A53T-α-synuclein转基因小鼠新生神经元与学习记忆的研究

Study on neonatal neurons and learning and memory in A53T-α-synucleintransgenic mice

目的探究A53T -α- synuclein转基因小鼠中α-突触核蛋白突变对小鼠学习记忆的影响及作用机制。方法选取基因鉴定阳性的A53T-α-synuclein转基因小鼠为实验组,同窝、同性别的阴性小鼠为对照组,Y型迷宫实验检测小鼠学习记忆能力,5 -漠脱氧尿囉腱核昔(5 -bromodeoxyuridine,BnrdU)、双皮质素(double cortin,DCX)荧光染色检测海马齿状回(dentate gyrus,DG)区新生神经元数量,高尔基染色观察海马锥体细胞形态,免疫荧光检测海马Fos蛋白表达水平。结果与对照组相比,A53T-α-synuclein转基因小鼠进入Y型迷宫新颖臂的次数、滞留时间以及活动距离均减少(P<0.05);DG区BrdU.DCX阳性细胞数量减少(P<0.05);锥体细胞胞体萎缩,树突分支及长度减少且树突棘密度降低(P<0.05);海马Fos蛋白表达水平下降(P<0.05).结论α-突触核蛋白错义突变可阻碍海马区神经发生,降低海马突触的可塑性,诱导Fos蛋白表达下调,进而导致小鼠空间学习记忆能力受损。

Objective To investigate the effect of α- synucleinmutation on learning and memory in A53T -α- synuclein transgenic mice and related mechanisms. Methods A53T -α- synuclein transgenic mice with positive gene identification were selected as an experimental group, while those with the same gender and negative identification were used as a control group. The spatial memory capacity of mice was detected by Y - maze test. 5 - Bromodeoxyuridine (BrdU) anddoublecortin (DCX) fluorescence staining were used to detect the number of newborn neurons in the dentate gyrus (DG) area. The morphology of hippocampal pyramidal cells was observed by Golgi staining, and the level of Fos protein in the hippocampus was detected by immunofluorescence. Results Compared with the control group, the number of A53T -α- synuclein transgenic mice entering into the Y - maze novel arm, retention time and activity distance were remarkably reduced (P < 0.05);the number of BrdU and DCX positive cells in DG area was decreased (P < 0.05);pyramidal cell body was shrunk, dendritic branch and length and the density of dendritic spines were reduced (P < 0.05);and level of Fos protein in the hippocampus was declined (P < 0. 05). Conclusions The missense mutation of α- synuclein can inhibit neurogenesis in the hippocampus, reduce the plasticity of hippocampal synapses, and induce the down -regulation of Fos protein expression, which leads to impaired spatial memory capacity in mice.