دورية أكاديمية
Conditional genetic deletion of CSF1 receptor in microglia ameliorates the physiopathology of Alzheimer’s disease
| العنوان: | Conditional genetic deletion of CSF1 receptor in microglia ameliorates the physiopathology of Alzheimer’s disease |
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| المؤلفون: | Vincent Pons, Pascal Lévesque, Marie-Michèle Plante, Serge Rivest |
| المصدر: | Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-15 (2021) |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Neurosciences. Biological psychiatry. Neuropsychiatry LCC:Neurology. Diseases of the nervous system |
| مصطلحات موضوعية: | mCSF, TREM2, β-Catenin, IL-34, Microglia, Innate immunity, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429 |
| الوصف: | Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS; their proliferation, activation, and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R. Methods Here, we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system; the knockout (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knockout at 3 months old, before plaque formation, and evaluated both 6- and 8-month-old groups of mice. Results Our findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate-control groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology are associated with a decrease in plaque volume in the cortex and hippocampus area. A compensating system seems to take place following the knockout, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain. Conclusions Our results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1758-9193 |
| Relation: | https://doaj.org/toc/1758-9193 |
| DOI: | 10.1186/s13195-020-00747-7 |
| URL الوصول: | https://doaj.org/article/71b2f38ee28e4a338324af38d1062578 |
| رقم الأكسشن: | edsdoj.71b2f38ee28e4a338324af38d1062578 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 17589193 |
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| DOI: | 10.1186/s13195-020-00747-7 |