Neuro‐immune and behavioral consequences of low dose radiation, social isolation and sex differences in the longevity MCAT mouse model

Abstract

AbstractBackgroundThe multi‐organ physiological responses to spaceflight stressors resemble aging on Earth. We simulate space environment together with environmental stress, as a model of accelerated aging. Redox dys‐homeostasis was shown to contribute to aging‐related pathologies such as Alzheimer’s and Parkinson’s. The MCAT transgenic mice (overexpressing human catalase in the mitochondria), have increased life span, delayed age‐related pathology and enhanced hippocampal spatial learning and memory.MethodOur study uses 1‐year old C57BL/6NJ male and female mice that underwent exposure to 0.5 gray of gamma radiation together with social isolation. In order to determine ROS contribution to neuro‐behavioral stress response, we used the longevity MCAT mouse model in which human catalase is overexpressed in the mitochondria. We aimed to determine whether in older mice quenching ROS, will mitigate the neuro‐behavioral consequences of low dose ionizing radiation and social isolation and whether sex differences will be detected. We have performed multiple behavioral tests which focused on performance, memory, physical stance, and stress, together with plasma and hippocampal neuro‐immune panels.ResultWe have detected both sex and radiation/isolation effects; the older females look physically better, are faster and perform better almost in all behavioral tasks compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation and isolation in many cases. Interestingly, many of the neuro‐immune changes caused by radiation and social isolation were mitigated in the MCAT mice. In a plasma multiplex cytokine panel, corticosterone (7‐ and 90‐days post radiation), and hippocampal cytokine and microglial activation at the end of the experiment, we have detected significant changes due to radiation, isolation, sex and genotype in both short and long post radiation period. Our focus is now on applying advanced statistical modeling to correlate the behavioral tests with our recent molecular findings to look for specific biomarkers that could predict behavioral deficits caused by various environmental stresses.ConclusionQuenching ROS in older mice partially mitigates neuro‐immune consequences of environmental stresses. Significant sex differences were detected, pointing out the importance of examining both sexes, for better personal medicine. The study points out that anti‐oxydant meassures could help older isolated population.