Age-related changes in glycogen synthase kinase 3 beta (GSK3 beta) immunoreactivity in the central nervous system of rats

Abstract

Although glycogen synthase kinase 3 beta (GSK3 beta) 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 GSK3 beta expression and GSK3 beta phosphorylation. Therefore, we examined age-related changes in immunoreactivities for GSK3 beta and phosphorylated GSK3 beta (pGSK3 beta) in the central nervous system. In aged rats, there were significant increases in GSK3 beta immunoreactivity in the cell bodies and processes of pyramidal cells in most cortical regions. GSK3 beta 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 GSK3 beta and pGSK3 beta was increased in the prefrontal cortex, while GSK3 beta and pGSK3P was differentially localized in the cerebellar cortex. The first demonstration of age-related alterations in immunoreactivities for GSK3 beta and pGSK3 beta in the basal forebrain area and cholinergic projection targets may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases including AD. (c) 2006 Published by Elsevier Ireland Ltd.