P39 immunoreactivity in glial cytoplasmic inclusions in brains with multiple system atrophy

Glial cytoplasmic inclusions (GCIs) characteristically occur in the oligodendrocytes of patients with multiple system atrophy (MSA). Cyclin-dependent kinase 5 (Cdk5) regulates cytoskeletal dynamism through phosphorylation of cytoskeletal proteins such as neurofilament proteins, tau and microtubule-associated protein 2. We examined the immunohistochemical localization of p39, a Cdk5 activator, in human brain specimens obtained post mortem from controls and patients with MSA. Among control specimens, p39 immunoreactivity was found in some neuronal somata and axons. Similar immunoreactivity was detected in MSA neuronal cell bodies and axons, but a number of inclusions were heavily labeled. These results suggest that p39 and Cdk5 are up-regulated in oligodendrocytes and may be involved in the formation of GCIs through phosphorylation of cytoskeletal proteins in oligodendrocytes in MSA.