Hu Hao, Cui Yiwen, Yang Jing, Cao Ying
Department of Urology, Peking University People's Hospital, Beijing, China.
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Peking University, Beijing, China.
Front Mol Neurosci. 2022 May 10;15:855376. doi: 10.3389/fnmol.2022.855376. eCollection 2022.
Neural innervations exert essential roles in the prostate. However, spatial distribution and regulatory function of such neural inputs are incompletely characterized. Here, we exploited the advanced whole-tissue immunolabeling and optical clearing technique to assess the 3D anatomy of autonomic innervations in the mouse and human prostate for the first time. We observed that sympathetic and parasympathetic inputs in the mouse prostate remained unaffected during castration-induced tissue regression. However, the pharmacologic destruction of sympathetic innervations in the mouse prostate led to sterile inflammation of the tissue, mimicking the disease condition of chronic non-bacterial prostatitis. Also, the genetic ablation of sympathetic inputs produced a similar inflammatory response. Furthermore, we showed that treatment of the specific β2-adrenergic receptor agonists could effectively mitigate the prostate inflammation caused by such sympathetic loss. Together, these results have elucidated the new immunomodulatory function of the sympathetic signal the β2-adrenergic receptor in prostate inflammatory disease.
神经支配在前列腺中发挥着重要作用。然而,此类神经输入的空间分布和调节功能尚未完全明确。在此,我们首次利用先进的全组织免疫标记和光学清除技术来评估小鼠和人类前列腺中自主神经支配的三维解剖结构。我们观察到,在去势诱导的组织退化过程中,小鼠前列腺中的交感神经和副交感神经输入未受影响。然而,小鼠前列腺中交感神经支配的药物性破坏导致组织无菌性炎症,类似于慢性非细菌性前列腺炎的疾病状态。此外,交感神经输入的基因消融也产生了类似的炎症反应。此外,我们还表明,特异性β2 - 肾上腺素能受体激动剂的治疗可有效减轻由这种交感神经缺失引起的前列腺炎症。总之,这些结果阐明了交感神经信号——β2 - 肾上腺素能受体在前列腺炎症性疾病中的新免疫调节功能。