中国实验动物学报2025，Vol.33Issue(9)：1312-1319,8.DOI:10.3969/j.issn.1005-4847.2025.09.007
基于A53T转基因小鼠注射α-突触核蛋白纤维加速建立帕金森病模型
Accelerated establishment of a Parkinson's disease model throughα-Syn PFF injection in A53T transgenic mice
摘要
Abstract
Objective This study sought to accelerate the establishment of a Parkinson's disease mouse model by intracerebral injection of α-synuclein preformed fibrils(α-Syn PFF)into B6-hSNCA-A53T transgenic mice to induce rapid development of Parkinson's-like pathological features.Methods C57BL/6J background α-Syn A53T transgenic mice were selected as the model group,with isogenic C57BL/6J mice as the control group.α-Syn PFF was delivered into the bilateral striatum using stereotactic brain injection.After modeling,the open-field test was used to assess spontaneous activity and anxiety-like behaviors,while the rotarod,grip strength,and pole tests evaluated motor coordination and limb muscle tone.The buried food test was conducted to assess olfactory function.Immunohistochemical staining was performed to investigate neuroinflammation and pathological α-synuclein in the mouse brain.Results Compared with the control group,1 month after the α-Syn PFF injection,model mice showed increased locomotion in the open-field test,with no significant differences in the rotarod,grip strength,or pole tests,but prolonged food-seeking time.Two months after model establishment,the model group showed significantly reduced locomotor activity in open field testing,impaired motor coordination in rotarod,grip strength and pole tests,and olfactory dysfunction in buried food tests.Phosphorylated α-synuclein accumulation was observed in the substantia nigra,cortex,and hippocampus,accompanied by pronounced microglial activation,Lewy body deposition,and substantial dopaminergic neuron loss in the substantia nigra.Conclusions A53T mice developed olfactory dysfunction and motor impairments more rapidly after α-Syn PFF injection.Significant pathological changes were observed,including the aggregation of α-synuclein/Lewy body in the substantia nigra,cortex,and hippocampus,and the loss of dopaminergic neurons in the substantia nigra.This model can serve as a rapidly established animal model for α-synucleinopathy-related Parkinson's disease.关键词
帕金森病/A53T转基因小鼠/动物模型/α-突触核蛋白预合成纤维/路易小体Key words
Parkinson's disease/A53T transgenic mice/animal model/α-Syn PFF/Lewy body分类
生物科学引用本文复制引用
周宇光,苏迎,刘亚岭,韦昕钰,姜佩文,邹春林..基于A53T转基因小鼠注射α-突触核蛋白纤维加速建立帕金森病模型[J].中国实验动物学报,2025,33(9):1312-1319,8.基金项目
广西自然科学基金面上项目(2025GXNSFA069384),国家自然科学基金(81971191).Funded by the General Program of Natural Science Foundation of Guangxi(2025GXNSFA069384),National Natural Science Foundation of China(81971191). （2025GXNSFA069384）
