Corticosteroid Receptors in the Brain: Transcriptional Mechanisms for Specificity and Context-Dependent Effects

Meijer, Onno C.; Buurstede, Jacobus C; Schaaf, Marcel J. M.

doi:10.1007/s10571-018-0625-2

Cited by 59 publications

(38 citation statements)

References 132 publications

(148 reference statements)

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“…Glucocorticoids secreted by adrenal glands can readily cross blood–brain barrier and plasma membranes of neurons. These steroid molecules then act as ligands to cytosolic GR, initiating their traversal to the inside of the nucleus where GR acts as transcription factor by binding to GRE and eventually change the molecular milieu of the neurons 51 , 52 . Our results suggest that maternal separation reduces the ability of glucocorticoids to initiate downstream molecular changes in the BLA neurons despite the greater concentration of the circulating ligand.…”

Section: Discussionmentioning

confidence: 99%

Early-life short-term environmental enrichment counteracts the effects of stress on anxiety-like behavior, brain-derived neurotrophic factor and nuclear translocation of glucocorticoid receptors in the basolateral amygdala

Hegde

Suresh

Mitra

2020

Sci Rep

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Early life is a decisive stage for the development of physiological and psychological characteristics of an individual. Any stress or disruption of healthy development at this stage has serious long-lasting consequences for the remaining life. Unfortunately, early life stress is a common occurrence in humans and other animals. In this context, we investigated if the provision of environmental enrichment during the pre-weaning phase of rat pups and dams could alter the consequences of early-life maternal-separation stress. Pre-weaning enrichment rescued the effects of maternal separation on the excess secretion of adrenal stress hormones and anxiety-like behavior during adulthood. Enrichment also reduced the effect of stress on the spine density of basolateral amygdala neurons, a brain region critical for stress-induced facilitation of emotional behaviors. Pre-weaning enrichment, provided during early-life, blunted the effects of maternal separation stress on decreased intra-nuclear translocation of glucocorticoid receptors within the amygdala neurons when tested later in adulthood. Early-life, pre-weaning environmental enrichment also increased the amount of brain-derived neurotrophic factor within adult basolateral amygdala. Our observations showed that environmental manipulation during early formative years could be utilized to build lifelong resilience to stress. Complex naturalistic housing and sensory enrichment is, thus, an useful buffer against an impoverished and stressful childhood.

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Section: Discussionmentioning

confidence: 99%

Early-life short-term environmental enrichment counteracts the effects of stress on anxiety-like behavior, brain-derived neurotrophic factor and nuclear translocation of glucocorticoid receptors in the basolateral amygdala

Hegde

Suresh

Mitra

2020

Sci Rep

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“…However, GRs are most abundant in hippocampus, contributing to its glucocorticoid responsiveness. Thus, hippocampus may represent the primary site of mitophagy inhibition as GR-PGC1α-NIX axis is actively triggered 61 . Furthermore, alterations in complexed connectivity between glia and neurons by glucocorticoid signaling could affect mitophagy levels in neurons via neuroregulatory molecules released from activated astrocytes or microglia.…”

Section: Discussionmentioning

confidence: 99%

BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects

et al. 2021

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Stress-induced glucocorticoids disturb mitochondrial bioenergetics and dynamics; however, instead of being removed via mitophagy, the damaged mitochondria accumulate. Therefore, we investigate the role of glucocorticoids in mitophagy inhibition and subsequent synaptic defects in hippocampal neurons, SH-SY5Y cells, and ICR mice. First, we observe that glucocorticoids decrease both synaptic density and vesicle recycling due to suppressed mitophagy. Screening data reveal that glucocorticoids downregulate BNIP3-like (BNIP3L)/NIX, resulting in the reduced mitochondrial respiration function and synaptic density. Notably, we find that glucocorticoids direct the glucocorticoid receptor to bind directly to the PGC1α promoter, downregulating its expression and nuclear translocation. PGC1α downregulation selectively decreases NIX-dependent mitophagy. Consistent with these results, NIX enhancer pre-treatment of a corticosterone-exposed mouse elevates mitophagy and synaptic density in hippocampus, improving the outcome of a spatial memory task. In conclusion, glucocorticoids inhibit mitophagy via downregulating NIX and that NIX activation represents a potential target for restoring synapse function.

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“…GR is expressed in neurons, oligodendrocytes, astrocytes and microglia of the brain and spinal cord [130,131]. Very little information is available on the location of each isoform in the human brain, but the GRβ isoform is much less expressed than GRα in the hippocampus (ratio 14,500:1) [132].…”

Section: Glucocorticoid Receptors: Multiple Isoforms But Limited Datamentioning

confidence: 99%

Astrocytoma: A Hormone-Sensitive Tumor?

Hirtz

Rech

Dubois-Pot-Schneider

et al. 2020

IJMS

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Astrocytomas and, in particular, their most severe form, glioblastoma, are the most aggressive primary brain tumors and those with the poorest vital prognosis. Standard treatment only slightly improves patient survival. Therefore, new therapies are needed. Very few risk factors have been clearly identified but many epidemiological studies have reported a higher incidence in men than women with a sex ratio of 1:4. Based on these observations, it has been proposed that the neurosteroids and especially the estrogens found in higher concentrations in women’s brains could, in part, explain this difference. Estrogens can bind to nuclear or membrane receptors and potentially stimulate many different interconnected signaling pathways. The study of these receptors is even more complex since many isoforms are produced from each estrogen receptor encoding gene through alternative promoter usage or splicing, with each of them potentially having a specific role in the cell. The purpose of this review is to discuss recent data supporting the involvement of steroids during gliomagenesis and to focus on the potential neuroprotective role as well as the mechanisms of action of estrogens in gliomas.

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Corticosteroid Receptors in the Brain: Transcriptional Mechanisms for Specificity and Context-Dependent Effects

Cited by 59 publications

References 132 publications

Early-life short-term environmental enrichment counteracts the effects of stress on anxiety-like behavior, brain-derived neurotrophic factor and nuclear translocation of glucocorticoid receptors in the basolateral amygdala

Early-life short-term environmental enrichment counteracts the effects of stress on anxiety-like behavior, brain-derived neurotrophic factor and nuclear translocation of glucocorticoid receptors in the basolateral amygdala

BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects

Astrocytoma: A Hormone-Sensitive Tumor?

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