Dietary blueberry before and/or after exposure to HZE particles attenuates neuroinflammation, oxidative stress, and cognitive 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; RABIN, BERNARD - University Of Maryland; Shukitt-Hale, Barbara

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 12/17/2021
Publication Date: 2/10/2022
Citation: Cahoon, D.S., Fisher, D.R., Zheng, T., Rabin, B.M., Shukitt Hale, B. 2022. Dietary blueberry before and/or after exposure to HZE particles attenuates neuroinflammation, oxidative stress, and cognitive deficits in rats [abstract]. Virtual Online NASA Human Research Program Investigators Workshop. Abstract #1133-000326.

Interpretive Summary:

Technical Abstract: On exploratory missions, such as to Mars, astronauts will be exposed to particles of high energy and charge (HZE particles). HZE exposure can induce neuroinflammation, oxidative stress (OS), and cognitive deficits, and is associated with increased risk for neurodegenerative disease. Studies have shown that feeding rats foods with anti-inflammatory and antioxidant properties such as blueberries (BB) before irradiation can protect against HZE-induced neuroinflammation, OS, and cognitive deficits; however, little is known about their benefits if administered after radiation exposure. This information is important due to the possibility of unpredictable radiation surges by solar flares, when sufficient pre-treatment time may not be available to administer protective agents. Therefore, the present experiment aimed to assess the efficacy of a BB supplemented diet as a protective (i.e., pre-HZE) and/or therapeutic (i.e., post-HZE) strategy to mitigate HZE-induced neuroinflammation, OS, and cognitive deficits. Male Sprague-Dawley rats (n=120, 2 mo old) were randomized to consume a 2% BB diet or control diet for 45 days pre-irradiation. Animals were whole-body irradiated with 150 cGy 56Fe or not irradiated (0 cGy). They were then fed either a 2% BB or control diet for 45 days post-irradiation to yield the following groups: 1) no BB (i.e., control diet only), 2) only pre-BB, 3) only post-BB, or 4) both pre- and post-BB. At the end of the post-irradiation period, the novel object recognition (NOR) test was performed to assess recognition memory. Protein levels of biomarkers for inflammation (e.g., glial fibrillary acidic protein [GFAP], inducible nitric oxide synthase [iNOS], cyclooxygenase-2 [COX-2]) and OS (e.g., NADPH oxidase [NOX2]) were assessed in the hippocampus and frontal cortex of rat brains using Western blot. For the NOR, % time with the novel object for each group was compared to 50% using a two-sample t-test, as cognitively healthy animals will spend greater than 50% of exploration time with the novel object. Neurochemical data were compared between groups using two-sample t-tests. For the NOR, results showed that percent time with the novel object was greater than 50% for all groups except irradiated rats on the control diet, indicating that all BB treatment periods (pre-, post- and pre-/post-BB) significantly attenuated HZE-induced deficits in recognition memory (p < 0.05). Preliminary results showed that HZE exposure increased markers of inflammation and OS in the frontal cortex and hippocampus relative to no irradiation. The effects of BB treatment period on HZE-induced inflammation and OS were variable, depending on the marker and brain region, but overall pre-/post-BB was the most effective. Results suggest that in addition to pre-treatments, BB post-treatments may be effective at attenuating HZE-induced cognitive deficits and neuroinflammation (e.g., GFAP, COX-2, iNOS) that persist after exposures end. Although more research is needed, the protective and therapeutic potential of BB may mitigate the neurodegenerative effects of radiation exposure in deep space on the CNS of astronauts, both during missions and after returning to Earth. This research was supported by NASA Grant NNX16AE06G.