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

Brain Research
Koichi TomitaKo Hosokawa

Abstract

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.

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Citations

Jul 7, 2009·The European Physical Journal. E, Soft Matter·N S Gov
Jul 16, 2015·The European Journal of Neuroscience·Anand KrishnanDouglas W Zochodne
Aug 25, 2015·Frontiers in Molecular Neuroscience·Thong C Ma, Dianna E Willis
Dec 15, 2017·Chinese Medical Journal·Bao-Guo JiangPei-Xun Zhang
Apr 25, 2017·Journal of Alzheimer's Disease : JAD·Edward FielderDiana Jurk
Oct 22, 2014·The Journal of Biological Chemistry·Sathi Mallick, Santosh R D'Mello

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