TY - JOUR
T1 - p21Cip1/WAF1 regulates radial axon growth and enhances motor functional recovery in the injured peripheral nervous system
AU - Tomita, Koichi
AU - Kubo, Tateki
AU - Matsuda, Ken
AU - Madura, Tomas
AU - Yano, Kenji
AU - Fujiwara, Tatsuji
AU - Tanaka, Hiroyuki
AU - Tohyama, Masaya
AU - Hosokawa, Ko
PY - 2006/4/7
Y1 - 2006/4/7
N2 - 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.
AB - 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.
KW - Axonal regeneration
KW - Neurofilament
KW - Neuronal regeneration-associated genes (RAGs)
KW - p21
KW - Peripheral nervous system
KW - Radial axon growth
UR - http://www.scopus.com/inward/record.url?scp=33645739618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645739618&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2006.01.120
DO - 10.1016/j.brainres.2006.01.120
M3 - Article
C2 - 16529725
AN - SCOPUS:33645739618
VL - 1081
SP - 44
EP - 52
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1
ER -