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首页> 外文期刊>CNS neuroscience & therapeutics. >Antiepileptics Topiramate and Levetiracetam Alleviate Behavioral Deficits and Reduce Neuropathology in APP swe/ PS 1dE9 Transgenic Mice
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Antiepileptics Topiramate and Levetiracetam Alleviate Behavioral Deficits and Reduce Neuropathology in APP swe/ PS 1dE9 Transgenic Mice

机译：抗癫痫药托吡酯和左乙拉西坦可缓解APP swe / PS 1dE9转基因小鼠的行为缺陷并减少神经病理学

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Summary Background The close relationship between epileptic seizure and Alzheimer's disease ( AD ) has been demonstrated in the past decade. Valproic acid, a traditional first‐line antiepileptic drug, exerted protective effects in transgenic models of AD . It remains uncertain whether new antiepileptic drugs could reverse neuropathology and behavioral deficits in AD transgenic mice. Aims APP swe/ PS 1dE9 transgenic mice were used in this study, which over express the Swedish mutation of amyloid precursor protein together with presenilin 1 deleted in exon 9. 7‐month‐old APP swe/ PS 1dE9 transgenic mice were treated daily with 20 mg/kg topiramate ( TPM ) and 50 mg/kg levetiracetam ( LEV ) for 30 days by intraperitoneal injection to explore the effects of TPM and LEV on the neuropathology and behavioral deficits. Results The results indicated that TPM and LEV alleviated behavioral deficits and reduced amyloid plaques in APP swe/ PS 1dE9 transgenic mice. TPM and LEV increased Aβ clearance and up‐regulated Aβ transport and autophagic degradation. TPM and LEV inhibited Aβ generation and suppressed γ‐secretase activity. TPM and LEV inhibited GSK ‐3β activation and increased the activation of AMPK /Akt activation. Further, TPM and LEV inhibited histone deacetylase activity in vivo . Conclusions Therefore, TPM and LEV might have the potential to treat AD effectively in patient care.
机译：背景技术在过去的十年中已经证明了癫痫发作和阿尔茨海默氏病（AD）之间的密切关系。丙戊酸是传统的一线抗癫痫药，在AD转基因模型中发挥保护作用。尚不确定新的抗癫痫药是否可以逆转AD转基因小鼠的神经病理学和行为缺陷。这项研究使用了Aims APP swe / PS 1dE9转基因小鼠，该基因过度表达了淀粉样前体蛋白的瑞典突变以及外显子9中缺失的早老素1。7个月大的APP swe / PS 1dE9转基因小鼠每天接受20只处理腹腔注射30 mg / kg托吡酯（TPM）和50 mg / kg左乙拉西坦（LEV）30天，以探讨TPM和LEV对神经病理学和行为缺陷的影响。结果结果表明，TPM和LEV可减轻APP swe / PS 1dE9转基因小鼠的行为缺陷并减少淀粉样斑块。 TPM和LEV增加Aβ清除率并上调Aβ转运和自噬降解。 TPM和LEV抑制Aβ生成并抑制γ-分泌酶活性。 TPM和LEV抑制GSK-3β激活并增加AMPK / Akt激活的激活。此外，TPM和LEV在体内抑制组蛋白脱乙酰基酶活性。结论因此，TPM和LEV可能具有在患者护理中有效治疗AD的潜力。

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