Prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice

The JAK/STAT signalling pathway is essential for cell communication and gene expression, particularly in brain development. Its dysregulation relates to neurological conditions such as Down syndrome and Noonan syndrome, impacting the shift from neuron to astrocyte production. Ruxolitinib, an FDA app...

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Main Authors: Azimzadeh, Mansour, Lim, Shi En, Mazhar, Nurul Syahirah, Ling, King Hwa, Cheah, Pike See
Format: Article
Language:English
Published: Pleiades Publishing 2024
Online Access:http://psasir.upm.edu.my/id/eprint/119356/
http://psasir.upm.edu.my/id/eprint/119356/1/119356.pdf
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author Azimzadeh, Mansour
Lim, Shi En
Mazhar, Nurul Syahirah
Ling, King Hwa
Cheah, Pike See
author_facet Azimzadeh, Mansour
Lim, Shi En
Mazhar, Nurul Syahirah
Ling, King Hwa
Cheah, Pike See
author_sort Azimzadeh, Mansour
building UPM Institutional Repository
collection Online Access
description The JAK/STAT signalling pathway is essential for cell communication and gene expression, particularly in brain development. Its dysregulation relates to neurological conditions such as Down syndrome and Noonan syndrome, impacting the shift from neuron to astrocyte production. Ruxolitinib, an FDA approved JAK1 and JAK2 inhibitor, is used to treat disorders associated with dysregulated JAK-STAT signaling. This study aimed to evaluate the possible effects of prenatal ruxolitinib treatment on wild-type C57BL/6 mice, their motor skills, neurobehavioral tests, and electrophysiological properties of hippocampal CA1 neurons during adulthood. Pregnant mice were administered non-toxic doses of ruxolitinib (30 mg/kg/day) orally from E13.5 to E20.5, and nine pups were delivered for each untreated and treated group for downstream analyses. Neurobehavioral and electrophysiological experiments were performed on 8.5–10.5-week-old mice. Administering ruxolitinib prenatally significantly improved muscle strength (p < 0.05). However, no changes were observed in learning ability, motor coordination, locomotor function, exploratory and anxiety related behaviour, or recognition memory (p > 0.05). Additionally, there were no significant differences in the input/output (IO) function or paired-pulse paradigm in hippocampal CA1 (p > 0.05). In conclusion, prenatal ruxolitinib treatment in C57BL/6 mice shows no adverse effects on behavioral, learning and memory but enhances muscle strength.
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spelling upm-1193562025-08-18T02:03:31Z http://psasir.upm.edu.my/id/eprint/119356/ Prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice Azimzadeh, Mansour Lim, Shi En Mazhar, Nurul Syahirah Ling, King Hwa Cheah, Pike See The JAK/STAT signalling pathway is essential for cell communication and gene expression, particularly in brain development. Its dysregulation relates to neurological conditions such as Down syndrome and Noonan syndrome, impacting the shift from neuron to astrocyte production. Ruxolitinib, an FDA approved JAK1 and JAK2 inhibitor, is used to treat disorders associated with dysregulated JAK-STAT signaling. This study aimed to evaluate the possible effects of prenatal ruxolitinib treatment on wild-type C57BL/6 mice, their motor skills, neurobehavioral tests, and electrophysiological properties of hippocampal CA1 neurons during adulthood. Pregnant mice were administered non-toxic doses of ruxolitinib (30 mg/kg/day) orally from E13.5 to E20.5, and nine pups were delivered for each untreated and treated group for downstream analyses. Neurobehavioral and electrophysiological experiments were performed on 8.5–10.5-week-old mice. Administering ruxolitinib prenatally significantly improved muscle strength (p < 0.05). However, no changes were observed in learning ability, motor coordination, locomotor function, exploratory and anxiety related behaviour, or recognition memory (p > 0.05). Additionally, there were no significant differences in the input/output (IO) function or paired-pulse paradigm in hippocampal CA1 (p > 0.05). In conclusion, prenatal ruxolitinib treatment in C57BL/6 mice shows no adverse effects on behavioral, learning and memory but enhances muscle strength. Pleiades Publishing 2024-10-27 Article PeerReviewed text en cc_by_4 http://psasir.upm.edu.my/id/eprint/119356/1/119356.pdf Azimzadeh, Mansour and Lim, Shi En and Mazhar, Nurul Syahirah and Ling, King Hwa and Cheah, Pike See (2024) Prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice. Neurochemical Journal, 18 (3). pp. 483-491. ISSN 1819-7124; eISSN: 1819-7132 https://link.springer.com/article/10.1134/S1819712424700168?error=cookies_not_supported&code=e0e8224d-c9b7-4237-a1a3-7e8b1c3d54d4 10.1134/s1819712424700168
spellingShingle Azimzadeh, Mansour
Lim, Shi En
Mazhar, Nurul Syahirah
Ling, King Hwa
Cheah, Pike See
Prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice
title Prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice
title_full Prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice
title_fullStr Prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice
title_full_unstemmed Prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice
title_short Prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice
title_sort prenatal ruxolitinib treatment improved muscle strength but showed no impact on the neurobehavioral and electrophysiological traits in adult mice
url http://psasir.upm.edu.my/id/eprint/119356/
http://psasir.upm.edu.my/id/eprint/119356/
http://psasir.upm.edu.my/id/eprint/119356/
http://psasir.upm.edu.my/id/eprint/119356/1/119356.pdf