PNAS：抗癫痫药物LEV可逆转老年痴呆症记忆力减退

美国Gladstone神经学研究实验室的科学家，进行了一项针对模拟阿尔茨海默氏病关键病症转基因小鼠的药物研究。在这项研究中，他们发现过去用于治疗癫痫的左乙拉西坦（levetiracetam,LEV）可抑制这些小鼠的大脑异常活动，并恢复记忆功能。8月6日这项研究发表在PNAS杂志上。

仅仅在美国，就有540万阿尔茨海默氏症患者，预计到2050年这一数字将增加达到近三倍。 "对于全球数以百万计的老年痴呆症患者，我们没有有效的药物，以防止或扭转记忆丧失，（这一疾病的标志性症状）"神经科学教授穆克博士说， "这项研究是建立在联系阿尔茨海默氏症和癫痫的早期发现的基础之上的。它为深入理解阿尔茨海默氏症的失忆现象提供了新的见解，并证实抗癫痫药物具有阻止失忆进程的能力。"

神经网络的健康活动，是大脑基本功能，如记忆的关键。阿尔茨海默氏症造成十分严重的大脑网络混乱，偶尔升级为癫痫发作。 "但是，过去这种神经网络中断是否也损害记忆，是未知的，"该论文的第一作者，博士后研究员帕斯卡尔·桑切斯说，"因此，我们筛选了7个FDA批准的抗癫痫药物，包括左乙拉西坦，应用于阿尔茨海默氏症的小鼠模型，以观察是否减少这些神经网络中断可以提高记忆力。"

研究结果支持这一假设：异常的网络活动可导致阿尔茨海默氏症小鼠突触和认知功能障碍。LEV也可能有助于改善AD高风险个体的相关异常症状。

编译自Epilepsy drug levetiracetam reverses memory loss in animal model of Alzheimer's disease

doi:10.1073/pnas.1121081109
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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.