Department of Neuroscience, Section of Human Anatomy, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.
Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy.
Cells. 2021 Mar 20;10(3):686. doi: 10.3390/cells10030686.
Microglia, besides being able to react rapidly to a wide range of environmental changes, are also involved in shaping neuronal wiring. Indeed, they actively participate in the modulation of neuronal function by regulating the elimination (or "pruning") of weaker synapses in both physiologic and pathologic processes. Mounting evidence supports their crucial role in early synaptic loss, which is emerging as a hallmark of several neurodegenerative diseases, including multiple sclerosis (MS) and its preclinical models. MS is an inflammatory, immune-mediated pathology of the white matter in which demyelinating lesions may cause secondary neuronal death. Nevertheless, primitive grey matter (GM) damage is emerging as an important contributor to patients' long-term disability, since it has been associated with early and progressive cognitive decline (CD), which seriously worsens the quality of life of MS patients. Widespread synapse loss even in the absence of demyelination, axon degeneration and neuronal death has been demonstrated in different GM structures, thus raising the possibility that synaptic dysfunction could be an early and possibly independent event in the neurodegenerative process associated with MS. This review provides an overview of microglial-dependent synapse elimination in the neuroinflammatory process that underlies MS and its experimental models.
小胶质细胞除了能够对广泛的环境变化迅速做出反应外，还参与了神经元连接的形成。事实上，它们通过调节生理和病理过程中较弱突触的消除（或“修剪”），积极参与神经元功能的调节。越来越多的证据支持它们在早期突触丢失中的关键作用，这正在成为包括多发性硬化症（MS）及其临床前模型在内的几种神经退行性疾病的标志。MS 是一种炎症性、免疫介导的白质疾病，脱髓鞘病变可能导致继发性神经元死亡。然而，原始灰质（GM）损伤正成为患者长期残疾的一个重要因素，因为它与早期和进行性认知能力下降（CD）有关，这严重恶化了 MS 患者的生活质量。在不同的 GM 结构中已经证明了广泛的突触丢失，即使没有脱髓鞘、轴突退化和神经元死亡，这就提出了突触功能障碍可能是与 MS 相关的神经退行性过程中的一个早期和可能独立的事件的可能性。这篇综述概述了 MS 及其实验模型中神经炎症过程中小胶质细胞依赖性突触消除的情况。
