瑞士苏黎世大学Adriano Aguzzi研究团队发现，NG2胶质细胞通过抑制小胶质细胞到神经元的前列腺素E2信号传导，来免受朊病毒的神经毒性。这一研究成果于2024年5月27日发表在国际顶尖学术期刊《自然—神经科学》上。

据悉，少突胶质谱系细胞，包括NG2胶质细胞，在各种神经退行性疾病中发生显著变化。

该团队确定了NG2胶质细胞针对朊病毒毒性的神经保护作用。朊病毒感染后，小脑类器官型培养片(COCS)和接种过朊病毒的小鼠脑内NG2胶质细胞被激活。在这两个模型系统中，NG2胶质细胞的缺失加剧了朊病毒诱导的神经退行和加速了朊病毒病理。NG2胶质细胞的缺失增强了小胶质细胞对前列腺素E2 (PGE2)的生物合成，通过与EP4受体的结合增强了朊病毒的神经毒性。

药理或遗传抑制PGE2生物合成可减轻COCS和小鼠中朊病毒诱导的神经退行，减少朊病毒感染后NG2-胶质细胞缺失的COCS中神经退行的增强，并抑制NG2-胶质细胞缺失小鼠中朊病毒疾病的加速。这些数据揭示了朊病毒疾病中NG2胶质细胞和小胶质细胞之间的非细胞自主相互作用，并表明PGE2信号可能代表了一种可用于朊病毒疾病的靶点。

附：英文原文

Title: NG2 glia protect against prion neurotoxicity by inhibiting microglia-to-neuron prostaglandin E2 signaling

Author: Liu, Yingjun, Guo, Jingjing, Matoga, Maja, Korotkova, Marina, Jakobsson, Per-Johan, Aguzzi, Adriano

Issue&Volume: 2024-05-27

Abstract: Oligodendrocyte-lineage cells, including NG2 glia, undergo prominent changes in various neurodegenerative disorders. Here, we identify a neuroprotective role for NG2 glia against prion toxicity. NG2 glia were activated after prion infection in cerebellar organotypic cultured slices (COCS) and in brains of prion-inoculated mice. In both model systems, depletion of NG2 glia exacerbated prion-induced neurodegeneration and accelerated prion pathology. Loss of NG2 glia enhanced the biosynthesis of prostaglandin E2 (PGE2) by microglia, which augmented prion neurotoxicity through binding to the EP4 receptor. Pharmacological or genetic inhibition of PGE2 biosynthesis attenuated prion-induced neurodegeneration in COCS and mice, reduced the enhanced neurodegeneration in NG2-glia-depleted COCS after prion infection, and dampened the acceleration of prion disease in NG2-glia-depleted mice. These data unveil a non-cell-autonomous interaction between NG2 glia and microglia in prion disease and suggest that PGE2 signaling may represent an actionable target against prion diseases.

DOI: 10.1038/s41593-024-01663-x

Source: https://www.nature.com/articles/s41593-024-01663-x