title: Effects of (56)Fe radiation on hippocampal function in mice deficient in chemokine receptor 2 (CCR2).
abstract: (56)Fe irradiation affects hippocampus-dependent cognition. The underlying mechanisms may involve alterations in neurogenesis, expression of the plasticity-related immediate early gene Arc, and inflammation. Chemokine receptor-2 (CCR2), which mediates the recruitment of infiltrating and resident microglia to sites of CNS inflammation, is upregulated by (56)Fe irradiation. CCR2 KO and wild-type mice were used to compare effects of (56)Fe radiation (600MeV, 0.25Gy) on hippocampal function using contextual fear conditioning involving tone shock pairing during training (+/+) and exposure to the same environment without tone shock pairings (-/-). In the -/- condition, irradiation enhanced habituation in WT mice, but not CCR2 KO mice, suggesting that a lack of CCR2 was associated with reduced cognitive performance. In the +/+ condition, irradiation reduced freezing but there was no genotype differences. There were no significant correlations between the number of Arc-positive cells in the dentate gyrus and freezing in either genotype. While measures of neurogenesis and gliogenesis appeared to be modulated by CCR2, there were no effects of genotype on the total numbers of newly born activated microglia before or after irradiation, indicating that other mechanisms are involved in the genotype-dependent radiation response.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA. raberj@ohsu.edu
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.forename: Antiño R
authors.initials: AR
authors.lastname: Allen
authors.forename: Susanna
authors.initials: S
authors.lastname: Rosi
authors.forename: Sourabh
authors.initials: S
authors.lastname: Sharma
authors.forename: Catherine
authors.initials: C
authors.lastname: Dayger
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Davis
authors.forename: John R
authors.initials: JR
authors.lastname: Fike
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D003213:Conditioning, Psychological / Q000528:radiation effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D060733:Electromagnetic Radiation; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000235:genetics* / Q000528:radiation effects*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D007504:Iron Radioisotopes / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology / Q000528:radiation effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000528:radiation effects; D009483:Neuropsychological Tests; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D054390:Receptors, CCR2 / Q000172:deficiency* / Q000235:genetics
chemical_list: C515335:Ccr2 protein, mouse; D003598:Cytoskeletal Proteins; D007504:Iron Radioisotopes; D009419:Nerve Tissue Proteins; D054390:Receptors, CCR2; C092069:activity regulated cytoskeletal-associated protein; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine