英国爱丁堡大学Giles E. Hardingham等研究人员合作发现，大脑皮层和丘脑里典型的突触和神经元特性的发展，可以在没有小胶质细胞的情况下进行。该项研究成果于2025年1月6日在线发表在《自然—神经科学》杂志上。

研究人员表明，先前归因于小胶质细胞的多个神经发育过程可以在没有小胶质细胞的情况下进行。通过使用一种缺乏小胶质细胞的基因修饰小鼠（Csf1r^?FIRE/?FIRE），研究人员发现，在小胶质细胞参与的阶段，海马CA1区和躯体感觉皮层的内在特性、突触数量和突触成熟大体正常。癫痫易感性和清醒状态下的海马-前额叶皮层相干性（这两个过程在小胶质细胞缺失基因的小鼠中会受到干扰）也正常。

同样，眼特异性输入在外侧膝状体核的分离，在没有小胶质细胞的情况下正常进行。对神经元和星形胶质细胞的单细胞和单核转录组分析，未发现由于小胶质细胞缺失引起的任何重大扰动。因此，大脑在没有小胶质细胞的情况下，能够表现出显著的适应性，完成发育过程中的突触修剪、成熟和连接。

研究人员表示，大脑常驻的巨噬细胞——小胶质细胞，被认为在突触修剪和成熟中发挥着积极作用，影响可塑性和回路级别的连接性。

附：英文原文

Title: Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus

Author: OKeeffe, Mary, Booker, Sam A., Walsh, Darren, Li, Mosi, Henley, Chloe, Simes de Oliveira, Laura, Liu, Mingshan, Wang, Xingran, Banqueri, Maria, Ridley, Katherine, Dissanayake, Kosala N., Martinez-Gonzalez, Cristina, Craigie, Kirsty J., Vasoya, Deepali, Leah, Tom, He, Xin, Hume, David A., Duguid, Ian, Nolan, Matthew F., Qiu, Jing, Wyllie, David J. A., Dando, Owen R., Gonzalez-Sulser, Alfredo, Gan, Jian, Pridans, Clare, Kind, Peter C., Hardingham, Giles E.

Issue&Volume: 2025-01-06

Abstract: Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1rFIRE/FIRE), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated. Seizure susceptibility and hippocampal-prefrontal cortex coherence in awake behaving animals, processes that are disrupted in mice deficient in microglia-enriched genes, are also normal. Similarly, eye-specific segregation of inputs into the lateral geniculate nucleus proceeds normally in the absence of microglia. Single-cell and single-nucleus transcriptomic analyses of neurons and astrocytes did not uncover any substantial perturbation caused by microglial absence. Thus, the brain possesses remarkable adaptability to execute developmental synaptic refinement, maturation and connectivity in the absence of microglia.

DOI: 10.1038/s41593-024-01833-x

Source: https://www.nature.com/articles/s41593-024-01833-x