Obata Hiroyuki, Naito Kiyohito, Kikui Ayaka, Nakamura Shinji, Suzuki Kaori, Kawakita So, Suzuki Takamaru, Goto Kenji, Nagura Nana, Sugiyama Yoichi, Nagaoka Isao, Ishijima Muneaki
Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
Department of Orthopaedics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.
Exp Ther Med. 2022 Sep 21;24(5):682. doi: 10.3892/etm.2022.11618. eCollection 2022 Nov.
The effects of aging on axon regeneration currently remain unclear. In addition, the up-regulated expression of neurotrophic factors that occurs within one week of peripheral nerve injury has been shown to play an important role in the axon regeneration. To investigate the effects of aging on axon regeneration, the expression of nerve-specific proteins immediately after peripheral nerve injury were compared between young and aged mice. A mouse peripheral nerve injury model was prepared using the sciatic nerve compression method. In each group, Luxol fast blue staining and immunofluorescence staining were performed to assess the degree of Wallerian degeneration in the sciatic nerve, and to evaluate the expression of repressor element 1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), nerve growth factor (NGF), and semaphorin 3A (Sema3A) in the dorsal root ganglion, respectively. Wallerian degeneration was observed in both young and aged mice after peripheral nerve injury. Significant increases were observed in the expression of REST/NRSF (P<0.0001), NT3 (P=0.0279), and Sema3A (P=0.0175) following peripheral nerve injury in young mice, while that of BDNF (P=0.5583) and NGF (P=0.9769) remained unchanged. On the other hand, no significant differences were noted in the expression of these nerve-specific proteins in aged mice. Based on the results of the present study, compensatory changes induced by peripheral nerve injury were initiated by the up-regulated expression of REST/NRSF in young mice, but not in aged mice.
衰老对轴突再生的影响目前仍不清楚。此外,已表明在周围神经损伤一周内发生的神经营养因子表达上调在轴突再生中起重要作用。为了研究衰老对轴突再生的影响,比较了年轻和老年小鼠在周围神经损伤后立即神经特异性蛋白的表达。采用坐骨神经压迫法制备小鼠周围神经损伤模型。在每组中,进行Luxol固蓝染色和免疫荧光染色,以评估坐骨神经的华勒氏变性程度,并分别评估背根神经节中阻遏元件1沉默转录因子(REST)/神经元限制性沉默因子(NRSF)、脑源性神经营养因子(BDNF)、神经营养因子3(NT3)、神经生长因子(NGF)和信号素3A(Sema3A)的表达。周围神经损伤后,在年轻和老年小鼠中均观察到华勒氏变性。年轻小鼠周围神经损伤后,REST/NRSF(P<0.0001)、NT3(P=0.0279)和Sema3A(P=0.0175)的表达显著增加,而BDNF(P=0.5583)和NGF(P=0.9769)的表达保持不变。另一方面,老年小鼠中这些神经特异性蛋白的表达没有显著差异。基于本研究结果,周围神经损伤诱导的代偿性变化在年轻小鼠中由REST/NRSF的表达上调引发,但在老年小鼠中则不然。