Glucocorticoids, genes and brain function

Juszczak, Grzegorz R.; Stankiewicz, Adrian

doi:10.1016/j.pnpbp.2017.11.020

Cited by 100 publications

(82 citation statements)

References 594 publications

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“…In addition, we explored the possibility that central CORT exposure regulates expression of putative CORT‐dependent genes and determined whether patterns of CORT‐dependent expression varied according to regional differences in CORT binding or CORT‐metabolic enzyme expression. Although CORT regulates a vast number of genes in the brain, 31 we know of no studies to assess the conservation of these pathways in songbirds, which are important models for learning and memory, speech, and neurodegeneration 41–44 …”

Section: Discussionmentioning

confidence: 99%

“…Differential expression and occupation of CORT receptors may explain the regional brain CORT variation that we observed. Upon binding to high affinity MR under basal and early stress conditions and low‐affinity GR under stressed conditions, the intracellular CORT‐receptor complexes translocate to the nucleus, where they act as transcription factors regulating numerous target genes in brain 31 . Although it is unclear how long the CORT‐receptor complex remains in the nucleus, it is possible that this “sequestering” of hormone could influence regional total CORT concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…In the second experiment, we asked whether CORT regulates neural expression of genes that are up‐regulated in the presence of CORT in mammals, and whether that expression is related to levels of 11βHSD2 or GR (which binds CORT at stress‐induced levels 24 ). We used an ex vivo slice culture technique to expose microdissected sections of adult zebra finch brain (CER, HP, caudal telencephalon [cTEL] and hypothalamus [HYP]) to physiological stress levels of CORT, then quantified expression of FKBP5, GILZ and SGK1, three CORT‐regulated genes in mammals 30‐32 . CORT treatment mimicking acute stress levels should up‐regulate expression of all three genes, with the greatest degree of up‐regulation in those regions expressing the most GR, namely the CER and cTEL, based on our previous work 22 .…”

Section: Introductionmentioning

confidence: 99%

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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: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Several additional genes with high peak scores are also known GR targets in mammals, including fkbp5 ( Fig. 2A; Table 1) a clinically important feedback regulator of the GR [17,[21][22][23][24]. Three of the genes in the top 35 (chac1, klf9, and fkbp5) were found in our previous study to be highly upregulated in larvae chronically exposed to cortisol (Table 1).…”

Section: Adults Derived From Cortisol-treated Embryos Differentially mentioning

confidence: 91%

“…Of ~20,000 scored peaks, that with the 3 rd highest score encompassed the promoter of klf9 ( Fig. 2A; Table 1), a known GR target gene that functions as a feedforward regulator of GR signaling [16][17][18][19][20]. Several additional genes with high peak scores are also known GR targets in mammals, including fkbp5 ( Fig.…”

Section: Adults Derived From Cortisol-treated Embryos Differentially mentioning

confidence: 99%

Chronic cortisol exposure in early development leads to neuroendocrine dysregulation in adulthood

Hartig

Zhu

King

et al. 2019

Preprint

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ObjectiveChronic early life stress can affect development of the neuroendocrine stress system, leading to its persistent dysregulation and consequently increased disease risk in adulthood. One contributing factor is thought to be epigenetic programming in response to chronic cortisol exposure during early development. We have previously shown that zebrafish embryos treated chronically with cortisol develop into adults with constitutively elevated whole body cortisol and aberrant immune gene expression. The objective of the experiments reported here was to further characterize the phenotype of those adults. ResultsWe find that adult zebrafish derived from cortisol-treated embryos have aberrant cortisol levels, tissue distribution, and dynamics, which correlate with differential activity of key glucocorticoid-responsive regulatory genes klf9 and fkbp5 in blood and brain.

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Inflammation and matrix metalloproteinase 9 (Mmp‐9) regulate photoreceptor regeneration in adult zebrafish

Silva

Nagashima

et al. 2020

Glia

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Brain injury activates complex inflammatory signals in dying neurons, surviving neurons, and glia. Here, we establish that inflammation regulates the regeneration of photoreceptors in the zebrafish retina and determine the cellular expression and function of the inflammatory protease, matrix metalloproteinase 9 (Mmp-9), during this regenerative neurogenesis. Following photoreceptor ablation, anti-inflammatory treatment suppresses the number of injury-induced progenitors and regenerated photoreceptors. Upon photoreceptor injury, mmp-9 is induced in Müller glia and Müller glia-derived photoreceptor progenitors. Deleting mmp-9 results in over production of injury-induced progenitors and regenerated photoreceptors, but over time the absence of Mmp-9 compromises the survival of the regenerated cones. At all time-points studied, the levels of tnf-α are significantly elevated in mutant retinas.Anti-inflammatory treatment in mutants rescues the defects in cone survival. These data provide a link between injury-induced inflammation in the vertebrate CNS, Mmp-9 function during neuronal regeneration and the requirement of Mmp-9 for the survival of regenerated cones.

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Glucocorticoids, genes and brain function

Cited by 100 publications

References 594 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)

Chronic cortisol exposure in early development leads to neuroendocrine dysregulation in adulthood

Inflammation and matrix metalloproteinase 9 (Mmp‐9) regulate photoreceptor regeneration in adult zebrafish

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