Lamotrigine protects against cognitive deficits,synapse and nerve cell damage,and hallmark neuropathologies in a mouse model of Alzheimer’s disease  

作　　者：Xin-Xin Fu Rui Duan Si-Yu Wang Qiao-Quan Zhang Bin Wei Ting Huang Peng-Yu Gong Yan E Teng Jiang Ying-Dong Zhang 

机构地区：[1]School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing,Jiangsu Province,China [2]Department of Neurology,Nanjing First Hospital,Nanjing Medical University,Nanjing,Jiangsu Province,China [3]Department of Pathology,Nanjing Brain Hospital,Nanjing Medical University,Nanjing,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2023年第1期189-193,共5页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China, No. 81771140 (to YDZ);the Natural Science Foundation of Jiangsu Province of China, No. BK20201117 (to YDZ);Jiangsu “Six One Project” for Distinguished Medical Scholars of China, No. LGY2020013 (to TJ)

摘　　要：Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular mechanisms remain unclear.In this study,amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice were used as a model of Alzheimer’s disease.Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months.The cognitive functions of animals were assessed using Morris water maze.Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay.The cell damage in the brain was investigated using hematoxylin and eosin staining.The levels of amyloid-βand the concentrations of interleukin-1β,interleukin-6 and tumor necrosis factor-αin the brain were measured using enzyme-linked immunosorbent assay.Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction.We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice;alleviated damage to synapses and nerve cells in the brain;and reduced amyloid-βlevels,tau protein hyperphosphorylation,and inflammatory responses.High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer’s disease-related neuropathologies may have been mediated by the regulation of Ptgds,Cd74,Map3k1,Fosb,and Spp1 expression in the brain.These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer’s disease.Furthermore,these data indicate that LTG may be a promising therapeutic drug for Alzheimer’s disease.

关 键 词：Alzheimer’s disease Alzheimer’s disease-related neuropathologies amyloid-βpathology APP/PS1 mice cognitive deficits damage of synapses and nerve cells high-throughput RNA sequencing LAMOTRIGINE neuroinflammation tau protein hyperphosphorylation 

分 类 号：R749.16[医药卫生—神经病学与精神病学]