Biomaterial Database

Repeated carbenoxolone injections during late pregnancy alter Snk-SPAR and PSD-95 expression in the hippocampus of rat pups. 2011

Pornprom Surakul, and Wattana Weerachatyanukul, and Nuanchan Chutabhakdikul

Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom 73170, Thailand.

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 (30mg/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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011297	Prenatal Exposure Delayed Effects	The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH.	Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D011897	Random Allocation	A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.	Randomization,Allocation, Random
D002229	Carbenoxolone	An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity.	Carbenoxalone,18alpha-Carbenoxolone,18alpha-Glycyrrhetinic Acid 3beta-O-Hemisuccinate,Biogastrone,Bioral,Carbeneoxolone,Carbenoxolone Disodium Salt,Carbenoxolone Sodium,Carbosan,Duogastrone,Glycyrrhetinic Acid 3-O-hemisuccinate,Pharmaxolon,Sanodin,18alpha Carbenoxolone,18alpha Glycyrrhetinic Acid 3beta O Hemisuccinate,3-O-hemisuccinate, Glycyrrhetinic Acid,3beta-O-Hemisuccinate, 18alpha-Glycyrrhetinic Acid,Acid 3-O-hemisuccinate, Glycyrrhetinic,Acid 3beta-O-Hemisuccinate, 18alpha-Glycyrrhetinic,Glycyrrhetinic Acid 3 O hemisuccinate
D005260	Female		Females
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000076122	Disks Large Homolog 4 Protein	A neuronal protein consisting of three PDZ DOMAINS, an SH3 DOMAIN, and a C-terminal guanylate kinase-like region (see MAGUK PROTEINS). It localizes to the POST-SYNAPTIC DENSITY and associates with the cytoplasmic tail of NMDA RECEPTORS and SHAKER POTASSIUM CHANNELS, playing a critical role in NMDA receptor-mediated SYNAPTIC PLASTICITY.	Discs Large Homolog 4 Protein,PSD-95 Protein,PSD95 Protein,Postsynaptic Density Protein 95,SAP-90 Protein,SAP90 Protein,Synapse-Associated Protein 90,PSD 95 Protein,SAP 90 Protein,Synapse Associated Protein 90
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia

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