Neuron-Glia Biology in Health and Disease, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
Neuron-Glia Biology in Health and Disease, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal; Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, Portugal.
Mult Scler Relat Disord. 2021 Jan;47:102622. doi: 10.1016/j.msard.2020.102622. Epub 2020 Nov 14.
Multiple sclerosis (MS) is a complex chronic immune disease in the central nervous system, causing neurological disability among young and middle-aged adults. Impaired cognition is now emerging as a major clinical symptom being present in more than 50% of MS patients. Recent data support that neuroinflammation mediated by glial cells plays a key part in MS course and, particularly, microglia is responsible for the pruning of synapses possibly impacting on vital neural networks maintenance. However, the knowledge of microglia-mediated mechanisms underlying cognitive impairment in MS is poor and unfortunately, there are no medicines to overcome this "invisible" symptom. Interestingly, the use of powerful diagnostic imaging tools as structural and functional MRI as well as PET brought new insights into some biological mechanisms, but no link between the possibility to use early visible alterations to predict cognitive deficits was clarified yet. In this review, we focus on the interplay between MS-related cognitive structures and neuroinflammation, specifically the presence of microglia and their reactivity. Moreover, we also discuss new imaging tools to assess cognitive impairment and to track microglia activation. Understanding the role of microglia in cognitive impairment and how it can be prevented may be a promising contribution to innovative therapeutic strategies that culminate in the improvement of MS patients' life quality.
多发性硬化症(MS)是一种中枢神经系统的复杂慢性自身免疫性疾病,导致年轻和中年成年人的神经功能障碍。现在认知障碍已成为超过 50%的 MS 患者的主要临床症状。最近的数据支持,由神经胶质细胞介导的神经炎症在 MS 病程中起着关键作用,特别是小胶质细胞负责突触修剪,这可能对重要的神经网络维持产生影响。然而,对于 MS 中认知障碍的小胶质细胞介导的机制的了解甚少,不幸的是,目前尚无药物可以克服这种“无形”的症状。有趣的是,使用强大的诊断成像工具,如结构和功能磁共振成像以及 PET,为一些生物学机制提供了新的见解,但仍未阐明是否可以利用早期可见的改变来预测认知缺陷。在这篇综述中,我们重点关注 MS 相关认知结构与神经炎症之间的相互作用,特别是小胶质细胞的存在及其反应性。此外,我们还讨论了评估认知障碍和跟踪小胶质细胞激活的新成像工具。了解小胶质细胞在认知障碍中的作用以及如何预防它可能是对创新治疗策略的一个有希望的贡献,最终可以提高 MS 患者的生活质量。