Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases

We have studied glucocorticoid receptors (GR) and actions in the spinal cord of the Wobbler mouse, a model for amyotrophic lateral sclerosis and infantile spinal muscular atrophy. Basal and stress levels of circulating corticosterone (CORT) were increased in Wobbler mice. Single point binding assays...

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Autores principales:	González Deniselle, M.C., González, S., Piroli, G., Ferrini, M., Lima, A.E., De Nicola, A.F.
Formato:	JOUR
Materias:	corticosterone dexamethasone glial fibrillary acidic protein glucocorticoid receptor ornithine decarboxylase amyotrophic lateral sclerosis animal experiment article controlled study degenerative disease female hereditary spinal muscular atrophy hippocampus male mouse nonhuman receptor down regulation spinal cord Amyotrophic Lateral Sclerosis Animals Astrocytes Cell Division Corticosterone Dexamethasone Disease Models, Animal Female Glial Fibrillary Acidic Protein Glucocorticoids Lumbosacral Region Male Mice Mice, Mutant Strains Neck Ornithine Decarboxylase Receptors, Glucocorticoid Sex Factors Spinal Cord Spinal Muscular Atrophies of Childhood
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_09600760_v60_n3-4_p205_GonzalezDeniselle
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_09600760_v60_n3-4_p205_GonzalezDeniselle
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spelling	todo:paper_09600760_v60_n3-4_p205_GonzalezDeniselle2023-10-03T15:53:29Z Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases González Deniselle, M.C. González, S. Piroli, G. Ferrini, M. Lima, A.E. De Nicola, A.F. corticosterone dexamethasone glial fibrillary acidic protein glucocorticoid receptor ornithine decarboxylase amyotrophic lateral sclerosis animal experiment article controlled study degenerative disease female hereditary spinal muscular atrophy hippocampus male mouse nonhuman receptor down regulation spinal cord Amyotrophic Lateral Sclerosis Animals Astrocytes Cell Division Corticosterone Dexamethasone Disease Models, Animal Female Glial Fibrillary Acidic Protein Glucocorticoids Lumbosacral Region Male Mice Mice, Mutant Strains Neck Ornithine Decarboxylase Receptors, Glucocorticoid Sex Factors Spinal Cord Spinal Muscular Atrophies of Childhood We have studied glucocorticoid receptors (GR) and actions in the spinal cord of the Wobbler mouse, a model for amyotrophic lateral sclerosis and infantile spinal muscular atrophy. Basal and stress levels of circulating corticosterone (CORT) were increased in Wobbler mice. Single point binding assays showed that cytosolic type II GR in the spinal cord of Wobbler mice of both sexes were slightly reduced compared with normal littermates. Saturation analysis further demonstrated a non-significant reduction in B(max) with increased K(d). In the hippocampus, however, we found downregulation of GR, a probable response to increased CORT levels. We also found that the basal activity of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, was higher in Wobbler mice than in control animals. Both groups showed a two-fold stimulation of ODC activity after treatment with dexamethasone (DEX). Additionally, Wobbler mice presented with an intense proliferation of astrocytes immunoreactive (ir) for glial fibrillary acidic protein (GFAP) in grey and white matter of the spinal cord. The enhanced GFAP-ir was attenuated after four days of treatment with a corticosterone (CORT) pellet implant, producing a pharmacological increase in peripheral circulating CORT. Taking into consideration the content of GR and the changes in ODC activity and GFAP-ir brought about by glucocorticoids, we suggest that Wobbler mice are hormone responsive. Further elucidation of glucocorticoid effects in this model may be relevant for understanding the possible use of hormones in human neurodegenerative diseases. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09600760_v60_n3-4_p205_GonzalezDeniselle
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	corticosterone dexamethasone glial fibrillary acidic protein glucocorticoid receptor ornithine decarboxylase amyotrophic lateral sclerosis animal experiment article controlled study degenerative disease female hereditary spinal muscular atrophy hippocampus male mouse nonhuman receptor down regulation spinal cord Amyotrophic Lateral Sclerosis Animals Astrocytes Cell Division Corticosterone Dexamethasone Disease Models, Animal Female Glial Fibrillary Acidic Protein Glucocorticoids Lumbosacral Region Male Mice Mice, Mutant Strains Neck Ornithine Decarboxylase Receptors, Glucocorticoid Sex Factors Spinal Cord Spinal Muscular Atrophies of Childhood
spellingShingle	corticosterone dexamethasone glial fibrillary acidic protein glucocorticoid receptor ornithine decarboxylase amyotrophic lateral sclerosis animal experiment article controlled study degenerative disease female hereditary spinal muscular atrophy hippocampus male mouse nonhuman receptor down regulation spinal cord Amyotrophic Lateral Sclerosis Animals Astrocytes Cell Division Corticosterone Dexamethasone Disease Models, Animal Female Glial Fibrillary Acidic Protein Glucocorticoids Lumbosacral Region Male Mice Mice, Mutant Strains Neck Ornithine Decarboxylase Receptors, Glucocorticoid Sex Factors Spinal Cord Spinal Muscular Atrophies of Childhood González Deniselle, M.C. González, S. Piroli, G. Ferrini, M. Lima, A.E. De Nicola, A.F. Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases
topic_facet	corticosterone dexamethasone glial fibrillary acidic protein glucocorticoid receptor ornithine decarboxylase amyotrophic lateral sclerosis animal experiment article controlled study degenerative disease female hereditary spinal muscular atrophy hippocampus male mouse nonhuman receptor down regulation spinal cord Amyotrophic Lateral Sclerosis Animals Astrocytes Cell Division Corticosterone Dexamethasone Disease Models, Animal Female Glial Fibrillary Acidic Protein Glucocorticoids Lumbosacral Region Male Mice Mice, Mutant Strains Neck Ornithine Decarboxylase Receptors, Glucocorticoid Sex Factors Spinal Cord Spinal Muscular Atrophies of Childhood
description	We have studied glucocorticoid receptors (GR) and actions in the spinal cord of the Wobbler mouse, a model for amyotrophic lateral sclerosis and infantile spinal muscular atrophy. Basal and stress levels of circulating corticosterone (CORT) were increased in Wobbler mice. Single point binding assays showed that cytosolic type II GR in the spinal cord of Wobbler mice of both sexes were slightly reduced compared with normal littermates. Saturation analysis further demonstrated a non-significant reduction in B(max) with increased K(d). In the hippocampus, however, we found downregulation of GR, a probable response to increased CORT levels. We also found that the basal activity of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, was higher in Wobbler mice than in control animals. Both groups showed a two-fold stimulation of ODC activity after treatment with dexamethasone (DEX). Additionally, Wobbler mice presented with an intense proliferation of astrocytes immunoreactive (ir) for glial fibrillary acidic protein (GFAP) in grey and white matter of the spinal cord. The enhanced GFAP-ir was attenuated after four days of treatment with a corticosterone (CORT) pellet implant, producing a pharmacological increase in peripheral circulating CORT. Taking into consideration the content of GR and the changes in ODC activity and GFAP-ir brought about by glucocorticoids, we suggest that Wobbler mice are hormone responsive. Further elucidation of glucocorticoid effects in this model may be relevant for understanding the possible use of hormones in human neurodegenerative diseases.
format	JOUR
author	González Deniselle, M.C. González, S. Piroli, G. Ferrini, M. Lima, A.E. De Nicola, A.F.
author_facet	González Deniselle, M.C. González, S. Piroli, G. Ferrini, M. Lima, A.E. De Nicola, A.F.
author_sort	González Deniselle, M.C.
title	Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases
title_short	Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases
title_full	Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases
title_fullStr	Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases
title_full_unstemmed	Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases
title_sort	glucocorticoid receptors and actions in the spinal cord of the wobbler mouse a model for neurodegenerative diseases
url	http://hdl.handle.net/20.500.12110/paper_09600760_v60_n3-4_p205_GonzalezDeniselle
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Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases

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