Abstract
Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is expressed abundantly in the nuclei of neurons and thought to regulate gene expressions mediated by the transcriptional factors such as CREB. We have been characterized CaMKIV comparing with other subtypes CaMKI and CaMKII in the hippocampal neurons. The basal CaMKIV activity is kept low by constant inactivation by associated protein phosphatase 2A, and the activation is transient because calcineurin inactivate CaMKIV after the neuronal stimuli, while the activities of CaMKI and CaMKII are sustained. In other words, CaMKIV is hard to be switched on and is easy to be switched off. Based on this fact, we thought the functions of CaMKIV are reflected in the animals after the chronic stimulation rather than the acute one. Recently, we found that chronic treatments of the rats with antidepressants increased CaMKIV activity and CREB phosphorylation in the prefrontal cortex and the hippocampus, suggesting the importance of CaMKIV in the effects of antidepressants. These results led us to perform the behavioral assessments of anxiety, depression and the sensitivity to antidepressants in CaMKIV-knockout mice by some experimental paradigms including the forced swim test, the tail suspension test and the novelty-suppressed feeding test. From the results of these experiments, it was suggested that CaMKIV is involved in some of the depression-related behaviors and the sensitivities to antidepressants. [J Physiol Sci. 2006;56 Suppl:S62]
