局灶性白质病变导致灰质炎症和突触丧失，这一成果由剑桥大学Ragnhildur Thóra Káradóttir小组经过不懈努力而取得。相关论文于2026年4月22日发表在《自然》杂志上。

为了解决这个问题，该课题组人员在临床相关的大鼠脑中产生了一个局灶性白质病变，解剖学上定义明确，这些病变发生在许多神经退行性疾病中。

本研究表明，局灶性白质病变引起短暂的神经元活动改变和小胶质细胞增生，随后突触丢失，灰质中小胶质细胞吞噬增加，如果髓鞘再生完成，这种情况就会逆转。灰质小胶质瘤通常被认为是有害的；然而，该研究团队发现它是再生的一个组成部分，并且在三种不同的母主题电路和损伤方法中是保守的。阻止灰质中的这些短暂变化会阻碍白质中的髓鞘再生。相反，诱导髓磷脂再生失败会导致慢性灰质神经炎症。这概括了低度炎症被认为是神经变性的主要机制。他们的发现揭示了一种将白质完整性与灰质功能相结合的再生可塑性形式，这可能是多种神经退行性疾病的基础，并强调了以髓鞘再生为目标预防慢性神经炎症的潜力。

研究人员表示，局灶性白质病变发生在大多数神经退行性疾病中。尽管发生在疾病早期，但白质病变被认为与灰质神经炎症、突触丧失和神经元活动改变无关，或继发于灰质神经炎症、突触丧失和神经元活动改变。值得注意的是，它们对神经元回路的功能影响仍未得到充分研究。

附：英文原文

Title: Focal white matter lesions drive grey matter inflammation and synapse loss

Author: de Faria, Omar, Vagionitis, Stavros, Lopez-Lopez, Andrea, Perry, Michael, Wong, Joseph Jo Yin, Rodrguez-Kirby, Leslie, Herv, Bastien, Varga, Balazs Viktor, Agirre, Eneritz, Ghosh, Sabrina, Timmler, Sebastian, Yucel, Mert, Setley, Andrew T., Evans, Kimberley Anne, Birgisdttir, Tanja Mist, Gslason, Sindri, Ng, Yan Ting, Kremler, Courtney, Gautier, Helene O. B., Kamen, Yasmine, Pivonkova, Helena, Volbracht, Katrin, Hildebrand, Felix, Cepeda, Christian A., Rueda-Carrasco, Javier, Hong, Soyon, Malliaras, George, Dietmann, Sabine, Castelo-Branco, Gonalo, Kradttir, Ragnhildur Thra

Issue&Volume: 2026-04-22

Abstract: Focal white matter lesions occur in most neurodegenerative disorders1,2,3. Despite occurring early in disease, white matter lesions are considered to be independent of, or secondary to, grey matter neuroinflammation, synapse loss and altered neuronal activity4,5,6,7. Notably, their functional effect on neuronal circuits remains understudied. To address this, we generated a focal white matter lesion in the rat brain within a clinically relevant, anatomically well-defined circuit, in which these lesions occur in many neurodegenerative disorders8,9,10. Here we show that focal white matter lesions evoke transient neuronal activity changes and microgliosis, with subsequent synapse loss and increased microglial engulfment in the grey matter, which is reversed if myelin regeneration completes. Grey matter microgliosis is often considered to be detrimental; however, we show that it is an integral part of regeneration and is conserved across three distinct mouse circuits and lesioning methods. Preventing these transient changes in the grey matter blocks myelin regeneration in the white matter. Conversely, inducing myelin regeneration failure leads to chronic grey matter neuroinflammation. This recapitulates the low-grade inflammation considered to be a dominant mechanism underlying neurodegeneration7,11,12. Our findings reveal a form of regenerative plasticity coupling white matter integrity to grey matter function, which may underlie multiple neurodegenerative conditions, and highlight the potential of targeting myelin regeneration to prevent chronic neuroinflammation.

DOI: 10.1038/s41586-026-10414-w

Source: https://www.nature.com/articles/s41586-026-10414-w