长期体内三光子成像揭示了健康和再生少突胶质发生的区域特异性差异，这一成果由美国科罗拉多大学Ethan G. Hughes研究组经过不懈努力而取得。2024年3月27日出版的《自然—神经科学》杂志发表了这项成果。

该团队利用三光子显微镜优越的成像深度，对成年小鼠的整个皮质柱和皮质下白质进行长期、纵向的体内三光子成像。研究团队发现，成人大脑皮层少突胶质细胞群的扩张速度高于白质。脱髓鞘后，白质中的少突胶质细胞替代增强，而皮层深层在再生少突胶质发生和转录异质性恢复方面表现出缺陷。总之，他们的研究结果表明，区域微环境调节着健康和疾病大脑中少突胶质细胞的种群动态和异质性。

据介绍，在成人中枢神经系统中，形成新髓鞘的少突胶质细胞的产生对损伤后的认知功能和再生至关重要。少突胶质发生在灰质和白质区域之间有所不同，表明局部线索驱动髓鞘形成和再生能力的区域差异。然而，由于无法在体内监测深部脑结构，少突胶质细胞群体的层特异性和区域特异性调节尚不清楚。

附：英文原文

Title: Long-term in vivo three-photon imaging reveals region-specific differences in healthy and regenerative oligodendrogenesis

Author: Thornton, Michael A., Futia, Gregory L., Stockton, Michael E., Budoff, Samuel A., Ramirez, Alexandra N., Ozbay, Baris, Tzang, Omer, Kilborn, Karl, Poleg-Polsky, Alon, Restrepo, Diego, Gibson, Emily A., Hughes, Ethan G.

Issue&Volume: 2024-03-27

Abstract: The generation of new myelin-forming oligodendrocytes in the adult central nervous system is critical for cognitive function and regeneration following injury. Oligodendrogenesis varies between gray and white matter regions, suggesting that local cues drive regional differences in myelination and the capacity for regeneration. However, the layer- and region-specific regulation of oligodendrocyte populations is unclear due to the inability to monitor deep brain structures in vivo. Here we harnessed the superior imaging depth of three-photon microscopy to permit long-term, longitudinal in vivo three-photon imaging of the entire cortical column and subcortical white matter in adult mice. We find that cortical oligodendrocyte populations expand at a higher rate in the adult brain than those of the white matter. Following demyelination, oligodendrocyte replacement is enhanced in the white matter, while the deep cortical layers show deficits in regenerative oligodendrogenesis and the restoration of transcriptional heterogeneity. Together, our findings demonstrate that regional microenvironments regulate oligodendrocyte population dynamics and heterogeneity in the healthy and diseased brain.

DOI: 10.1038/s41593-024-01613-7

Source: https://www.nature.com/articles/s41593-024-01613-7