Intrinsic expression of transcortin in neural cells of the mouse brain: a histochemical and molecular study

Sivukhina, Elena; Helbling, Jean‐Christophe; Minni, Amandine; Schäfer, Hans Hendrik; Pallet, Véronique; Jirikowski, Gustav F.; Moisan, Marie‐Pierre

doi:10.1242/jeb.076893

Cited by 19 publications

(11 citation statements)

References 40 publications

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“…Although hypothetical, the local expression of CBGs in brain may account for this discrepancy. CBGs are widely expressed in rodent and human brain, 25,54‐56 and, although their function is still unclear, they may serve as cellular mediators of CORT action in the absence of CORT receptors or as mechanisms enhancing CORT transport to classical receptors 26,57 . The songbird CBG sequence has recently been identified 58 and our very preliminary work suggests that the protein is expressed, albeit at quite low levels, in the zebra finch brain (M.A.…”

Section: Discussionmentioning

confidence: 85%

The stressed brain: regional and stress‐related corticosterone and stress‐regulated gene expression in the adult zebra finch (Taeniopygia guttata)

Rensel

Schlinger

2020

J Neuroendocrinology

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Glucocorticoids (CORT) are well‐known as important regulators of behaviour and cognition at basal levels and under stress. However, the precise mechanisms governing CORT action and functional outcomes of this action in the brain remain unclear, particularly in model systems other than rodents. In the present study, we investigated the dynamics of CORT regulation in the zebra finch, an important model system for vocal learning, neuroplasticity and cognition. We tested the hypothesis that CORT is locally regulated in the zebra finch brain by quantifying regional and stress‐related variation in total CORT across brain regions. In addition, we used an ex vivo slice culture system to test whether CORT regulates target gene expression uniquely in discrete regions of the brain. We documented a robust increase in brain CORT across regions after 30 minutes of restraint stress but, interestingly, baseline and stress‐induced CORT levels varied between regions. In addition, CORT treatment of brain slice cultures differentially affected expression of three CORT target genes: it up‐regulated expression of FKBP5 in most regions and SGK1 in the hypothalamus only, whereas GILZ was unaffected by CORT treatment across all brain regions investigated. The specific mechanisms producing regional variation in CORT and CORT‐dependent downstream gene expression remain unknown, although these data provide additional support for the hypothesis that the songbird brain employs regulatory mechanisms that result in precise control over the influence of CORT on glucocorticoid‐sensitive neural circuits.

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Section: Discussionmentioning

confidence: 85%

The stressed brain: regional and stress‐related corticosterone and stress‐regulated gene expression in the adult zebra finch (Taeniopygia guttata)

Rensel

Schlinger

2020

J Neuroendocrinology

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“…GCs can also be preferentially imported into (or out of) cells and tissues by ATP-binding cassette (ABC) transporters, potentially resulting in local accumulation of specific GCs that are present in circulating blood (12,44). Finally, GCs may be sequestered by high-affinity binding to membrane and cytoplasmic proteins, such as corticosteroid-binding globulin (39) and glutathione S-transferase (40,41). Such proteins could affect access of GCs to their cognate receptors.…”

Section: Discussionmentioning

confidence: 99%

Steroid Profiling Reveals Widespread Local Regulation of Glucocorticoid Levels During Mouse Development

et al. 2014

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Glucocorticoids (GCs) are produced by the adrenal glands and circulate in the blood to coordinate organismal physiology. In addition, different tissues may independently regulate their local GC levels via local GC synthesis. Here, we find that in the mouse, endogenous GCs show tissue-specific developmental patterns, rather than mirroring GCs in the blood. Using solid-phase extraction, HPLC, and specific immunoassays, we quantified endogenous steroids and found that in tissues of female and male mice, (1) local GC levels can be much higher than systemic GC levels, (2) local GCs follow age-related patterns different from those of systemic GCs, and (3) local GCs have identities different from those of systemic GCs. For example, whereas corticosterone is the predominant circulating adrenal GC in mice, high concentrations of cortisol were measured in neonatal thymus, bone marrow, and heart. The presence of cortisol was confirmed with liquid chromatography-tandem mass spectrometry. In addition, gene expression of steroidogenic enzymes was detected across multiple tissues, consistent with local GC production. Our results demonstrate that local GCs can differ from GCs in circulating blood. This finding suggests that steroids are widely used as local (paracrine or autocrine) signals, in addition to their classic role as systemic (endocrine) signals. Local GC regulation may even be the norm, rather than the exception, especially during development.

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“…Expression of both CBG mRNA and protein have been identified that are localized to the hippocampus (Sivukhina et al, 2013a, 2013b, 2006), and it appears that CBG expression in hippocampal tissue is intrinsic rather than derived from cerebrospinal fluid or plasma (Jirikowski et al, 2007; Orchinik et al, 1997; Sivukhina and Jirikowski, 2014). Thus, it is possible that decreased extracellular CBG could prolong stress-induced elevations in free extracellular corticosterone levels in the ventral hippocampus that are not observed in the plasma.…”

Section: Discussionmentioning

confidence: 99%

Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress

Bray

Scholl

et al. 2016

Brain Research

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Amphetamine withdrawal is associated with heightened anxiety-like behavior, which is directly driven by blunted stress-induced glucocorticoid receptor-dependent serotonin release in the ventral hippo-campus. This suggests that glucocorticoid availability in the ventral hippocampus during stress may be reduced during amphetamine withdrawal. Therefore, we tested whether amphetamine withdrawal alters either peripheral or hippocampal corticosterone stress responses. Adult male rats received amphetamine (2.5 mg/kg, ip) or saline for 14 days followed by 2 weeks of withdrawal. Contrary to our prediction, microdialysis samples from freely-moving rats revealed that restraint stress-induced corticosterone levels in the ventral hippocampus are enhanced by amphetamine withdrawal relative to controls. In separate groups of rats, plasma corticosterone levels increased immediately after 20 min of restraint and decreased to below stress-naïve levels after 1 h, indicating negative feedback regulation of corticosterone following stress. However, plasma corticosterone responses were similar in amphetamine-withdrawn and control rats. Neither amphetamine nor stress exposure significantly altered protein expression or enzyme activity of the steroidogenic enzymes 11β-hydroxysteroid dehydrogenase (11β-HSD1) or hexose-6-phosphate dehydrogenase (H6PD) in the ventral hippocampus. Our findings demonstrate for the first time that amphetamine withdrawal potentiates stress-induced corticosterone in the ventral hippo-campus, which may contribute to increased behavioral stress sensitivity previously observed during amphetamine withdrawal. However, this is not mediated by either changes in plasma corticosterone or hippocampal steroidogenic enzymes. Establishing enhanced ventral hippocampal corticosterone as a direct cause of greater stress sensitivity may identify the glucocorticoid system as a novel target for treating behavioral symptoms of amphetamine withdrawal.

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Intrinsic expression of transcortin in neural cells of the mouse brain: a histochemical and molecular study

Abstract: SUMMARYCorticosteroid binding globulin (CBG, transcortin) has been shown to be expressed in the brain of rat and human species. In this study, we examined the CBG brain expression and cDNA structure in mice, comparing wild-type (Cbg

Cited by 19 publications

References 40 publications

The stressed brain: regional and stress‐related corticosterone and stress‐regulated gene expression in the adult zebra finch (Taeniopygia guttata)

The stressed brain: regional and stress‐related corticosterone and stress‐regulated gene expression in the adult zebra finch (Taeniopygia guttata)

Steroid Profiling Reveals Widespread Local Regulation of Glucocorticoid Levels During Mouse Development

Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress

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