Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups

Homeostasis of circulating cortisol is maintained by the 11β-HSD2 enzyme which inactivates cortisol into cortisone. It is abundantly expressed in the placenta where it protects the fetus from high levels of maternal glucocorticoids (GCs). Maternal administration of Carbenoxolone (Cbx), a powerful 11...

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Main Authors: Pornprom Surakul, Wattana Weerachatyanukul, Nuanchan Chutabhakdikul
Other Authors: Mahidol University
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Published: 2018
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spelling th-mahidol.127882018-05-03T15:39:56Z Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups Pornprom Surakul Wattana Weerachatyanukul Nuanchan Chutabhakdikul Mahidol University Neuroscience Homeostasis of circulating cortisol is maintained by the 11β-HSD2 enzyme which inactivates cortisol into cortisone. It is abundantly expressed in the placenta where it protects the fetus from high levels of maternal glucocorticoids (GCs). Maternal administration of Carbenoxolone (Cbx), a powerful 11β-HSD2 inhibitor, leads to an increase in fetal cortisol. Previous data showed that intrauterine environment plays a crucial role in determining hippocampal structure and function. Exposure of pregnant rats to high levels of GC leads to low birth weight in offspring and an increased risk of age related memory and cognitive deficits later in life. Glutamate receptors are localized in the postsynaptic density (PSD), where many signaling proteins, cytoskeleton proteins, and ion channels are found. Any change in the number of these molecules can influence the morphology and function of the dendritic spine. We proposed that repeated Cbx injections during late pregnancy may alter the scaffolding proteins of the NMDA receptor in the pup's brain. We investigated the effects of repeated maternal Cbx injections on the scaffolding proteins of NMDA receptor in the hippocampus of rat pups. We showed that injecting pregnant rats with Cbx injections (30. mg/kg) during GD 14-21 leads to a significant decrease in SPAR (Spine Associated Rap Guanylate kinase activating protein) (p < 0.001) and PSD-95 (p < 0.05) but a significant increase in Snk (Serum inducible kinase) (p < 0.001) in the pup's hippocampus at P40. In general, Snk is induced by neuronal activity and plays an important role in phosphorylating SPAR. The phosphorylated SPAR is then recognized and degraded by ubiquitin proteasome system (UPS), causing the depletion of SPAR and PSD-95 from the spines. The results suggest that fetal exposure to excessive GC levels may activate the Snk/SPAR pathway and lead to the depletion of SPAR and PSD-95. Since GCs drugs are commonly used in various obstetric and pediatric conditions, it is important to consider the risks and benefits of prenatal GCs exposure in order to prevent neurodevelopmental delay in the offspring. © 2011 Elsevier Ireland Ltd. 2018-05-03T08:39:56Z 2018-05-03T08:39:56Z 2011-04-20 Article Neuroscience Letters. Vol.494, No.1 (2011), 75-79 10.1016/j.neulet.2011.02.060 03043940 2-s2.0-79953044213 https://repository.li.mahidol.ac.th/handle/123456789/12788 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79953044213&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Neuroscience
spellingShingle Neuroscience
Pornprom Surakul
Wattana Weerachatyanukul
Nuanchan Chutabhakdikul
Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups
description Homeostasis of circulating cortisol is maintained by the 11β-HSD2 enzyme which inactivates cortisol into cortisone. It is abundantly expressed in the placenta where it protects the fetus from high levels of maternal glucocorticoids (GCs). Maternal administration of Carbenoxolone (Cbx), a powerful 11β-HSD2 inhibitor, leads to an increase in fetal cortisol. Previous data showed that intrauterine environment plays a crucial role in determining hippocampal structure and function. Exposure of pregnant rats to high levels of GC leads to low birth weight in offspring and an increased risk of age related memory and cognitive deficits later in life. Glutamate receptors are localized in the postsynaptic density (PSD), where many signaling proteins, cytoskeleton proteins, and ion channels are found. Any change in the number of these molecules can influence the morphology and function of the dendritic spine. We proposed that repeated Cbx injections during late pregnancy may alter the scaffolding proteins of the NMDA receptor in the pup's brain. We investigated the effects of repeated maternal Cbx injections on the scaffolding proteins of NMDA receptor in the hippocampus of rat pups. We showed that injecting pregnant rats with Cbx injections (30. mg/kg) during GD 14-21 leads to a significant decrease in SPAR (Spine Associated Rap Guanylate kinase activating protein) (p < 0.001) and PSD-95 (p < 0.05) but a significant increase in Snk (Serum inducible kinase) (p < 0.001) in the pup's hippocampus at P40. In general, Snk is induced by neuronal activity and plays an important role in phosphorylating SPAR. The phosphorylated SPAR is then recognized and degraded by ubiquitin proteasome system (UPS), causing the depletion of SPAR and PSD-95 from the spines. The results suggest that fetal exposure to excessive GC levels may activate the Snk/SPAR pathway and lead to the depletion of SPAR and PSD-95. Since GCs drugs are commonly used in various obstetric and pediatric conditions, it is important to consider the risks and benefits of prenatal GCs exposure in order to prevent neurodevelopmental delay in the offspring. © 2011 Elsevier Ireland Ltd.
author2 Mahidol University
author_facet Mahidol University
Pornprom Surakul
Wattana Weerachatyanukul
Nuanchan Chutabhakdikul
format Article
author Pornprom Surakul
Wattana Weerachatyanukul
Nuanchan Chutabhakdikul
author_sort Pornprom Surakul
title Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups
title_short Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups
title_full Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups
title_fullStr Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups
title_full_unstemmed Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups
title_sort repeated carbenoxolone injections during late pregnancy alter snk-spar and psd-95 expression in the hippocampus of rat pups
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/12788
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