Microglia depletion and repopulation do not alter the effects of cranial irradiation on hippocampal neurogenesis.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8800478 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2139 (Electronic) Linking ISSN: 08891591 NLM ISO Abbreviation: Brain Behav Immun Subsets: MEDLINE
    • Publication Information:
      Publication: <2000- > : Amsterdam : Elsevier
      Original Publication: San Diego : Academic Press, [c1987-
    • Subject Terms:
      Neurogenesis*/radiation effects ; Neurogenesis*/physiology ; Microglia*/metabolism ; Microglia*/radiation effects ; Hippocampus*/metabolism ; Cranial Irradiation*/adverse effects ; Mice, Transgenic*; Animals ; Mice ; Neural Stem Cells/metabolism ; Neural Stem Cells/radiation effects ; Neurons/metabolism ; Male ; Chemokine CCL2/metabolism ; Mice, Inbred C57BL
    • Abstract:
      Cranial radiotherapy can cause lifelong cognitive complications in childhood brain tumor survivors, and reduced hippocampal neurogenesis is hypothesized to contribute to this. Following irradiation (IR), microglia clear dead neural progenitors and give rise to a neuroinflammatory microenvironment, which promotes a switch in surviving progenitors from neuronal to glial differentiation. Recently, depletion and repopulation of microglia were shown to promote neurogenesis and ameliorate cognitive deficits in various brain injury models. In this study, we utilized the Cx3cr1 CreERt2-YFP/+ Rosa26 DTA /+ transgenic mouse model to deplete microglia in the juvenile mouse brain before subjecting them to whole-brain IR and investigated the short- and long-term effects on hippocampal neurogenesis. Within the initial 24 h after IR, the absence of microglia led to an accumulation of dead cells in the subgranular zone, and 50-fold higher levels of the chemokine C-C motif ligand 2 (CCL2) in sham brains and 7-fold higher levels after IR. The absence of microglia, and the subsequent repopulation within 10 days, did neither affect the loss of proliferating or doublecortin-positive cells, nor the reduced growth of the granule cell layer. Our results argue against a role for a pro-inflammatory microenvironment in the dysregulation of hippocampal neurogenesis and suggest that the observed reduction of neurogenesis was solely due to IR.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Apoptosis; CCL2; Doublecortin; Late complications; Microglia depletion; Microglia repopulation; Neuroinflammation; Phagocytosis
    • Accession Number:
      0 (Chemokine CCL2)
    • Publication Date:
      Date Created: 20240901 Date Completed: 20241206 Latest Revision: 20241206
    • Publication Date:
      20241209
    • Accession Number:
      10.1016/j.bbi.2024.08.055
    • Accession Number:
      39218233