Long-term hyperglycemia aggravatesα-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model
作者机构：Laboratory of Research in Parkinson’s Disease and Related DisordersHealth Sciences InstituteChina Medical UniversityShenyang 110122China Neural Plasticity and Repair UnitDepartment of Experimental Medical SciencesLund University22184 LundSweden
出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)
年 卷 期：2022年第11卷第1期
页 面：747-762页
核心收录：
学科分类：0710[理学-生物学] 0402[教育学-心理学(可授教育学、理学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 1010[医学-医学技术（可授医学、理学学位）] 100204[医学-神经病学] 1009[医学-特种医学] 10[医学]
基 金：the National Natural Science Foundation of China(31800898,81430025,and U1801681 to J-Y.L.and W.L.) the Key Field Research Development Program of Guangdong Province(2018B030337001) the Swedish Research Council(2019-01551),EU-JPND research(αSynProtec and REfrAME)and EU-Horizon2020(MSCA-ITN-2016,SynDeGen) ParkinsonFonden,the Strategic Research Area Multipark(Multidisciplinary research in Parkinson’s disease at Lund University) Hjärnfodens(PS2018-0062) Svenska Sällskapet för Medicinsk Forskning(SSMF,P18-0194)
主 题：Hyperglycemia Diabetes mellitus Parkinson’s disease Neurodegeneration Neuroinflammation
摘 要：Background:Growing evidence suggests an association between Parkinson’s disease(PD)and diabetes mellitus(DM).At the cellular level,long-term elevated levels of glucose have been shown to lead to nigrostriatal degeneration in PD ***,the underlying mechanism is still ***,we have elucidated the potential of type 2 diabetes mellitus(T2DM)in facilitating PD progression,involving aggregation of both alpha-synuclein(α-syn)and islet amyloid polypeptide in the pancreatic and brain ***,due to the complicated effect of insulin resistance on PD onset,the actual mechanism of hyperglycemia-induced dopaminergic degeneration remains ***:We employed the type 1 diabetes mellitus(T1DM)model induced by streptozotocin(STZ)injection in a transgenic mouse line(BAC-α-syn-GFP)overexpressing humanα-syn,to investigate the direct effect of elevated blood glucose on nigrostriatal ***:STZ treatment induced more severe pathological alterations in the pancreatic islets and T1DM symptoms inα-syn-overexpressing mice than in wild-type mice,at one month and three months after STZ *** tests evaluating motor performance confirmed the nigrostriatal ***,there was a marked decrease in dopaminergic profiles and an increase ofα-syn accumulation and Serine 129(S129)phosphorylation in STZ-treatedα-syn mice compared with the vehicle-treated *** addition,more severe neuroinflammation was observed in the brains of the STZ-treatedα-syn ***:Our results solidify the potential link between DM and PD,providing insights into how hyperglycemia induces nigrostriatal degeneration and contributes to pathogenic mechanisms in PD.
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