Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
Metab Brain Dis. 2022 Mar;37(3):689-700. doi: 10.1007/s11011-021-00888-0. Epub 2022 Jan 31.
Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly. In the light of increasing AD prevalence and lack of effective treatment, new strategies to prevent or reverse this condition are needed. Levetiracetam (LEV) is a newer antiepileptic drug that is commonly used to treat certain types of seizures. Researches indicated that LEV has several other pharmacological activities, including improvement of cognitive function. In this study, the recovery effects of chronic (28 days) administration of LEV (50, 100, and 150 mg/kg, ip) on cognitive deficits caused by the intracerebroventricular (icv) injection of streptozotocin (STZ), as a model for sporadic AD, were evaluated in rats. We also considered the protective effects of LEV against hippocampal cell loss, oxidative damage, acetylcholinesterase (AChE) activity, neuroinflammation, and tauopathy caused by STZ. LEV (100 and 150 mg/kg) significantly attenuated the STZ-induced learning and memory impairments in the passive avoidance and Morris water maze (MWM) tasks. In addition, LEV suppressed STZ-induced hippocampal neuronal loss, while restored alterations in the redox status (lipid peroxides and glutathione), AChE activity, proinflammatory cytokines (IL-1β, IL-6, TNF-α), and hyperphosphorylation of tau linked to STZ administration. In conclusion, our study demonstrated that LEV alleviated hippocampal cell death and memory deficits in STZ-AD rats, through mitigating oxidative damage, suppression of proinflammatory cytokines expression, and inhibition of abnormal tau hyperphosphorylation.
阿尔茨海默病（AD）是老年人中最常见的神经退行性疾病。鉴于 AD 的患病率不断上升和缺乏有效治疗方法，需要新的策略来预防或逆转这种疾病。左乙拉西坦（LEV）是一种较新的抗癫痫药物，常用于治疗某些类型的癫痫发作。研究表明，LEV 具有其他几种药理学活性，包括改善认知功能。在这项研究中，评估了慢性（28 天）给予 LEV（腹腔注射 50、100 和 150mg/kg）对侧脑室（icv）注射链脲佐菌素（STZ）引起的认知障碍的恢复作用，作为散发性 AD 的模型，在大鼠中。我们还考虑了 LEV 对 STZ 引起的海马细胞丢失、氧化损伤、乙酰胆碱酯酶（AChE）活性、神经炎症和tau 病的保护作用。LEV（100 和 150mg/kg）显著减轻了 STZ 诱导的被动回避和 Morris 水迷宫（MWM）任务中的学习和记忆障碍。此外，LEV 抑制了 STZ 诱导的海马神经元丢失，同时恢复了与 STZ 给药相关的氧化状态改变（脂质过氧化物和谷胱甘肽）、AChE 活性、促炎细胞因子（IL-1β、IL-6、TNF-α）和 tau 的异常磷酸化。总之，我们的研究表明，LEV 通过减轻氧化损伤、抑制促炎细胞因子表达和抑制异常 tau 过度磷酸化，缓解了 STZ-AD 大鼠的海马细胞死亡和记忆障碍。
