Kaur Arvinder, Goel Rajesh Kumar
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 140401, India.
Neurochem Res. 2025 May 14;50(3):163. doi: 10.1007/s11064-025-04413-y.
Alzheimer's disease (AD) is comorbid condition in epilepsy. Mitochondrial dysfunction serves as a common disease mechanism. This study aimed to develop a new mouse of epilepsy-associated AD by inhibiting mitochondrial complex-I and exploring neurochemistry to identify therapeutic targets. Swiss albino mice were divided into naïve, corneal kindled (CK), and rotenone corneal kindled (RCK) groups. CK underwent epileptogenesis by using 6 Hz corneal kindling model (15 mA, 20 V, 6-Hz, 3 s for 15 days), while RCK underwent both epileptogenesis and mitochondrial dysfunction via rotenone administration (2.5 mg/kg, i.p daily). RCK mice exhibited generalised tonic-clonic seizures, cognitive deficits, oxidative stress, and Aβ/tau deposition. Neurochemical analysis showed increased glutamate, kynurenine, and reduced GABA, taurine, monoamines, antioxidants, and acetylcholinesterase activity. The RCK model replicates construct and face validity of both epilepsy and AD, may serve as a new model to investigate shared disease mechanisms and associated altered neurotransmitter as therapeutic approach.
阿尔茨海默病（AD）是癫痫的共病情况。线粒体功能障碍是一种常见的疾病机制。本研究旨在通过抑制线粒体复合体I并探索神经化学以确定治疗靶点，从而建立一种新的癫痫相关性AD小鼠模型。将瑞士白化小鼠分为未处理组、角膜点燃（CK）组和鱼藤酮角膜点燃（RCK）组。CK组采用6赫兹角膜点燃模型（15毫安、20伏、6赫兹、3秒，共15天）进行癫痫诱导，而RCK组通过腹腔注射鱼藤酮（2.5毫克/千克，每日一次）同时进行癫痫诱导和线粒体功能障碍诱导。RCK小鼠表现出全身强直阵挛性发作、认知缺陷、氧化应激以及Aβ/ tau沉积。神经化学分析显示谷氨酸、犬尿氨酸增加，而γ-氨基丁酸、牛磺酸、单胺类、抗氧化剂以及乙酰胆碱酯酶活性降低。RCK模型复制了癫痫和AD的结构效度和表面效度，可作为一种新模型来研究共同的疾病机制以及相关的神经递质改变作为治疗方法。
