癲癇是一種非常難治療的疾病。研究人員在日前在線出版的《自然—神經(jīng)學(xué)》（Nature Neuroscience）期刊上報告說，大腦中某種對酸性物質(zhì)敏感的分子能阻止與癲癇有關(guān)的疾病的發(fā)作,。這將有助于開發(fā)出針對癲癇治療的藥物。
癲癇是一種伴有或不伴有昏迷或痙攣的突然發(fā)生的以運動神經(jīng),、感覺或心理失常為特征的疾病,，但吸入含高水平二氧化碳的氣體則可阻止這種疾病的發(fā)作。這種附加的二氧化碳酸化了大腦,，但目前尚不清楚為什么酸化能阻止神經(jīng)細胞的激動,，從而阻止疾病的發(fā)作。
John Wemmie和同事推測,，神經(jīng)細胞膜中一種對酸性敏感的ASIC通道也許與此有關(guān),。為了驗證這種假設(shè)，他們培育出一種缺少ASIC通道分子的模式小鼠,，再讓這種小鼠患上癲癇,。與正常的接受同樣治療的癲癇小鼠相比，缺少ASIC通道分子的癲癇小鼠出現(xiàn)了更為嚴重的驚厥和痙攣,。吸入二氧化碳有助于阻止正常小鼠這種疾病的發(fā)作,，卻對缺失ASIC1a的小鼠卻沒有效果?？茖W(xué)家們還發(fā)現(xiàn),，ASIC1a的區(qū)域有更多被抑止的神經(jīng)細胞，而酸性環(huán)境中會強有力地刺激ASIC1a,。
這些結(jié)果也許能解釋為什么酸性能阻止癲癇的發(fā)作,，并推測ASIC1a是開發(fā)癲癇治療藥物的一個新靶標,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
