癫痫是一种非常难治疗的疾病。研究人员在日前在线出版的《自然—神经学》(Nature Neuroscience)期刊上报告说,大脑中某种对酸性物质敏感的分子能阻止与癫痫有关的疾病的发作。这将有助于开发出针对癫痫治疗的药物。
癫痫是一种伴有或不伴有昏迷或痉挛的突然发生的以运动神经、感觉或心理失常为特征的疾病,但吸入含高水平二氧化碳的气体则可阻止这种疾病的发作。这种附加的二氧化碳酸化了大脑,但目前尚不清楚为什么酸化能阻止神经细胞的激动,从而阻止疾病的发作。
John Wemmie和同事推测,神经细胞膜中一种对酸性敏感的ASIC通道也许与此有关。为了验证这种假设,他们培育出一种缺少ASIC通道分子的模式小鼠,再让这种小鼠患上癫痫。与正常的接受同样治疗的癫痫小鼠相比,缺少ASIC通道分子的癫痫小鼠出现了更为严重的惊厥和痉挛。吸入二氧化碳有助于阻止正常小鼠这种疾病的发作,却对缺失ASIC1a的小鼠却没有效果。科学家们还发现,ASIC1a的区域有更多被抑止的神经细胞,而酸性环境中会强有力地刺激ASIC1a。
这些结果也许能解释为什么酸性能阻止癫痫的发作,并推测ASIC1a是开发癫痫治疗药物的一个新靶标。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Neuroscience,11, 816 - 822,Adam E Ziemann,John A Wemmie
Seizure termination by acidosis depends on ASIC1a
Adam E Ziemann1,2,9, Mikael K Schnizler3,9, Gregory W Albert4, Meryl A Severson4, Matthew A Howard III4,5, Michael J Welsh1,2,3,5,6 & John A Wemmie5,7,8
AbstractMost seizures stop spontaneously; however, the molecular mechanisms that terminate seizures remain unknown. Observations that seizures reduced brain pH and that acidosis inhibited seizures indicate that acidosis halts epileptic activity. Because acid-sensing ion channel 1a (ASIC1a) is exquisitely sensitive to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a, which would terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant-induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented seizure progression. CO2inhalation, long known to lower brain pH and inhibit seizures, required ASIC1a to interrupt tonic-clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. Our results identify ASIC1a as an important element in seizure termination when brain pH falls and suggest both a molecular mechanism for how the brain stops seizures and new therapeutic strategies.