α-synuclein A53T mutation impairs cognitive function in mice

doi:10. 3969 / j.issn.1671-7856. 2020. 05. 002

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α-synuclein A53T mutation impairs cognitive function in mice
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                        10. 3969 / j.issn.1671-7856. 2020. 05. 002
                    
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                        WANG ManshiWANG Manshi
1.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, National Health Commission of the People’s Republic of China; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China. 2. Hebei Key Laboratory of Forensic Medicine; College of Forensic Medicine, Hebei Medical University; Hebei Collaborative InNovation Center of Forensic Medical Molecular Identifications, Shijiazhuang 050017
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ZHANG Ling1ZHANG Ling
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, National Health Commission of the People’s Republic of China; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China
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QIN Chuan1QIN Chuan
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, National Health Commission of the People’s Republic of China; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China
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CONG Bin2CONG Bin
Hebei Key Laboratory of Forensic Medicine; College of Forensic Medicine, Hebei Medical University; Hebei Collaborative InNovation Center of Forensic Medical Molecular Identifications, Shijiazhuang 050017
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Affiliation:1.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, National Health Commission of the People’s Republic of China; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China. 2. Hebei Key Laboratory of Forensic Medicine; College of Forensic Medicine, Hebei Medical University; Hebei Collaborative InNovation Center of Forensic Medical Molecular Identifications, Shijiazhuang 050017
Clc Number:R-33
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Abstract:

Objective To explore changes in motor coordination, cognitive function, and anxiety-like behavior as well as pathological characteristics in α-synuclein A53T transgenic mice. Methods We used α-synuclein A53T transgenic mice with a C57BL/ 6 background as the experimental group, and included a negative control group. The open field and cylinder tests were used to examine mouse anxiety levels, the rotarod and grip tests were used to evaluate movement disorders, and the Morris water maze and a fear conditioning test were used to evaluate cognitive ability. Pathological features were studied using immunohistochemical staining and mitochondrial morphology was observed via electron microscopy. Results Compared with the control group, α-synuclein A53T transgenic mice moved a greater distance, indicating that the mice were overactive. Further, freezing time was decreased, indicating cognitive impairment. We found no differences in performance in the cylinder test, rotarod test, grip test, or Morris water maze. In the α-synuclein A53T transgenic mice, levels of phosphorylated α-synuclein in the substantia nigra, striatum, piriform cortex, and hippocampus were increased, and we found Lewy bodies in the prefrontal cortex. Further, increased deposition of α-synuclein in the substantia nigra and striatum was observed, and the number of TH cells in the substantia nigra decreased significantly. Compared with the control group, mitochondria fission in the amygdala was increased, and the mitochondrial contents were unclear. Conclusions Cognitive function was impaired in α-synuclein A53T transgenic mice. Pathological characteristics included α-synuclein / LBs deposits in the prefrontal and piriform cortex, decreases in dopaminergic neurons in the substantia nigra, and altered mitochondrial morphology in the amygdala. α-synuclein A53T transgenic mice may be an appropriate model of synucleinopathy-related cognitive disease such as Lewy body dementia and dementia related to Parkinson’s disease.

Key words:α-synuclein A53T transgenic mice; mouse model; behavior; cognitive; mitochondria

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Received:October 21,2019
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Online: June 19,2020
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