MKP-1UP-regulation Atributed To Depression-like Behavior In UT-B Null Mice

Objective: To investigate the behavior effects on mice by UT-Bdeletion; observe the morphological changes in hippocampus of mice byUT-B deletion, measure urea and NO content in hippocampus of UT-B nullmice, and detect MKP-1and MAPK signaling changes, discuss molecularmechanism of depress-like behavior in UT-B null mice.Methods:1.8-12weeks of age, body and weight matched, femalewild-type and UT-B null mice for20of each group, were performed forcedswimming test, elevated plus maze test and open field test, to evaluateautonomous behavior between wild-type mice and the UT-B null mice.2.HE staining and immunohistochemistry were performed to observemorphological changes and expression of MKP-1in hippocampus ofwild-type and UT-B null mice.3. Urea and NO detection kits were used tomeasure the urea and NO content in hippocampus of wild-type and UT-Bnull mice.4. Western Blot were performed to detect expression level ofMKP-1、MAPK signaling in hippocampus of mice.Results:1. Forced swimming test results show that: Compare towild-type, UT-B null mice exhibited longer passive immobility time (123±19vs86±13s, P=0.0012<0.05).2. Elevated plus maze test resultsshow that: the open arms time (OT)、the open arms entries(OE)、thepercentage of total entries into the open-arms(OE％)、the percentage ofopen-arms time(OT％) were:(74.79±13.70vs12.71±3.17s，P=0.0109<0.05);(12.50±1.65vs4.75±0.56, P=0.0021<0.05);(58.63±4.28%vs27.25±3.29%, P=0.0009<0.05);(31.61±6.71%vs7.69±2.30%, P=0.0426<0.05).3.Open-field test results show that: the activity time in the centralarea、the activity distance in the central area、the activity distance in thecentral area were:（32.08±7.96s vs13.50±2.96s, P=0.025<0.05）；（873.5±137.1mm vs594.8±190.8mm，P=0.778>0.05）；（10110±756.3mm vs13770±844.7mm，P=0.025<0.05）.4. Density of neuron inhippocampus decreased and staining of MKP-1increased in UT-B null mice.5. Concentration of urea and NO in hippocampus between UT-B knockoutmice and wild-type mice were （16.7±2.0mM vs11.6±1.4mM，p=0.004<0.001） and （1.05±0.07μmol/gprot vs1.29±0.06μmol/gprot，p=0.04<0.05）respectively, indicated significantlyincreased urea and decreased NO level in hippocampus of UT-B knockoutmice.6. MKP-1expression level was up-regulated531.9%whereas pERKand pJNK expression level significantly down-regulated39.1%and21.3%respectively with pp38level intact.Conclusion:1.The results of Forced swimming, Elevated plus mazetest and Open-field test indicated UT-B null mice with depressive-like behavior.2. The decrease magnitude of neuron, accumulated urea andshortage of NO in hippocampus were induced by UT-B deletion.3.Hypoxia induced MKP-1expression up-regulated in hippocampus, whichspecifically decreased the expression level of pERK and pJNK andattributed to the depressive-like behavior in UT-B null mice.