Age-related changes in glycogen synthase kinase 3β (GSK3β) immunoreactivity in the central nervous system of rats

Although glycogen synthase kinase 3β (GSK3β) is emerging as a prominent drug target in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and stroke, very little is known about age-related changes in GSK3β expression and GSK3β phosphorylation. Therefore, we examined age-related changes in immunoreactivities for GSK3β and phosphorylated GSK3β (pGSK3β) in the central nervous system. In aged rats, there were significant increases in GSK3β immunoreactivity in the cell bodies and processes of pyramidal cells in most cortical regions. GSK3β immunoreactivity was also significantly increased in the pyramidal layer of CA1-3 regions, and the granule cell layer of dentate gyrus. Age-related increases were prominent in lateral septal nuclei, compared to the medial septal nuclei. Interestingly, both GSK3β and pGSK3β was increased in the prefrontal cortex, while GSK3β and pGSK3β was differentially localized in the cerebellar cortex. The first demonstration of age-related alterations in immunoreactivities for GSK3β and pGSK3β in the basal forebrain area and cholinergic projection targets may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases including AD.