Journal
ONCOTARGET
Volume 7, Issue 50, Pages 82305-82323Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12929
Keywords
irradiation; neurogenesis; neuroinflammation; microglia; monocyte; macrophage
Categories
Funding
- Swedish Research Council
- Swedish Childhood Cancer Foundation
- Swedish Cancer Foundation
- Governmental grants to scientists working in health care (ALF) in Gothenburg and Stockholm
- Swedish Board of Radiation Safety
- Frimurare Barnhus Foundation
- Wilhelm and Martina Lundgren Foundation
- Marta and Gunnar V. Philipson Foundation
- Swedish Brain Foundation
- China Scholarship Council [2010704001]
- National Nature Science Foundation of China [31271152]
- Health Department of Henan Province
- Innovation Scientists and Technicians Troop Construction Projects of Henan Province
- grant for excellent PhD student at Zhengzhou University [201011460187]
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The relative contribution of resident microglia and peripheral monocyte-derived macrophages in neuroinflammation after cranial irradiation is not known. A single dose of 8 Gy was administered to postnatal day 10 (juvenile) or 90 (adult) CX3CR1(GFP/+) CCR2(RFP/+) mouse brains. Microglia accumulated in the subgranular zone of the hippocampal granule cell layer, where progenitor cell death was prominent. The peak was earlier (6 h vs. 24 h) but less pronounced in adult brains. The increase in juvenile, but not adult, brains was partly attributed to proliferation. Microglia numbers then decreased over time to 39% (juvenile) and 58% (adult) of controls 30 days after irradiation, largely as a result of cell death. CD68 was expressed in 90% of amoeboid microglia in juvenile hippocampi but only in 9% of adult ones. Isolated hippocampal microglia revealed reduced CD206 and increased IL1-beta expression after irradiation, more pronounced in juvenile brains. CCL2 and IL-1 beta increased after irradiation, more in juvenile hippocampi, and remained elevated at all time points. In summary, microglia activation after irradiation was more pronounced, protracted and pro-inflammatory by nature in juvenile than in adult hippocampi. Common to both ages was long-lasting inflammation and the absence of monocyte-derived macrophages.
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