Androgen regulates neuritin mRNA levels in an in vivo model of steroid-enhanced peripheral nerve regeneration
Androgen regulates neuritin mRNA levels in an in vivo model of steroid-enhanced peripheral nerve regeneration
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DOI：
10.1089/neu.2007.0466
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发表时间：
2008-05-01
影响因子：
4.2
通讯作者：
Jones, Kathryn J.
中科院分区：
文献类型：
--
作者：
Fargo, Keith N.;Alexander, Thomas D.;Jones, Kathryn J.
叙利亚仓鼠面神经挤压损伤后，雄激素治疗可提高轴突再生率，缩短恢复时间。体外实验证明，雄激素促进运动神经元神经突生长的能力依赖于神经素——一种参与中枢神经系统创伤性损伤后神经元连接重建的蛋白质，它受到几种神经营养和神经再生因子的控制——我们假设神经素是雄激素提高体内周围神经再生率能力的中介。对面神经切开的仓鼠进行睾酮治疗，损伤后2天神经素mRNA水平增加300%。氟他胺是一种雄激素受体阻滞剂，已知可阻止雄激素增强神经再生，同时治疗氟他胺可消除睾酮上调神经素mRNA水平的能力。在一项确证性的体外实验中，雄激素二氢睾酮在转染了雄激素受体的运动神经元-神经母细胞瘤细胞中诱导了类似100%的神经球蛋白mRNA水平的增加，而在没有雄激素受体的细胞中则没有。这些数据证实了神经素受雄激素控制，提示神经素是雄激素促进损伤后周围神经再生的重要效应器。鉴于神经素现已被证明参与中枢和外周损伤的反应，并且似乎是几种神经营养和神经治疗药物的常见效应分子，了解神经素途径是创伤性神经系统损伤临床管理的重要目标。
Following crush injury to the facial nerve in Syrian hamsters, treatment with androgens enhances axonal regeneration rates and decreases time to recovery. It has been demonstrated in vitro that the ability of androgen to enhance neurite outgrowth in motoneurons is dependent on neuritin-a protein that is involved in the re-establisment of neuronal connectivity following traumatic damage to the central nervous system and that is under the control of several neurotrophic and neuroregenerative factors-and we have hypothesized that neuritin is a mediator of the ability of androgen to increase peripheral nerve regeneration rates in vivo. Testosterone treatment of facial nerve-axotomized hamsters resulted in a similar to 300% increase in neuritin mRNA levels 2 days post-injury. Simultaneous treatment with flutamide, an androgen receptor blocker that is known to prevent androgen enhancement of nerve regeneration, abolished the ability of testosterone to upregulate neuritin mRNA levels. In a corroborative in vitro experiment, the androgen dihydrotestosterone induced a similar to 100% increase in neuritin mRNA levels in motoneuron-neuroblastoma cells transfected with androgen receptors, but not in cells without androgen receptors. These data confirm that neuritin is under the control of androgens, and suggest that neuritin is an important effector of androgen in enhancing peripheral nerve regeneration following injury. Given that neuritin has now been shown to be involved in responses to both central and peripheral injuries, and appears to be a common effector molecule for several neurotrophic and neurotherapeutic agents, understanding the neuritin pathway is an important goal for the clinical management of traumatic nervous system injuries.