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Cranial irradiation mediated spine loss is sex-specific and complement receptor-3 dependent in male mice.

Abstract
Cranial irradiation is the main therapeutic treatment for primary and metastatic malignancies in the brain. However, cranial radiation therapy produces long-term impairment in memory, information processing, and attention that contribute to a decline in quality of life. The hippocampal neural network is fundamental for proper storage and retrieval of episodic and spatial memories, suggesting that hippocampal signaling dysfunction could be responsible for the progressive memory deficits observed following irradiation. Previous rodent studies demonstrated that irradiation induces significant loss in dendritic spine number, alters spine morphology, and is associated with behavioral task deficits. Additionally, the literature suggests a common mechanism in which synaptic elimination via microglial-mediated phagocytosis is complement dependent and associated with cognitive impairment in aging as well as disease. We demonstrate sexual dimorphisms in irradiation-mediated alterations of microglia activation markers and dendritic spine density. Further, we find that the significant dendritic spine loss observed in male mice following irradiation is microglia complement receptor 3 (CR3)-dependent. By identifying sex-dependent cellular and molecular factors underlying irradiation-mediated spine loss, therapies can be developed to counteract irradiation-induced cognitive decline and improve patient quality of life.
AuthorsJoshua J Hinkle, John A Olschowka, Tanzy M Love, Jacqueline P Williams, M Kerry O'Banion
JournalScientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 18899 (12 11 2019) ISSN: 2045-2322 [Electronic] England
PMID31827187 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Receptors, Complement
Topics
  • Animals
  • Cell Shape (radiation effects)
  • Cranial Irradiation
  • Dendritic Spines (metabolism, pathology, radiation effects)
  • Female
  • Hippocampus (pathology, radiation effects)
  • Male
  • Mice
  • Mice, Knockout
  • Microglia (pathology, radiation effects)
  • Receptors, Complement (genetics, metabolism)
  • Sex Factors

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