Microglia limit the expansion of β-amyloid plaques in a mouse model of Alzheimer’s disease
| Autor: | Wanling Hu, Julia Tsai, Wen-Biao Gan, Ruohe Zhao, Wei Li |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Dendritic spine Mice Transgenic Plaque Amyloid lcsh:Geriatrics Time-Lapse Imaging lcsh:RC346-429 Amyloid beta-Protein Precursor 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Atrophy Immune system Alzheimer Disease medicine Animals Senile plaques Two-photon imaging Molecular Biology lcsh:Neurology. Diseases of the nervous system APP/PS1 Diphtheria toxin Amyloid beta-Peptides Microglia Microglia depletion business.industry Brain medicine.disease Molecular medicine 3. Good health Disease Models Animal lcsh:RC952-954.6 030104 developmental biology medicine.anatomical_structure Aβ plaque nervous system Neurology (clinical) Alzheimer's disease business Alzheimer’s disease 030217 neurology & neurosurgery Research Article CX3CR1CreER/+:R26DTR/+ |
| Zdroj: | Molecular Neurodegeneration, Vol 12, Iss 1, Pp 1-11 (2017) Molecular Neurodegeneration |
| ISSN: | 1750-1326 |
| DOI: | 10.1186/s13024-017-0188-6 |
| Popis: | Microglia are known as resident immune cells in the brain. β-amyloid (Aβ) plaques in the brain of Alzheimer’s disease (AD) are surrounded by microglia, but whether and how microglia affect the formation and maintenance of plaques remains controversial. We depleted microglia by injecting diphtheria toxin (DT) in CX 3 CR1 CreER/+ :R26 DTR/+ (CX 3 CR1-iDTR) mice crossed with APPswe/PSEN1dE9 (APP/PS1) mice. Intravital time-lapse imaging was performed to examine changes in the number and size of Congo Red-labeled amyloid plaques over 1–2 weeks. We also examined spine density and shaft diameter of dendrites passing through plaques in a PSAPP mouse model of AD (PS1 M146L line 6.2 × Tg2576) crossed with Thy1 YFP H-line mice. We found that DT administration to CX 3 CR1-iDTR mice efficiently ablated microglia within one week and that microglia repopulated in the second week after DT administration. Microglia depletion didn’t affect the number of amyloid plaques, but led to ~13% increase in the size of Aβ plaques within one week. Moreover, microglia repopulation was associated with the stabilization of plaque size during the second week. In addition, we found dendritic spine loss and shaft atrophy in the distal parts of dendrites passing through plaques. Our results demonstrate the important role of microglia in limiting the growth of Aβ plaques and plaque-associated disruption of neuronal connection. |
| Databáze: | OpenAIRE |
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