Differential development and electrophysiological activity in cultured cortical neurons from the mouse and cynomolgus monkey  

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作  者:Xue-Yan Zhang Jun Li Cai-Juan Li Ying-Qi Lin Chun-Hui Huang Xiao Zheng Xi-Chen Song Zhu-Chi Tu Xiao-Jiang Li Sen Yan 

机构地区:[1]Guangdong Key Laboratory of Non-Human Primate Models,Guangdong-Hongkong-Macao Institute of CNS Regeneration,Jinan University,Guangzhou,Guangdong Province,China [2]Key Laboratory of CNS Regeneration,Ministry of Education,Jinan University,Guangzhou,Guangdong Province,China

出  处:《Neural Regeneration Research》2021年第12期2446-2452,共7页中国神经再生研究(英文版)

基  金:This work was supported by the National Natural Science Foundation of China,No.81922026(to SY);the National Key Research and Development Program of China Stem Cell and Translational Research,No.2017YFA0105104(to SY);Key Field Research and Development Program of Guangdong Province,No.2018B030337001(to XJL);Guangdong Key Laboratory of Non-human Primate Models of Brain Diseases,No.2020B121201006(to XJL);Guangzhou Key Research Program on Brain Science,No.202007030008(to SY);the Fundamental Research Funds for the Central Universities,No.21619104(to SY).

摘  要:In vitro cultures of primary cortical neurons are widely used to investigate neuronal function.However,it has yet to be fully investigated whether there are significant differences in development and function between cultured rodent and primate cortical neurons,and whether these differences influence the utilization of cultured cortical neurons to model pathological conditions.Using in vitro culture techniques combined with immunofluorescence and electrophysiological methods,our study found that the development and maturation of primary cerebral cortical neurons from cynomolgus monkeys were slower than those from mice.We used a microelectrode array technique to compare the electrophysiological differences in cortical neurons,and found that primary cortical neurons from the mouse brain began to show electrical activity earlier than those from the cynomolgus monkey.Although cultured monkey cortical neurons developed slowly in vitro,they exhibited typical pathological features-revealed by immunofluorescent staining-when infected with adeno-associated viral vectors expressing mutant huntingtin(HTT),the Huntington’s disease protein.A quantitative analysis of the cultured monkey cortical neurons also confirmed that mutant HTT significantly reduced the length of neurites.Therefore,compared with the primary cortical neurons of mice,cultured monkey cortical neurons have longer developmental and survival times and greater sustained physiological activity,such as electrophysiological activity.Our findings also suggest that primary cynomolgus monkey neurons cultured in vitro can simulate a cell model of human neurodegenerative disease,and may be useful for investigating time-dependent neuronal death as well as treatment via neuronal regeneration.All mouse experiments and protocols were approved by the Animal Care and Use Committee of Jinan University of China(IACUC Approval No.20200512-04)on May 12,2020.All monkey experiments were approved by the IACUC protocol(IACUC Approval No.LDACU 20190820-01)on August 23,2019 for anim

关 键 词:Axion-MEA electrical activities human disease model Huntington’s disease HTT monkey neuron morphometric analysis mouse neuron neurodegenerative diseases primary culture 

分 类 号:R459.9[医药卫生—治疗学] R363[医药卫生—临床医学]

 

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