Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour

Anna Kovalchuk, Richelle Mychasiuk, Arif Muhammad, Shakhawat Hossain, Slava Ilnytskyy, Abhijit Ghose, Charles Kirkby, Esmaeel Ghasroddashti, Olga Kovalchuk, Bryan Kolb

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

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 neurocognitive 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 fH2AX. 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.

Original languageEnglish
Pages (from-to)4385-4398
Number of pages14
JournalOncotarget
Volume7
Issue number4
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

Keywords

  • Behaviour
  • Brain
  • Gene expression
  • Neuroanatomy
  • Radiation therapy

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