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Title: Changes in gene expression in the rat hippocampus following exposure to 56 fe particles and protection by berry diets

Author
item Shukitt-Hale, Barbara
item LAU, FRANCIS C. - Interhealth Nutraceutical
item CHENG, VIVIAN - Tufts University
item LUSKIN, KATHARINE - University Of Connecticut
item CAREY, AMANDA - Northeastern University
item CARRIHILL-KNOLL, KIRSTY - University Of Maryland
item RABIN, BERNARD M. - University Of Maryland
item Joseph, James

Submitted to: Central Nervous System Agents in Medicinal Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/10/2012
Publication Date: 3/12/2013
Citation: Shukitt Hale, B., Lau, F., Cheng, V., Luskin, K., Carey, A., Carrihill-Knoll, K., Rabin, B., Joseph, J.A. 2013. Changes in gene expression in the rat hippocampus following exposure to 56 fe particles and protection by berry diets. Central Nervous System Agents in Medicinal Chemistry. 13:36-42.

Interpretive Summary: Exposing young rats to particles of high energy and charge, such as iron, increases stress and disrupts behavior, including special learning and memory. In the present study, we examined whether gene expression in an area of the brain that is important in memory is affected by iron radiation 36 hours post-irradiation, and if pre-feeding with blueberry (BB) or strawberry (SB) diets could prevent problems with gene expression. Brain tissue was gathered from 4 rats/group 36 hours post irradiation with high energy iron particles. For the diet studies, 3 rats/group were irradiated with iron after 8 weeks of being fed either a 2% BB or 2% SB diet. Changes in gene expression due to this radiation were analyzed, and we found that genes that interact with the regulation of growth of brain cells were changed after irradiation. Genes that regulate cell death showed increased activity whereas genes that control cell reproduction were suppressed, possibly to get rid of damaged cells and to stop DNA damage from spreading to new cells. Supplementation with the berry diets enhanced brain cell communication and cell signaling by increasing the activity of protective stress signals. Therefore, these data suggest that iron particle irradiation causes gene deficits in rats, which can be improved by berry fruit diets.

Technical Abstract: Exposing young rats to particles of high energy and charge (HZE particles), such as 56Fe, enhances indices of oxidative stress and inflammation and disrupts behavior, including spatial learning and memory. In the present study, we examined whether gene expression in the hippocampus, an area of the brain important in memory, is affected by exposure to 56Fe particles 36 hours post-irradiation, and if pre-feeding with blueberry (BB) or strawberry (SB) antioxidant diets could ameliorate irradiation-induced deficits in gene expression. Therefore, 4 rats/group were euthanized 36 hours post whole-body irradiation with 1.5 Gy or 2.5 Gy of 1 GeV/n high-energy 56Fe particles. For the diet studies, 3 rats/group were irradiated with 2.5 Gy of 56Fe following 8 weeks supplementation with either a 2% BB or a 2% SB diet. Alterations in gene expression profile induced by radiation were analyzed by pathway-focused microarrays on the inflammatory cytokines and genes involved in NF-kappaB signal transduction pathways. We found that genes that directly or indirectly interact in the regulation of growth and differentiation of neurons were changed following irradiation. Genes that regulate apoptosis were up-regulated whereas genes that modulate cellular proliferation were down-regulated, possibly to eliminate damaged cells and to stop cell proliferation to prevent DNA damage caused by radiation to new cells. Supplementation with the berry diets enhanced neuronal communication and cell signaling by gene up-regulation of some of the protective stress signals (e.g., increased activation of c-Jun and increased gap junction function, both of which were lowered by radiation). Therefore, these data suggest that 56Fe particle irradiation causes deficits in gene expression in rats which are ameliorated by berry fruit diets.