Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates
| Autor: | Claire M. Bringuier, Jean-Christophe Perez, Emilie Aloy, Gaëtan Poulen, Nicolas Lonjon, Christophe Goze-Bac, Maida Cardoso, Yannick Nicolas Gerber, Hassan Boukhaddaoui, Florence E. Perrin, Emaëlle V.F. Artus, Nadine Mestre-Francés |
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| Přispěvatelé: | Mécanismes moléculaires dans les démences neurodégénératives (MMDN), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire Charles Coulomb (L2C), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Perrin, Florence, Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Regional Imaging Platform, Montpellier Ressources Imagerie (MRI), BioCampus, Montpellier, France, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology [SDV]Life Sciences [q-bio] primates Medicine (miscellaneous) microglia Gene Expression Transcriptome Mice 0302 clinical medicine Oral administration Receptor Pharmacology Toxicology and Pharmaceutics (miscellaneous) Spinal cord injury ComputingMilieux_MISCELLANEOUS 0303 health sciences Microglia rodent medicine.anatomical_structure Receptors Granulocyte-Macrophage Colony-Stimulating Factor [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] medicine.symptom Cheirogaleidae Spinal cord pathology Research Paper proliferation Neurogenesis Central nervous system Mice Transgenic Anisoles Lesion 03 medical and health sciences Downregulation and upregulation medicine Animals [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Neuroinflammation Spinal Cord Injuries 030304 developmental biology Cell Proliferation Inflammation business.industry Recovery of Function Functional recovery medicine.disease spinal cord injury Mice Inbred C57BL Disease Models Animal Pyrimidines Neuroinflammatory Diseases Cancer research business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Theranostics Theranostics, 2021, 11 (18), pp.8640-8659. ⟨10.7150/thno.61833⟩ Theranostics, Ivyspring International Publisher, 2021, 11 (18), pp.8640-8659. ⟨10.7150/thno.61833⟩ |
| ISSN: | 1838-7640 |
| DOI: | 10.7150/thno.61833⟩ |
| Popis: | No curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery.In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia, we thus used an oral administration of GW2580, a CSF1R inhibitor.First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissues preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity.Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves functional motor function recovery, and promotes tissue protection. Notably, three months after lesion microglia reactivity returned to baseline value.Finally, to initiate the investigation on molecular mechanisms induced by a transient post-SCI GW2580-treatment, we used microglia-specific transcriptomic analysis in mice. Notably, we detected a downregulation in the expression of inflammatory-associated genes and we identified genes that were up-regulated by SCI and further downregulated by the treatment.Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation. |
| Databáze: | OpenAIRE |
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