Sex-dependent impact of Il6 deficiency in Parkinson’s disease miceOA
Parkinson’s disease(PD)is a prevalent neurodegenerative disorder accompanied by neuroinflammation.Many studies have demonstrated that interleukin-6(IL-6)exhibits both anti-inflammatory and pro-inflammatory effects in the central nervous system,yet its role in PD remains controversial.In this study,Il6−/−(knockout),Il6+/−,and wild-type mice were utilized to investigate the impact of IL-6 on the pathology of MPTP-orα-SynucleinA53T-induced PD mice.Our findings revealed that Il6 deficiency exacerbated motor dysfunction in both female and male mice.MPTP intoxication resulted in earlier and more extensive injuries to the dopaminergic system and heightened glial reaction in the nigrostriatal pathway of female Il6−/−mice compared with male Il6−/−mice,which only displayed more severe dopaminergic neuronal loss at 7 days after MPTP administration.Toxicα-Synuclein overexpression in the substantia nigra region caused earlier motor dysfunction and aggravated dopaminergic neurodegeneration in female Il6−/−mice.In Il6+/−mice,MPTP-induced depletion of dopaminergic nerve fibers was unaffected,although astrocyte activation was attenuated.Moreover,intraperitoneal administration of recombinant IL-6(rIL-6)partially ameliorated MPTP-induced motor dysfunction and striatal dopaminergic terminal depletion in both wild-type and knockout mice.Our findings underscore the crucial role of IL-6 in the inflammatory pathology of PD,highlighting sex-dependent differences,and suggest that rIL-6 holds potential promise for PD therapy.
Fangzheng Chen;Yufei Duan;Mengze Wang;Zhaolin Liu;Jiayin Zhao;Guangchun Fan;Yongtao He;Hongtian Dong;Xiaoshuang Zhang;Rong Fang;Yunhe Zhang;Xin Ya;Chenye Shen;Xiwen Tang;Yuanyuan Ma;Mei Yu;Renyuan Zhou;Jian Fei;Fang Huang
Department of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,ChinaSchool of Life Science and Technology,Tongji University,Shanghai 200092,China Shanghai Engineering Research Center for Model Organisms,Shanghai Model Organisms Center,INC.,Pudong District,Shanghai 201203,ChinaDepartment of Translational Neuroscience,Department of Urology,Jing’an District Centre Hospital of Shanghai,National Key Laboratory of Brain Function and Diseases and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,China
医药卫生
IL-6MPTPNeuroinflammationParkinson’s diseaserIL-6
《Genes & Diseases》 2026 (4)
P.723-741,19
supported by the National Natural Science Foundation of China(No.32271003)the Science and Technology Commission of Shanghai Municipality,China(No.24141901200)the Shanghai Municipal Science and Technology Major Project(China)(No.2018SHZDZX01)ZJLab,the Shanghai Center for Brain Science and Brain Inspired Technology,the Innovative Research Team of High Level Local University in Shanghai,China.
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