Low dose radiation effects on the brain – from mechanisms and behavioral outcomes to mitigation strategies

ABSTRACT

Based on the most recent estimates by the Canadian Cancer Society, 2 in 5 Canadians will develop cancer in their lifetimes. More than half of all cancer patients receive some type of radiation therapy, and all patients undergo radiation-based diagnostics. While radiation is one of the most important diagnostic and treatments modalities, high-dose cranial radiation therapy causes numerous central nervous system side-effects, including declines in cognitive function, memory, and attention. While the mechanisms of these effects have been studies, they still need to be further elucidated. On the other hand, the effects of low dose radiation as well as indirect radiation bystander effects on the brain remain elusive.

We pioneered analysis of the molecular and cellular effects of low dose direct, bystander and scatter radiation on the brain. Using a rat model, we showed that low dose radiation exposures cause molecular and cellular changes in the brain and impacts animal behavior. Here we reflect upon our recent findings and current state of knowledge in the field, and suggest novel radiation effect biomarkers and means of prevention. We propose strategies and interventions to prevent and mitigate radiation effects on the brain.

KEYWORDS:

• bystander effects
• epigenetics
• hippocampus
• prefrontal cortex

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

A.K. was a recipient of the Alberta Cancer Foundation Dr. Cyril Kay Graduate Scholarship, Alberta Innovates - Health Solutions Graduate Scholarship, the CIHR-Canada Graduate Scholarship and the Canada-Vanier Graduate Scholarship.