title: Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.
abstract: Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.
authors.affiliation: Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Kovalchuk
authors.affiliation: Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Richelle
authors.initials: R
authors.lastname: Mychasiuk
authors.affiliation: Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Arif
authors.initials: A
authors.lastname: Muhammad
authors.affiliation: Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Shakhawat
authors.initials: S
authors.lastname: Hossain
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada.
authors.forename: Slava
authors.initials: S
authors.lastname: Ilnytskyy
authors.affiliation: Jack Ady Cancer Center, Alberta Health Services, Lethbridge, AB, Canada.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ghose
authors.affiliation: Jack Ady Cancer Center, Alberta Health Services, Lethbridge, AB, Canada.|Department of Physics and Astronomy and Department of Oncology, University of Calgary, Calgary, AB, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Kirkby
authors.affiliation: Jack Ady Cancer Center, Alberta Health Services, Lethbridge, AB, Canada.|Department of Physics and Astronomy and Department of Oncology, University of Calgary, Calgary, AB, Canada.
authors.forename: Esmaeel
authors.initials: E
authors.lastname: Ghasroddashti
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada.|Alberta Epigenetics Network, Calgary, AB, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
authors.affiliation: Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.|Alberta Epigenetics Network, Calgary, AB, Canada.|Canadian Institute for Advanced Research, Toronto, ON, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kolb
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology* / Q000528:radiation effects; D015153:Blotting, Western; D001921:Brain / Q000502:physiology* / Q000528:radiation effects; D024201:Bystander Effect / Q000528:radiation effects*; D005260:Female; D005720:Gamma Rays; D008099:Liver / Q000528:radiation effects*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans
keywords: behaviour; brain; gene expression; neuroanatomy; radiation therapy