Dietary Blueberry before and/or after Exposure to High Energy and Charge Particle Radiation Attenuates Neuroinflammation, Oxidative Stress, Glial Cell Activation, and Memory Deficits in Rats

Authors: CAHOON, DANIELLE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Fisher, Derek; ZHENG, TONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RABIN, BERNARD - University Of Maryland; Shukitt Hale, Barbara

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/7/2025
Publication Date: 1/10/2025
Citation: Cahoon, D., Fisher, D.R., Zheng, T., Lamon-Fava, S., Wu, D., Rabin, B.M., Shukitt Hale, B. 2025. Dietary Blueberry before and/or after Exposure to High Energy and Charge Particle Radiation Attenuates Neuroinflammation, Oxidative Stress, Glial Cell Activation, and Memory Deficits in Rats. Journal of Nutrition. Volume 155, Issue 3/ Pages 690-702. https://doi.org/10.1016/j.tjnut.2025.01.011.
DOI: https://doi.org/10.1016/j.tjnut.2025.01.011

Interpretive Summary: Exposure to stressors that increase inflammation and oxidative stress (OS), such as radiation, lead to deficits in memory. Blueberries (BB) have been shown to reduce inflammation and OS when administered to rodents before application of stressors, but it is unknown if BBs will help if they are administered after the stressor takes place. Therefore, this study investigated the effects of pre-, post-, and pre-/post-BB on inflammation, OS, and recognition memory in rats exposed to radiation. Rats ate a 2% BB or control diet for 45 days prior to and following radiation. Results showed that irradiation produced memory deficits, and increased OS and inflammation in the rats’ brains. All BB treatments (pre-, post-, pre-/post-irradiation) were similarly effective at reducing radiation-induced deficits. These findings suggest that dietary interventions may be effective even if given after the stressor happens.

Technical Abstract: Exposure to acute neuroinflammatory and oxidative-stress (OS)-inducing stressors, such as high energy and charge (HZE) particle irradiation, produces accelerated aging in the brain, leading to cognitive deficits, and may increase risk for neurodegenerative disease. Dietary interventions using foods with anti-inflammatory and antioxidant polyphenols, such as blueberries (BB) attenuate these changes when administered to rodents before or both before and after HZE particle exposure, but the effects of post-treatments on these outcomes have not been established. Post-stressor treatments may be important to repair initial damage and prevent progressive inflammation, OS, and glial cell activation, particularly when pre-treatments are not feasible. The present experiment assessed the differential efficacy and mechanistic targets of a BB-supplemented diet administered before and/or after acute stress with HZE particle irradiation (150 cGy 56Fe) on neuroinflammation, OS, glial cell activation, and recognition memory deficits. Male Sprague-Dawley rats (n=120) consumed a 2% BB or control diet for 45 days pre- and/or post-irradiation. Results showed that irradiation produced recognition memory deficits on the novel object recognition test and increased the mRNA and/or protein expression of neuroinflammatory factors (e.g., tumor necrosis factor-' [TNF'], inducible nitric oxide synthase [iNOS], cyclooxygenase-2 [COX-2], phosphorylated I kappa B-alpha [pIkB-a]), one mediator of oxidative stress (NADPH oxidase [NOX2]), and glial cell markers for microglia and astrocyte activity (CD68 and glial fibrillary acidic protein [GFAP]) in the frontal cortex and hippocampus of rats 45 days after irradiation. All BB treatments (pre-, post-, pre-/post-irradiation) were similarly effective at reducing 56Fe-induced neuroinflammation, OS, glial activation, and memory deficits. These findings support the use of dietary post-treatments with antioxidant and anti-inflammatory properties to attenuate biochemical changes in the brain and memory deficits following acute neuroinflammatory/OS-inducing stressors, in addition to having protective benefits.