Mapping and computer assisted morphometry and microdensitometry of glucocorticoid receptor immunoreactive neurons and glial cells in the rat central nervous system

Cintra, A.; Zoli, Michèle; Rosén, L.; Agnati, Luigi F.; Okret, Sam; Wikström, Ann Charlotte; Gustafsson, J.-Å.; Fuxé, Kjell

doi:10.1016/0306-4522(94)90481-2

Cited by 162 publications

(89 citation statements)

References 34 publications

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“…As astrocytes tightly cover brain vessels (Mathiisen et al, 2010), their location renders them also susceptible to endocrine factors, including GCs. The GR is expressed by astrocytes in vitro and in vivo (Bohn et al, 1994;Cintra et al, 1994;Johnson et al 2005;Kasckow et al, 2009;Simard et al, 1999;Vielkind et al, 1990;Yu et al 2011), and its activation has been shown to alter functions such as glucose metabolism (Allaman et al, 2004), glutamate transport (Zschocke et al, 2005) and calcium signaling (Simard et al, 1999; for reviews, see Garcia-Segura and Melcangi, 2006;Jauregui-Huerta et al 2010). In this study, we aimed to test whether astrocytes are a target of morphine-induced GC signaling and to identify the astrocyte-specific transcriptional targets of the GR.…”

Section: Introductionmentioning

confidence: 99%

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Ślęzak

Korostyński

Gieryk

et al. 2013

Glia

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Chronic opioid use leads to the structural reorganization of neuronal networks, involving genetic reprogramming in neurons and glial cells. Our previous in vivo studies have revealed that a significant fraction of the morphine-induced alterations to the striatal transcriptome included glucocorticoid (GC) receptor (GR)-dependent genes. Additional analyses suggested glial cells to be the locus of these changes. In the current study, we aimed to differentiate the direct transcriptional effects of morphine and a GR agonist on primary striatal neurons and astrocytes. Whole-genome transcriptional profiling revealed that while morphine had no significant effect on gene expression in both cell types, dexamethasone significantly altered the transcriptional profile in astrocytes but not neurons. We obtained a complete dataset of genes undergoing the regulation, which includes genes related to glucose metabolism (Pdk4), circadian activity (Per1) and cell differentiation (Sox2). There was also an overlap between morphine-induced transcripts in striatum and GR-dependent transcripts in cultured astrocytes. We further analyzed the regulation of expression of one gene belonging to both groups, serum and GC regulated kinase 1 (Sgk1). We identified two transcriptional variants of Sgk1 that displayed selective GR-dependent upregulation in cultured astrocytes but not neurons. Moreover, these variants were the only two that were found to be upregulated in vivo by morphine in a GR-dependent fashion. Our data suggest that the morphine-induced, GR-dependent component of transcriptome alterations in the striatum is confined to astrocytes. Identification of this mechanism opens new directions for research on the role of astrocytes in the central effects of opioids. V V C 2013 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Ślęzak

Korostyński

Gieryk

et al. 2013

Glia

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“…The dentate gyrus was the only region in which CORT caused a decrease in the expression level of all analyzed fos family transcripts. These are interesting observations, as they demonstrate for the first time that despite the presence of GR and MR in most of the hippocampal subregions (Cintra et al, 1994;Joels and Dekloet, 1994), CORT can induce a differential early decrease of c-fos, fosB and fra-1 transcripts which may lead to unique plasticity changes in this region compared to the other hippocampal subregions.…”

Section: Discussionmentioning

confidence: 71%

“…Surprisingly, at 0.8 h CORT stimulated junB transcript levels in the S1. Notably, the S1 expresses predominantly GR and low or no detectable levels of MR (Ahima et al, 1991;Cintra et al, 1994), thus the effects of CORT on IEG expression may be mainly mediated by GR. This suggests that junB may have a special role in mediating GR-induced changes in cortical vs hippocampal plasticity.…”

Section: Discussionmentioning

confidence: 99%

“…neurotrophic factors (Parrelli et al, 1998). Both receptors are highly prevalent and co-expressed in the majority of the hippocampal neurons (Cintra et al, 1994;Van Eekelen and De Kloet, 1992). Emerging evidence suggests that the inducible transcription factor and immediate early gene (IEG) c-Fos is essential for neuronal cell survival through its regulation of downstream genes such as BDNF (Zhang et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Time-course of immediate early gene expression in hippocampal subregions of adrenalectomized rats after acute corticosterone challenge

Hansson

Fuxé

2008

Brain Research

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Corticosterone hormones mediate the stress response and function in the survival of hippocampal neurons via activation of gluco-(GR) and mineralocorticoid (MR) receptors. Activated GR and MR couple the corticosterone signal through immediate early genes (IEGs) to the late expression of downstream genes, such as neurotrophic factors. The potential importance of IEGs in GR/MRdependent plasticity in the brain is largely unknown. We examined the region-and time-dependent transcriptional profiles of six IEGs (c-fos, fosB, fra-1, junB, c-jun and egr-1) by in situ hybridization after acute corticosterone challenge in the hippocampus and the primary somatosensory cortex (S1). Adrenalectomized rats and subsequent hormone injections were used as a model system to eliminate interference of endogenous corticosterone on IEG expression.In the hippocampus, a single corticosterone dose (10 mg/kg, s.c.) caused a widespread and transient reduction of fosB mRNA after 0.8 h, whereas changes in both c-fos and fra-1 mRNA levels were restricted to the dentate gyrus region. Corticosterone treatment gave rise to a delayed and significant reduction of junB mRNA signals after 2 h in all hippocampal regions, which reversed to increase at 4 h. C-jun and egr-1 mRNA levels were unaffected by corticosterone treatment. On the contrary, in the S1, IEG expression seems to be unaffected by corticosterone treatment, with the exception of a transient increase of junB transcripts at 0.8 h.The early reduction in c-fos family and junB transcripts may contribute to the GR/MR-dependent changes on hippocampal plasticity and may be dependent on rapid corticosteroid signaling.

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“…An extensive study of multiple brain regions of healthy male rats based on computer-assisted morphometric and microdensitometric evaluation of the GR immunoreactivity (Cintra et al, 1994) revealed important variations between them. Areas like the frontal lobe, cingulate cortex, olfactory nuclei, basal forebrain, most parts of basal ganglia, thalamus and parietal cortex contain high levels of GR-expressing neurons and low GR-expressing glia (neuronal-to-glial density ratio 3-11…”

Section: Molecular Basis Of Gc Actions Within the Brainmentioning

confidence: 99%

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

Kalafatakis

Russell

Ζάρρος³

et al. 2016

Neuroscience & Biobehavioral Reviews

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Glucocorticoids mediate plethora of actions throughout the human body. Within the brain, they modulate aspects of immune system and neuroinflammatory processes, interfere with cellular metabolism and viability, interact with systems of neurotransmission and regulate neural rhythms. The influence of glucocorticoids on memory and emotional behaviour is well known and there is increasing evidence for their involvement in many neuropsychiatric pathologies. These effects, which at times can be in opposing directions, depend not only on the concentration of glucocorticoids but also the duration of their presence, the temporal relationship between their fluctuations, the co-influence of other stimuli, and the overall state of brain activity. Moreover, they are region-and cell type-specific. The molecular basis of such diversity of effects lies on the orchestration of the spatiotemporal interplay between glucocorticoid-and mineralocorticoid receptors, and is achieved through complex dynamics, mainly mediated via the circadian and ultradian pattern of glucocorticoid secretion. More sophisticated methodologies are therefore required to better approach the study of these hormones and improve the effectiveness of glucocorticoid-based therapeutics.

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Mapping and computer assisted morphometry and microdensitometry of glucocorticoid receptor immunoreactive neurons and glial cells in the rat central nervous system

Cited by 162 publications

References 34 publications

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Astrocytes are a neural target of morphine action via glucocorticoid receptor‐dependent signaling

Time-course of immediate early gene expression in hippocampal subregions of adrenalectomized rats after acute corticosterone challenge

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

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