Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse
Chronic exposure to high circulating levels of glucocorticoids has detrimental effects on health, including metabolic abnormalities, as exemplified in Cushing’s syndrome (CS). Magnetic resonance imaging (MRI) studies have found volumetric changes in gray and white matter of the brain in CS patients...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-02-01
|
Series: | Frontiers in Neuroscience |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.604103/full |
id |
doaj-e596fd4c771e4e17bbc71da6814d87aa |
---|---|
record_format |
Article |
spelling |
doaj-e596fd4c771e4e17bbc71da6814d87aa2021-02-10T09:35:46ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-02-011510.3389/fnins.2021.604103604103Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO MouseJorge Miguel Amaya0Ernst Suidgeest1Isabelle Sahut-Barnola2Typhanie Dumontet3Nathanaëlle Montanier4Guilhem Pagès5Cécile Keller6Louise van der Weerd7Louise van der Weerd8Alberto M. Pereira9Antoine Martinez10Onno C. Meijer11Department of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, NetherlandsGénétique Reproduction et Développement, Université Clermont-Auvergne, CNRS, INSERM, Clermont-Ferrand, FranceGénétique Reproduction et Développement, Université Clermont-Auvergne, CNRS, INSERM, Clermont-Ferrand, FranceGénétique Reproduction et Développement, Université Clermont-Auvergne, CNRS, INSERM, Clermont-Ferrand, FranceINRAE, AgroResonance, QuaPA UR370, Saint-Genès-Champanelle, FranceINRAE, AgroResonance, QuaPA UR370, Saint-Genès-Champanelle, FranceDepartment of Radiology, Leiden University Medical Center, Leiden, NetherlandsHuman Genetics Department, Leiden University Medical Center, Leiden, NetherlandsDepartment of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsINRAE, AgroResonance, QuaPA UR370, Saint-Genès-Champanelle, FranceDepartment of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsChronic exposure to high circulating levels of glucocorticoids has detrimental effects on health, including metabolic abnormalities, as exemplified in Cushing’s syndrome (CS). Magnetic resonance imaging (MRI) studies have found volumetric changes in gray and white matter of the brain in CS patients during the course of active disease, but also in remission. In order to explore this further, we performed MRI-based brain volumetric analyses in the AdKO mouse model for CS, which presents its key traits. AdKO mice had reduced relative volumes in several brain regions, including the corpus callosum and cortical areas. The medial amygdala, bed nucleus of the stria terminalis, and hypothalamus were increased in relative volume. Furthermore, we found a lower immunoreactivity of myelin basic protein (MBP, an oligodendrocyte marker) in several brain regions but a paradoxically increased MBP signal in the male cingulate cortex. We also observed a decrease in the expression of glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) and ionized calcium-binding adapter molecule 1 (IBA1, a marker for activated microglia) in the cingulate regions of the anterior corpus callosum and the hippocampus. We conclude that long-term hypercorticosteronemia induced brain region-specific changes that might include aberrant myelination and a degree of white matter damage, as both repair (GFAP) and immune (IBA1) responses are decreased. These findings suggest a cause for the changes observed in the brains of human patients and serve as a background for further exploration of their subcellular and molecular mechanisms.https://www.frontiersin.org/articles/10.3389/fnins.2021.604103/fullglucocorticoidgliamyelin basic proteinglial fibrillary acidic proteinionized calcium binding adaptor molecule 1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jorge Miguel Amaya Ernst Suidgeest Isabelle Sahut-Barnola Typhanie Dumontet Nathanaëlle Montanier Guilhem Pagès Cécile Keller Louise van der Weerd Louise van der Weerd Alberto M. Pereira Antoine Martinez Onno C. Meijer |
spellingShingle |
Jorge Miguel Amaya Ernst Suidgeest Isabelle Sahut-Barnola Typhanie Dumontet Nathanaëlle Montanier Guilhem Pagès Cécile Keller Louise van der Weerd Louise van der Weerd Alberto M. Pereira Antoine Martinez Onno C. Meijer Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse Frontiers in Neuroscience glucocorticoid glia myelin basic protein glial fibrillary acidic protein ionized calcium binding adaptor molecule 1 |
author_facet |
Jorge Miguel Amaya Ernst Suidgeest Isabelle Sahut-Barnola Typhanie Dumontet Nathanaëlle Montanier Guilhem Pagès Cécile Keller Louise van der Weerd Louise van der Weerd Alberto M. Pereira Antoine Martinez Onno C. Meijer |
author_sort |
Jorge Miguel Amaya |
title |
Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse |
title_short |
Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse |
title_full |
Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse |
title_fullStr |
Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse |
title_full_unstemmed |
Effects of Long-Term Endogenous Corticosteroid Exposure on Brain Volume and Glial Cells in the AdKO Mouse |
title_sort |
effects of long-term endogenous corticosteroid exposure on brain volume and glial cells in the adko mouse |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2021-02-01 |
description |
Chronic exposure to high circulating levels of glucocorticoids has detrimental effects on health, including metabolic abnormalities, as exemplified in Cushing’s syndrome (CS). Magnetic resonance imaging (MRI) studies have found volumetric changes in gray and white matter of the brain in CS patients during the course of active disease, but also in remission. In order to explore this further, we performed MRI-based brain volumetric analyses in the AdKO mouse model for CS, which presents its key traits. AdKO mice had reduced relative volumes in several brain regions, including the corpus callosum and cortical areas. The medial amygdala, bed nucleus of the stria terminalis, and hypothalamus were increased in relative volume. Furthermore, we found a lower immunoreactivity of myelin basic protein (MBP, an oligodendrocyte marker) in several brain regions but a paradoxically increased MBP signal in the male cingulate cortex. We also observed a decrease in the expression of glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) and ionized calcium-binding adapter molecule 1 (IBA1, a marker for activated microglia) in the cingulate regions of the anterior corpus callosum and the hippocampus. We conclude that long-term hypercorticosteronemia induced brain region-specific changes that might include aberrant myelination and a degree of white matter damage, as both repair (GFAP) and immune (IBA1) responses are decreased. These findings suggest a cause for the changes observed in the brains of human patients and serve as a background for further exploration of their subcellular and molecular mechanisms. |
topic |
glucocorticoid glia myelin basic protein glial fibrillary acidic protein ionized calcium binding adaptor molecule 1 |
url |
https://www.frontiersin.org/articles/10.3389/fnins.2021.604103/full |
work_keys_str_mv |
AT jorgemiguelamaya effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT ernstsuidgeest effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT isabellesahutbarnola effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT typhaniedumontet effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT nathanaellemontanier effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT guilhempages effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT cecilekeller effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT louisevanderweerd effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT louisevanderweerd effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT albertompereira effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT antoinemartinez effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse AT onnocmeijer effectsoflongtermendogenouscorticosteroidexposureonbrainvolumeandglialcellsintheadkomouse |
_version_ |
1724275413700575232 |