Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
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 proc...
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Nature Research
2021
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2-s2.0-85101446415 Lee H.-C.; Hamzah H.; Leong M.P.-Y.; Md Yusof H.; Habib O.; Zainal Abidin S.; Seth E.A.; Lim S.-M.; Vidyadaran S.; Mohd Moklas M.A.; Abdullah M.A.; Nordin N.; Hassan Z.; Cheah P.-S.; Ling K.-H. Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice 2021 Scientific Reports 11 1 10.1038/s41598-021-83222-z https://www.scopus.com/inward/record.uri?eid=2-s2.0-85101446415&doi=10.1038%2fs41598-021-83222-z&partnerID=40&md5=bd59ec493f7c72b6d7626540688eb66f 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. © 2021, The Author(s). Nature Research 20452322 English Article All Open Access; Gold Open Access |
author |
Lee H.-C.; Hamzah H.; Leong M.P.-Y.; Md Yusof H.; Habib O.; Zainal Abidin S.; Seth E.A.; Lim S.-M.; Vidyadaran S.; Mohd Moklas M.A.; Abdullah M.A.; Nordin N.; Hassan Z.; Cheah P.-S.; Ling K.-H. |
spellingShingle |
Lee H.-C.; Hamzah H.; Leong M.P.-Y.; Md Yusof H.; Habib O.; Zainal Abidin S.; Seth E.A.; Lim S.-M.; Vidyadaran S.; Mohd Moklas M.A.; Abdullah M.A.; Nordin N.; Hassan Z.; Cheah P.-S.; Ling K.-H. Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice |
author_facet |
Lee H.-C.; Hamzah H.; Leong M.P.-Y.; Md Yusof H.; Habib O.; Zainal Abidin S.; Seth E.A.; Lim S.-M.; Vidyadaran S.; Mohd Moklas M.A.; Abdullah M.A.; Nordin N.; Hassan Z.; Cheah P.-S.; Ling K.-H. |
author_sort |
Lee H.-C.; Hamzah H.; Leong M.P.-Y.; Md Yusof H.; Habib O.; Zainal Abidin S.; Seth E.A.; Lim S.-M.; Vidyadaran S.; Mohd Moklas M.A.; Abdullah M.A.; Nordin N.; Hassan Z.; Cheah P.-S.; Ling K.-H. |
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 |
publishDate |
2021 |
container_title |
Scientific Reports |
container_volume |
11 |
container_issue |
1 |
doi_str_mv |
10.1038/s41598-021-83222-z |
url |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85101446415&doi=10.1038%2fs41598-021-83222-z&partnerID=40&md5=bd59ec493f7c72b6d7626540688eb66f |
description |
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. © 2021, The Author(s). |
publisher |
Nature Research |
issn |
20452322 |
language |
English |
format |
Article |
accesstype |
All Open Access; Gold Open Access |
record_format |
scopus |
collection |
Scopus |
_version_ |
1818940560623271936 |