Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer’s disease mice
| العنوان: | Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer’s disease mice |
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| المؤلفون: | Romain Fol, Kristin Michaelsen-Preusse, Martin Korte, Nathalie Cartier, Jérôme Braudeau, Sandro Alves, Guillaume Churlaud, David Klatzmann, Mickael Audrain, Benoit Souchet |
| المساهمون: | Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Zoological Institute, Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig], Helmholtz Centre for Infection Research (HZI), Université Paris-Sud - Paris 11 (UP11) - Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Institut National de la Santé et de la Recherche Médicale (INSERM), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Université Pierre et Marie Curie - Paris 6 (UPMC) - CHU Pitié-Salpêtrière [APHP], Technische Universität Braunschweig [Braunschweig], Helmholtz - Centre for Infection Research, HAL-UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany., Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC) |
| المصدر: | Brain-A Journal of Neurology Brain-A Journal of Neurology, 2016, ⟨10.1093/brain/aww330⟩ Brain-A Journal of Neurology, Oxford University Press (OUP), 2016, <10.1093/brain/aww330> Brain-A Journal of Neurology, Oxford University Press (OUP), 2016, ⟨10.1093/brain/aww330⟩ |
| بيانات النشر: | HAL CCSD, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Pathology, Hippocampus, Morris water navigation task, Plaque, Amyloid, Amyloid beta-Protein Precursor, Mice, 0302 clinical medicine, Aldesleukin, Aged, 80 and over, Neurons, Neuronal Plasticity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Neurodegeneration, AAV, 3. Good health, Female, Alzheimer's disease, Psychology, Antipsychotic Agents, medicine.medical_specialty, Dendritic Spines, Mice, Transgenic, Presenilin, Immunomodulation, 03 medical and health sciences, Gene therapy, Alzheimer Disease, Presenilin-1, medicine, Animals, Humans, Neuroinflammation, Aged, Memory Disorders, Excitatory Postsynaptic Potentials, medicine.disease, Disease Models, Animal, 030104 developmental biology, Gene Expression Regulation, Case-Control Studies, Astrocytes, Synapses, Synaptic plasticity, Interleukin-2, Neurology (clinical), Therapy, Neuroscience, 030217 neurology & neurosurgery, Immunosuppression, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Neurological diseases |
| الوصف: | International audience; Interleukin-2 (IL-2)-deficient mice have cytoarchitectural hippocampal modifications and impaired learning and memory ability reminiscent of Alzheimer’s disease. IL-2 stimulates regulatory T cells whose role is to control inflammation. As neuroinflammation contributes to neurodegeneration, we investigated IL-2 in Alzheimer’s disease. Therefore, we investigated IL-2 levels in hippocampal biopsies of patients with Alzheimer’s disease relative to age-matched control individuals. We then treated APP/PS1ΔE9 mice having established Alzheimer’s disease with IL-2 for 5 months using single administration of an AAV-IL-2 vector. We first found decreased IL-2 levels in hippocampal biopsies of patients with Alzheimer’s disease. In mice, IL-2-induced systemic and brain regulatory T cells expansion and activation. In the hippocampus, IL-2 induced astrocytic activation and recruitment of astrocytes around amyloid plaques, decreased amyloid-β42/40 ratio and amyloid plaque load, improved synaptic plasticity and significantly rescued spine density. Of note, this tissue remodelling was associated with recovery of memory deficits, as assessed in the Morris water maze task. Altogether, our data strongly suggest that IL-2 can alleviate Alzheimer’s disease hallmarks in APP/PS1ΔE9 mice with established pathology. Therefore, this should prompt the investigation of low-dose IL-2 in Alzheimer’s disease and other neuroinflammatory/neurodegenerative disorders. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0006-8950 1460-2156 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53b96ad51b1ef8f12599eedaa9bc918aTest https://hal.sorbonne-universite.fr/hal-01430973/documentTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....53b96ad51b1ef8f12599eedaa9bc918a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00068950 14602156 |
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