p21Cip1/WAF1 regulates radial axon growth and enhances motor functional recovery in the injured peripheral nervous system

Koichi Tomita, Tateki Kubo, Ken Matsuda, Tomas Madura, Kenji Yano, Tatsuji Fujiwara, Hiroyuki Tanaka, Masaya Tohyama, Ko Hosokawa

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)


    Recent studies have provided evidence that p21Cip1/WAF1 has not only cell cycle-associated activities but also other biological activities like neurite elongation. To investigate the role of p21Cip1/WAF1 in the in vivo axonal regeneration in the peripheral nervous system, we developed a p21Cip1/WAF1 knockout (KO) mice sciatic nerve injury model. We performed quantitative assessments of the functional, histological, and electrophysiological recoveries after sciatic nerve injury in p21Cip1/WAF1 KO mice and compared the results with those of the wild-type mice. p21Cip1/WAF1 KO mice showed a significant delay of the motor functional recovery between 21 and 42 days after sciatic nerve injury. The values of motor conduction velocity in p21Cip1/WAF1 KO mice were significantly lower than those in the wild-type mice on postoperative day 28. The mean percent neural tissue and the mean nerve axon width of p21Cip1/WAF1 KO mice were significantly less than those of the wild-type mice, which was caused by hyperphosphorylation of neurofilaments. Therefore, p21Cip1/WAF1 was considered to be involved in radial axon growth and to be essential for the motor functional recovery following peripheral nervous system injury.

    Original languageEnglish
    Pages (from-to)44-52
    Number of pages9
    JournalBrain Research
    Issue number1
    Publication statusPublished - 2006 Apr 7


    • Axonal regeneration
    • Neurofilament
    • Neuronal regeneration-associated genes (RAGs)
    • p21
    • Peripheral nervous system
    • Radial axon growth

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Clinical Neurology
    • Developmental Biology
    • Molecular Biology


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