Hirano bodies and other cytoskeletal abnormalities develop in fetal rat CNS grafts isolated for long periods in peripheral nerve

Abstract

Dissociated cells from the telencephalic region of 12-day-old rat embryos were cultured in vitro for 3–5 days and transplanted into segments of the sciatic nerve of adult inbred rats. Transplanted progenitor cells survived, differentiated, and expressed various morphological and molecular features characteristics of neurons and glia. Six to twelve months after grafting, many neurons underwent changes compatible with an alteration of their cytoskeleton. These included; (1) a strong perikaryal immunoreactivity to the monoclonal antibody RT97, directed against the 200-kDa phosphorylated neurofilament subunit and (2) the formation of Hirano bodies within dendrites. Similar cytoskeletal abnormalities are seen as part of the spectrum of changes that occur in some human neurodegenerative diseases and in aging. The approach we have used may provide new possibilities for the study of the pathogenesis of these lesions under controlled laboratory conditions.