背景:多发性硬化(MS)是一种自身免疫性神经退行性疾病,其主要标志是白质和灰质结构中炎性病变的发生。在MS患者和相应的小鼠模型中越来越多的证据报道了由炎症脱髓鞘驱动的离子稳态受损,从而深刻影响信号传播。然而,局灶性炎性病变对单细胞和网络功能的影响迄今尚未完全阐明.
目的:在本研究中,我们试图确定局部皮质炎性病变对听觉系统丘脑神经元兴奋性和放电模式的影响。此外,我们测试了雷替加宾(RTG)的神经保护作用,一个特定的Kv7通道开启器,关于疾病的结果。
方法:为了类似于人类疾病,我们集中施用促炎细胞因子,TNF-α和IFN-γ,在MOG35-55免疫小鼠的初级听觉皮层(A1)中。此后,我们研究了诱导的炎症环境对传入丘脑皮质(TC)神经元的影响,通过进行离体记录。此外,我们探索了用RTG进行Kv7通道调制对听觉信息处理的影响,使用体内电生理方法。
结果:我们的结果表明,皮质炎性病变严重影响了邻近TC神经元的兴奋性和放电模式。值得注意的是,RTG恢复了控制样值和TC色调图。
结论:我们的结果表明,RTG治疗可能会有力地减轻炎症引起的兴奋性改变,并保留上升的信息处理。
BACKGROUND: Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease, whose primary hallmark is the occurrence of inflammatory lesions in white and grey matter structures. Increasing evidence in MS patients and respective murine models reported an impaired ionic homeostasis driven by inflammatory-demyelination, thereby profoundly affecting signal propagation. However, the impact of a focal inflammatory lesion on single-cell and network functionality has hitherto not been fully elucidated.
OBJECTIVE: In this study, we sought to determine the consequences of a localized cortical inflammatory lesion on the excitability and firing pattern of thalamic neurons in the auditory system. Moreover, we tested the neuroprotective effect of Retigabine (RTG), a specific Kv7 channel opener, on disease outcome.
METHODS: To resemble the human disease, we focally administered pro-inflammatory cytokines, TNF-α and IFN-γ, in the primary auditory cortex (A1) of MOG35-55 immunized mice. Thereafter, we investigated the impact of the induced inflammatory milieu on afferent thalamocortical (TC) neurons, by performing ex vivo recordings. Moreover, we explored the effect of Kv7 channel modulation with RTG on auditory information processing, using in vivo electrophysiological approaches.
RESULTS: Our results revealed that a cortical inflammatory lesion profoundly affected the excitability and firing pattern of neighboring TC neurons. Noteworthy, RTG restored control-like values and TC tonotopic mapping.
CONCLUSIONS: Our results suggest that RTG treatment might robustly mitigate inflammation-induced altered excitability and preserve ascending information processing.