title: Fish oil improves gene targets of Down syndrome in C57BL and BALB/c mice.
abstract: We have considered a novel gene targeting approach for treating pathologies and conditions whose genetic bases are defined using diet and nutrition. One such condition is Down syndrome, which is linked to overexpression of RCAN1 on human chromosome 21 for some phenotypes. We hypothesize that a decrease in RCAN1 expression with dietary supplements in individuals with Down syndrome represents a potential treatment. Toward this, we used in vivo studies and bioinformatic analysis to identify potential healthy dietary RCAN1 expression modulators. We observed Rcan1 isoform 1 (Rcan1-1) protein reduction in mice pup hippocampus after a 4-week curcumin and fish oil supplementation, with only fish oil reduction being statistically significant. Focusing on fish oil, we observed a 17% Rcan1-1 messenger RNA (mRNA) and 19% Rcan1-1 protein reduction in BALB/c mice after 5 weeks of fish oil supplementation. Fish oil supplementation starting at conception and in a different mouse strain (C57BL) led to a 27% reduction in hippocampal Rcan1-1 mRNA and a 34% reduction in spleen Rcan1-1 mRNA at 6 weeks of age. Hippocampal protein results revealed a modest 11% reduction in RCAN1-1, suggesting translational compensation. Bioinformatic mining of human fish oil studies also revealed reduced RCAN1 mRNA expression, consistent with the above studies. These results suggest the potential use of fish oil in treating Down syndrome and support our strategy of using select healthy dietary agents to treat genetically defined pathologies, an approach that we believe is simple, healthy, and cost-effective.
authors: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors: Peter A
authors: PA
authors: Zmijewski
authors: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors: Linda Y
authors: LY
authors: Gao
authors: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors: Abhinav R
authors: AR
authors: Saxena
authors: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors: Nastacia K
authors: NK
authors: Chavannes
authors: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors: Shazaan F
authors: SF
authors: Hushmendy
authors: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors: Devang L
authors: DL
authors: Bhoiwala
authors: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA. Electronic address: crawfod@mail.amc.edu.
authors: Dana R
authors: DR
authors: Crawford
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins; D019587:Dietary Supplements; D004314:Down Syndrome / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D015536:Down-Regulation; D005260:Female; D005395:Fish Oils / Q000627:therapeutic use*; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity; D013154:Spleen / Q000254:growth & development / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; C511512:DSCR1 protein, mouse; D005395:Fish Oils; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger
keywords: Diet; Down syndrome; Fish oil; Gene expression; Hippocampus; Nutraceuticals; RCAN1