Ruan Yu, Cheng Jin, Dai Jiafeng, Ma Zhengwen, Luo Shiyu, Yan Run, Wang Lizhao, Zhou Jinrui, Yu Bin, Tong Xiaoping, Shen Hongxing, Zhou Libing, Yuan Ti-Fei, Han Qi
Songjiang Research Institute, Shanghai Songjiang District Central Hospital, Department of Anatomy and Physiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Department of Spine Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Sci Adv. 2023 Oct 6;9(40):eadh0183. doi: 10.1126/sciadv.adh0183.
Spinal cord injury (SCI) often leads to physical limitations, persistent pain, and major lifestyle shifts, enhancing the likelihood of prolonged psychological stress and associated disorders such as anxiety and depression. The mechanisms linking stress with regeneration remain elusive, despite understanding the detrimental impact of chronic stress on SCI recovery. In this study, we investigated the effect of chronic stress on primary sensory axon regeneration using a preconditioning lesions mouse model. Our data revealed that chronic stress-induced mitochondrial cristae loss and a decrease in oxidative phosphorylation (OXPHOS) within primary sensory neurons, impeding central axon regrowth. Corticosterone, a stress hormone, emerged as a pivotal player in this process, affecting satellite glial cells by reducing Kir4.1 expression. This led to increased neuronal hyperactivity and reactive oxygen species levels, which, in turn, deformed mitochondrial cristae and impaired OXPHOS, crucial for axonal regeneration. Our study underscores the need to manage psychological stress in patients with SCI for effective sensory-motor rehabilitation.
脊髓损伤（SCI）常导致身体功能受限、持续性疼痛和生活方式的重大改变，增加了长期心理压力及相关疾病（如焦虑和抑郁）的发生可能性。尽管了解慢性应激对SCI恢复的有害影响，但应激与再生之间的联系机制仍不清楚。在本研究中，我们使用预处理损伤小鼠模型研究了慢性应激对初级感觉轴突再生的影响。我们的数据显示，慢性应激导致初级感觉神经元内线粒体嵴丢失和氧化磷酸化（OXPHOS）减少，从而阻碍中枢轴突再生。应激激素皮质酮在这一过程中起关键作用，它通过降低Kir4.1的表达影响卫星神经胶质细胞。这导致神经元活动过度增加和活性氧水平升高，进而使线粒体嵴变形并损害OXPHOS，而OXPHOS对轴突再生至关重要。我们的研究强调，为实现有效的感觉运动康复，有必要对脊髓损伤患者的心理压力进行管理。
