美國Gladstone神經(jīng)學(xué)研究實驗室的科學(xué)家,，進(jìn)行了一項針對模擬阿爾茨海默氏病關(guān)鍵病癥轉(zhuǎn)基因小鼠的藥物研究,。在這項研究中,，他們發(fā)現(xiàn)過去用于治療癲癇的左乙拉西坦（levetiracetam,LEV）可抑制這些小鼠的大腦異?；顒?，并恢復(fù)記憶功能,。8月6日這項研究發(fā)表在PNAS雜志上,。
僅僅在美國，就有540萬阿爾茨海默氏癥患者，預(yù)計到2050年這一數(shù)字將增加達(dá)到近三倍,。 "對于全球數(shù)以百萬計的老年癡呆癥患者,，我們沒有有效的藥物，以防止或扭轉(zhuǎn)記憶喪失,，（這一疾病的標(biāo)志性癥狀）"神經(jīng)科學(xué)教授穆克博士說,， "這項研究是建立在聯(lián)系阿爾茨海默氏癥和癲癇的早期發(fā)現(xiàn)的基礎(chǔ)之上的。它為深入理解阿爾茨海默氏癥的失憶現(xiàn)象提供了新的見解,，并證實抗癲癇藥物具有阻止失憶進(jìn)程的能力,。"
神經(jīng)網(wǎng)絡(luò)的健康活動，是大腦基本功能,，如記憶的關(guān)鍵,。阿爾茨海默氏癥造成十分嚴(yán)重的大腦網(wǎng)絡(luò)混亂，偶爾升級為癲癇發(fā)作,。 "但是,，過去這種神經(jīng)網(wǎng)絡(luò)中斷是否也損害記憶，是未知的,，"該論文的第一作者,，博士后研究員帕斯卡爾·桑切斯說，"因此,，我們篩選了7個FDA批準(zhǔn)的抗癲癇藥物,，包括左乙拉西坦，應(yīng)用于阿爾茨海默氏癥的小鼠模型,，以觀察是否減少這些神經(jīng)網(wǎng)絡(luò)中斷可以提高記憶力,。"
研究結(jié)果支持這一假設(shè)：異常的網(wǎng)絡(luò)活動可導(dǎo)致阿爾茨海默氏癥小鼠突觸和認(rèn)知功能障礙。LEV也可能有助于改善AD高風(fēng)險個體的相關(guān)異常癥狀,。（生物谷bioon.com）
編譯自Epilepsy drug levetiracetam reverses memory loss in animal model of Alzheimer's disease
doi:10.1073/pnas.1121081109
PMC:
PMID:
Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model
Pascal E. Sancheza,b,Lei Zhua,b,Laure Verreta,b,Keith A. Vossela,b,Anna G. Orra,b,John R. Cirritoc,Nino Devidzea,Kaitlyn Hoa,Gui-Qiu Yua,Jorge J. Palopa,b, andLennart Muckea,b,1
In light of the rising prevalence of Alzheimer’s disease (AD), new strategies to prevent, halt, and reverse this condition are needed urgently. Perturbations of brain network activity are observed in AD patients and in conditions that increase the risk of developing AD, suggesting that aberrant network activity might contribute to AD-related cognitive decline. Human amyloid precursor protein (hAPP) transgenic mice simulate key aspects of AD, including pathologically elevated levels of amyloid-β peptides in brain, aberrant neural network activity, remodeling of hippocampal circuits, synaptic deficits, and behavioral abnormalities. Whether these alterations are linked in a causal chain remains unknown. To explore whether hAPP/amyloid-β–induced aberrant network activity contributes to synaptic and cognitive deficits, we treated hAPP mice with different antiepileptic drugs. Among the drugs tested, only levetiracetam (LEV) effectively reduced abnormal spike activity detected by electroencephalography. Chronic treatment with LEV also reversed hippocampal remodeling, behavioral abnormalities, synaptic dysfunction, and deficits in learning and memory in hAPP mice. Our findings support the hypothesis that aberrant network activity contributes causally to synaptic and cognitive deficits in hAPP mice. LEV might also help ameliorate related abnormalities in people who have or are at risk for AD.
