Bone marrow-derived cells are known to infiltrate the adult brain and fuse with cerebellar Purkinje cells. Histological observations that such heterotypic cell fusion events are substantially more frequent following cerebellar injury suggest they could have a role in the protection of mature brain neurons. To date, the possibility that cell fusion can preserve or restore the structure and function of adult brain neurons has not been directly addressed; indeed, though frequently suggested, the possibility of benefit has always been rather speculative. Here we report, for the first time, that fusion of a bone marrow-derived cell with a neuron in vivo, in the mature brain, results in the formation of a spontaneously firing neuron. Notably, we also provide evidence supporting the concept that heterotypic cell fusion acts as a biological mechanism to repair pathological changes in Purkinje cell structure and electrophysiology. We induced chronic central nervous system inflammation in chimeric mice expressing bone marrow cells tagged with enhanced green fluorescent protein. Subsequent in-depth histological analysis revealed significant Purkinje cell injury. In addition, there was an increased incidence of cell fusion between bone marrow-derived cells and Purkinje cells, revealed as enhanced green fluorescent protein-expressing binucleate heterokaryons. These fused cells resembled healthy Purkinje cells in their morphology, soma size, ability to synthesize the neurotransmitter gamma-aminobutyric acid, and synaptic innervation from neighbouring cells. Extracellular recording of spontaneous firing ex vivo revealed a shift in the predominant mode of firing of non-fused Purkinje cells in the context of cerebellar inflammation. By contrast, the firing patterns of fused Purkinje cells were the same as in healthy control cerebellum, indicating that fusion of bone marrow-derived cells with Purkinje cells mitigated the effects of cell injury on electrical activity. Together, our histological and electrophysiological results provide novel fundamental insights into physiological processes by which nerve cells are protected in adult life.

众所周知，骨髓来源的细胞会浸润成人大脑并与小脑浦肯野细胞融合。组织学观察表明，这种异型细胞融合事件在小脑损伤后更为频繁，这表明它们可能在保护成熟脑神经元方面发挥作用。迄今为止，尚未直接解决细胞融合可以保留或恢复成人脑神经元结构和功能的可能性。事实上，尽管经常被提及，但受益的可能性一直是相当投机的。在这里，我们首次报道，在成熟大脑中，骨髓衍生细胞与体内神经元的融合导致形成自发放电的神经元。尤其，我们还提供了支持异型细胞融合作为修复浦肯野细胞结构和电生理学病理变化的生物学机制这一概念的证据。我们在表达用增强的绿色荧光蛋白标记的骨髓细胞的嵌合小鼠中诱导了慢性中枢神经系统炎症。随后深入的组织学分析揭示了显着的浦肯野细胞损伤。此外，骨髓来源的细胞和浦肯野细胞之间的细胞融合发生率增加，显示为增强的绿色荧光蛋白表达双核异核体。这些融合细胞在形态、体细胞大小、合成神经递质 γ-氨基丁酸的能力以及来自邻近细胞的突触神经支配方面与健康的浦肯野细胞相似。离体自发放电的细胞外记录揭示了在小脑炎症背景下非融合浦肯野细胞的主要放电模式发生了变化。相比之下，融合浦肯野细胞的放电模式与健康对照小脑中的相同，表明骨髓衍生细胞与浦肯野细胞的融合减轻了细胞损伤对电活动的影响。总之，我们的组织学和电生理学结果为成人生活中保护神经细胞的生理过程提供了新的基本见解。表明骨髓来源的细胞与浦肯野细胞的融合减轻了细胞损伤对电活动的影响。总之，我们的组织学和电生理学结果为成人生活中保护神经细胞的生理过程提供了新的基本见解。表明骨髓来源的细胞与浦肯野细胞的融合减轻了细胞损伤对电活动的影响。总之，我们的组织学和电生理学结果为成人生活中保护神经细胞的生理过程提供了新的基本见解。