The neurotrophin receptor p75NTR in Schwann cells is implicated in remyelination and motor recovery after peripheral nerve injury

Koichi Tomita, Tateki Kubo, Ken Matsuda, Toshihiro Fujiwara, Kenji Yano, Jonathan M. Winograd, Masaya Tohyama, K. O. Hosokawa

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    66 Citations (Scopus)

    Abstract

    The function of the p75NTR neurotrophin receptor (p75 NTR) in nervous system regeneration is still controversial. Part of that controversy may be due to the fact that p75NTR is expressed by both neuronal and glial cell types and may have very distinct and even contradictory roles in each population. In this study, to elucidate the in vivo function of p75NTR in Schwann cells during remyelination after peripheral nerve injury, we established a new animal model for p75 NTR-deficient Schwann cell transplantation in nude mice. We performed quantitative assessments of the functional, histological, and electrophysiological recovery after sciatic nerve injury, and compared them with those of the p75NTR(+/+) Schwann cell transplanted animals. At 7-10 weeks after injury, the motor recovery in the p75NTR(-/-) Schwann cell transplanted animals was significantly impaired compared with that in the p75NTR(+/+) Schwann cell transplanted animals. The lower number of the retrogradely labeled motoneurons and the hypomyelination in the p75 NTR(-/-) Schwann cell transplanted animals were evident at 6 and 10 weeks after injury. At 10 weeks after injury, the radial growth in the axon caliber was also impaired in the p75NTR(-/-) Schwann cell transplanted animals. Measurement of the amount of myelin proteins and the nerve conduction velocity at 10 weeks after injury reflected these results. In summary, the p75NTR expression in Schwann cells is important for remyelination process, and the motor recovery after injury is impaired due to impaired axonal growth, remyelination, and radial growth in the axon calibers.

    Original languageEnglish
    Pages (from-to)1199-1208
    Number of pages10
    JournalGLIA
    Volume55
    Issue number11
    DOIs
    Publication statusPublished - 2007 Aug 15

    Keywords

    • p75 in Schwann cell
    • Peripheral nerve injury
    • Radial growth
    • Remyelination
    • Schwann cell transplantation

    ASJC Scopus subject areas

    • Immunology

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