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| Home > Publications Database > Deletion of muscarinic acetylcholine receptor 3 in microglia impacts brain ischemic injury. |
| Home > Publications Database > Deletion of muscarinic acetylcholine receptor 3 in microglia impacts brain ischemic injury. |
| Journal Article | DZNE-2021-00452 |
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2021
Academic Press
Orlando, Fla.
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Please use a persistent id in citations: doi:10.1016/j.bbi.2020.09.008
Abstract: Microglia are the immune cells of the brain and become activated during any type of brain injury. In the middle cerebral artery occlusion (MCAo) model, a mouse model for ischemic stroke, we have previously shown that microglia and invaded monocytes upregulate the expression of the muscarinic acetylcholine receptor 3 (M3R) in the ischemic lesion. Here we tested whether this upregulation has an impact on the pathogenesis of MCAo. We depleted the m3R receptor in microglia, but not in circulating monocytes by giving tamoxifen to CX3CR1-CreERT+/+M3Rflox/flox (M3RKOmi) animals 3 weeks prior to MCAo. We found that M3RKOmi male mice had bigger lesions, more pronounced motor deficits after one week and cognitive deficits after about one month compared to control males. The density of Iba1+ cells was lower in the lesions of M3RKO male mice in the early, but not in the late disease phase. In females, these differences were not significant. By giving tamoxifen 1 week prior to MCAo, we depleted m3R in microglia and in circulating monocytes (M3RKOmi/mo). Male M3RKOmi/mo did not differ in lesion size, but had a lower survival rate, showed motor deficits and a reduced accumulation of Iba1+ positive cells into the lesion site. In conclusion, our data suggest that the upregulation of m3R in microglia and monocytes in stroke has a beneficial effect on the clinical outcome in male mice.
Keyword(s): Animals (MeSH) ; Brain (MeSH) ; Brain Ischemia (MeSH) ; Disease Models, Animal (MeSH) ; Female (MeSH) ; Infarction, Middle Cerebral Artery (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Microglia (MeSH) ; Receptor, Muscarinic M3: genetics (MeSH) ; Stroke (MeSH) ; Brain macrophages ; MCAo model ; Microglia ; Muscarinic acetylcholine receptor ; Stroke ; Receptor, Muscarinic M3
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