Cell Reports (Jun 2020)

Radiation Triggers a Dynamic Sequence of Transient Microglial Alterations in Juvenile Brain

  • Ahmed M. Osman,
  • Ying Sun,
  • Terry C. Burns,
  • Liqun He,
  • Nigel Kee,
  • Nuria Oliva-Vilarnau,
  • Androniki Alevyzaki,
  • Kai Zhou,
  • Lauri Louhivuori,
  • Per Uhlén,
  • Eva Hedlund,
  • Christer Betsholtz,
  • Volker M. Lauschke,
  • Julianna Kele,
  • Klas Blomgren

Journal volume & issue
Vol. 31, no. 9

Abstract

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Summary: Cranial irradiation (IR), an effective tool to treat malignant brain tumors, triggers a chronic pro-inflammatory microglial response, at least in the adult brain. Using single-cell and bulk RNA sequencing, combined with histology, we show that the microglial response in the juvenile mouse hippocampus is rapid but returns toward normal within 1 week. The response is characterized by a series of temporally distinct homeostasis-, sensome-, and inflammation-related molecular signatures. We find that a single microglial cell simultaneously upregulates transcripts associated with pro- and anti-inflammatory microglial phenotypes. Finally, we show that juvenile and adult irradiated microglia are already transcriptionally distinct in the early phase after IR. Our results indicate that microglia are involved in the initial stages but may not be responsible for driving long-term inflammation in the juvenile brain.

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