Impaired expression of ciliary neurotrophic factor in Charcot-Marie-Tooth type 1A neuropathy

Lucilla Nobbio, Fulvia Fiorese, Tiziana Vigo, Michele Cilli, Gianfranco Gherardi, Marina Grandis, Roberto Cosimo Melcangi, Gianluigi Mancardi, Michele Abbruzzese, Angelo Schenone

Research output: Contribution to journalArticle

Abstract

We investigated the contribution of Schwann cell-derived ciliary neurotrophic factor (CNTF) to the pathogenesis of Charcot-Marie-Tooth disease type 1A (CMT1A) and addressed the question as to whether it plays a role in the development of axonal damage observed in the disease, with aging. Ciliary neurotrophic factor was underexpressed in experimental CMT1A but not in other models of hereditary neuropathies. Sciatic nerve crush experiments and dosage of CNTF at different time points showed that expression of this trophic factor remained significantly lower in CMT1A rats than in normal controls; moreover, in uninjured CMT1A sciatic nerves CNTF levels further decreased with ageing, thus paralleling the molecular signs of axonal impairment, that is increased expression of non-phosphorylated neurofilaments and amyloid precursor protein. Administration of CNTF to dorsal root ganglia cultures reduced dephosphorylation of neurofilaments in CMT1A cultures, without improving demyelination. Taken together, these results provide further evidence that the production of CNTF by Schwann cells is markedly reduced in CMT1A. Moreover, the observations suggest that trophic support to the axon is impaired in CMT1A and that further studies on the therapeutic use of trophic factors or their derivatives in experimental and human CMT1A are warranted.

Original languageEnglish
Pages (from-to)441-455
Number of pages15
JournalJournal of Neuropathology and Experimental Neurology
Volume68
Issue number5
DOIs
Publication statusPublished - May 2009

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Keywords

  • Axonal impairment
  • Charcot-Marie-Tooth
  • Ciliary neurotrophic factor (CNTF)
  • CMT1A
  • Demyelination
  • DRG cultures
  • Neuroprotection
  • Peripheral myelin protein 22 (PMP22)
  • Schwann cells (SCs)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Nobbio, L., Fiorese, F., Vigo, T., Cilli, M., Gherardi, G., Grandis, M., Melcangi, R. C., Mancardi, G., Abbruzzese, M., & Schenone, A. (2009). Impaired expression of ciliary neurotrophic factor in Charcot-Marie-Tooth type 1A neuropathy. Journal of Neuropathology and Experimental Neurology, 68(5), 441-455. https://doi.org/10.1097/NEN.0b013e31819fa6ba