The role of JAK-STAT signalling pathway promotes neurogenic-to-gliogenic shift in the brain of Ts1cje mouse model for Down syndrome
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1
Universiti Putra Malaysia, Genetics & Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences, Malaysia
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2
Universiti Putra Malaysia, Department of Biomedical Science, Faculty of Medicine & Health Sciences, Malaysia
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3
Universiti Putra Malaysia, Immunology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Malaysia
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4
Universiti Putra Malaysia, Department of Human Anatomy, Faculty of Medicine and Health Sciences, Malaysia
The JAK-STAT signalling pathway has a pleiotropy function; it also plays a key role in gliogenesis. This has raised the possibility that it may be dysregulated during brain development and lead to over production of glial cells in the brain of Down syndrome (DS) individuals and in mouse model. The gliogenic shift in the DS brain may contribute to the intellectual disability, deficit in learning and memory impairment. Therefore, understanding the role of JAK-STAT signalling in the DS brain may implicate the underlying mechanism(s) causing the shift and provide novel therapeutics targets for therapy among DS individuals. In this study, the whole brain from Ts1Cje and disomic mice was collected at embryonic day (E) 10.5, E15 and postnatal day (P) 1. Here, we focus on JAK1, JAK2, STAT1, STAT3 and STAT6, which have been shown to express highly or stably during early brain development. In this study, phosphorylated (p) JAK2, and pSTAT6 were downregulated in Ts1Cje at both E15 and P1 when compared to the wild-type group. Inhibition of JAK2 has been reported to reduce neuronal precursor cell (NPCs) proliferation and sensitize cells to oxidative stress, while STAT6 has been postulated to function as an oxidative stress sensor. However, the whole brain total RNA and protein lysate samples were obtained from a pool of heterogeneous cells and potentially mask the true biological differences between those cells specifically expressing the gene/protein. Gene/protein expression analysis is currently being performed on a more homogenous cell pool, the multipotent progenitor cells that can be cultured in the form of neurospheres. The primary cells were isolated from the E15.5 cerebral cortex was carried out. To further explore the role of JAK-STAT signalling pathway in gliogenic shift, the Ts1Cje neurosphere culture will be treated with JAKs inhibitor, and the phenotypic changes during neurogenesis will be analysed.
Acknowledgements
The study was supported by Malaysian Ministry of Higher Education's Fundamental Research Grant Scheme awarded to P.-S. Cheah (FRGS/1/2015/SKK08/UPM/02/1) and Malaysian Ministry of Science, Technology and Innovation's Sciencefund grant awarded to K.-H. Ling (02-01-04-SF2336).
Keywords:
Down Syndrome,
in vivo,
Signalling pathway,
JAK-STAT pathways,
neurogenic-to-gliogenic
Conference:
14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016.
Presentation Type:
O01: Postgraduate Travel Awardees Oral Session 1
Topic:
14th Meeting of the Asian-Pacific Society for Neurochemistry
Citation:
Lee
H,
Nordin
N,
Vidyadaran
S,
Cheah
P and
Ling
K
(2016). The role of JAK-STAT signalling pathway promotes neurogenic-to-gliogenic shift in the brain of Ts1cje mouse model for Down syndrome.
Conference Abstract:
14th Meeting of the Asian-Pacific Society for Neurochemistry.
doi: 10.3389/conf.fncel.2016.36.00080
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Received:
04 Aug 2016;
Published Online:
11 Aug 2016.
*
Correspondence:
Mr. Han-Chung Lee, Universiti Putra Malaysia, Genetics & Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences, Serdang, Selangor, Malaysia, l.han.chung@gmail.com
Dr. King-Hwa Ling, Universiti Putra Malaysia, Genetics & Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences, Serdang, Selangor, Malaysia, lkh@upm.edu.my