Centro Europeo per la Ricerca sul Cervello (CERC)/Fondazione Santa Lucia, Rome, Italy.
Neurol Sci. 2010 Nov;31(Suppl 2):S255-9. doi: 10.1007/s10072-010-0369-3.
Multiple sclerosis (MS) is characterized by auto-reactive T cells that respond to central nervous system (CNS)-based antigens and affect motor, sensory as well as behavioral and cognitive functions. Cognitive deficits are now considered an early manifestation of the disease in MS patients. However, the pathophysiology responsible for the cognitive symptoms in MS remains unclear. Increasing evidence from a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE), suggests a correlation between the synaptopathy induced by microglia activation in the early phase of the disease and cognitive dysfunction. In particular, EAE causes deficits in hippocampal-dependent learning and memory that are associated with early microglial activation, synaptic loss and neurodegeneration. Interestingly, inflammatory cytokines released from infiltrating lymphocytes or activated microglia are able to alter synaptic transmission. Increased glutamate-mediated transmission and loss of GABAergic inputs were observed in EAE. They may thus underlie cognitive dysfunction in this model and in MS.
多发性硬化症（MS）的特征是自身反应性 T 细胞对中枢神经系统（CNS）相关抗原的反应，并影响运动、感觉以及行为和认知功能。认知缺陷现在被认为是 MS 患者疾病的早期表现。然而，导致 MS 患者认知症状的病理生理学仍不清楚。越来越多来自 MS 的小鼠模型，实验性自身免疫性脑脊髓炎（EAE）的证据表明，疾病早期小胶质细胞激活引起的突触病与认知功能障碍之间存在相关性。特别是，EAE 导致海马依赖学习和记忆的缺陷，这些缺陷与早期小胶质细胞激活、突触丢失和神经退行性变有关。有趣的是，从浸润淋巴细胞或激活的小胶质细胞释放的炎症细胞因子能够改变突触传递。在 EAE 中观察到谷氨酸能介导的传递增加和 GABA 能输入的丢失。因此，它们可能是该模型和 MS 中认知功能障碍的基础。
