Neuronal activity after nerve injury can enhance axon regeneration and the restoration of function. The mechanism for this enhancement relies in part on hormone receptors, and we previously demonstrated that systemic androgen receptor antagonism blocked the effect of exercise or electrical stimulation on enhancing axon regeneration after nerve injury in both sexes. Here, we tested the hypothesis that the site of this androgen receptor signaling is both neuronal and involves the classical, genomic signaling pathway. In vivo, dorsal root ganglion neurons successfully regenerate in response to activity-dependent neuronal activation, and conditional deletion of the DNA-binding domain of the androgen receptor in adults blocks this effect in males and females. Motoneurons in males and females also respond in this manner, but we also observed a sex difference. In vitro, cultured sensory dorsal root ganglion neurons respond to androgens via traditional androgen receptor signaling mechanisms leading to enhanced neurite growth and did not respond to a testosterone conjugate that is unable to cross the cell membrane. Given our previous observation of a requirement for activity-dependent androgen receptor signaling to promote regeneration in both sexes, we interpret our results to indicate that genomic neuronal androgen receptor signaling is required for activity-dependent axon regeneration in both sexes.

中文翻译：

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神经元雄激素受体是周围神经再生的活性依赖性增强所必需的

神经损伤后的神经元活动可增强轴突再生和功能恢复。这种增强的机制部分依赖于激素受体，我们之前证明，全身性雄激素受体拮抗作用阻断了运动或电刺激对增强两性神经损伤后轴突再生的作用。在这里，我们检验了这种雄激素受体信号传导位点既是神经元又涉及经典基因组信号通路的假设。在体内，背根神经节神经元响应活动依赖性神经元激活而成功再生，成人雄激素受体的 DNA 结合结构域的条件性缺失阻断了男性和女性的这种效应。男性和女性的运动神经元也以这种方式作出反应，但我们也观察到了性别差异。在体外，培养的感觉背根神经节神经元通过传统的雄激素受体信号传导机制对雄激素产生反应，导致神经突生长增强，并且对不能穿过细胞膜的睾酮结合物没有反应。鉴于我们之前观察到需要活动依赖性雄激素受体信号传导来促进两性再生，我们解释我们的结果表明基因组神经元雄激素受体信号传导是两性活动依赖性轴突再生所必需的。