Increased 14-3-3 immunoreactivity in glial elements in patients with multiple sclerosis.

14-3-3 proteins have been shown to be increased in the cerebrospinal fluid from patients with several kinds of neurological diseases, including multiple sclerosis (MS). To investigate whether 14-3-3 proteins are closely related to the pathogenesis of MS, we performed immunohistochemical studies for 14-3-3 in autopsied brains from ten patients with MS, five patients with progressive multifocal leukoencephalopathy (PML), and seven normal control subjects. Formalin-fixed, paraffin-embedded sections from all cases were immunostained with a specific anti-14-3-3 antibody, and some sections from the MS cases were double-immunostained with antibodies raised against 14-3-3 and glial markers. In the normal control brains, 14-3-3 immunoreactivity was localized mainly in the neuronal somata and processes, and some glial cells showed only weak immunoreactivity. In the plaque lesions from the MS cases, the astrocytes and oligodendrocytes were intensely immunostained, and strong immunoreactivity was also found in some microglia and macrophages, most of which were located in the perivascular areas. In the PML brains, a similar immunolabeling pattern was observed in the demyelinated lesions, in which the astrocytes and oligodendrocytes exhibited dense 14-3-3 immunoreactivity. Our results suggest that 14-3-3 may be up-regulated in the glial cells, especially in astrocytes and oligodendrocytes, in patients with MS or PML. The exaggerated 14-3-3 accumulation in these glial elements may be associated with the pathogenesis of both demyelinating disorders.