Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice

Abstract Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogen...

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Autores principales:	Han-Chung Lee, Hamizun Hamzah, Melody Pui-Yee Leong, Hadri Md Yusof, Omar Habib, Shahidee Zainal Abidin, Eryse Amira Seth, Siong-Meng Lim, Sharmili Vidyadaran, Mohamad Aris Mohd Moklas, Maizaton Atmadini Abdullah, Norshariza Nordin, Zurina Hassan, Pike-See Cheah, King-Hwa Ling
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2cbcfa33d8b42fb93d9fbc95b27e345
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spelling	oai:doaj.org-article:b2cbcfa33d8b42fb93d9fbc95b27e3452021-12-02T14:04:39ZTransient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice10.1038/s41598-021-83222-z2045-2322https://doaj.org/article/b2cbcfa33d8b42fb93d9fbc95b27e3452021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83222-zhttps://doaj.org/toc/2045-2322Abstract Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0–30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.Han-Chung LeeHamizun HamzahMelody Pui-Yee LeongHadri Md YusofOmar HabibShahidee Zainal AbidinEryse Amira SethSiong-Meng LimSharmili VidyadaranMohamad Aris Mohd MoklasMaizaton Atmadini AbdullahNorshariza NordinZurina HassanPike-See CheahKing-Hwa LingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Han-Chung Lee Hamizun Hamzah Melody Pui-Yee Leong Hadri Md Yusof Omar Habib Shahidee Zainal Abidin Eryse Amira Seth Siong-Meng Lim Sharmili Vidyadaran Mohamad Aris Mohd Moklas Maizaton Atmadini Abdullah Norshariza Nordin Zurina Hassan Pike-See Cheah King-Hwa Ling Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
description	Abstract Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0–30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.
format	article
author	Han-Chung Lee Hamizun Hamzah Melody Pui-Yee Leong Hadri Md Yusof Omar Habib Shahidee Zainal Abidin Eryse Amira Seth Siong-Meng Lim Sharmili Vidyadaran Mohamad Aris Mohd Moklas Maizaton Atmadini Abdullah Norshariza Nordin Zurina Hassan Pike-See Cheah King-Hwa Ling
author_facet	Han-Chung Lee Hamizun Hamzah Melody Pui-Yee Leong Hadri Md Yusof Omar Habib Shahidee Zainal Abidin Eryse Amira Seth Siong-Meng Lim Sharmili Vidyadaran Mohamad Aris Mohd Moklas Maizaton Atmadini Abdullah Norshariza Nordin Zurina Hassan Pike-See Cheah King-Hwa Ling
author_sort	Han-Chung Lee
title	Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
title_short	Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
title_full	Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
title_fullStr	Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
title_full_unstemmed	Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
title_sort	transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b2cbcfa33d8b42fb93d9fbc95b27e345
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Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice

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