期刊
NEUROCHEMISTRY INTERNATIONAL
卷 114, 期 -, 页码 71-79出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2018.01.006
关键词
A53T mice; Parkinson's disease; Alpha-synuclein; Non-motor symptoms; Dopamine transporter
资金
- NSFC [31471114, 31771110, 81430024]
- National Key Research and Development Program of China [2016YFC1306500]
- Key Research and Development Program of Shandong Province [216GSF201053]
- Qingdao Municipal Science and Technology Project [16-2-2-nsh]
- State Key Laboratory of Neuroscience [SKLN-201607]
- Taishan Scholars Construction Project
Alpha-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD). A robust transgenic mouse model has been generated that overexpresses the mutant human A53T alpha-synuclein under the mouse prion protein gene promoter; these mice develop age-dependent motor deficits. Recently, compared to wild-type (WT) littermates, A53T alpha-synuclein mice were reported to display non-motor symptom deficits, e.g., anxiety-like and depressive-like behaviors, odor discrimination and detection impairments, and gastrointestinal dysfunction, at 6 months of age or older. However, the differences between heterozygous and homozygous mice in terms of non-motor symptoms and whether the genomic DNA levels of alpha-synuclein correlate with the symptoms have not yet been elucidated. In the present work, we used littermate WT and heterozygous and homozygous A53T mice that were characterized by a modified genotyping protocol and observed a unilateral decline in the dopamine transporter (DAT) distribution from 3 months to 12 months of age in homozygous mice. We evaluated non motor symptoms by measuring colon motility, anxiety-like and depressive-like behaviors, and motor coordination. The results showed that homozygous A53T mice exhibited earlier abnormal non-motor symptoms compared to their heterozygous littermates. The severity of impaired colon motility as well as anxiety-like and depressive-like behaviors were correlated with the genomic DNA levels of A53T mutant alpha-synuclein. More noticeable, motor coordination aberrances were also observed in homozygous A53T mice. This study provides direct evidence that the genomic DNA levels of mutant alpha-synuclein correlate with non-motor symptoms in an A53T mouse model, indicating that the genomic DNA levels of mutant alpha-synuclein should be tightly manipulated in PD model studies. (C) 2018 Elsevier Ltd. All rights reserved.
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