Department of Neuroscience and Physiology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Interdisciplinary Program in Neuroscience, College of Natural Science, Seoul National University, Seoul, Republic of Korea.
Mol Pain. 2021 Jan-Dec;17:17448069211020918. doi: 10.1177/17448069211020918.
Although microglia activation plays an important role in the development of nerve injury-induced neuropathic pain, the molecular mechanisms of spinal cord microglia activation in nerve injury are not completely understood. Recently, two injured sensory neuron-derived molecules, colony stimulating factor-1 (CSF-1) and GT1b, were proposed to trigger spinal cord microglia activation, yet their relationship and relative contribution to microglia activation have not been addressed. In the present study, the role of GT1b and CSF-1 in microglia activation and proliferation was characterized. GT1b stimulation upregulated proinflammatory mediators such as IL-1β, TNF-α, and NADPH oxidase 2 (Nox2), without microglia proliferation. Conversely, CSF-1 stimulation induced microglia proliferation with minimal proinflammatory gene induction. Notably, neither GT1b nor CSF-1 induced mechanical hypersensitivity in female mice; however, they induced similar microglial proliferation in both male and female mice. Taken together, our data indicate that injured sensory neuron-derived GT1b and CSF-1 activate spinal cord microglia in concert through distinct activation pathways.
虽然小胶质细胞的激活在神经损伤引起的神经性疼痛的发展中起着重要作用，但脊髓小胶质细胞在神经损伤中激活的分子机制尚不完全清楚。最近，两种损伤感觉神经元衍生的分子，集落刺激因子-1（CSF-1）和 GT1b，被提出触发脊髓小胶质细胞的激活，然而，它们之间的关系及其对小胶质细胞激活的相对贡献尚未得到解决。在本研究中，表征了 GT1b 和 CSF-1 在小胶质细胞激活和增殖中的作用。GT1b 刺激上调了促炎介质，如白细胞介素-1β、肿瘤坏死因子-α 和 NADPH 氧化酶 2（Nox2），但不会引起小胶质细胞增殖。相反，CSF-1 刺激诱导小胶质细胞增殖，而促炎基因的诱导作用很小。值得注意的是，GT1b 和 CSF-1 均不会引起雌性小鼠的机械性痛敏；然而，它们在雄性和雌性小鼠中均诱导类似的小胶质细胞增殖。总之，我们的数据表明，损伤感觉神经元衍生的 GT1b 和 CSF-1 通过不同的激活途径协同激活脊髓小胶质细胞。
