Academic Journal

Partial microglial depletion and repopulation exert subtle but differential effects on amyloid pathology at different disease stages

التفاصيل البيبلوغرافية
العنوان: Partial microglial depletion and repopulation exert subtle but differential effects on amyloid pathology at different disease stages
المؤلفون: L. H. D. Le, M. K. O’Banion, A. K. Majewska
المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-11 (2024)
بيانات النشر: Nature Portfolio, 2024.
سنة النشر: 2024
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract Colony-stimulating factor-1-receptor (CSF1R) inhibitors have been widely used to rapidly deplete microglia from the brain, allowing the remaining microglia population to self-renew and repopulate. These new-born microglia are thought to be “rejuvenated” and have been shown to be beneficial in several disease contexts and in normal aging. Their role in Alzheimer’s disease (AD) is thus of great interest as they represent a potential disease-modifying therapy. Here, we explored the differential effects of microglial depletion and repopulation during amyloid pathology progression using 5xFAD mice. We utilized the CSF1R inhibitor PLX3397 to induce microglial self-renewal and tracked microglia-plaque dynamics with in vivo imaging. We observed transient improvement in plaque burden on different timescales depending on the animal’s age. While the improvement in plaque burden did not persist in any age group, renewing microglia during mid- to late-pathology might still be beneficial as we observed a potential improvement in microglial sensitivity to noradrenergic signaling. Altogether, our findings provide further insights into the therapeutic potential of microglial renewal in AD.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-024-81910-0
URL الوصول: https://doaj.org/article/a2bcdd65fb174c7c9c00d687207bf528
رقم الانضمام: edsdoj.2bcdd65fb174c7c9c00d687207bf528
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-024-81910-0