Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Brain Immunology and Glia Center, Department of Cell Biology and Neuroscience, University of Virginia, Charlottesville, VA 22908, USA.
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Cell Rep. 2021 May 4;35(5):109080. doi: 10.1016/j.celrep.2021.109080.
Although an imbalance between neuronal excitation and inhibition underlies seizures, clinical approaches that target these mechanisms are insufficient in containing seizures in patients with epilepsy, raising the need for alternative approaches. Brain-resident microglia contribute to the development and stability of neuronal structure and functional networks that are perturbed during seizures. However, the extent of microglial contributions in response to seizures in vivo remain to be elucidated. Using two-photon in vivo imaging to visualize microglial dynamics, we show that severe seizures induce formation of microglial process pouches that target but rarely engulf beaded neuronal dendrites. Microglial process pouches are stable for hours, although they often shrink in size. We further find that microglial process pouches are associated with a better structural resolution of beaded dendrites. These findings provide evidence for the structural resolution of injured dendrites by microglia as a form of neuroprotection.
虽然神经元兴奋和抑制之间的失衡是癫痫发作的基础，但针对这些机制的临床方法在控制癫痫患者的癫痫发作方面效果不足，这就需要寻找替代方法。脑内小胶质细胞有助于神经元结构和功能网络的发育和稳定，而这些网络在癫痫发作期间会受到干扰。然而，小胶质细胞在体内对癫痫发作的反应程度仍有待阐明。我们使用双光子在体成像来可视化小胶质细胞的动力学，结果表明严重的癫痫发作会诱导小胶质细胞突起形成囊泡，这些囊泡靶向但很少吞噬珠状神经元树突。小胶质细胞突起囊泡可以稳定数小时，尽管它们经常会缩小。我们还发现，小胶质细胞突起囊泡与珠状树突更好的结构分辨率有关。这些发现为小胶质细胞对损伤树突的结构分辨率提供了证据，这是一种神经保护形式。
