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

Lee, Han-Chung and Hamzah, Hamizun and Leong, Melody Pui-Yee and Yusof, Hadri Md and Habib, Omar and Abidin, Shahidee Zainal and Seth, Eryse Amira and Lim, Siong-Meng and Vidyadaran, Sharmili and Moklas, Mohamad Aris Mohd 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 (1). ISSN 2045-2322, DOI

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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 S100 beta 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.

Item Type: Article
Funders: Ministry of Energy, Science, Technology, Environment and Climate Change (MESTECC), Malaysia[02-01-04-SF2336], MOHE Fundamental Research Grant Scheme[04-01-15-1663FR], Malaysian Ministry of Higher Education MyBrain scholarships, JPA scholarship
Uncontrolled Keywords: Central-nervous-system;JAK2 inhibitor;Clinical-chemistry; Pathway;Astrocytes;Activation;Persistence;Modulation;Resistance;Efficacy
Subjects: Q Science > QL Zoology
R Medicine
R Medicine > R Medicine (General)
Depositing User: Ms Zaharah Ramly
Date Deposited: 15 Sep 2022 06:46
Last Modified: 15 Sep 2022 06:46

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