دورية أكاديمية
Levodopa partially rescues microglial numerical, morphological, and phagolysosomal alterations in a monkey model of Parkinson’s disease
| العنوان: | Levodopa partially rescues microglial numerical, morphological, and phagolysosomal alterations in a monkey model of Parkinson’s disease |
|---|---|
| المؤلفون: | Lecours, Cynthia, St-Pierre, Marie-Kim, Picard, Katherine, Bordeleau, Maude, Bourque, Melanie, Awogbindin, Ifeoluwa Oluleke, Benadjal, Amin, Ibanez, Fernando González, Gagnon, Dave, Cantin, Leo, Parent, Martin, Di Paolo, Therese, Tremblay, Marie-Eve |
| المساهمون: | Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval Québec (ULaval)-Université Laval Québec (ULaval), McGill University = Université McGill Montréal, Canada, University of Ibadan, Institut de Biologie Intégrative (IFR-BI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Laval Québec (ULaval), University of Victoria Canada (UVIC), University of British Columbia (UBC) |
| المصدر: | ISSN: 0889-1591. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Basal ganglia, MPTP monkey model, Microglia, Neuroinflammation, Parkinson’s disease, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology |
| الوصف: | International audience ; Parkinson's disease (PD) is the most common neurodegenerative motor disorder. The mechanisms underlying the onset and progression of Levodopa (L-Dopa)-induced dyskinesia (LID) during PD treatment remain elusive. Emerging evidence implicates functional modification of microglia in the development of LID. Thus, understanding the link between microglia and the development of LID may provide the knowledge required to preserve or promote beneficial microglial functions, even during a prolonged L-Dopa treatment. To provide novel insights into microglial functional alterations in PD pathophysiology, we characterized their density, morphology, ultrastructure, and degradation activity in the sensorimotor functional territory of the putamen, using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) cynomolgus monkeys. A subset of MPTP monkeys was treated orally with L-Dopa and developed LID similar to PD patients. Using a combination of light, confocal and transmission electron microscopy, our quantitative analyses revealed alterations of microglial density, morphology and phagolysosomal activity following MPTP intoxication that were partially normalized with L-Dopa treatment. In particular, microglial density, cell body and arborization areas were increased in the MPTP monkeys, whereas L-Dopa-treated MPTP animals presented a microglial phenotype similar to the control animals. At the ultrastructural level, microglia did not differ between groups in their markers of cellular stress or aging. Nevertheless, microglia from the MPTP monkeys displayed reduced numbers of endosomes, compared with control animals, that remained lower after L-Dopa treatment. Microglia from MPTP monkeys treated with L-Dopa also had increased numbers of primary lysosomes compared with non-treated MPTP animals, while secondary and tertiary lysosomes remained unchanged. Moreover, a decrease microglial immunoreactivity for CD68, considered a marker of phagocytosis and lysosomal activity, was measured in the MPTP monkeys treated ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32755645; hal-02986878; https://hal.sorbonne-universite.fr/hal-02986878Test; https://hal.sorbonne-universite.fr/hal-02986878/documentTest; https://hal.sorbonne-universite.fr/hal-02986878/file/1-s2.0-S0889159120305365-main.pdfTest; PUBMED: 32755645 |
| DOI: | 10.1016/j.bbi.2020.07.044 |
| الإتاحة: | https://doi.org/10.1016/j.bbi.2020.07.044Test https://hal.sorbonne-universite.fr/hal-02986878Test https://hal.sorbonne-universite.fr/hal-02986878/documentTest https://hal.sorbonne-universite.fr/hal-02986878/file/1-s2.0-S0889159120305365-main.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.C428EAB8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.bbi.2020.07.044 |
|---|