动物造模 z-bio 2022-03-08 810

　　Objective To explore the changes of cognitive function, motor function, anxiety-like behavior and pathological changes in α-synuclein A53T transgenic mice.

　　Methods α-synuclein A53T transgenic mice with a background of C57BL/6 were selected as the experimental group, and littermate negative mice were used as the control group. The anxiety state of the mice was detected by the open field and cylinder tests; the motor coordination ability and forelimb tension of the mice were evaluated by the rotarod and grip tests; the cognitive abilities of the mice were evaluated by the water maze and conditioned fear tests. The pathological characteristics in the brain of the model mice were studied by immunohistochemical staining; mitochondrial changes in the brain of the model mice were observed by electron microscope.

　　Results Compared with the control group, the α-synuclein A53T transgenic mice had increased movement distance, showing hyperactivity; shortened time for conditioned fear memory, and appeared cognitive impairment; cylinder, rotarod and grasping force tests and water maze No statistical difference was found in the experiment. In the model group, the phosphorylation levels of α-synuclein in the substantia nigra, striatum, piriform cortex and hippocampus were increased, the deposition of Lewy bodies in the prefrontal lobe, the deposition of α-synuclein in the substantia nigra, and the number of TH-positive cells in the substantia nigra were significantly increased. Compared with the control group, the mitochondrial cristae and their contents in the brain of the mice in the model group were unclear, and the mitochondrial morphology was changed.

　　Conclusion Synuclein A53T transgenic mice have impaired cognitive function, which occurs earlier than motor impairment; the pathological features are the deposition of α-synuclein/LBs in the prefrontal lobe and cortex, the loss of substantia nigra dopaminergic neurons and the changes in mitochondrial morphology , can be used as an animal model of synuclein-related cognitive disorders such as dementia with Lewy bodies and Parkinson's disease.