Study On The Abnormal Brain Information Processing And Its Relationship With IGF2 In Mice With Aversive Stimulation

Objective To explore the effect of anxiety-like/depression-like behaviors on spatial learning and memory ability and the relationship between this effect and hippocampal insulin-like growth factor 2(IGF2)level and plasma glucocorticoid level.Methods This study consists of two parts.In the first part,Anxiety-like/depression-like behaviors were induced by forced swimming(FS).Anxiety-like/depression-like behaviors and spatial learning and memory ability were evaluated by open-field test and Morris water maze test,respectively.The number of c-Fos positive cells in the hippocampus was detected by immunohistochemistry.The m RNA levels of IGF2,IGF2 R,Glucocorticoid receptor(NR3C1)as well as the negative regulatory factors of NR3C1,FK506 binding protein5(FKBP5)in the hippocampus were analyzed using quantitative real-time PCR(Q-RT-PCR)technology.In the second part,a mouse model of acute stress was established by the step-down test.The effect of stress model in mice was evaluated by the open-field test.The m RNA levels of IGF2,immediate early genes Arc and Zif268 in the hippocampus were analyzed using quantitative real-time PCR(Q-RT-PCR)technology.The glucocorticoid level in the mice plasma was determined by enzyme-linked immunosorbent assay(ELISA)technology.Results In the first part,open-field test showed that FS could lead to anxiety-like/depression-like behavior in mice,which mainly characterized by the shortened moving distance,the prolonged silent period,and easy access to the central area of open-field.Morris water maze test showed that FS impaired the spatial learning and memory ability in mice,which mainly characterized by the prolonged incubation period of mice step into the platform,and the significantly prolonged time required to enter the platform quadrant,viz.impaired memory consolidation and recurrence.The results of immunohistochemistry showed that FS could increase the expression level of c-Fos in the hippocampus of mice.The detection result of Q-RT-PCR showed that the behavioral alterations were accompanied by the decrease in the m RNA expression level of IGF2,FKBP5 and the increased expression level of NR3C1 in the hippocampus,but the expression level of IGF2 receptor in the hippocampus had no significant difference.In the second part,ELISA result showed that the behavioral alterations were accompanied by the observably decrease in the glucocorticoid level of mice plasma.Compared with the stress group,the levels of plasma glucocorticoid in mice treated with glucocorticoid were significantly higher than those in the stress group,but there was no significant difference of plasma glucocorticoid levels between the mice treated with glucocorticoid and the control group.The detection result of Q-RT-PCR showed that the behavioral alterations were accompanied by the decrease in the m RNA expression level of IGF2 and the increased expression level of immediate early genes Arc and Zif268 in the hippocampus,but after glucocorticoid supplementation,the expression level of Arc was not significantly changed,the expression level of Zif268 was decreased and the expression level of IGF2 was significantly increased.Conclusion FS and step-down test lead to the anxiety-like/depression-like behaviors and the spatial learning and memory ability impairment in mice.Behavioral change is associated with the increased NR3C1 level,the decreased IGF2 level and the decreased plasma glucocorticoid level.