tg mice harboring the entire human SNCA and its gene expression regulatory regions with A53T mutation, two single-nucleotide polymorphisms and a Rep1 polymorphism. These A53T-SNCA-BAC Tg mice showed hyposmia and RBD-like symptom with α-synucleinopathy and dopaminergic neurodegeneration. In this time, we investigated gastrointestinal dysfunction, and neuropathology of the gastrointestinal system in A53T-SNCA-BAC Tg mice.
Results: In A53T-SNCA-BAC Tg mice, accumulation of Proteinase K-resistant phosphorylated alpha-synuclein was observed in the Myenteric and submucosal ganglions in the intestinal tract. From 9 months of age, A53T-SNCA-BAC Tg mice showed a prolonged whole gut transit time by a method of intragastric administration of carmine dye.
Conclusion: A53T-SNCA-BAC Tg mice showed constipation-like symptoms in addition to olfactory disturbances and RBD-like symptoms. We believe that A53T-SNCA-BAC Tg mice with multiple prodromal symptoms will contribute to the elucidation of the pathogenesis of Parkinson’s disease and the development of disease-modifying therapies in the future.
To cite this abstract in AMA style:T. Taguchi, M. Ikuno, H. Yamakado, R. Takahashi. A53T-SNCA-BAC transgenic mouse exhibits multiple prodromal symptoms of Parkinson’s disease: Gastrointestinal dysfunction, hyposmia and RBD-like behavior. [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/a53t-snca-bac-transgenic-mouse-exhibits-multiple-prodromal-symptoms-of-parkinsons-disease-gastrointestinal-dysfunction-hyposmia-and-rbd-like-behavior/. Accessed December 3, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/a53t-snca-bac-transgenic-mouse-exhibits-multiple-prodromal-symptoms-of-parkinsons-disease-gastrointestinal-dysfunction-hyposmia-and-rbd-like-behavior/