复旦大学脑科学研究院刘本龙小组报道了成纤维细胞生长因子8通过脊柱FGFR3信号抑制神经毒性星形胶质细胞并减轻神经性疼痛。2025年10月30日出版的《神经科学通报》杂志发表了这项成果。

该课题组人员报道，神经损伤（SNI）诱导补体成分3 (C3⁺）和S100钙结合蛋白A10 (S100A10⁺）SDH中的星形胶质细胞亚群，具有升高的小胶质细胞因子，包括白细胞介素-1α、肿瘤坏死因子-α和补体成分1q。转录组学、免疫组织化学和Western blot分析显示，在向A1样表型单向转变的过程中，多种反应性星形胶质细胞状态共同激活。成纤维细胞生长因子8 (FGF8)，一种通过FGFR3介导的神经保护因子，减轻了小胶质细胞诱导的C3⁺在SNI小鼠鞘内给药后，星形胶质细胞的体外反应性和脊髓C3表达的抑制和机械异常性痛。这些发现揭示了小胶质细胞-星形胶质细胞信号轴促进A1反应性，并通过调节星形胶质细胞异质性将FGF8定位为神经性疼痛的有希望的治疗候选者。

研究人员表示，脊髓背角（SDH）中的星形胶质细胞在神经病变条件下表现出多种反应性表型，但驱动这种多样性的机制及其在慢性疼痛中的意义尚不清楚。

附：英文原文

Title: Fibroblast Growth Factor 8 Suppresses Neurotoxic Astrocytes and Alleviates Neuropathic Pain via Spinal FGFR3 Signaling

Author: Liu, Huizhu, Yi, Lanxing, Li, Guiling, Wang, Kangli, Wang, Hongsheng, Zhang, Yuqiu, Liu, Benlong

Issue&Volume: 2025-10-30

Abstract: Astrocytes in the spinal dorsal horn (SDH) exhibit diverse reactive phenotypes under neuropathic conditions, yet the mechanisms driving this diversity and its implications in chronic pain remain unclear. Here, we report that spared nerve injury (SNI) induces marked upregulation of both complement component 3 (C3, A1-like) and S100 calcium-binding protein A10 (S100A10, A2-like) astrocyte subpopulations in the SDH, with elevated microglial cytokines including interleukin-1α, tumor necrosis factor-α, and complement component 1q. Transcriptomic, immunohistochemical, and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype. Fibroblast growth factor 8 (FGF8), a neuroprotective factor via FGFR3, mitigated microglia-induced C3 astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice. These findings reveal a microglia–astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.

DOI: 10.1007/s12264-025-01533-x

Source: https://link.springer.com/article/10.1007/s12264-025-01533-x