Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease  

作　　者：Li-Fen Liu Yu-Tong Liu Dan-Dan Wu Jie Cheng Na-Na Li Ya-Ni Zheng Liang Huang Qiong-Lan Yuan 

机构地区：[1]Department of Neurology,Shanghai Tongji Hospital,Tongji University School of Medicine,Shanghai,China [2]Department of Radiology,University of Nebraska Medical Center,Omaha,NE,USA [3]Department of Human Anatomy,Histology&Embryology,Tongji University School of Medicine,Shanghai,China

出　　处：《Neural Regeneration Research》2023年第9期2019-2028,共10页中国神经再生研究（英文版）

基　　金：supported by the Notional Natural Science Foundation of China,Nos.81371213 and 8107098 7;the Natural Science Foundation of Shanghai,No.21ZR1468400 (all to QLY)。

摘　　要：Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.

关 键 词：5-hydroxytryptamin receptor 3 Alzheimer’s disease amyloid beta plaques CALCINEURIN cognitive deficits HTR3 interneurons iCa2+ nuclear factor of activated T-cells transgenic amyloid precursor protein and presenilin-1 mice TROPISETRON 

分 类 号：R285.5[医药卫生—中药学]