Cao Liang, Yan Wei-Hong, Pi Wenjun, Zhang Yi, Xiong Yan-Xiang, Yong V Wee, Xue Mengzhou, Li Qing, Zheng Chunfu, Yang Leiluo
Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Henan International Joint Laboratory of Intracerebral Hemorrhage and Brain Injury, Zhengzhou, Henan, China.
Department of Traumatic Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Brain Res Bull. 2025 Feb;221:111217. doi: 10.1016/j.brainresbull.2025.111217. Epub 2025 Jan 20.
Cerebrospinal fluid-contacting neurons (CSF-cNs) exhibit neural stem cell (NSC) properties both in vitro and in vivo, and they may play a critical role in recovery after spinal cord injury (SCI). GABA receptors (GABABRs) are expressed in Pkd2l1 CSF-cNs. However, their role in Pkd2l1 CSF-cNs still needs to be discovered. In this study, we observed a significant reduction in GABAR expression in a murine model 7 d after SCI. We further discovered that GABAR activation enhanced the proliferation of Pkd2l1 CSF-cNs while inhibiting apoptosis. Additionally, this activation mitigated vacuole loss and neuronal damage in the pericentral canal region of the spinal cord, attenuated myelin and axonal loss within the spinal cord, and facilitated motor function recovery in SCI model mice. Mechanistically, GABAR primed quiescent Pkd2l1 CSF-cNs for cell cycle reentry through the activation of PI3K/Akt signaling. Our findings suggest that GABAR activation enhances the NSC potential of Pkd2l1 CSF-cNs, ultimately enabling post-SCI recovery in murine models.
脑脊液接触神经元（CSF-cNs）在体外和体内均表现出神经干细胞（NSC）特性，并且它们可能在脊髓损伤（SCI）后的恢复中发挥关键作用。GABA受体（GABABRs）在Pkd2l1脑脊液接触神经元中表达。然而，它们在Pkd2l1脑脊液接触神经元中的作用仍有待发现。在本研究中，我们观察到脊髓损伤后7天的小鼠模型中GABAR表达显著降低。我们进一步发现，GABAR激活增强了Pkd2l1脑脊液接触神经元的增殖，同时抑制了细胞凋亡。此外，这种激活减轻了脊髓中央管周围区域的空泡损失和神经元损伤，减轻了脊髓内的髓鞘和轴突损失，并促进了脊髓损伤模型小鼠的运动功能恢复。机制上，GABAR通过激活PI3K/Akt信号通路使静止的Pkd2l1脑脊液接触神经元为细胞周期重新进入做好准备。我们的研究结果表明，GABAR激活增强了Pkd2l1脑脊液接触神经元的神经干细胞潜能，最终实现了小鼠模型脊髓损伤后的恢复。
