The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus
Open accessAbstract
Regulation of the hypothalamic–pituitary–adrenal (HPA) axis is critical for adaptation to environmental changes. The principle regulator of the HPA axis is corticotrophin-releasing hormone (CRH), which is made in the parventricular nucleus and is an important target of negative feedback by glucocorticoids. However, the molecular mechanisms that regulate CRH are not fully understood. Disruption of normal HPA axis activity is a major risk factor of neuropsychiatric disorders in which decreased expression of the glucocorticoid receptor (GR) has been documented. To investigate the role of the GR in CRH neurons, we have targeted the deletion of the GR, specifically in the parventricular nucleus. Impairment of GR function in the parventricular nucleus resulted in an enhancement of CRH expression and an up-regulation of hypothalamic levels of BDNF and disinhibition of the HPA axis. BDNF is a stress and activity-dependent factor involved in many activities modulated by the HPA axis. Significantly, ectopic expression of BDNF in vivo increased CRH, whereas reduced expression of BDNF, or its receptor TrkB, decreased CRH expression and normal HPA functions. We find the differential regulation of CRH relies upon the cAMP response-element binding protein coactivator CRTC2, which serves as a switch for BDNF and glucocorticoids to direct the expression of CRH.
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“Additional evidence for CORT acting directly on PVN neurons comes from studies where targeted deletion of GR in the PVN increased CRH expression and CORT and ACTH levels in male mice (Jeanneteau et al., 2012).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Jeanneteau et al., 2012
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“This cross-talk between BDNF and CRH may be at least partly mediated by the CREB and MAPK pathway and is involved in the enhancement of fear memory under stress (187).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
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“The administration of BDNF in vivo induces increased CRH level and reduction of BDNF or its receptor normalizes the CRH level and thus, the HPA axis.”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
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“Moreover, there is a feedback loop whereby directly regulates CRH, and thus, the HPA axis (187).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
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“For BDNF, its expression level responds to stress-related HPA axis activation.”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
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“BDNF directly regulates the HPA axis.”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
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“Finally, the broad disruption of the GR allele in the CNS [GRNesCre (5)] and its targeted deletion in the forebrain [forebrain-specific GR knock-out; FBGRKO mice] (119), or the PVN all resulted in the disinhibition of the HPA axis (120).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [120]
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Citations
Cites
Physiology and neurobiology of stress and adaptation: central role of the brain
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Cited by
Sorted by citations
Items 201–251 of 251
Stress Responsiveness of BDNF/TrkB Signaling in the Neuroendocrine System and Future Implications
Azogu‐Sepe, I., & Plamondon, H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813156-5.00013-3 · Cited by 3
“BDNF plays a putative role in the regulation of the brain’s stress and reward systems and is considered a stress-responsive intercellular messenger in HPA axis activity.(37,62,63) The neurotrophin is reported to balance the ability of GCs to influence CRH expression within the PVN via a unique mechanism involving CREB…”
BackgroundKumar, A., Kumar, P., Pareek, V., Faiq, M. A., Raza, K., Prasoon, P., Mochan, S., & Sharma, V. (2017) · Preprints.org · doi:10.20944/preprints201710.0047.v1 · Cited by 3
“A raised BDNF level was found associated with learning social avoidance behaviour in model animals and mediated through CRH (from PVN of hypothalamus) (77, 78).”
BackgroundInfluentialHusain, J., Bakhareva, A., Pace, A. L. D., Noterman, M. F., Herrera, G. M., & Erdös, B. (2025) · Scientific Reports · doi:10.1038/s41598-025-32428-6 · Cited by 2
Herselman, M. F., Luo, S. Y., Lin, L., Zhou, X., & Bobrovskaya, L. (2026) · Physiological Reports · doi:10.14814/phy2.70870 · Cited by 3
“BDNF has been shown to induce corticotropin-releasing hormone in the hypothalamus (Jeanneteau et al., 2012), while EE has been found to attenuate markers of HPA axis output such as corticosterone in male rodents (Dandi et al., 2023).”
BDNF/TrkB Signaling in the Brain–Kidney Axis Under Functional Stress
Beknazarova, A., Kuvaeva, V., Baltin, M. E., Mutig, K., & Bobylev, A. G. (2026) · Biology · doi:10.3390/biology15090696 · Cited by 2
“Within the hypothalamic–pituitary axis (HPA), BDNF has been linked to the regulation of corticotropin-releasing hormone (CRH) and stress reactivity, providing a mechanistic entry point for neuroendocrine modulation of systemic hemodynamics during functional stress [19].”
InfluentialCorrone, M., Nanev, A., Amato, I., Bicknell, R., Piantella, S., Maruff, P. T., van den Buuse, M., & Wright, B. J. (2023) · European Journal of Neuroscience · doi:10.1111/ejn.16153 · Cited by 2
“…BDNF signalling and expression (Gourley et al., 2009; Jeanneteau et al., 2008; Pradhan et al., 2019; Smith et al., 1995), whereas BDNF can regulate the stress response through modulation of corticotrophin-releasing factor (CRF) gene expression (Givalois et al., 2004; Jeanneteau et al., 2012).”
Shemery, A., Gibson, M., Gorrell, E., Daniel, D., Piontkivska, H., & Novak, C. M. (2025) · F1000Research · doi:10.12688/f1000research.152034.2 · Cited by 2
Maty, H. N., & Hassan, A. A. (2020) · Al-mağallaẗ al-ʻirāqiyyaẗ li-l-ʻulūm al-bayṭariyyaẗ/Iraqi journal of veterinary sciences · doi:10.33899/ijvs.2019.125565.1082 · Cited by 2
MicroRNAs: An Important Signature Molecule to Improve Health and Welfare in Livestock: A Review
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Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposurePreprint
Rasiah, N. P., Rosenegger, D. G., Daviu, N., Füzesi, T., Muir, J., Sterley, T.-L., & Bains, J. S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.27.064725 · Cited by 2
Kadhim, H. J. (2024) · World s Veterinary Journal · doi:10.54203/scil.2024.wvj57 · Cited by 1
Transcriptomic profiling of hypothalamic development in female rats
Hilz, E. N., Streifer, M., Milewski, T. M., & Gore, A. C. (2025) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2025.112616 · Cited by 1
“BDNF is a neurotrophin influenced by stress that regulates neuronal survival and plasticity (Bath et al., 2013; Labelle and Leclerc, 2000), and works in concert with glucocorticoids to regulate activity of the HPA axis (Jeanneteau et al., 2012).”
Corrone, M., Jaehne, E. J., Zelko, M. D., Fanson, K. V., Wright, B. J., & van den Buuse, M. (2026) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2026.108157 · Cited by 1
O'Neill, M. (2026) · International Journal of Cognitive Sciences · doi:10.3390/ijcs2020012 · Cited by 1
“Inhibiting inputs include glucocorticoid receptor (GR)-mediated sequestration of coactivators and inflammatory pathway disruption (Jeanneteau et al., 2012; Tsimpolis et al., 2024).”
León‐Rodríguez, A., Fernández‐Arjona, M. D. M., Pedraza, C., López‐Aranda, M. F., Visser, R., & López-Ávalos, M. D. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1828445 · Cited by 1
“Targeted deletion of GR in the PVN resulted in hyperactivation of the axis (165).”
Zalachoras, I., & Meijer, O. C. (2016) · Epigenetics and human health · doi:10.1007/978-3-319-24493-8_3 · Cited by 1
Neuroendocrinology of Energy Homeostasis
Preiato, V. L., Vicennati, V., Garelli, S., & Pagotto, U. (2018) · Endocrinology · doi:10.1007/978-3-319-44444-4_16 · Cited by 1
Assessment of brain and hippocampal volume in patients with Cushing’s disease
Frankowska, E., Kidziński, R., & Zieliński, G. (2022) · Endokrynologia Polska · doi:10.5603/ep.a2022.0062 · Cited by 1
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Zantaraia, T., Гоженко, А. І., & Popovych, I. L. (2024) · Quality in Sport · doi:10.12775/qs.2024.21.53009 · Cited by 1
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“The commissural subnucleus of the NTS (cNTS) is key to glucose metabolism and feeding behavior (Wehrwein et al, 2010; Jeanneteau et al., 2012; Cuéllar et al, AC CE PT ED M AN US CR IP T 2015; Cedernaes et al., 2016).”
BackgroundThe Endocrine Regulation of Energy and Body Weight
Preiato, V. L., Vicennati, V., Gambineri, A., & Pagotto, U. (2018) · Endocrinology · doi:10.1007/978-3-319-44675-2_22 · Cited by 1
Cruickshank, N. C. (2017) · ScholarWorks -A service of University of Vermont Libraries (University of Vermont) · Cited by 1
Calcineurin signaling as a target for the treatment of alcohol abuse and neuroinflammatory disorders
Ronan, P. J., Flynn, S., & Beresford, T. P. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.06.008 · Cited by 1
Brain-Derived Neurotrophic Factor and Its Role in Stress-Related Disorders
Notaras, M. J., & van den Buuse, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813156-5.00023-6 · Cited by 1
Gao, J., Chen, Y., Su, D., Marshall, C., & Xiao, M. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/202283 · Cited by 1
“Downregulation of BDNF-TrkB-CREB signaling pathway in the hippocampus of APPswe/PS1dE9 mice Downregulation of BDNF-TrkB-CREB (cAMP response-element binding protein) signaling pathway is one of the main pathophysiological changes in depression and AD (Berry et al., 2012; Jeanneteau et al., 2012).”
BackgroundKlampfl, S. M. (2015) · University of Regensburg Publication Server (University of Regensburg) · doi:10.5283/epub.31369
Nutrition and hydration implications for trained athletes
Killer, S. C. (2014) · Loughborough University Institutional Repository (Loughborough University)
Functional characterization of Phosphodiesterase-4A in behavior and obesity
Hansen, R. (2014) · doi:10.33915/etd.583
“In addition, it has also been shown that elevations of BDNF (which could result from increased cAMP/pCREB inPDE4A KO) in the PVN increase CRF release, and subsequent activation of the HPA axis (Jeanneteau et al. 2012).”
BackgroundGenetic Overlap Between Depression and Cardiometabolic Disorders
Amare, A. T., Schubert, K. O., & Baune, B. T. (2016) · Springer eBooks · doi:10.1007/978-3-319-32480-7_15
Chen, R., Mizuno, T., Sakamoto, D., Usuda, D., Mori, M., Takahashi, M., Kato, N., Sumino, H., & Kanda, T. (2013) · The Internet Journal of Thoracic and Cardiovascular Surgery
Neuroendocrinology of Energy Homeostasis
Preiato, V. L., Vicennati, V., Garelli, S., & Pagotto, U. (2017) · Endocrinology · doi:10.1007/978-3-319-38681-2_16-1
Lu, T., Xia, J.-C., Long, T., & Qin, D.-N. (2019) · Activitas Nervosa Superior · doi:10.1007/s41470-019-00055-y
Genome-wide epigenomic stress response in the European sea bass ( Dicentrarchus labrax , L.)Preprint
Krick, M., Desmarais, É., Σαμαράς, Α., Guéret, É., Dimitroglou, A., Pavlidis, M. A., Tsigenopoulos, C. S., & Guinand, B. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.19.160812
The Endocrine Regulation of Energy and Body Weight
Preiato, V. L., Vicennati, V., Gambineri, A., & Pagotto, U. (2016) · Endocrinology · doi:10.1007/978-3-319-27318-1_22-1
Influence of Attachment Behavior in Psychosis
Kim, Y. (2022) · Korean Journal of Schizophrenia Research · doi:10.16946/kjsr.2022.25.2.23
Shemery, A., Gibson, M., Gorrell, E., Daniel, D., Piontkivska, H., & Novak, C. M. (2024) · F1000Research · doi:10.12688/f1000research.152034.1
Ghrelin Regulates Food Intake in the Ventral Tegmental Area During Chronic Psychosocial Stress
Smith, A. (2024) · Carleton University's Institutional Repository (MacOdrum Library, Carleton University) · doi:10.22215/etd/2024-16006
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Expression of Neurotrophin Genes in the Hypothalamus of Stressed and Allopregnanolone-Infused Sheep
Młotkowska, P., Osuch, B., Marciniak, E., ROSZKOWICZ-OSTROWSKA, K. I., & Misztal, T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262010062
“High levels of phosphorylated Trk β (p-Trk β ) were detected in CRH neurons, suggesting that autocrine BDNF-Trk β signaling pathway may amplify HPA axis activation [25].”
Krick, M., Desmarais, É., Σαμαράς, Α., Guéret, É., Dimitroglou, A., Pavlidis, M., Tsigenopoulos, C. S., & Guinand, B. (2021) · Figshare · doi:10.6084/m9.figshare.13843684
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Ferahkaya, H., Uzun, N., Ağır, H., Kılınç, İ., Akkuş, A., Çoşkun, F., Akça, Ö. F., & Bi̇lgi̇ç, A. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1774449
“This fi nding suggests that increased BDNF levels may function as a compensatory mechanism against the potential adverse effects of (41).”
Halalopathy: Integrating Traditional Healing and Modern Medicine for Holistic Healthcare
Alzeer, J. (2026) · Springer eBooks · doi:10.1007/978-981-95-6378-4_7
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Balancing inflammation under stress: glucocorticoid regulation of innate immune pathways
Kenney, K. M., & Burgener, S. S. (2026) · Bioscience Reports · doi:10.1042/bsr20250146
“This challenge has been somewhat overcome in models with targeted deletion of the GR in T cells [258,259], neurons [260], dendritic cells [261], and macrophages [262,263].”
THE EFFECTS OF SUGAR INTAKE ON ENERGY CONTROL
Zhao, C. (2015) · University Libraries (University of Maryland) · doi:10.13016/m25s6d
Jiang, Y. (2013) · VTechWorks (Virginia Tech)
Metadata
- Authors
- Jeanneteau, F. D., Lambert, W. M., Ismaili, N., Bath, K. G., Lee, F. S., Garabedian, M. J., & Chao, M. V.
- Affiliations
- New York University (US)
- Department of Microbiology, New York University School of Medicine, New York, NY 10016;
- Brown University (US)
- Weill Cornell Medicine (US)
- Department of Cell Biology, Department of Physiology, Department of Neuroscience, and Department of Psychiatry, Skirball Institute of Biomolecular Medicine, and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-01-09
- Volume
- 109
- Issue
- 4
- Pages
- 1305-1310
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3268297
- OpenAlex
- W2021067562
- Cited by
- 252
- References
- 38
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 18 · 2023: 12 · 2022: 12 · 2021: 17 · 2020: 18 · 2019: 18 · 2018: 18 · 2017: 27 · 2016: 19 · 2015: 17 · 2014: 15 · 2013: 24 · 2012: 15
- FWCI
- 9.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute of Biomedical Innovation
- National Institutes of Health (NS-21072)
- National Institute of Mental Health (R01MH086651, MH086651)
- National Institute of Allergy and Infectious Diseases (5T32 AI07180-29, T32AI007180)
- National Institute of Neurological Disorders and Stroke (R01NS021072, NS-21072, R56NS021072)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- brain-derived neurotrophic factor, glucocorticoids, corticotropin-releasing factor, hypothalamic-pituitary-adrenal axis, hypothalamus, glucocorticoid receptor, CRTC2, TrkB receptor, CREB, stress response, negative feedback
- MeSH terms
- Analysis of Variance, Animals, Corticotropin-Releasing Hormone, Glucocorticoids, Homeostasis, Hypothalamo-Hypophyseal System, Hypothalamus, Immunohistochemistry, Mice, Inbred C57BL, Neurons, Pituitary-Adrenal System, Receptors, Glucocorticoid, Transcription Factors, Trans-Activators, Mutagenesis, Site-Directed, Rats, Sprague-Dawley, Mice, Knockout, Microscopy, Confocal, Brain-Derived Neurotrophic Factor, Chromatin Immunoprecipitation, Mice, Rats, Real-Time Polymerase Chain Reaction
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