Nerve growth factor signaling of p75 induces differentiation and ceramide-mediated apoptosis in schwann cells cultured from degenerating nerves

Citation
H. Hirata et al., Nerve growth factor signaling of p75 induces differentiation and ceramide-mediated apoptosis in schwann cells cultured from degenerating nerves, GLIA, 36(3), 2001, pp. 245-258
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
GLIA
ISSN journal
0894-1491 → ACNP
Volume
36
Issue
3
Year of publication
2001
Pages
245 - 258
Database
ISI
SICI code
0894-1491(200112)36:3<245:NGFSOP>2.0.ZU;2-0
Abstract
In peripheral nerve regeneration or remyelination, immature Schwann cells e xpressing p75(NTR) play cardinal roles in the support and regeneration of a xons (Griffin JW, Hoffman PN. Peripheral Neuropathy 361-376, 1993). Only on e of four to six Schwann cells participate in remyelination of damaged or r egenerating axons. The rest of the cells, or supernumerary Schwann cells, s how severe atrophy and gradually decrease in number, reestablishing a 1:1 a xon-Schwann cell relationship (Said G, Duckett S. Acta Neuropathol (Berl) 5 3:173-179, 1981). Recent reports demonstrated that severely atrophied super numerary Schwann cells are eliminated by apoptosis during axonal regenerati on or remyelination (Hirata H, Hibasami H. Apoptosis 3:353-360, 1998; Berci ano MT, Calle E. Acta Neuropathol (Berl) 95:269-279, 1998). The mechanism t o induce selective death of supernumerary Schwann cells without causing any damage to axon-associated Schwann cells or axons remains to be determined. In this article, we report that p75(NTR), the low-affinity receptor for al l members of neurotrophins, signals both cell differentiation and apoptosis through intracellular ceramide elevation. The final response is dependent on the intracellular ceramide level and Schwann cells modulate their respon se by changing expression level of p75(NTR). This effect was selective for nerve growth factor (NGF). Taken together, the present study suggests that NGF contributes both to phenotypic regulation and to elimination of the ded ifferentiated Schwann cells, while supporting survival or regeneration of c ertain types of axons during peripheral nerve repair or regeneration. (C) 2 001 Wiley-Liss, Inc.