5-Hydroxytryptamine:a potential therapeutic target in amyotrophic lateral sclerosis

作     者：Shi-Shi Jiang Meng-Ni Gong Wei Rao Wen Chai Wen-Zhi Chen Xiong Zhang Hong-Bing Nie Ren-Shi Xu Shi-Shi Jiang;Meng-Ni Gong;Wei Rao;Wen Chai;Wen-Zhi Chen;Xiong Zhang;Hong-Bing Nie;Ren-Shi Xu

作者机构：Medical College of Nanchang UniversityDepartment of NeurologyJiangxi Provincial People’s HospitalThe First Affiliated Hospital of Nanchang Medical CollegeClinical College of Nanchang Medical CollegeNanchangJiangxi ProvinceChina Department of NeurologyThe First Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina Department of NeurologyMaoming People’s HospitalMaomingGuangdong ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2023年第18卷第9期

页      面：2047-2055页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,Nos.30560042,81160161,81360198 82160255 Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021 Jiangxi Provincial Department of Science and Technology,Nos.20142BBG70062,20171 BAB215022,20192BAB205043 Health and Family Planning Commission of Jiangxi Province,No.20181019 (all to RSX) 

主　　题：5-hydroxytryptamine amyotrophic lateral sclerosis astrocytes granisetron microglia neuron piboserod ritanserin SOD1-G93A TAR DNA-binding protein 43 

摘      要：Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis(ALS) is closely linked to 5-hydroxytryptamine(5-HT).To investigate this further,we administered 5-HT receptor antagonists to SOD1*G93A transgenic(ALS mouse model) and wide-type *** involved intraperitoneal injections of either granisetron,piboserod,or ritanserin,which inhibit the 5-HT3,5-HT4,and 5-HT2 receptors,*** transgenic mice were found to have fewer5-HT-positive cells in the spinal cord compared with wide-type *** found that the administration of granisetron reduced the body weight of the transgenic mice,while piboserod and ritanserin worsened the motor functioning,as assessed using a hanging wire ***,none of the 5-HT receptor antagonists affected the disease *** analyzed the distribution and/or expression of TAR DNA binding protein 43(TDP-43) and superoxide dismutase 1 G93A(SOD1-G93A),which fo rm abnormal aggregates in *** found that the expression of these proteins increased following the administration of all three 5-HT receptor *** addition,the disease-related mislocalization of TD P-43 to the cytoplasm increased markedly for all three *** ce rtain anatomical regions,the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of *** results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells.5-HT co uld therefore be a potential therapeutic target for amyotrophic lateral sclerosis.