韩国首尔大学医学院Sang Jeong Kim团队发现，小脑贝格曼胶质细胞整合有害信息并调节防御性痛觉行为。2025年1月2日出版的《自然—神经科学》杂志发表了这一最新研究成果。

据介绍，小脑会受到有害刺激和病理性疼痛的激活，但它在有害信息处理中的作用仍不明确。

该研究组发现，在小鼠中，皮肤电刺激诱导去甲肾上腺素（NA）从小脑皮层的蓝斑（LC）末梢释放。伯格曼胶质细胞（BG）通过以一种整合的方式（‘火焰’反应），增加细胞内钙来积累这些蓝斑-去甲肾上腺素（LC-NA）信号。足底辣椒素注射也引起了伯格曼胶质细胞“火焰”反应。

小脑皮质蓝斑末梢或伯格曼胶质细胞的化学发生失活，或α1-肾上腺素能受体的伯格曼胶质细胞特异性敲低，可抑制伯格曼胶质细胞火焰，减少有害舔舐，并对神经损伤引起的慢性神经性疼痛具有镇痛作用。

此外，化学发生激活伯格曼胶质细胞，或足底注射辣椒素可减少浦肯野细胞放电，这可能解除了对小脑深部核输出活性的抑制。这些结果表明伯格曼胶质细胞，在计算来自蓝斑的疼痛信息，和通过调节小脑输出调节疼痛相关行为方面发挥作用。

附：英文原文

Title: Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors

Author: Kim, Seung Ha, Lee, Jaegeon, Jang, Mirae, Roh, Seung-Eon, Kim, Soobin, Lee, Ji Hwan, Seo, Jewoo, Baek, Jinhee, Hwang, Jae Yoon, Baek, In Seon, Lee, Yong-Seok, Shigetomi, Eiji, Lee, C. Justin, Koizumi, Schuichi, Kim, Sun Kwang, Kim, Sang Jeong

Issue&Volume: 2025-01-02

Abstract: The cerebellum is activated by noxious stimuli and pathological pain but its role in noxious information processing remains unknown. Here, we show that in mice, cutaneous noxious electrical stimuli induced noradrenaline (NA) release from locus coeruleus (LC) terminals in the cerebellar cortex. Bergmann glia (BG) accumulated these LC–NA signals by increasing intracellular calcium in an integrative manner (‘flares’). BG flares were also elicited in response to an intraplantar capsaicin injection. Chemogenetic inactivation of LC terminals or BG in the cerebellar cortex or BG-specific knockdown of α1-adrenergic receptors suppressed BG flares, reduced nocifensive licking and had analgesic effects in nerve injury-induced chronic neuropathic pain. Moreover, chemogenetic activation of BG or an intraplantar capsaicin injection reduced Purkinje cell firing, which may disinhibit the output activity of the deep cerebellar nuclei. These results suggest a role for BG in computing noxious information from the LC and in modulating pain-related behaviors by regulating cerebellar output.

DOI: 10.1038/s41593-024-01807-z

Source: https://www.nature.com/articles/s41593-024-01807-z