3月龄α-突触核蛋白A53T转基因小鼠认知功能的改变

CHANGES IN COGNITIVE FUNCTION OF 3-MONTH-OLD TRANSGENIC MICE EXPRESSING A53T HUMAN Α-SYNUCLEIN

目的探讨α-突触核蛋白A53T转基因小鼠早期认知功能的改变及其可能的机制。方法选取3月龄α-突触核蛋白A53T转基因小鼠和野生型小鼠,采用新物体识别和转棒仪实验观察小鼠的认知及运动功能,采用Western Blot方法观察小鼠海马和前额叶皮质内脑源性神经营养因子(BDNF)表达,采用免疫组织化学的方法观察小鼠黑质多巴胺能神经元数目。结果新物体识别实验表明,与野生型小鼠相比,A53T转基因小鼠出现认知功能障碍。Western Blot检测显示,A53T转基因小鼠的海马和前额叶皮质内BDNF的表达较野生型小鼠下调(t=2.584、4.189,P<0.05)。A53T转基因小鼠在旋转棒上的停留时间与野生型小鼠相比差异无显著性(P>0.05),黑质多巴胺能神经元的数目与野生型小鼠相比也无明显改变(P>0.05)。结论 3月龄A53T转基因小鼠出现认知功能障碍且早于运动症状的发生。

Objective To investigate the early changes in cognitive function and the underlying mechanism in transgenic（Tg）mice expressing A53T humanα-synuclein. Methods Three-month-old Tg mice expressing A53T humanα-synuclein and wild-type（WT）mice were selected in this study.The cognitive function and motor coordination of the mice were evaluated by novel object recognition test and rota-rod test.The brain-derived neurotrophic factor（BDNF）expression in the hippocampus and prefrontal cortex of the mice was investigated by Western blot analysis.The number of dopaminergic neurons in the substantia nigra of the mice was determined by immunohistochemistry. Results By novel object recognition test,we found that the 3-month-old Tg mice exhibited cognitive disorders compared with the WT mice.The Western blot analysis indicated that the BDNF expression in the hippocampus and prefrontal cortex was down-regulated in the Tg mice,as opposed to the WT mice,the difference is significant（t=2.584 and 4.189,P〈0.05）.There were no significant differences in the retention time on the rotarod and the number of dopaminergic neurons in the substantia nigra between the Tg mice and WT mice（P〉0.05）. Conclusion This study indicates the presence of cognitive disorders,which occurs prior to motor coordination disorders,in the 3-month-old Tg mice expressing A53T humanα-synuclein.