Corticosterone actions on the hippocampal brain-derived neurotrophic factor expression are mediated by Exon IV promoter
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Brain-derived neurotrophic factor (BDNF) expression is strongly regulated by adrenocorticosteroids via activated gluco- and mineralocorticoid receptors. Four separate promoters are located upstream of the BDNF noncoding exons I to IV and may thus be involved in adrenocorticosteroid-mediated gene regulation. In adrenalectomised rats, corticosterone (10 mg/kg s.c.) induces a robust down-regulation of both BDNF mRNA and protein levels in the hippocampus peaking at 2-8 h. To study the role of the individual promoters in the corticosterone response, we employed exon-specific riboprobe in situ hybridisation as well as real-time polymerase chain reaction (PCR) in the dentate gyrus. We found a down-regulation, mainly of exon IV and the protein-coding exon V, in nearby all hippocampal subregions, but exon II was only down-regulated in the dentate gyrus. Exon I and exon III transcripts were not affected by corticosterone treatment. The results could be confirmed with real-time PCR in the dentate gyrus. It appears as if the exon IV promoter is the major target for corticosterone-mediated transcriptional regulation of BDNF in the hippocampus.
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BDNF and corticosteroids oppose each other, with BDNF reversing reduced excitability in hippocampal neurons induced by stress levels of corticosterone.
“BDNF and corticosteroids appear to oppose each other – with BDNF reversing reduced excitability in hippocampal neurons induced by stress levels of corticosterone (Hansson et al., 2006).”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Hansson et al., 2006
BDNF and corticosteroids oppose each other, with BDNF reversing reduced excitability in hippocampal neurons induced by stress levels of corticosterone.
“BDNF and corticosteroids appear to oppose each other - with BDNF reversing reduced excitability in hippocampal neurons induced by stress levels of corticosterone.83”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [83]
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- Authors
- Hansson, A. C., Sommer, W. H., Metsis, M., Strömberg, I., Agnati, L. F., & Fuxe, K.
- Affiliations
- Karolinska Institutet (SE)
- National Institute on Alcohol Abuse and Alcoholism (US)
- Umeå University (SE)
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Hansson, A. C.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2005-12-15
- Volume
- 18
- Issue
- 2
- Pages
- 104-114
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W1976481435
- Cited by
- 104
- References
- 61
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 10
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- Marcus Foundation
- Vetenskapsrådet
- Marcus och Amalia Wallenbergs minnesfond
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- corticosterone, brain-derived neurotrophic factor, BDNF expression, hippocampus, glucocorticoid receptor, mineralocorticoid receptor, dentate gyrus, transcriptional regulation, adrenalectomy
- MeSH terms
- Adrenalectomy, Analysis of Variance, Animals, Corticosterone, Exons, Gene Expression Regulation, Hippocampus, Male, Promoter Regions, Genetic, RNA, Messenger, Time Factors, Transcription, Genetic, Down-Regulation, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Rats
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