Constitutive activity and differential localization of p38α and p38β MAPKs in adult mouse brain

To understand the roles of p38 mitogen-activated protein kinase (p38 MAPK) isoforms in adult mouse brain, in vivo activities and detailed expression patterns of two p38 isoforms, p38α and p38β, were examined by using biochemical and immunohistochemical analyses. The result indicated that the activity of both p38α and p38β MAPKs in normal adult mouse brain was remarkably high, and the nuclear pool of the p38 isoforms was primarily responsible for most of the constitutive p38 MAPK activity in brain. Both p38α and p38β were highly expressed in brain areas including cerebral cortex, hippocampus, cerebellum, and few nuclei of the brainstem. At the subcellular level, p38α was distributed in dendrites and in cytoplasmic and nuclear regions of cell body of neurons, which is in contrast to p38β, since p38β was preferentially expressed in nucleus of neurons. These results suggest that the p38 pathway may play an important role, not only in inflammation and neuronal cell death as previously suggested, but also in normal physiology of adult mouse brain.ope