Glial conditioned medium enables jimpy oligodendrocytes to express properties of normal oligodendrocytes: production of myelin antigens and membranes

Cultures of cerebral cells from 2-day-old jimpy (jp) and normal animals were immunocytochemically stained with antibodies to galactocerebroside, 2', 3'-cyclic nucleotide 3'-phosphohydrolase and proteolipid protein (PLP). As the normal cultures mature, oligodendrocytes express these markers in cell bodies, in processes and in expansive membrane sheets produced along the lengths of cell processes. In contrast, oligodendrocytes from jp cultures do not produce large membrane sheets and their total numbers are reduced. Only rarely do jp oligodendrocytes exhibit immunostaining for PLP. Thus, jp oligodendrocytes grown in vitro mimic deficiencies of jp CNS in situ. In order to examine the effect of environment and cell-cell interactions on expression of the jp mutation we grew jp cerebral cells in the presence of medium conditioned for short periods by normal cerebral cells. Under these conditions jp oligodendroglia appeared nearly normal by immunostaining criteria. Their numbers were increased; they were able to produce and maintain membrane sheets; and some cells expressed PLP. These results show that jp oligodendrocytes have the capacity to express certain normal phenotypic parameters, and when given an appropriate environment they do so. The effects of normal conditioned medium may be due to a secreted factor, possibly produced by the astrocytes, which constitute the vast majority of cells in the conditioning cultures. The dramatic effect of normal glial conditioned medium on jp oligodendrocytes suggests that the steps leading to hypomyelination in jp are exceedingly complex and may involve glial-glial interactions.