Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model

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Lv, Yi QingChina Medical University, Shenyang (författare)

Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model

Artikel/kapitelEngelska2022

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2022-03-07
Springer Science and Business Media LLC,2022

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LIBRIS-ID:oai:lup.lub.lu.se:e38d8638-b4f7-477a-937a-82b13f5d356b
https://lup.lub.lu.se/record/e38d8638-b4f7-477a-937a-82b13f5d356bURI
https://doi.org/10.1186/s40035-022-00288-zDOI

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Språk:engelska
Sammanfattning på:engelska

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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 models. However, the underlying mechanism is still unclear. Previously, 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 tissues. However, due to the complicated effect of insulin resistance on PD onset, the actual mechanism of hyperglycemia-induced dopaminergic degeneration remains unknown. Methods: We employed the type 1 diabetes mellitus (T1DM) model induced by streptozotocin (STZ) injection in a transgenic mouse line (BAC-α-syn-GFP) overexpressing human α-syn, to investigate the direct effect of elevated blood glucose on nigrostriatal degeneration. Results: STZ treatment induced more severe pathological alterations in the pancreatic islets and T1DM symptoms in α-syn-overexpressing mice than in wild-type mice, at one month and three months after STZ injections. Behavioral tests evaluating motor performance confirmed the nigrostriatal degeneration. Furthermore, there was a marked decrease in dopaminergic profiles and an increase of α-syn accumulation and Serine 129 (S129) phosphorylation in STZ-treated α-syn mice compared with the vehicle-treated mice. In addition, more severe neuroinflammation was observed in the brains of the STZ-treated α-syn mice. Conclusion: 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.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
Diabetes mellitus
Hyperglycemia
Neurodegeneration
Neuroinflammation
Parkinson’s disease

Biuppslag (personer, institutioner, konferenser, titlar ...)

Yuan, LinChina Medical University, Shenyang (författare)
Sun, Yan V.China Medical University, Shenyang (författare)
Dou, Hao WenChina Medical University, Shenyang (författare)
Su, Ji HuiChina Medical University, Shenyang (författare)
Hou, Zhi PanChina Medical University, Shenyang (författare)
Li, Jia YiLund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang(Swepub:lu)mphy-jli (författare)
Li, WenLund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang(Swepub:lu)med-wnl (författare)
China Medical University, ShenyangNeural plasticitet och reparation (creator_code:org_t)

Sammanhörande titlar

Ingår i:Translational Neurodegeneration: Springer Science and Business Media LLC112047-9158

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Av författaren/redakt...: Lv, Yi Qing; Yuan, Lin; Sun, Yan V.; Dou, Hao Wen; Su, Ji Hui; Hou, Zhi Pan; visa fler...; Li, Jia Yi; Li, Wen; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Neurologi

Artiklar i publikationen: Translational Ne ...

Av lärosätet: Lunds universitet

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