Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration.
Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration.
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咯利普兰诱导的 cAMP 升高或细胞外基质中抑制性蛋白聚糖的软骨素酶 ABC 分解可促进周围神经再生。
DOI：
10.1016/j.expneurol.2009.08.026
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发表时间：
2010
影响因子：
5.3
通讯作者：
Gordon,T
中科院分区：
文献类型：
--
作者：
Udina,E;Ladak,A;Furey,M;Brushart,T;Tyreman,N;Gordon,T
中枢神经系统中髓鞘和细胞外基质蛋白聚糖的抑制性生长环境可以通过升高神经元cAMP或用软骨素酶ABC（ChABC）降解抑制性蛋白聚糖来克服。在这项研究中，我们询问是否有类似的机制在周围神经再生中起作用，其中有效的沃勒变性缓慢地去除髓鞘和细胞外蛋白多糖。我们修复横断腓总神经（CP）在大鼠和无论是升高cAMP的轴突切断神经元皮下咯利普兰，磷酸二酯酶IV的特异性抑制剂，和/或促进降解蛋白多糖在远端神经残端的局部ChABC管理。在1周和2周时，罗利普兰治疗显著增加了穿过修复部位再生轴突的运动神经元的数量，并且在2周时增加了穿过修复部位再生轴突的感觉神经元的数量。ChABC的局部应用有类似的效果，以咯利普兰治疗促进运动轴突再生，效果没有更大的咯利普兰和ChABC同时给药时。我们的结论是，通过提高cAMP或降解远端神经残端中的蛋白多糖来阻断轴突再生抑制剂，可促进横断神经手术修复后的外周轴突再生。可能的是，升高的cAMP足以促进轴突长出，尽管存在抑制性生长环境，使得同时酶促蛋白聚糖降解不会比升高的cAMP或单独的蛋白聚糖降解促进更多的轴突再生。
The inhibitory growth environment of myelin and extracellular matrix proteoglycans in the central nervous system may be overcome by elevating neuronal cAMP or degrading inhibitory proteoglycans with chondroitinase ABC (ChABC). In this study, we asked whether similar mechanisms operate in peripheral nerve regeneration where effective Wallerian degeneration removes myelin and extracellular proteoglycans slowly. We repaired transected common peroneal (CP) nerve in rats and either elevated cAMP in the axotomized neurons by subcutaneous rolipram, a specific inhibitor of phosphodiesterase IV, and/or promoted degradation of proteoglycans in the distal nerve stump by local ChABC administration. Rolipram treatment significantly increased the number of motoneurons that regenerated axons across the repair site at 1 and 2 weeks, and increased the number of sensory neurons that regenerated axons across the repair site at 2 weeks. Local application of ChABC had a similar effect to rolipram treatment in promoting motor axon regeneration, the effect being no greater when rolipram and ChABC were administered simultaneously. We conclude that blocking inhibitors of axon regeneration by elevating cAMP or degrading proteoglycans in the distal nerve stump promotes peripheral axon regeneration after surgical repair of a transected nerve. It is likely that elevated cAMP is sufficient to encourage axon outgrowth despite the inhibitory growth environment such that simultaneous enzymatic proteoglycan degradation does not promote more axon regeneration than either elevated cAMP or proteoglycan degradation alone.