ArticleNeurobiology of stress2021
Combinatorial actions of glucocorticoid and mineralocorticoid stress hormone receptors are required for preventing neurodegeneration of the mouse hippocampus.
Article in Neurobiology of stress, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Impact of environmental enrichment and allostatic load induced by repeated mixing on the transcriptome of three porcine brain tissues.Molecular brain · 2026Article
- A modifiable driver of dementia: cognitive impairment in primary aldosteronism.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Glucocorticoid Receptor Translational Isoforms Generate Unique Glucocorticoid Responses in the Mouse Brain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Corticosterone-Induced Depression in Rats: Region-Specific and Time-Dependent Dysregulation of Glutamatergic Signaling, Synaptic Markers, and MMP-2 Expression.Molecular neurobiology · 2025Article
- Mineralocorticoid receptor deletion alters spontaneous behavior in an automated home-cage monitoring apparatus.Hormones and behavior · 2025Article
- Mineralocorticoid receptor knockout alters hippocampal CA2 neurons to become like those in CA1.Communications biology · 2025Article
- Molecular interactions of glucocorticoid and mineralocorticoid receptors define novel transcription and biological functions.The Journal of biological chemistry · 2025Article
- The glucocorticoid receptor potentiates aldosterone-induced transcription by the mineralocorticoid receptor.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Stress biomarkers and child development in young children in Bangladesh.Psychoneuroendocrinology · 2024Article
- Imbalanced glucocorticoid and mineralocorticoid stress hormone receptor function has sex-dependent and independent regulatory effects in the mouse hippocampus.Neurobiology of stress · 2024Article
- The cortisol switch between vulnerability and resilience.Molecular psychiatry · 2024Review
- The Molecular Gut-Brain Axis in Early Brain Development.International journal of molecular sciences · 2022Review
- Alteration of the neuronal and glial cell profiles in Neu1-deficient zebrafish.Glycoconjugate journal · 2022Article
- Brain mineralocorticoid receptor in health and disease: From molecular signalling to cognitive and emotional function.British journal of pharmacology · 2022Article
- Brain mineralocorticoid and glucocorticoid receptor balance in neuroendocrine regulation and stress-related psychiatric etiopathologies.Current opinion in endocrine and metabolic research · 2022Review
- Mineralocorticoid receptor and glucocorticoid receptor work alone and together in cell-type-specific manner: Implications for resilience prediction and targeted therapy.Neurobiology of stress · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic stress contributes to numerous human pathologies including cognition impairments and psychiatric disorders. Glucocorticoids are primary stress hormones that activate two closely related nuclear receptors, the glucocorticoid (GR) and mineralocorticoid receptor (MR), that are both highly expressed in the hippocampus. To investigate potential combinatorial actions of hippocampal GR and MR, we developed mice with conditional knockout of both GR and MR in the hippocampus and compared them to their single knockout counterparts. Mice lacking MR alone or both GR and MR in the hippocampus exhibited altered expression of multiple CA2-specific neuronal markers and enhanced cue-dependent learning in a conditioned fear test. Provocatively, in contrast to the single knockouts, mice depleted of both GR and MR showed profound neurodegeneration of the hippocampus. Neuronal death was increased and neurogenesis was reduced in the dentate gyrus of the double knockout mice. Global gene expression assays of the knockout mice revealed a synergistic increase in the number of dysregulated genes in the hippocampus lacking both GR and MR. This large cohort of genes reliant on both GR and MR for expression was strongly associated with cell death and cell proliferation pathways. GR/MR complexes were detected in CA1 and dentate gyrus neurons suggesting receptor heterodimers contribute to the joint actions of GR and MR. These findings reveal an obligate role for MR signaling in regulating the molecular phenotype of CA2 neurons and demonstrate that combinatorial actions of GR and MR are essential for preserving dentate gyrus neurons and maintaining hippocampal health.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.