Mapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson’s disease mice
Abstract Efforts to develop disease-modifying treatments for Parkinson’s disease (PD) have been hindered by the lack of animal models replicating all hallmarks of PD and the insufficient attention to extra-nigrostriatal regions pathologically critical for the prodromal appearance of non-motor sympto...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-00872-w |
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| author | Matteo Santoro Rachel K. Lam Sarah E. Blumenfeld Weiqi Tan Peter Ciari Emily K. Chu Nay L. Saw Daniel Ryskamp Rijsketic Jennifer S. Lin Boris D. Heifets Mehrdad Shamloo |
| author_facet | Matteo Santoro Rachel K. Lam Sarah E. Blumenfeld Weiqi Tan Peter Ciari Emily K. Chu Nay L. Saw Daniel Ryskamp Rijsketic Jennifer S. Lin Boris D. Heifets Mehrdad Shamloo |
| author_sort | Matteo Santoro |
| collection | DOAJ |
| description | Abstract Efforts to develop disease-modifying treatments for Parkinson’s disease (PD) have been hindered by the lack of animal models replicating all hallmarks of PD and the insufficient attention to extra-nigrostriatal regions pathologically critical for the prodromal appearance of non-motor symptoms. Among PD models, 6-hydroxydopamine (6-OHDA) infusion in mice has gained prominence since 2012, primarily focusing on the nigrostriatal region. This study characterized tyrosine hydroxylase-positive neuron and fiber loss across the brain following a unilateral 6-OHDA (20 µg) infusion into the dorsal striatum. Our analysis integrates immunolabeling, brain clearing (iDISCO+), light sheet microscopy, and computational methods, including fMRI and machine learning tools. We also examined sex differences, disease progression, neuroinflammatory responses, and pro-apoptotic signaling in nigrostriatal regions of C57BL/6 mice exposed to varying 6-OHDA dosages (5, 10, or 20 µg) followed by 1, 7, and 14 days of recovery. This comprehensive, spatiotemporal analysis of 6-OHDA-induced pathology was used to map the time course of neuronal degeneration and the onset of neuroinflammation. |
| format | Article |
| id | doaj-art-1d1c75c577cf496b9a416dd5cc7e30e1 |
| institution | DOAJ |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-1d1c75c577cf496b9a416dd5cc7e30e12025-08-20T03:00:57ZengNature Portfolionpj Parkinson's Disease2373-80572025-02-0111111710.1038/s41531-025-00872-wMapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson’s disease miceMatteo Santoro0Rachel K. Lam1Sarah E. Blumenfeld2Weiqi Tan3Peter Ciari4Emily K. Chu5Nay L. Saw6Daniel Ryskamp Rijsketic7Jennifer S. Lin8Boris D. Heifets9Mehrdad Shamloo10Department of Neurosurgery, Stanford University School of MedicineDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of MedicineDepartment of Neurosurgery, Stanford University School of MedicineAbstract Efforts to develop disease-modifying treatments for Parkinson’s disease (PD) have been hindered by the lack of animal models replicating all hallmarks of PD and the insufficient attention to extra-nigrostriatal regions pathologically critical for the prodromal appearance of non-motor symptoms. Among PD models, 6-hydroxydopamine (6-OHDA) infusion in mice has gained prominence since 2012, primarily focusing on the nigrostriatal region. This study characterized tyrosine hydroxylase-positive neuron and fiber loss across the brain following a unilateral 6-OHDA (20 µg) infusion into the dorsal striatum. Our analysis integrates immunolabeling, brain clearing (iDISCO+), light sheet microscopy, and computational methods, including fMRI and machine learning tools. We also examined sex differences, disease progression, neuroinflammatory responses, and pro-apoptotic signaling in nigrostriatal regions of C57BL/6 mice exposed to varying 6-OHDA dosages (5, 10, or 20 µg) followed by 1, 7, and 14 days of recovery. This comprehensive, spatiotemporal analysis of 6-OHDA-induced pathology was used to map the time course of neuronal degeneration and the onset of neuroinflammation.https://doi.org/10.1038/s41531-025-00872-w |
| spellingShingle | Matteo Santoro Rachel K. Lam Sarah E. Blumenfeld Weiqi Tan Peter Ciari Emily K. Chu Nay L. Saw Daniel Ryskamp Rijsketic Jennifer S. Lin Boris D. Heifets Mehrdad Shamloo Mapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson’s disease mice npj Parkinson's Disease |
| title | Mapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson’s disease mice |
| title_full | Mapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson’s disease mice |
| title_fullStr | Mapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson’s disease mice |
| title_full_unstemmed | Mapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson’s disease mice |
| title_short | Mapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson’s disease mice |
| title_sort | mapping of catecholaminergic denervation neurodegeneration and inflammation in 6 ohda treated parkinson s disease mice |
| url | https://doi.org/10.1038/s41531-025-00872-w |
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