NYMC Faculty Publications

Effects of UHDR and Conventional Irradiation on Behavioral and Cognitive Performance and the Percentage of Ly6G+ CD45+ Cells in the Hippocampus

Ariel Chaklai, Department of Behavioral Neuroscience, Oregon Health Science University, Portland, OR 97239, USA.
Pamela Canaday, Knight Flow Cytometry Core OHSU, Portland, OR 97239, USA.
Abigail O'Niel, Department of Behavioral Neuroscience, Oregon Health Science University, Portland, OR 97239, USA.
Francis A. Cucinotta, Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, NV 89154, USA.
Austin Sloop, Department of Radiation Oncology, Geisel School of Medicine, The Thayer School of Engineering, The Dartmouth Cancer Center, at Dartmouth College and the Dartmouth-Hitchcock Medical Center (DHMC), Hanover, NH 03755, USA.
David Gladstone, Department of Radiation Oncology, Geisel School of Medicine, The Thayer School of Engineering, The Dartmouth Cancer Center, at Dartmouth College and the Dartmouth-Hitchcock Medical Center (DHMC), Hanover, NH 03755, USA.
Brian Pogue, Department of Medical Physics, University of Wisconsin, Madison, WI 53705, USA.
Rongxiao Zhang, Department of Radiation Medicine, New York Medical College, Westchester Medical Center, Valhalla, NY 10595, USA.
Jacob Sunnerberg, Department of Radiation Oncology, Geisel School of Medicine, The Thayer School of Engineering, The Dartmouth Cancer Center, at Dartmouth College and the Dartmouth-Hitchcock Medical Center (DHMC), Hanover, NH 03755, USA.
Alireza Kheirollah, Department of Radiation Oncology, Geisel School of Medicine, The Thayer School of Engineering, The Dartmouth Cancer Center, at Dartmouth College and the Dartmouth-Hitchcock Medical Center (DHMC), Hanover, NH 03755, USA.
Charles R. Thomas, Department of Radiation Oncology, Geisel School of Medicine, The Thayer School of Engineering, The Dartmouth Cancer Center, at Dartmouth College and the Dartmouth-Hitchcock Medical Center (DHMC), Hanover, NH 03755, USA.
P Jack Hoopes, Department of Radiation Oncology, Geisel School of Medicine, The Thayer School of Engineering, The Dartmouth Cancer Center, at Dartmouth College and the Dartmouth-Hitchcock Medical Center (DHMC), Hanover, NH 03755, USA.
Jacob Raber, Department of Behavioral Neuroscience, Oregon Health Science University, Portland, OR 97239, USA.

Author Type(s)

Faculty

DOI

10.3390/ijms241512497

Journal Title

International Journal of Molecular Sciences

Document Type

Article

Publication Date

8-6-2023

Department

Radiation Medicine

Abstract

We assessed the effects of conventional and ultra-high dose rate (UHDR) electron irradiation on behavioral and cognitive performance one month following exposure and assessed whether these effects were associated with alterations in the number of immune cells in the hippocampus using flow cytometry. Two-month-old female and male C57BL/6J mice received whole-brain conventional or UHDR irradiation. UHDR mice were irradiated with 9 MeV electrons, delivered by the Linac-based/modified beam control. The mice were irradiated or sham-irradiated at Dartmouth, the following week shipped to OHSU, and behaviorally and cognitively tested between 27 and 41 days after exposure. Conventional- and UHDR-irradiated mice showed impaired novel object recognition. During fear learning, conventional- and UHDR-irradiated mice moved less during the inter-stimulus interval (ISI) and UHDR-irradiated mice also moved less during the baseline period (prior to the first tone). In irradiated mice, reduced activity levels were also seen in the home cage: conventional- and UHDR-irradiated mice moved less during the light period and UHDR-irradiated mice moved less during the dark period. Following behavioral and cognitive testing, infiltrating immune cells in the hippocampus were analyzed by flow cytometry. The percentage of Ly6G+ CD45+ cells in the hippocampus was lower in conventional- and UHDR-irradiated than sham-irradiated mice, suggesting that neutrophils might be particularly sensitive to radiation. The percentage of Ly6G+ CD45+ cells in the hippocampus was positively correlated with the time spent exploring the novel object in the object recognition test. Under the experimental conditions used, cognitive injury was comparable in conventional and UHDR mice. However, the percentage of CD45+ CD11b+ Ly6+ and CD45+ CD11b+ Ly6G- cells in the hippocampus cells in the hippocampus was altered in conventional- but not UHDR-irradiated mice and the reduced percentage of Ly6G+ CD45+ cells in the hippocampus might mediate some of the detrimental radiation-induced cognitive effects.

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