Objective:To investigate the role of mitogen-activated protein kinase phosphatase-1 (MKP-1) on depressive-like behaviors and hippocampal neuron apoptosis in chronic unpredictable mild stress (CUMS) rats.Methods:A total of 36 Sprague-Dawley male rats were randomly divided into 4 groups using a random number table, including the control group( n=8), CUMS group( n=8), virus control group( n=10), and MKP-1 down-regulated group( n=10), with 8 rats in each group. Except for the control group, rats in other groups were stressed by CUMS model of depression. Rats in the virus control group and MKP-1 down-regulated group received adeno-associated virus injections in the hippocampal CA1 and CA3 regions before CUMS modeling. Sucrose preference test, forced swimming test, and open field test were used to observe the behavioral changes of rats. Western blotting was used to detect the protein expression of MKP-1, B-cell lymphoma-2 gene (Bcl-2) and B-cell lymphoma-2 gene-related X protein (Bax), in the hippocampus. TUNEL staining was utilized to observe the morphology of apoptotic cells in the hippocampus CA1 area. Repeated measures variance was used to analyze body weight and behaviors, while an independent sample t-test was used to analyze protein levels. Results:Compared with the control group, the body weight of rats in the CUMS group decreased ( F=44.664); the sucrose preference rate decreased ( F=14.978); the forced swimming immobility time increased ( F=8.436); the number of defecation in the open field test increased ( F=9.572); the relative expression level of MKP-1 and Bax/Bcl-2 also significantly increased ( t=4.415,3.410), P<0.05 for all; Compared with the virus control group, rats in the MKP-1 down-regulation group showed a higher sucrose preference rate ( F=11.922) and a shorter forced swimming immobility time ( F=12.868), furthermore, the activity distance ratio in the central area increased ( F=6.291), the number of uprights in the open field test increased ( F=14.372), and the relative expression levels of MKP-1 and Bax/Bcl-2 ( t=3.775,6.193) decreased, P<0.05 for all. The number of DNA fragments in the nucleus of the hippocampal CA1 region of the CUMS group was significantly more than that of the control group. In comparison, the number of DNA fragments in the nucleus of the MKP-1 down-regulated group was substantially less than that of the virus control group. Conclusion:Down-regulation of MKP-1 gene alleviated depressive-like behavior and hippocampal neuron apoptosis in CUMS rats.

Objective:To investigate the role of mitogen-activated protein kinase phosphatase-1 (MKP-1) on depressive-like behaviors and hippocampal neuron apoptosis in chronic unpredictable mild stress (CUMS) rats.Methods:A total of 36 Sprague-Dawley male rats were randomly divided into 4 groups using a random number table, including the control group( n=8), CUMS group( n=8), virus control group( n=10), and MKP-1 down-regulated group( n=10), with 8 rats in each group. Except for the control group, rats in other groups were stressed by CUMS model of depression. Rats in the virus control group and MKP-1 down-regulated group received adeno-associated virus injections in the hippocampal CA1 and CA3 regions before CUMS modeling. Sucrose preference test, forced swimming test, and open field test were used to observe the behavioral changes of rats. Western blotting was used to detect the protein expression of MKP-1, B-cell lymphoma-2 gene (Bcl-2) and B-cell lymphoma-2 gene-related X protein (Bax), in the hippocampus. TUNEL staining was utilized to observe the morphology of apoptotic cells in the hippocampus CA1 area. Repeated measures variance was used to analyze body weight and behaviors, while an independent sample t-test was used to analyze protein levels. Results:Compared with the control group, the body weight of rats in the CUMS group decreased ( F=44.664); the sucrose preference rate decreased ( F=14.978); the forced swimming immobility time increased ( F=8.436); the number of defecation in the open field test increased ( F=9.572); the relative expression level of MKP-1 and Bax/Bcl-2 also significantly increased ( t=4.415,3.410), P<0.05 for all; Compared with the virus control group, rats in the MKP-1 down-regulation group showed a higher sucrose preference rate ( F=11.922) and a shorter forced swimming immobility time ( F=12.868), furthermore, the activity distance ratio in the central area increased ( F=6.291), the number of uprights in the open field test increased ( F=14.372), and the relative expression levels of MKP-1 and Bax/Bcl-2 ( t=3.775,6.193) decreased, P<0.05 for all. The number of DNA fragments in the nucleus of the hippocampal CA1 region of the CUMS group was significantly more than that of the control group. In comparison, the number of DNA fragments in the nucleus of the MKP-1 down-regulated group was substantially less than that of the virus control group. Conclusion:Down-regulation of MKP-1 gene alleviated depressive-like behavior and hippocampal neuron apoptosis in CUMS rats.

Objective To investigate the effect of enriched environment (EE) on behavior and expression of mitogenactivated protein kinase phosphatase-1 (MKP-1) in hippocampus of depression rats induced by chronic unpredicted mild stress (CUS) and to provide clues for the molecular mechanism of treating depression.Methods Forty Sprague-Dawley rats were randomly divided into control group,CUS group,fluoxetine group and EE group,with 10 rats in each group.The rats in CUS group,fluoxetine group and EE group were given 8 weeks of CUS,and from the fifth week,the rats in EE group and fluoxetine group were given EE and fluoxetine for 4 weeks,respectively.The changes of behavioristic of the rats in the four groups were evaluated by body mass gain,open field test,and sucrose preference.The expression of MKP-1 in hippocampus was detected by Western blot.Results There was no significant difference in body mass,distance of horizontal movement,the number of upright,the times of passing through the grid and sucrose preference index among the four groups(P ＞ 0.05).After modeling,compared with the control group,the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index in the CUS group,fluoxetine group and EE group were decreased significantly(P ＜ 0.05);there was no significant difference in the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index among the CUS group,fluoxetine group and EE group(P ＞ 0.05).After intervening by fluoxetine and EE,the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index in the CUS group were lower than those in the control group(P ＜0.05);but there was no significant difference in the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index between the control group and the fluoxetine group and EE group(P ＞ 0.05).Compared with the CUS group,the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index in the fluoxetine group and EE group were higher(P ＜ 0.05);there was no significant difference in the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index between the fluoxetine group and EE group (P ＞ 0.05).The expression of MKP-1 in hippocampus of CUS group and EE group was higher than that in the control group (P ＜0.05).There was no significant difference in the expression of MKP-1 in hippocampus between the fluoxetine group and control group(P ＞ 0.05).Compared with the CUS group,the expression of MKP-1 in hippocampus in the fluoxetine group decreased (P ＜ 0.05).There was no significant difference in the expression of MKP-1 in hippocampus between the EE group and CUS group(P ＞0.05).Compared with the fluoxetine group,the expression of MKP-1 in hippocampus in the EE group was higher(P ＜ 0.05).Conclusion EE can significantly improve depressive symptoms in rats,but it has no significant effect on MKP-1 protein expression in hippocampus,and EE may not act on depression by affecting MKP-1.