英國科學(xué)家發(fā)現(xiàn),，老鼠大腦內(nèi)缺乏ATP1A3基因可能引發(fā)嚴重的癲癇癥狀。該研究結(jié)果發(fā)表在最新一期的《美國國家科學(xué)院院刊》上,。
有些人會因為頭部受到重創(chuàng),、腦部腫瘤、其他神經(jīng)疾病等而引發(fā)癲癇,?？茖W(xué)家一直認為，大部分癲癇可能由基因引起,，但一直未能獲得證實,。
英國利茲大學(xué)的神經(jīng)學(xué)家斯蒂芬·克拉克特領(lǐng)導(dǎo)的研究團隊將正常老鼠與患有癲癇的老鼠進行雜交，并通過基因工程的方法讓正常老鼠擁有額外的ATP1A3基因的復(fù)制。額外的復(fù)制彌補了ATP1A3基因的缺乏,，因此,，其后代沒有癲癇癥狀，其平衡鈉和鉀濃度的酶也處于正常狀態(tài),。
研究人員稱,，在老鼠和人類中，ATP1A3基因都負責(zé)調(diào)節(jié)大腦中鈉和鉀的濃度,。ATP1A3基因產(chǎn)生一種酶,，該酶就像鈉鉀泵一樣，可以調(diào)節(jié)大腦中鈉和鉀的濃度,?；忌狭税d癇的老鼠缺乏ATP1A3基因，生成的酶不活躍,，不足以平衡鈉和鉀的濃度,，因此，老鼠的癲癇會定期發(fā)作,。
研究人員篩查了許多癲癇病人的DNA樣本,，以證實是否同樣的基因缺陷使一些人更容易患上癲癇，他們稱,，人類和老鼠基因99%的匹配度意味著該基因可能在人體內(nèi)也起作用,。
研究人員指出，在癲癇病患者中,，大腦處于高度興奮狀態(tài),，這意味著，當癲癇病人的大腦遭受刺激時,，會更容易出現(xiàn)神經(jīng)元放電的情況,，讓癲癇癥狀更加明顯，鈉和鉀影響著神經(jīng)元放電活動,。
科學(xué)家表示,，如果該研究能應(yīng)用于人類，將有助于找到治療癲癇的全新方法,。一種方法是給病人提供人工合成的鈉鉀泵酶來幫助調(diào)解大腦中鈉和鉀的濃度,；也可以設(shè)計藥物來激活這個不再活躍的酶。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS August 3, 2009, doi: 10.1073/pnas.0904817106
Mutation I810N in the α3 isoform of Na+,K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS
Steven J. Clapcotea,b,1, Steven Duffya, Gang Xiea, Greer Kirshenbauma,c, Allison R. Becharda, Vivien Rodacker Schackd, Janne Petersend, Laleh Sinaia,c, Bechara J. Saaba,c, Jason P. Lerche, Berge A. Minassianc,e, Cameron A. Ackerleye, John G. Sledc,e, Miguel A. Cortezc,e, Jeffrey T. Hendersonc, Bente Vilsend and John C. Rodera,c
aSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;
bInstitute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom;
cDepartments of Medical Biophysics, Medical Genetics, Paediatrics, and Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada M5S 1A1;
dDepartment of Physiology and Biophysics, Centre for Membrane Pumps in Cells and Disease–PUMPKIN, Danish National Research Foundation, University of Aarhus, DK-8000 Aarhus, Denmark; and
eMouse Imaging Centre, Program in Genetics and Genome Biology, and Divisions of Neurology and Pathology, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8
In a mouse mutagenesis screen, we isolated a mutant, Myshkin (Myk), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and neuronal degeneration in the hippocampus. Positional cloning and functional analysis revealed that Myk/+ mice carry a mutation (I810N) which renders the normally expressed Na+,K+-ATPase α3 isoform inactive. Total Na+,K+-ATPase activity was reduced by 42% in Myk/+ brain. The epilepsy in Myk/+ mice and in vitro hyperexcitability could be prevented by delivery of additional copies of wild-type Na+,K+-ATPase α3 by transgenesis, which also rescued Na+,K+-ATPase activity. Our findings reveal the functional significance of the Na+,K+-ATPase α3 isoform in the control of epileptiform activity and seizure behavior.
