Upregulation of phosphorylated αB-crystallin in the brain of children and young adults with Down syndrome

Abstract

Our previous proteomic studies disclosed upregulation of αB-crystallin, a small heat shock protein, in the brain tissue of Ts65Dn mice, a mouse model for Down syndrome (DS). To validate data obtained in model animals, we studied at present the levels and distribution of total αB-crystallin and its forms phosphorylated at Ser-45 and Ser-59 in the brain tissues of DS subjects and age-matched controls at 4 months to 23 years of age. On immunoblots from frontal cortex and white matter, αB-crystallin and its form phosphorylated at Ser-59 were detectable already in infants, whereas αB-crystallin phosphorylated at Ser-45 appeared in small amounts in older children. Although the levels of total αB-crystallin were modestly increased in DS subjects, the amounts of both phosphorylated forms were much higher (up to ∼550%) in the group of older children and young adults with DS than in age-matched controls. Immunoreactivity to αB-crystallin occurred not only in a subset of oligodendrocytes and some subpial and perivascular astrocytes, which was reported earlier, but also in GFAP-positive astrocytes accumulating at the sites of ependymal injury as well as some GFAP/platelet-derived growth factor receptor α-positive cells in both DS and control brains, which is a novel observation. Given that the chaperone and anti-apoptotic activities of αB-crystallin are phosphorylation-dependent, we propose that enhanced phosphorylation of αB-crystallin in the brains of young DS subjects might reflect a cytoprotective mechanism mobilized in response to stress conditions induced or augmented by the effect of genes encoded by the triplicated chromosome 21.