Unit of Neurology & Neurorehabilitation, IRCCS Neuromed, 86077 Pozzilli (IS), Italy.
Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
Int J Mol Sci. 2020 Sep 23;21(19):6982. doi: 10.3390/ijms21196982.
In multiple sclerosis (MS), inflammation alters synaptic transmission and plasticity, negatively influencing the disease course. In the present study, we aimed to explore the influence of the proinflammatory cytokine IL-1β on peculiar features of associative Hebbian synaptic plasticity, such as input specificity, using the paired associative stimulation (PAS). In 33 relapsing remitting-MS patients and 15 healthy controls, PAS was performed on the abductor pollicis brevis (APB) muscle. The effects over the motor hot spot of the APB and abductor digiti minimi (ADM) muscles were tested immediately after PAS and 15 and 30 min later. Intracortical excitability was tested with paired-pulse transcranial magnetic stimulation (TMS). The cerebrospinal fluid (CSF) levels of IL-1β were calculated. In MS patients, PAS failed to induce long-term potentiation (LTP)-like effects in the APB muscle and elicited a paradoxical motor-evoked potential (MEP) increase in the ADM. IL-1β levels were negatively correlated with the LTP-like response in the APB muscle. Moreover, IL-1β levels were associated with synaptic hyperexcitability tested with paired-pulse TMS. Synaptic hyperexcitability caused by IL-1β may critically contribute to alter Hebbian plasticity in MS, inducing a loss of topographic specificity.
在多发性硬化症 (MS) 中，炎症改变了突触传递和可塑性，对疾病进程产生负面影响。在本研究中，我们旨在探讨促炎细胞因子 IL-1β 对联想海伯尔突触可塑性的特殊特征的影响，例如使用成对关联刺激 (PAS) 的输入特异性。在 33 名复发缓解型 MS 患者和 15 名健康对照者中，对拇指外展短肌 (APB) 进行 PAS。在 PAS 后即刻以及 15 和 30 分钟后，测试对 APB 和小趾外展肌 (ADM) 肌肉的运动热点的影响。使用成对脉冲经颅磁刺激 (TMS) 测试皮质内兴奋性。计算脑脊液 (CSF) 中 IL-1β 的水平。在 MS 患者中，PAS 未能在 APB 肌肉中诱导类似长时程增强 (LTP) 的效应，并在 ADM 中引起矛盾的运动诱发电位 (MEP) 增加。IL-1β 水平与 APB 肌肉中的类似 LTP 反应呈负相关。此外，IL-1β 水平与使用成对脉冲 TMS 测试的突触超兴奋性相关。IL-1β 引起的突触超兴奋性可能会严重影响 MS 中海伯尔可塑性的改变，导致拓扑特异性丧失。
