Abstract

Oligodendrocytes (OLs) are the primary targets in the autoimmune disease multiple sclerosis (MS). Cell receptors belonging to the tumor necrosis factor receptor (TNF-R) superfamily, such as TNF receptors and fas, are implicated in signaling the injury response of OLs. The p75 neurotrophin receptor (p75^NTR), another member of the TNF-R superfamily, has been reported to mediate nerve growth factor (NGF)-induced apoptosis in some neural systems. To address the potential relationship between p75^NTR signaling and OL injury, we assayed adult human OLs cultured under several different conditions for p75^NTR and tyrosine kinase receptor trkA expression, for NGF-mediated apoptosis, and for NGF-mediated jun kinase (JNK) or nuclear factor (NF) κB activation. In the current study, we have found expression of p75^NTR on cultured adult CNS-derived human OLs but not on other glial cells. TrkA was not detected on these OLs in any of the culture conditions tested. Treatment of the OLs with varying concentrations of NGF over a range of time periods resulted in no significant increase in numbers of terminal transferase (TdT)-mediated d-uridine triphosphate (UTP)-biotin nick-end labeling positive OLs, whereas significant cell death was observed using TNF-α. Furthermore, unlike TNF-α treatment, NGF treatment did not significantly activate JNK, although both TNF-α and NGF induced nuclear translocation of NF-κB. These findings contrast with the recent report of NGF-mediated apoptosis in the OLs of neonatal rats matured in vitro, which express p75^NTR but not trkA (Casaccia-Bonnefil et al., 1996), and suggest that, at least in humans, p75^NTRsignaling may mediate responses other than apoptosis of OLs.