Novkovic T, Shchyglo O, Gold R, Manahan-Vaughan D
Department of Neurophysiology, Medical Faculty, Ruhr University Bochum, Germany; International Graduate School of Neuroscience, Ruhr University Bochum, Germany.
International Graduate School of Neuroscience, Ruhr University Bochum, Germany; Neurological University Clinic, St. Josef Hospital, Medical Faculty, Ruhr University Bochum, Germany.
Neuroscience. 2015 Nov 19;309:100-12. doi: 10.1016/j.neuroscience.2015.03.008. Epub 2015 Mar 17.
Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease that is characterized by demyelination and axonal damage in the nervous system. One obvious consequence is a cumulative loss of muscle control. However, cognitive dysfunction affects roughly half of MS sufferers, sometimes already early in the disease course. Although long-term (remote) memory is typically unaffected, the ability to form new declarative memories becomes compromised. A major structure for the encoding of new declarative memories is the hippocampus. Encoding is believed to be mediated by synaptic plasticity in the form of long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength. Here, in an animal model of MS we explored whether disease symptoms are accompanied by a loss of functional neuronal integrity, synaptic plasticity, or hippocampus-dependent learning ability. In mice that developed MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), passive properties of CA1 pyramidal neurons were unaffected, although the ability to fire action potentials became reduced in the late phase of EAE. LTP remained normal in the early phase of MOG35-55-induced EAE. However, in the late phase, LTP was impaired and LTP-related spatial memory was impaired. In contrast, LTD and hippocampus-dependent object recognition memory were unaffected. These data suggest that in an animal model of MS hippocampal function becomes compromised as the disease progresses.
多发性硬化症（MS）是一种进行性炎症性自身免疫疾病，其特征是神经系统中的脱髓鞘和轴突损伤。一个明显的后果是肌肉控制能力逐渐丧失。然而，认知功能障碍影响大约一半的MS患者，有时在疾病进程早期就已出现。虽然长期（远期）记忆通常不受影响，但形成新的陈述性记忆的能力会受到损害。用于编码新陈述性记忆的一个主要结构是海马体。据信，编码是通过突触可塑性以突触强度的长时程增强（LTP）和长时程抑制（LTD）的形式介导的。在此，在MS的动物模型中，我们探究了疾病症状是否伴随着功能性神经元完整性的丧失、突触可塑性或海马体依赖性学习能力的丧失。在发生髓鞘少突胶质细胞糖蛋白35-55（MOG35-55）诱导的实验性自身免疫性脑脊髓炎（EAE）的小鼠中，CA1锥体神经元的被动特性未受影响，尽管在EAE后期动作电位发放能力降低。在MOG35-55诱导的EAE早期，LTP保持正常。然而，在后期，LTP受损且与LTP相关的空间记忆受损。相比之下，LTD和海马体依赖性物体识别记忆未受影响。这些数据表明，在MS的动物模型中，随着疾病进展，海马体功能会受到损害。
