Glial and Neuronal Glucocorticoid Receptor Immunoreactive Cell Populations in Developing, Adult, and Aging Braina

Cintra, A.; Bhatnagar, Maheep; Chadi, Gerson; Tinner, B.; Lindberg, Jakob; Gustafsson, Jan‐Åke; Agnati, Luigi F.; Fuxé, Kjell

doi:10.1111/j.1749-6632.1994.tb39210.x

Cited by 60 publications

(23 citation statements)

References 25 publications

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“…Double-label immunohistochemical analysis of GR and GFAP showed that nuclei with low GR immunoreactivity were frequently localized adjacent to astroglial cytoplasmic GFAP structures (Figure 4D), identifying them as likely astrocyte nuclei or were not clearly associated with GFAP but instead were aligned in parallel to white matter fibers, identifying them as likely oligodendrocytes (Figure 4C). These findings are consistent with the interpretation that glial cell nuclei contain low concentrations of GR relative to those in neurons (81, 88). …”

Section: Resultssupporting

confidence: 90%

“…Figure 4, A and B, illustrate that pyramidal neurons exhibited intense GR immunostaining compared with that of glial cells scattered throughout other layers and white matter, as reported previously for rats (88). Double-label immunohistochemical analysis of GR and GFAP showed that nuclei with low GR immunoreactivity were frequently localized adjacent to astroglial cytoplasmic GFAP structures (Figure 4D), identifying them as likely astrocyte nuclei or were not clearly associated with GFAP but instead were aligned in parallel to white matter fibers, identifying them as likely oligodendrocytes (Figure 4C).…”

Section: Resultssupporting

confidence: 82%

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Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging

et al. 2013

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Although glucocorticoids (GCs) are known to exert numerous effects in the hippocampus, their chronic regulatory functions remain poorly understood. Moreover, evidence is inconsistent regarding the long-standing hypothesis that chronic GC exposure promotes brain aging/Alzheimer disease. Here, we adrenalectomized male F344 rats at 15 months of age, maintained them for 3 months with implanted corticosterone (CORT) pellets producing low or intermediate (glucocorticoid receptor–activating) blood levels of CORT, and performed microarray/pathway analyses in hippocampal CA1. We defined the chronic GC-dependent transcriptome as 393 genes that exhibited differential expression between intermediate and low CORT groups. Short-term CORT (4 days) did not recapitulate this transcriptome. Functional processes/pathways overrepresented by chronic CORT–up-regulated genes included learning/plasticity, differentiation, glucose metabolism, and cholesterol biosynthesis, whereas processes overrepresented by CORT–down-regulated genes included inflammatory/immune/glial responses and extracellular structure. These profiles indicate that GCs chronically activate neuronal/metabolic processes while coordinately repressing a glial axis of reactivity/inflammation. We then compared the GC transcriptome with a previously defined hippocampal aging transcriptome, revealing a high proportion of common genes. Although CORT and aging moved expression of some common genes in the same direction, the majority were shifted in opposite directions by CORT and aging (eg, glial inflammatory genes down-regulated by CORT are up-regulated with aging). These results contradict the hypothesis that GCs simply promote brain aging and also suggest that the opposite direction shifts during aging reflect resistance to CORT regulation. Therefore, we propose a new model in which aging-related GC resistance develops in some target pathways, whereas GC overstimulation develops in others, together generating much of the brain aging phenotype.

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 82%

Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging

et al. 2013

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“…In this context, the observed relationship between reduced cingulate gyrus and increased salivary cortisol secretion after awaking in our study extended that preclinical finding. As reported previously, the cingulate gyrus contains high densities of glucocorticoid receptors in most layers [14] which may make it one of the most vulnerable parts to the neurotoxicity of increased glucocorticoids. In addition, the cingulate gyrus also plays a crucial role in the regulation of the HPA axis [41], and thus glucocorticoids induced damage to this area may diminish its ability to exert negative feedback control resulting in more glucocorticoid secretions.…”

Section: Discussionmentioning

confidence: 77%

“…In addition, it is quite interesting that the altered brain regions reported in subjects with early life stress contain high concentrations of glucocorticoid receptors and act as well-documented roles in regulating HPA activity [14]. Hence, stress-related dysfunction of the HPA axis and atrophy of the regulator regions may precipitate a vicious circle which will result in greater exposure to glucocorticoids and more severe damage to these brain regions.…”

Section: Introductionmentioning

confidence: 99%

Reduced Cingulate Gyrus Volume Associated with Enhanced Cortisol Awakening Response in Young Healthy Adults Reporting Childhood Trauma

Lu¹,

Gao²,

Wei³

et al. 2015

Holistic Perspectives on Trauma

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Background: Preclinical studies have demonstrated the relationship between stress-induced increased cortisol levels and atrophy of specific brain regions, however, this association has been less revealed in clinical samples. The aim of the present study was to investigate the changes and associations of the hypothalamic-pituitary-adrenal (HPA) axis activity and gray matter volumes in young healthy adults with self-reported childhood trauma exposures.

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“…PRYKHOZHIJ, MARSICO, AND MEIJSING receptor (MR) in rat neurons 34,35 and glia, 36 although further studies will be necessary to confirm their sites of expression and regulation. Identification of pronephros (''pronephric proximal convoluted tubule'') and ''interrenal primordium'' terms in this analysis may be significant since in the mammalian system kidney is a primary target of mineralocorticoids, but not of glucocorticoids because of glucocorticoid inactivation by the HSD11B2 enzyme.…”

mentioning

confidence: 99%

Zebrafish Expression Ontology of Gene Sets (ZEOGS): A Tool to Analyze Enrichment of Zebrafish Anatomical Terms in Large Gene Sets

2013

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The zebrafish (Danio rerio) is an established model organism for developmental and biomedical research. It is frequently used for high-throughput functional genomics experiments, such as genome-wide gene expression measurements, to systematically analyze molecular mechanisms. However, the use of whole embryos or larvae in such experiments leads to a loss of the spatial information. To address this problem, we have developed a tool called Zebrafish Expression Ontology of Gene Sets (ZEOGS) to assess the enrichment of anatomical terms in large gene sets. ZEOGS uses gene expression pattern data from several sources: first, in situ hybridization experiments from the Zebrafish Model Organism Database (ZFIN); second, it uses the Zebrafish Anatomical Ontology, a controlled vocabulary that describes connected anatomical structures; and third, the available connections between expression patterns and anatomical terms contained in ZFIN. Upon input of a gene set, ZEOGS determines which anatomical structures are overrepresented in the input gene set. ZEOGS allows one for the first time to look at groups of genes and to describe them in terms of shared anatomical structures. To establish ZEOGS, we first tested it on random gene selections and on two public microarray datasets with known tissue-specific gene expression changes. These tests showed that ZEOGS could reliably identify the tissues affected, whereas only very few enriched terms to none were found in the random gene sets. Next we applied ZEOGS to microarray datasets of 24 and 72 h postfertilization zebrafish embryos treated with beclomethasone, a potent glucocorticoid. This analysis resulted in the identification of several anatomical terms related to glucocorticoid-responsive tissues, some of which were stage-specific. Our studies highlight the ability of ZEOGS to extract spatial information from datasets derived from whole embryos, indicating that ZEOGS could be a useful tool to automatically analyze gene expression pattern features of any large zebrafish gene set.

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Glial and Neuronal Glucocorticoid Receptor Immunoreactive Cell Populations in Developing, Adult, and Aging Braina

Cited by 60 publications

References 25 publications

Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging

Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging

Reduced Cingulate Gyrus Volume Associated with Enhanced Cortisol Awakening Response in Young Healthy Adults Reporting Childhood Trauma

Zebrafish Expression Ontology of Gene Sets (ZEOGS): A Tool to Analyze Enrichment of Zebrafish Anatomical Terms in Large Gene Sets

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