Search: (WFRF:(Lin Hui Yi)) srt2:(2022) >
Long-term hyperglyc...
Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model
-
- Lv, Yi Qing (author)
- China Medical University, Shenyang
-
- Yuan, Lin (author)
- China Medical University, Shenyang
-
- Sun, Yan V. (author)
- China Medical University, Shenyang
-
show more...
-
- Dou, Hao Wen (author)
- China Medical University, Shenyang
-
- Su, Ji Hui (author)
- China Medical University, Shenyang
-
- Hou, Zhi Pan (author)
- China Medical University, Shenyang
-
- Li, Jia Yi (author)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang
-
- Li, Wen (author)
- Lund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang
-
show less...
-
(creator_code:org_t)
- 2022-03-07
- 2022
- English.
-
In: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 11
- Related links:
-
http://dx.doi.org/10... (free)
-
show more...
-
https://translationa...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Diabetes mellitus
- Hyperglycemia
- Neurodegeneration
- Neuroinflammation
- Parkinson’s disease
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database