Neu differentiation factor regulates tau protein and mRNA in cultured neonatal oligodendrocytes

Axonal signals activate myelinogenesis via regulation of the extent to whic h oligodendrocyte (OLG) processes wrap around the axon. The cytoskeleton in OLG processes is actively involved in myelination and is a putative target for axonal regulation of myelination. The axon-associated neuregulins may regulate the cytoskeleton extensions in OLG processes. Here, we report that the neuregulin neu. differentiation factor (NDF) increases the expression of tau mRNA and tau protein in OLGs. Treatment of neonatal OLGs with alpha -NDF or beta -NDF resulted in dramatic increases in the length of OLG proce sses, which appeared either as singular unbranched extensions or as a netwo rk of extensively branched processes, By immunoblot analysis with tau-1 mAb , which recognizes the dephosphorylated form of the tau proteins, neonatal OLGs treated with alpha -NDF or beta -NDF, had an increase in tau protein l evels. The increase of tau levels in beta -NDF-treated cells is much greate r than the twofold increase present in alpha -NDF-treated cells. By immunob lot analysis with the phosphorylation-insensitive tau-5 mAb, beta -NDF-trea ted cells had a twofold increase in tau. Immunoblot analysis suggest that a lpha -NDF and beta -NDF promote a twofold increase in the tau protein level s in OLG, with the beta -factor also promoting a tau dephosphorylation. Usi ng promoters spanning the aminoterminal region of tau, we found that OLGs t reated with alpha -NDF or beta -NDF contained approximately twofold more ta u mRNA than untreated cells. However, there was no qualitative difference b etween control and NDF-treated cells in the pattern of tau mRNA isoforms ex pressed. A model is proposed in which the axonal NDF-induced regulation of tau expression in OLGs may be part of the mechanism by which the axon regul ates myelination. (C) 2001 Wiley-Liss, Inc.