AEG-1基因敲除对幼年小鼠认知功能的影响

The effects of AEG-1 knockout on cognitive function in juvenile mice

目的:探究海马神经元的星形胶质细胞上调基因-1(AEG-1)敲除(AEG-1 KO)对幼年小鼠认知功能的影响及分子机制。方法:Intellicage一体智能行为学系统检测AEG-1 KO幼年小鼠认知功能的变化;免疫荧光染色检测AEG-1 KO幼年小鼠海马区AEG-1蛋白的表达水平;尼氏染色检测AEG-1 KO幼年小鼠海马厚度的变化;高尔基染色检测AEG-1 KO幼年小鼠海马神经元树突和树突棘的变化;Western Blot检测AEG-1 KO幼年小鼠海马神经元tau蛋白、微管相关蛋白2(MAP2)和血清糖皮质激素诱导的激酶1(SGK1)的变化。结果:与对照组相比,AEG-1 KO幼年小鼠访问正确角落且喝到水的百分比下降(P<0.05);AEG-1 KO幼年小鼠海马CA1、CA3和DG区AEG-1蛋白的表达量降低(P<0.05);AEG-1 KO幼年小鼠海马厚度无差异(P>0.05);AEG-1 KO幼年小鼠海马CA1、CA3和DG区神经元树突总长度变短和树突棘密度降低(P<0.05);AEG-1 KO幼年小鼠海马神经元tau蛋白表达量无差异(P>0.05),但MAP2蛋白表达量降低(P<0.05)和SGK1蛋白表达量增加(P<0.05)。结论:AEG-1基因敲除的幼年小鼠认识功能受损,其机制可能与下调海马神经元MAP2蛋白表达及上调SGK1蛋白表达并进而影响神经元树突发育有关。

Objective:To investigate the effects of astrocyte elevated gene-1(AEG-1)knockout(AEG-1 KO)on cognitive function in juvenile mice and analyze the molecular mechanism.Methods:Intellicage was conducted to evaluate the changes of cognitive function in AEG-1 KO juvenile mice.Immunofluorescence staining was used to detect the protein expression levels of AEG-1 of hippocampus in AEG-I KO juvenile mice.Nissl staining was used to detect the changes of hippocampal thickness in AEG-I KO juvenile mice.Golgi staining was used to detect the changes of hippocampal neuronal dendrites and dendritic spines in AEG-1 KO juvenile mice.Western Blot was used to detect the changes of the protein expression levels of tau,microtubule-associated protein 2(MAP2)and serum-glucocorticoid-induced kinase 1(SGK1)of hippocampus in AEG-1 KO juvenile mice.Results:Compared with the control group,the percentage of times that AEG-1 KO juvenile mice visited the correct corner and drank water decreased(P<0.05);The expression of AEG-1 protein in hippocampal CA1,CA3,and DG regions of AEG-1 KO juvenile mice was decreased(P<0.05);however,there was no difference in hippocampal thickness in AEG-1 KO juvenile mice(P>0.05);the total length of dendrites and the density of dendritic spines in hippocampal CA1,CA3,and DG regions of AEG-1 KO juvenile mice were decreased(P<0.05);there was no difference in tau expression in hippocampal neuron of AEG-1 KO juvenile mice(P>0.05),but the expression of MAP2 protein decreased(P<0.05),and SCK1 protein expression increased(P<0.05).Conclusion:The cognitive function of juvenile mice with AEG-1 gene is impaired,which may be related to the down-regulation of MAP2 protein expression and up-regulation of SGK1 protein expression in hippocampal neurons,thus affecting the development of neuronal dendrites.