Transient lysosomal activation is essential for p75 nerve growth factor receptor expression in myelinated Schwann cells during Wallerian degeneration.
- Author:
Junyang JUNG
1
;
Wenting CAI
;
So Young JANG
;
Yoon Kyoung SHIN
;
Duk Joon SUH
;
Jong Kuk KIM
;
Hwan Tae PARK
Author Information
- Publication Type:Original Article
- Keywords: Schwann cells; Lysosomes; p75NGFR; Demyelination; Wallerian degeneration
- MeSH: Axons; Cell Dedifferentiation; Chloroquine; Demyelinating Diseases; Lysosomes; Myelin Sheath; Nerve Growth Factor; Peripheral Nervous System; RNA, Messenger; Schwann Cells; Tumor Necrosis Factor-alpha; Wallerian Degeneration
- From:Anatomy & Cell Biology 2011;44(1):41-49
- CountryRepublic of Korea
- Language:English
- Abstract: Myelinated Schwann cells in the peripheral nervous system express the p75 nerve growth factor receptor (p75NGFR) as a consequence of Schwann cell dedifferentiation during Wallerian degeneration. p75NGFR has been implicated in the remyelination of regenerating nerves. Although many studies have shown various mechanisms underlying Schwann cell dedifferentiation, the molecular mechanism contributing to the re-expression of p75NGFR in differentiated Schwann cells is largely unknown. In the present study, we found that lysosomes were transiently activated in Schwann cells after nerve injury and that the inhibition of lysosomal activation by chloroquine or lysosomal acidification inhibitors prevented p75NGFR expression at the mRNA transcriptional level in an ex vivo Wallerian degeneration model. Lysosomal acidification inhibitors suppressed demyelination, but not axonal degeneration, thereby suggesting that demyelination mediated by lysosomes may be an important signal for inducing p75NGFR expression. Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be involved in regulating p75NGFR expression in Schwann cells. In this study, we found that removing TNF-alpha in vivo did not significantly suppress the induction of both lysosomes and p75NGFR. Thus, these findings suggest that lysosomal activation is tightly correlated with the induction of p75NGFR in demyelinating Schwann cells during Wallerian degeneration.
