Combined Ionizing Radiation Caused Cognition and Non-Cognition Behavior Benefits and Modulated Microglial Activity in Wild-Type and Alzheimer’s-like Transgenic Mice

Alzheimer's disease (AD) is one of the primary causes of disability and dependency among aging populations worldwide. Neuroinflammation may be a potential therapeutic target in AD. Moreover, ionizing radiation may be a tool for modulating neuroinflammation. Here, we used three mouse lines-C57Bl/6 and the transgenic AD models 5xFAD and Tau P301S-to investigate the effects of combined ionizing radiation (γ-rays and carbon-12 nuclei) on emotional state, cognitive abilities, and markers of microglial activation. The obtained data show that combined irradiation results in enhanced exploratory behavior and spatial learning in the C57Bl/6 mice. The same changes, as well as a decrease in anxiety, were found in the Tau P301S mice. Irradiation of the 5xFAD mice resulted in improved welfare and ability to discriminate odors. At the same time, irradiation led to an increase in the level of pro- and anti-inflammatory cytokines in the prefrontal cortex and, to a lesser extent, in the hippocampus of the C57Bl/6 and Tau P301S mice. An increase in macrophage inflammatory protein-1α in the prefrontal cortex and a decrease in interleukin 2β in the hippocampus were found in the 5xFAD mice. Taken together, our data indicate that ionizing radiation exposure is an adequate tool to modulate microglial activity in the brain and may provide cognitive and non-cognitive behavioral benefits in neurodegenerative disease conditions.