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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Springer
2021
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| Online Access: | http://psasir.upm.edu.my/id/eprint/93421/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884429/ |
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| author | Lee, Han Chung Hamzah, Hamizun Leong, Melody Pui Yee Md Yusof, Hadri Hadi Habib, Omar Zainal Abidin, Shahidee Mohamed Seth, Eryse Amira LIm, Siong Meng Vidyadaran, Sharmili Mohd Moklas, Mohamad Aris Abdullah, Maizaton Atmadini Nordin, Norshariza Hassan, Zurina Cheah, Pike See Ling, King Hwa |
| author_facet | Lee, Han Chung Hamzah, Hamizun Leong, Melody Pui Yee Md Yusof, Hadri Hadi Habib, Omar Zainal Abidin, Shahidee Mohamed Seth, Eryse Amira LIm, Siong Meng Vidyadaran, Sharmili Mohd Moklas, Mohamad Aris Abdullah, Maizaton Atmadini Nordin, Norshariza Hassan, Zurina Cheah, Pike See Ling, King Hwa |
| author_sort | Lee, Han Chung |
| building | UPM Library |
| collection | Institutional Repository |
| content_provider | Universiti Putra Malaysia |
| content_source | UPM Institutional Repository |
| continent | Asia |
| country | Malaysia |
| 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. |
| format | Article |
| id | my.upm.eprints-93421 |
| institution | Universiti Putra Malaysia |
| publishDate | 2021 |
| publisher | Springer |
| record_format | eprints |
| spelling | my.upm.eprints-934212023-01-12T04:58:12Z http://psasir.upm.edu.my/id/eprint/93421/ Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice Lee, Han Chung Hamzah, Hamizun Leong, Melody Pui Yee Md Yusof, Hadri Hadi Habib, Omar Zainal Abidin, Shahidee Mohamed Seth, Eryse Amira LIm, Siong Meng Vidyadaran, Sharmili Mohd Moklas, Mohamad Aris Abdullah, Maizaton Atmadini Nordin, Norshariza Hassan, Zurina Cheah, Pike See Ling, King Hwa 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. Springer 2021-02-15 Article PeerReviewed Lee, Han Chung and Hamzah, Hamizun and Leong, Melody Pui Yee and Md Yusof, Hadri Hadi and Habib, Omar and Zainal Abidin, Shahidee and Mohamed Seth, Eryse Amira and LIm, Siong Meng and Vidyadaran, Sharmili and Mohd Moklas, Mohamad Aris and Abdullah, Maizaton Atmadini and Nordin, Norshariza and Hassan, Zurina and Cheah, Pike See and Ling, King Hwa (2021) Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice. Scientific Reports, 11. art. no. 3847. pp. 1-15. ISSN 2045-2322 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884429/ 10.1038/s41598-021-83222-z |
| spellingShingle | Lee, Han Chung Hamzah, Hamizun Leong, Melody Pui Yee Md Yusof, Hadri Hadi Habib, Omar Zainal Abidin, Shahidee Mohamed Seth, Eryse Amira LIm, Siong Meng Vidyadaran, Sharmili Mohd Moklas, Mohamad Aris Abdullah, Maizaton Atmadini Nordin, Norshariza Hassan, Zurina Cheah, Pike See Ling, King Hwa Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice |
| title | 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_short | 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 |
| url | http://psasir.upm.edu.my/id/eprint/93421/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884429/ |
| url_provider | http://psasir.upm.edu.my/ |