Effects of shRNA-mediated knockdown of CaMKⅡβ on behavior and neurotransmitter levels in depressed mice

Abstract:

Objective：To investigate the effects of short hairpin RNA（shRNA）-mediated knockdown of calcium/calmodulin-dependent protein kinase Ⅱ beta（CaMKⅡβ） on behavior and neurotransmitter levels in depressed mice. Methods：Forty-five mice were ran－domly divided into control group，model group，and experimental group. The experimental group received an intracortical injection of CaMKⅡβ shRNA adeno-associated virus at 1×109 CFU/mouse，and both the control group and model group received an intracortical injection of control shRNA adeno-associated virus at 1×109 CFU/mouse. After four weeks of infection，chronic unpredictable stress was applied in both the model group and experimental group to develop an animal model of depression，followed by tail suspension，forced swimming，sugar water consumption，and covered box tests. The levels of dopamine（DA），5-hydroxytryptamine（5-HT），and norepinephrine（NE） in the prefrontal cortex of three groups of mice were determined by enzyme-linked immunosorbent assay. Results：Compared with the control group and model group，the experimental group had significantly lower CaMKⅡβ expression with CaMKⅡβ shRNA adeno-associated virus（P<0.05）. There was no significant difference in the number of horizontal and vertical movements between the three groups（P>0.05）. Compared with the control group，both the model group and experimental group had significantly longer immobility time in tail suspension and forced swimming tests and less sugar water consumption（P<0.05）. Compared with the model group，the experimental group had significantly longer immobility time in tail suspension and forced swimming tests and less sugar water consumption（P<0.05）. Compared with the control group，both the model group and experimental group had significantly lower levels of DA，5-HT，and NE（P<0.05）. Compared with the model group，the experimental group had signifi－cantly higher levels of DA，5-HT，and NE（P<0.05）. Conclusion：Adeno-associated virus-mediated CaMKⅡβ shRNA can signifi－cantly down-regulate the level of CaMKⅡβ and up-regulate the levels of DA，5-HT，and NE in brain tissue，thus achieving the effect of treating depression.