Neurochemical differences in learning and memory paradigms among rats supplemented with anthocyanin-rich blueberry diets and exposed to acute doses of 56Fe particles

Authors: POULOSE, SHIBU - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RABIN, BERNARD - University Of Maryland; BIELINSKI, DONNA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Kelly, Megan; Miller, Marshall; Thangthaeng, Nopporn; Shukitt-Hale, Barbara

Submitted to: Life Sciences in Space Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2016
Publication Date: 2/1/2017
Citation: Poulose, S.M., Rabin, B.M., Bielinski, D.F., Kelly, M.E., Miller, M.G., Thangthaeng, N., Shukitt Hale, B. 2017. Neurochemical differences in learning and memory paradigms among rats supplemented with anthocyanin-rich blueberry diets and exposed to acute doses of 56Fe particles. Life Sciences in Space Research. 12:16-23.

Interpretive Summary: The protective effects of blueberries on brain health are particularly important under conditions that can lead to “accelerated aging.” One such condition is exposure of astronauts to space radiation, which is known to cause decreases in brain function due to biochemical changes in brain cells. We tested the effects of short-term exposure to radiation on the rat brain, and found that radiation primarily affects memory and not learning ability. Importantly, we observed that specific brain regions failed to use cellular mechanisms that would have protected them from damage. To further examine these protective mechanisms, we have fed young rats with diets rich in blueberries, prior to irradiation. Exposure to radiation caused significant biochemical changes in the two critical regions of the brain involved in learning and memory. Blueberry-rich diet significantly decreased the same biochemical changes that were increased by radiation in the two brain regions. Tests of learning and memory indicated that exposure to radiation did not affect rats’ ability to learn something new, but did affect their ability to remember something previously learned. Overall results indicate that a blueberry-rich diet provides an effective way to reduce decreases in brain function in the event of short-term radiation exposure.

Technical Abstract: The protective effects of anthocyanin-rich blueberries (BB) on brain health are well documented and are particularly important under conditions of high oxidative stress, which can lead to “accelerated aging.” One such scenario is exposure to space radiation, consisting of high-energy and -charge particles (HZE), which are known to cause cognitive dysfunction and deleterious neurochemical alterations. We recently tested the behavioral and neurochemical effects of acute exposure to HZE particles such as 56Fe, within 24–48 h after exposure, and found that radiation primarily affects memory and not learning. Importantly, we observed that specific brain regions failed to upregulate antioxidant and anti-inflammatory mechanisms in response to this insult. To further examine these endogenous response mechanisms, we have supplemented young rats with diets rich in BB, which are known to contain high amounts of antioxidant-phytochemicals, prior to irradiation. Exposure to 56Fe caused significant neurochemical changes in hippocampus and frontal cortex, the two critical regions of the brain involved in cognitive function. BB supplementation significantly attenuated protein carbonylation, which was significantly increased by exposure to 56Fe in the hippocampus and frontal cortex. Moreover, BB supplementation significantly reduced radiation-induced elevations in NADPH-oxidoreductase-2 (NOX2) and cyclooxygenase-2 (COX-2), and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus and frontal cortex. Behavioral results indicate that exposure to 56Fe particles did not affect novel object recognition when the conditioning day occurred within 24 hr (“Memory” group) or when the test day occurred within 40 hr of irradiation (“Learning” group). Overall results indicate that 56Fe particles may induce their toxic effects on hippocampus and frontal cortex by reactive oxygen species (ROS) overload, which can cause alterations in the neuronal environment, eventually leading to hippocampal neuronal death and subsequent impairment of cognitive function. Blueberry supplementation provides an effective preventative measure to reduce the ROS load on the CNS in an event of acute HZE exposure.