The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice

Mutant Wobbler mice are models for human amyotrophic lateral sclerosis (ALS). In addition to spinal cord degeneration, Wobbler mice show high levels of blood corticosterone, hyperactivity of the hypothalamic-pituitary-adrenal axis and abnormalities of the hippocampus. Hypersecretion of glucocorticoi...

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Autores principales:	Meyer, M., Gonzalez Deniselle, M.C., Hunt, H., Kloet, E.R.D., De Nicola, A.F.
Formato:	JOUR
Materias:	Astrogliosis CORT108297 Corticosterone Glucocorticoid receptor antagonist Hippocampus Microglia Neurogenesis Wobbler mice binding protein brain protein cort 108297 cort108297 corticosterone doublecortin glial fibrillary acidic protein glucocorticoid receptor ionized calcium binding adapter molecule 1 neuron specific nuclear protein recombinant hormone unclassified drug antiinflammatory agent CORT 108297 doublecortin protein fused heterocyclic rings heterocyclic compound microtubule associated protein nerve protein NeuN protein, mouse neuropeptide nuclear protein adrenal cortex disease animal experiment animal model article astrocyte astrocyte hypertrophy astrocytosis cell activity cell count cell function controlled study corticosterone blood level dentate gyrus doublecortin+ neuroblast drug brain level drug effect drug mechanism drug receptor binding drug response glial fibrillary acidic protein+astrocyte hippocampus hypercorticosteronemia hypertrophy ionized calcium binding adapter molecule 1+microglia microglia mouse nervous system parameters neuroblast neuron specific nuclear protein+ cell nonhuman phenotype treatment duration animal antagonists and inhibitors cell culture comparative study cytology disease model drug effects enzyme immunoassay female fluorescent antibody technique human metabolism mouse mutant nerve cell physiology Western blotting Animals Anti-Inflammatory Agents Astrocytes Aza Compounds Blotting, Western Cells, Cultured Disease Models, Animal Female Fluorescent Antibody Technique Glial Fibrillary Acidic Protein Heterocyclic Compounds with 4 or More Rings Humans Immunoenzyme Techniques Mice Mice, Neurologic Mutants Microtubule-Associated Proteins Nerve Tissue Proteins Neurons Neuropeptides Nuclear Proteins Receptors, Glucocorticoid
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_09600760_v143_n_p40_Meyer
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_09600760_v143_n_p40_Meyer
record_format	dspace
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Astrogliosis CORT108297 Corticosterone Glucocorticoid receptor antagonist Hippocampus Microglia Neurogenesis Wobbler mice binding protein brain protein cort 108297 cort108297 corticosterone doublecortin glial fibrillary acidic protein glucocorticoid receptor ionized calcium binding adapter molecule 1 neuron specific nuclear protein recombinant hormone unclassified drug antiinflammatory agent CORT 108297 corticosterone doublecortin protein fused heterocyclic rings glial fibrillary acidic protein glucocorticoid receptor heterocyclic compound microtubule associated protein nerve protein NeuN protein, mouse neuropeptide nuclear protein adrenal cortex disease animal experiment animal model article astrocyte astrocyte hypertrophy astrocytosis cell activity cell count cell function controlled study corticosterone blood level dentate gyrus doublecortin+ neuroblast drug brain level drug effect drug mechanism drug receptor binding drug response glial fibrillary acidic protein+astrocyte hippocampus hypercorticosteronemia hypertrophy ionized calcium binding adapter molecule 1+microglia microglia mouse nervous system parameters neuroblast neuron specific nuclear protein+ cell nonhuman phenotype treatment duration animal antagonists and inhibitors cell culture comparative study cytology disease model drug effects enzyme immunoassay female fluorescent antibody technique hippocampus human metabolism mouse mutant nerve cell physiology Western blotting Animals Anti-Inflammatory Agents Astrocytes Aza Compounds Blotting, Western Cells, Cultured Corticosterone Disease Models, Animal Female Fluorescent Antibody Technique Glial Fibrillary Acidic Protein Heterocyclic Compounds with 4 or More Rings Hippocampus Humans Immunoenzyme Techniques Mice Mice, Neurologic Mutants Microglia Microtubule-Associated Proteins Nerve Tissue Proteins Neurons Neuropeptides Nuclear Proteins Receptors, Glucocorticoid
spellingShingle	Astrogliosis CORT108297 Corticosterone Glucocorticoid receptor antagonist Hippocampus Microglia Neurogenesis Wobbler mice binding protein brain protein cort 108297 cort108297 corticosterone doublecortin glial fibrillary acidic protein glucocorticoid receptor ionized calcium binding adapter molecule 1 neuron specific nuclear protein recombinant hormone unclassified drug antiinflammatory agent CORT 108297 corticosterone doublecortin protein fused heterocyclic rings glial fibrillary acidic protein glucocorticoid receptor heterocyclic compound microtubule associated protein nerve protein NeuN protein, mouse neuropeptide nuclear protein adrenal cortex disease animal experiment animal model article astrocyte astrocyte hypertrophy astrocytosis cell activity cell count cell function controlled study corticosterone blood level dentate gyrus doublecortin+ neuroblast drug brain level drug effect drug mechanism drug receptor binding drug response glial fibrillary acidic protein+astrocyte hippocampus hypercorticosteronemia hypertrophy ionized calcium binding adapter molecule 1+microglia microglia mouse nervous system parameters neuroblast neuron specific nuclear protein+ cell nonhuman phenotype treatment duration animal antagonists and inhibitors cell culture comparative study cytology disease model drug effects enzyme immunoassay female fluorescent antibody technique hippocampus human metabolism mouse mutant nerve cell physiology Western blotting Animals Anti-Inflammatory Agents Astrocytes Aza Compounds Blotting, Western Cells, Cultured Corticosterone Disease Models, Animal Female Fluorescent Antibody Technique Glial Fibrillary Acidic Protein Heterocyclic Compounds with 4 or More Rings Hippocampus Humans Immunoenzyme Techniques Mice Mice, Neurologic Mutants Microglia Microtubule-Associated Proteins Nerve Tissue Proteins Neurons Neuropeptides Nuclear Proteins Receptors, Glucocorticoid Meyer, M. Gonzalez Deniselle, M.C. Hunt, H. Kloet, E.R.D. De Nicola, A.F. The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice
topic_facet	Astrogliosis CORT108297 Corticosterone Glucocorticoid receptor antagonist Hippocampus Microglia Neurogenesis Wobbler mice binding protein brain protein cort 108297 cort108297 corticosterone doublecortin glial fibrillary acidic protein glucocorticoid receptor ionized calcium binding adapter molecule 1 neuron specific nuclear protein recombinant hormone unclassified drug antiinflammatory agent CORT 108297 corticosterone doublecortin protein fused heterocyclic rings glial fibrillary acidic protein glucocorticoid receptor heterocyclic compound microtubule associated protein nerve protein NeuN protein, mouse neuropeptide nuclear protein adrenal cortex disease animal experiment animal model article astrocyte astrocyte hypertrophy astrocytosis cell activity cell count cell function controlled study corticosterone blood level dentate gyrus doublecortin+ neuroblast drug brain level drug effect drug mechanism drug receptor binding drug response glial fibrillary acidic protein+astrocyte hippocampus hypercorticosteronemia hypertrophy ionized calcium binding adapter molecule 1+microglia microglia mouse nervous system parameters neuroblast neuron specific nuclear protein+ cell nonhuman phenotype treatment duration animal antagonists and inhibitors cell culture comparative study cytology disease model drug effects enzyme immunoassay female fluorescent antibody technique hippocampus human metabolism mouse mutant nerve cell physiology Western blotting Animals Anti-Inflammatory Agents Astrocytes Aza Compounds Blotting, Western Cells, Cultured Corticosterone Disease Models, Animal Female Fluorescent Antibody Technique Glial Fibrillary Acidic Protein Heterocyclic Compounds with 4 or More Rings Hippocampus Humans Immunoenzyme Techniques Mice Mice, Neurologic Mutants Microglia Microtubule-Associated Proteins Nerve Tissue Proteins Neurons Neuropeptides Nuclear Proteins Receptors, Glucocorticoid
description	Mutant Wobbler mice are models for human amyotrophic lateral sclerosis (ALS). In addition to spinal cord degeneration, Wobbler mice show high levels of blood corticosterone, hyperactivity of the hypothalamic-pituitary-adrenal axis and abnormalities of the hippocampus. Hypersecretion of glucocorticoids increase hippocampus vulnerability, a process linked to an enriched content of glucocorticoid receptors (GR). Hence, we studied if a selective GR antagonist (CORT108297) with null affinity for other steroid receptors restored faulty hippocampus parameters of Wobbler mice. Three months old genotyped Wobbler mice received s.c. vehicle or CORT108297 during 4 days. We compared the response of doublecortin (DCX)+ neuroblasts in the subgranular layer of the dentate gyrus (DG), NeuN+ cells in the hilus of the DG, glial fibrillary acidic protein (GFAP)+ astrocytes and the phenotype of Iba1+ microglia in CORT108297-treated and vehicle-treated Wobblers. The number of DCX+ cells in Wobblers was lower than in control mice, whereas CORT108297 restored this parameter. After CORT108297 treatment, Wobblers showed diminished astrogliosis, and changed the phenotype of Iba1+ microglia from an activated to a quiescent form. These changes occurred without alterations in the hypercorticosteronemia or the number of NeuN+ cells of the Wobblers. In a separate experiment employing control NFR/NFR mice, treatment with corticosterone for 5 days reduced DCX+ neuroblasts and induced astrocyte hypertrophy, whereas treatment with CORT108297 antagonized these effects. Normalization of neuronal progenitors, astrogliosis and microglial phenotype by CORT108297 indicates the usefulness of this antagonist to normalize hippocampus parameters of Wobbler mice. Thus, CORT108297 opens new therapeutic options for the brain abnormalities of ALS patients and hyperadrenocorticisms. © 2014 Elsevier Ltd.
format	JOUR
author	Meyer, M. Gonzalez Deniselle, M.C. Hunt, H. Kloet, E.R.D. De Nicola, A.F.
author_facet	Meyer, M. Gonzalez Deniselle, M.C. Hunt, H. Kloet, E.R.D. De Nicola, A.F.
author_sort	Meyer, M.
title	The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice
title_short	The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice
title_full	The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice
title_fullStr	The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice
title_full_unstemmed	The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice
title_sort	selective glucocorticoid receptor modulator cort108297 restores faulty hippocampal parameters in wobbler and corticosterone-treated mice
url	http://hdl.handle.net/20.500.12110/paper_09600760_v143_n_p40_Meyer
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spelling	todo:paper_09600760_v143_n_p40_Meyer2023-10-03T15:53:23Z The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice Meyer, M. Gonzalez Deniselle, M.C. Hunt, H. Kloet, E.R.D. De Nicola, A.F. Astrogliosis CORT108297 Corticosterone Glucocorticoid receptor antagonist Hippocampus Microglia Neurogenesis Wobbler mice binding protein brain protein cort 108297 cort108297 corticosterone doublecortin glial fibrillary acidic protein glucocorticoid receptor ionized calcium binding adapter molecule 1 neuron specific nuclear protein recombinant hormone unclassified drug antiinflammatory agent CORT 108297 corticosterone doublecortin protein fused heterocyclic rings glial fibrillary acidic protein glucocorticoid receptor heterocyclic compound microtubule associated protein nerve protein NeuN protein, mouse neuropeptide nuclear protein adrenal cortex disease animal experiment animal model article astrocyte astrocyte hypertrophy astrocytosis cell activity cell count cell function controlled study corticosterone blood level dentate gyrus doublecortin+ neuroblast drug brain level drug effect drug mechanism drug receptor binding drug response glial fibrillary acidic protein+astrocyte hippocampus hypercorticosteronemia hypertrophy ionized calcium binding adapter molecule 1+microglia microglia mouse nervous system parameters neuroblast neuron specific nuclear protein+ cell nonhuman phenotype treatment duration animal antagonists and inhibitors cell culture comparative study cytology disease model drug effects enzyme immunoassay female fluorescent antibody technique hippocampus human metabolism mouse mutant nerve cell physiology Western blotting Animals Anti-Inflammatory Agents Astrocytes Aza Compounds Blotting, Western Cells, Cultured Corticosterone Disease Models, Animal Female Fluorescent Antibody Technique Glial Fibrillary Acidic Protein Heterocyclic Compounds with 4 or More Rings Hippocampus Humans Immunoenzyme Techniques Mice Mice, Neurologic Mutants Microglia Microtubule-Associated Proteins Nerve Tissue Proteins Neurons Neuropeptides Nuclear Proteins Receptors, Glucocorticoid Mutant Wobbler mice are models for human amyotrophic lateral sclerosis (ALS). In addition to spinal cord degeneration, Wobbler mice show high levels of blood corticosterone, hyperactivity of the hypothalamic-pituitary-adrenal axis and abnormalities of the hippocampus. Hypersecretion of glucocorticoids increase hippocampus vulnerability, a process linked to an enriched content of glucocorticoid receptors (GR). Hence, we studied if a selective GR antagonist (CORT108297) with null affinity for other steroid receptors restored faulty hippocampus parameters of Wobbler mice. Three months old genotyped Wobbler mice received s.c. vehicle or CORT108297 during 4 days. We compared the response of doublecortin (DCX)+ neuroblasts in the subgranular layer of the dentate gyrus (DG), NeuN+ cells in the hilus of the DG, glial fibrillary acidic protein (GFAP)+ astrocytes and the phenotype of Iba1+ microglia in CORT108297-treated and vehicle-treated Wobblers. The number of DCX+ cells in Wobblers was lower than in control mice, whereas CORT108297 restored this parameter. After CORT108297 treatment, Wobblers showed diminished astrogliosis, and changed the phenotype of Iba1+ microglia from an activated to a quiescent form. These changes occurred without alterations in the hypercorticosteronemia or the number of NeuN+ cells of the Wobblers. In a separate experiment employing control NFR/NFR mice, treatment with corticosterone for 5 days reduced DCX+ neuroblasts and induced astrocyte hypertrophy, whereas treatment with CORT108297 antagonized these effects. Normalization of neuronal progenitors, astrogliosis and microglial phenotype by CORT108297 indicates the usefulness of this antagonist to normalize hippocampus parameters of Wobbler mice. Thus, CORT108297 opens new therapeutic options for the brain abnormalities of ALS patients and hyperadrenocorticisms. © 2014 Elsevier Ltd. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09600760_v143_n_p40_Meyer

The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice

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