Disrupted interferon-related molecular networks and the over-expressed Ifnar1 in the brain of adult Ts1Cje mouse model of Down syndrome

Abstract

Event Abstract Back to Event Disrupted interferon-related molecular networks and the over-expressed Ifnar1 in the brain of adult Ts1Cje mouse model of Down syndrome Kai-Leng Tan1, Han-Chung Lee2, King-Hwa Ling2, Hamish. S. Scott3, Mei-I Lai4, Sharmili Vidyadaran4 and Pike-See Cheah1* 1 Universiti Putra Malaysia, Department of Human Anatomy, Genetics & Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences, Malaysia 2 Universiti Putra Malaysia, Department of Biomedical Science, Genetics & Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences, Malaysia 3 University of Adelaide, Department of Molecular Pathology, SA Pathology and Centre for Cancer Biology, School of Medicine, Faculty of Health Sciences, Australia 4 Universiti Putra Malaysia, Department of Pathology, Genetics & Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences, Malaysia Down syndrome (DS) is a chromosomal disorder resulting from trisomy of human chromosome 21 (HSA21) and all DS individual exhibit cognitive impairment. Ts1Cje mouse model of DS has a triplicated region of mouse chromosome 16 (MMU16) which is homologous to HSA21. Three interferon receptor genes (Ifnar1, Ifnar2 and Ifngr2) are located at the triplicated region in MMU16 and also in HSA21. In this study, we aimed to determine the disrupted molecular networks and the role of the candidate gene in the neurogenic-to-gliogenic shift of Ts1Cje mouse brain. A functional transcriptome analysis was performed on the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points: postnatal day (P)1, P15, P30 and P84. Functional clustering analysis of the identified 317 differentially expressed genes reported interferon-related signalling networks as the most significantly dysregulated pathway in Ts1Cje postnatal brain. Both Ifnar1 and Stat1 were found over-expressed in P84 Ts1Cje cerebral cortex and cerebellum when compared to wild type littermates through qRT-PCR and western blotting analysis. Subsequently, the role of triplicated Ifnar1 was determined by treating Ifnar1 antagonist on differentiating neural stem cells derived from the SVZ of adult Ts1Cje. The assessment on the antagonistic effect of Ifnar1 antagonist reported successful attenuation on the aberrant Stat1 expression in the Ts1Cje group to an expression level which was similar to the wild type group. Acknowledgements This work was supported by Sciencefund Grant, MOSTI, Malaysia (02-01-04-SF1306) awarded to P-SC; and K-HL was a recipient of the Melbourne International Fee Remission Scholarship and Universiti Putra Malaysia Staff Training Scholarship, and a Adelaide Fees Scholarship International equivalent. K-LT and H-CL were a recipient of Malaysian Ministry of Higher Education MyPhD scholarship. Keywords: Brain, Down Syndrome, Neuroinflammation, molecular genetics, Signalling pathway Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Tan K, Lee H, Ling K, Scott H, Lai M, Vidyadaran S and Cheah P (2016). Disrupted interferon-related molecular networks and the over-expressed Ifnar1 in the brain of adult Ts1Cje mouse model of Down syndrome. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00159 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Dr. Pike-See Cheah, Universiti Putra Malaysia, Department of Human Anatomy, Genetics & Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences, Serdang, Selangor, Malaysia, cheahpikesee@upm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kai-Leng Tan Han-Chung Lee King-Hwa Ling Hamish. S. Scott Mei-I Lai Sharmili Vidyadaran Pike-See Cheah Google Kai-Leng Tan Han-Chung Lee King-Hwa Ling Hamish. S. Scott Mei-I Lai Sharmili Vidyadaran Pike-See Cheah Google Scholar Kai-Leng Tan Han-Chung Lee King-Hwa Ling Hamish. S. Scott Mei-I Lai Sharmili Vidyadaran Pike-See Cheah PubMed Kai-Leng Tan Han-Chung Lee King-Hwa Ling Hamish. S. Scott Mei-I Lai Sharmili Vidyadaran Pike-See Cheah Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.