nature-medicine201212-6

来自德国Hamburg-Eppendorf大学的科学家研究发现实验性自身免疫脑脊髓炎和多发性硬化症中TRPM4阳离子通道可以介导轴突和神经元变性,表明干扰TRPM4可以演变为一种信号神经保护策略而应用于临床。

-2012年12月《自然-医学》


中文翻译


【题目】实验性自身免疫脑脊髓炎和多发性硬化症中TRPM4阳离子通道介导轴突和神经元变性

【译文】多发性硬化症(中枢神经系统的一种炎症疾病)中,轴突和神经元丢失是不可逆神经疾病的主要原因。然而,炎症条件下是什么分子促进轴突和神经元损伤尚不清楚。本研究表明瞬时型感受器电位褪黑激素4(TRPM4)阳离子通道在该过程中至关重要。TRPM4在小鼠和人神经密质中表达,但它也在实验性自身免疫性脑脊髓炎(EAE)小鼠和人多发硬化症组织中的炎症性CNS损害中的轴突内有所表达。通过使用抗糖尿病药格列苯脲的TRPM4的缺陷或药理学抑制会导致轴突和神经元变性减少,并抑制EAE中临床疾病分数,但这并不改变EAE相关免疫功能。此外,在体外Trpm4−/−小鼠神经元受到保护以免受炎症效应机制,如兴奋毒性应激和能量缺陷的伤害。电生理记录揭示了在兴奋毒性刺激条件下,TRPM4-依赖的神经元离子流入和肿胀细胞膨大。因此,干扰TRPM4可以演变为一种信号神经保护策略。

英文原稿


[Title]: TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis

[Authors]:Benjamin Schattling1 Karin Steinbach1, 2, 3 Edda Thies1, 4 Martin Kruse5 Aurélie Menigoz6 Friederike Ufer1 Veit Flockerzi7 Wolfgang Brück8 Olaf Pongs5 Rudi Vennekens6 Matthias Kneussel4 Marc Freichel9 Doron Merkler2, 3, 8 Manuel A Friese1

[Abstract]In multiple sclerosis, an inflammatory disease of the central nervous system (CNS), axonal and neuronal loss are major causes for irreversible neurological disability. However, which molecules contribute to axonal and neuronal injury under inflammatory conditions remains largely unknown. Here we show that the transient receptor potential melastatin 4 (TRPM4) cation channel is crucial in this process. TRPM4 is expressed in mouse and human neuronal somata, but it is also expressed in axons in inflammatory CNS lesions in experimental autoimmune encephalomyelitis (EAE) in mice and in human multiple sclerosis tissue. Deficiency or pharmacological inhibition of TRPM4 using the antidiabetic drug glibenclamide resulted in reduced axonal and neuronal degeneration and attenuated clinical disease scores in EAE, but this occurred without altering EAE-relevant immune function. Furthermore, Trpm4−/− mouse neurons were protected against inflammatory effector mechanisms such as excitotoxic stress and energy deficiency in vitro. Electrophysiological recordings revealed TRPM4-dependent neuronal ion influx and oncotic cell swelling upon excitotoxic stimulation. Therefore, interference with TRPM4 could translate into a new neuroprotective.

原文地址

http://www.nature.com/nm/journal/v18/n12/abs/nm.3015.html

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