Brain-engrafted macrophages provide protection against therapeutic irradiation and secondary concussive injury
| Autor: | Xi Feng, Sharon Liu, McKenna Becker, Susanna Rosi, Maria Serena Paladini, Zoe Boosalis, Sonali Gupta, David Chen, Nalin Gupta, Elma S. Frias |
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| Rok vydání: | 2019 |
| Předmět: |
Functional role
0303 health sciences Microglia Intermediate phenotype Concussive injury Biology Embryonic stem cell Transcriptome 03 medical and health sciences Haematopoiesis 0302 clinical medicine medicine.anatomical_structure medicine Progenitor cell Neuroscience 030217 neurology & neurosurgery 030304 developmental biology |
| Popis: | Brain resident microglia have a distinct origin compared to macrophages in other organs. Under physiological conditions, microglia are maintained by self-renewal from the local pool, independent of hematopoietic progenitors. Pharmacological depletion of microglia during therapeutic whole-brain irradiation prevents synaptic loss and long-term recognition memory deficits but the mechanisms behind these protective effects are unknown. Here we demonstrate that after a combination of therapeutic whole-brain irradiation and microglia depletion, macrophages originating from circulating monocytes engraft into the brain and replace the microglia pool. Comparisons of transcriptomes reveal that brain-engrafted macrophages have an intermediate phenotype that resembles both monocytes and embryonic microglia. Brain-engrafted macrophages display reduced phagocytic activity for synaptic compartments compared to microglia from normal brains in response to a secondary concussive brain injury. In addition to sparing mice from brain radiotherapy-induced long-term cognitive deficits, replacement of microglia by brain-engrafted macrophages can prevent concussive injury-induced memory loss. These results demonstrate the long-term functional role of brain-engrafted macrophages as a possible therapeutic tool against radiation-induced cognitive deficits. |
| Databáze: | OpenAIRE |
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