神经干细胞特异性LSD1基因敲除对小鼠情绪及记忆的影响

Effects of neural stem cell LSD1 conditional knockout on the mood and memory in mice

目的条件敲除小鼠神经干细胞LSD1基因后,通过观察小鼠神经细胞增殖情况及小鼠行为的表现,揭示LSD1的神经生物学功能。方法将LSD1(flox/flox)转基因小鼠与神经干细胞特异性表达Cre重组酶的Nestin-cre(Tg)转基因小鼠进行的杂交,即利用Cre-Lox P系统,繁殖出LSD1(flox/flox)Nestin-cre(Tg)基因型小鼠,即为所需神经干细胞LSD1条件性敲除小鼠(LSD1-CKO),LSD1(flox/flox)做为对照小鼠。进一步运用免疫荧光染色方法检测小鼠海马DG区神经细胞的增殖;并通过小鼠的糖水偏好、强迫游泳及新物体识别等实验检测小鼠的行为表现。结果与LSD1(flox/flox)小鼠相比,LSD1-CKO小鼠海马区神经细胞增殖显著降低(P=0.023);糖水偏好系数降低(P=0.0075);强迫游泳实验中不动时间明显增加(P<0.05);并在新物体识别实验中表现出记忆力显著下降现象(P=0.0019)。结论小鼠脑神经干细胞敲除LSD1基因,海马区神经细胞增殖降低,LSD1-CKO小鼠表现出负面情绪和记忆障碍。

Objective To study the function of LSD1 in the development of neurons and the influence of LSD1 on mood and memory-related behavior in mice. Methods The LSD1（ flox / flox）transgenic mice were crossed with Nestin-cre（ Tg）transgenic mice,using Cre-Lox P recombination system,to generate LSD1 conditional knockout of neural stem cell（ LSD1-CKO） mice,LSD1（ flox/ flox）Nestin-cre（ Tg）mice,and LSD1（ flox/ flox）mice as control. The neuron proliferation in LSD1-CKO mice was further detected by immunofluorescence staining. At the same time,the mood and memory-related behavior of LSD1-CKO mice were examined using several methods： sucrose preference test（ SPT）,forced swimming test（ FST） and novel-object recognition（ NOR） assay. Results In the LSD1 brain-specific CKO mice,the neuron proliferation rate in the hippocampus was significantly reduced（ P = 0. 023）,the preference for sucrose was reduced（ P = 0. 0075）,immobility duration during the forced swimming test was increased（ P〈0. 05）,and LSD1-CKO mice also exhibits memory-decline（ P= 0. 0019） during the novel-object recognition test. Conclusions Depletion of LSD1 in mouse brain neural stem cells leads to significant reduction of the neuron proliferation in the hippocampus. LSD1-CKO mice show more negative emotionsand memory impairment.