The role of JAK-STAT signalling in the developing brain of Ts1Cje mouse model for Down syndrome

Introduction: The JAK-STAT signalling pathway is essential for proper regulation of the gliogenesis process during brain development. Both Down syndrome (DS) individuals and DS mouse model showed reduced number of neuron but increase number of astrocyte in the brain; suggesting that dysregulation of...

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Main Authors: Lee, Han Chung, Nordin, Norshariza, Vidyadaran, Sharmili, Cheah, Pike See, Ling, King Hwa
Format: Conference or Workshop Item
Language:English
Published: 2015
Online Access:http://psasir.upm.edu.my/id/eprint/75599/
http://psasir.upm.edu.my/id/eprint/75599/1/The%20role%20of%20JAK-STAT%20signalling%20in%20the%20developing%20brain%20of%20Ts1Cje%20mouse%20model%20for%20Down%20syndrome.pdf
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author Lee, Han Chung
Nordin, Norshariza
Vidyadaran, Sharmili
Cheah, Pike See
Ling, King Hwa
author_facet Lee, Han Chung
Nordin, Norshariza
Vidyadaran, Sharmili
Cheah, Pike See
Ling, King Hwa
author_sort Lee, Han Chung
building UPM Institutional Repository
collection Online Access
description Introduction: The JAK-STAT signalling pathway is essential for proper regulation of the gliogenesis process during brain development. Both Down syndrome (DS) individuals and DS mouse model showed reduced number of neuron but increase number of astrocyte in the brain; suggesting that dysregulation of JAK-STAT signalling pathway may have occurred and led to neurogenic-to-gliogenic shift in the DS brain. Such a shift in the DS brain may contribute to the intellectual disability seen in the DS individual and learning and memory impairment in the mouse model. Therefore, understanding the role JAK-STAT signalling in the DS brain at early stage may implicate the underlying mechanism(s) causing the shift and provide novel therapeutics targets for cognition therapy among DS individuals. Method: In this study, the whole brain of Ts1Cje and disomic mice was collected at embryonic day (E) 10.5, E14 and postnatal day (P) 1.5. Here, we focus on Jak1, Jak2, Stat1, Stat3 and Stat6, which have been shown to express highly or stably during early brain development. Results: Both RT-qPCR and western blot analysis revealed the expression of Jak1 as significantly reduced in Ts1Cje at E14. In addition, phosphorylated Jak2 and Stat6 expression levels were decreased in Ts1Cje at E14 as compared to disomic mice. Our findings suggest that JAK1 is important for astrocytic differentiation while JAK2 is essential for neural stem cells proliferation and STAT6 is crucial in mediating immune signalling. Thus, further investigation on the function of Jak1, Jak2 and Stat6 may provide insight into neurogenic-to-gliogenic shift occur in the DS brain.
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spelling upm-755992019-11-12T02:31:18Z http://psasir.upm.edu.my/id/eprint/75599/ The role of JAK-STAT signalling in the developing brain of Ts1Cje mouse model for Down syndrome Lee, Han Chung Nordin, Norshariza Vidyadaran, Sharmili Cheah, Pike See Ling, King Hwa Introduction: The JAK-STAT signalling pathway is essential for proper regulation of the gliogenesis process during brain development. Both Down syndrome (DS) individuals and DS mouse model showed reduced number of neuron but increase number of astrocyte in the brain; suggesting that dysregulation of JAK-STAT signalling pathway may have occurred and led to neurogenic-to-gliogenic shift in the DS brain. Such a shift in the DS brain may contribute to the intellectual disability seen in the DS individual and learning and memory impairment in the mouse model. Therefore, understanding the role JAK-STAT signalling in the DS brain at early stage may implicate the underlying mechanism(s) causing the shift and provide novel therapeutics targets for cognition therapy among DS individuals. Method: In this study, the whole brain of Ts1Cje and disomic mice was collected at embryonic day (E) 10.5, E14 and postnatal day (P) 1.5. Here, we focus on Jak1, Jak2, Stat1, Stat3 and Stat6, which have been shown to express highly or stably during early brain development. Results: Both RT-qPCR and western blot analysis revealed the expression of Jak1 as significantly reduced in Ts1Cje at E14. In addition, phosphorylated Jak2 and Stat6 expression levels were decreased in Ts1Cje at E14 as compared to disomic mice. Our findings suggest that JAK1 is important for astrocytic differentiation while JAK2 is essential for neural stem cells proliferation and STAT6 is crucial in mediating immune signalling. Thus, further investigation on the function of Jak1, Jak2 and Stat6 may provide insight into neurogenic-to-gliogenic shift occur in the DS brain. 2015 Conference or Workshop Item PeerReviewed text en http://psasir.upm.edu.my/id/eprint/75599/1/The%20role%20of%20JAK-STAT%20signalling%20in%20the%20developing%20brain%20of%20Ts1Cje%20mouse%20model%20for%20Down%20syndrome.pdf Lee, Han Chung and Nordin, Norshariza and Vidyadaran, Sharmili and Cheah, Pike See and Ling, King Hwa (2015) The role of JAK-STAT signalling in the developing brain of Ts1Cje mouse model for Down syndrome. In: 26th Annual Scientific Meeting of Malaysian Society of Neurosciences (MSN 2015), 5-7 June 2015, WEIL Hotel, Ipoh, Perak. (p. 38).
spellingShingle Lee, Han Chung
Nordin, Norshariza
Vidyadaran, Sharmili
Cheah, Pike See
Ling, King Hwa
The role of JAK-STAT signalling in the developing brain of Ts1Cje mouse model for Down syndrome
title The role of JAK-STAT signalling in the developing brain of Ts1Cje mouse model for Down syndrome
title_full The role of JAK-STAT signalling in the developing brain of Ts1Cje mouse model for Down syndrome
title_fullStr The role of JAK-STAT signalling in the developing brain of Ts1Cje mouse model for Down syndrome
title_full_unstemmed The role of JAK-STAT signalling in the developing brain of Ts1Cje mouse model for Down syndrome
title_short The role of JAK-STAT signalling in the developing brain of Ts1Cje mouse model for Down syndrome
title_sort role of jak-stat signalling in the developing brain of ts1cje mouse model for down syndrome
url http://psasir.upm.edu.my/id/eprint/75599/
http://psasir.upm.edu.my/id/eprint/75599/1/The%20role%20of%20JAK-STAT%20signalling%20in%20the%20developing%20brain%20of%20Ts1Cje%20mouse%20model%20for%20Down%20syndrome.pdf