Expression of α- and β-synucleins in cultured astrocytes and the effects of inflammatory cytokines

Abstract

α- and β-Synucleins (αS and βS) are concentrated in presynaptic nerve terminals. αS is now known to be a major component of Lewy bodies in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), as well as of oligodendroglial cytoplasmic inclusions in multiple system atrophy (MSA). Moreover, αS-positive inclusions in both astrocytic and oligodendroglial cells have also been detected in PD and DLB brains. However, these proteins have not been identified in glial cells in the normal human brain. We determined whether αS and βS might be expressed in glial cells. αS mRNA and protein were detected in normal human astrocytes and U251 human astrocytic glioma cells in vitro. Immunohistochemically, αS immunoreactivity was found in the cytoplasm of astrocytes and oligodendrocytes in vibratome sections of brain tissue taken from normal human subjects. βS immunoreactivity was also found in the astrocytes but not in the oligodendrocytes. Interleukin-1 increased the level of αS mRNA and protein in U251 cells, on the other hand, interleukin-1 decreased the level of βS mRNA and protein. These findings suggest that αS-immunoreactive glial inclusions may be a consequence of altered protein structure rather than de novo expression of αS and that a critical balance between αS and βS might be involved in inflammatory processes.