Activation of Calcium/Calmodulin‐Dependent Kinase II in the Medial Prefrontal Cortex Mediates Spinal Cord Injury‐Related Cognitive and Affective Changes

Purpose Research has documented a high prevalence of cognitive and affective impairments in individuals with spinal cord injury (SCI). However, the molecular mechanisms underlying these deficits remain poorly understood. In this study, to investigate the molecular basis of cognitive and affective dysfunctions following SCI, we examined the role of calcium/calmodulin‐dependent kinase II (CaMKII) activation, with a specific focus on its phosphorylated form (pCaMKII), using a rat model of SCI. Method Experimental results demonstrated that SCI led to spatial memory deficits as well as depression‐ and anxiety‐like behaviors, as evidenced by performance in the Morris water maze (MWM), elevated plus maze (EPM), and forced swim test (FST). Compared to the sham group, increased levels of pCaMKII were observed in the medial prefrontal cortex (mPFC) at Day 56 after SCI. Moreover, inhibiting CaMKII phosphorylation via microinjection of KN‐93—a CaMKII activation inhibitor—into the mPFC alleviated depression‐like behavior and cognitive deficits, but not anxiety‐like behavior. Finds and Conclusion These findings suggest that CaMKII activation in the mPFC may play an important role in mediating negative emotional states following SCI.