Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

SIRT1 in the BNST modulates chronic stress-induced anxiety of male mice via FKBP5 and corticotropin-releasing factor signaling

Molecular Psychiatry volume 28, pages 5101–5117 (2023)Cite this article

Subjects

Abstract

Although clinical reports have highlighted association of the deacetylase sirtuin 1 (SIRT1) gene with anxiety, its exact role in the pathogenesis of anxiety disorders remains unclear. The present study was designed to explore whether and how SIRT1 in the mouse bed nucleus of the stria terminalis (BNST), a key limbic hub region, regulates anxiety. In a chronic stress model to induce anxiety in male mice, we used site- and cell-type-specific in vivo and in vitro manipulations, protein analysis, electrophysiological and behavioral analysis, in vivo MiniScope calcium imaging and mass spectroscopy, to characterize possible mechanism underlying a novel anxiolytic role for SIRT1 in the BNST. Specifically, decreased SIRT1 in parallel with increased corticotropin-releasing factor (CRF) expression was found in the BNST of anxiety model mice, whereas pharmacological activation or local overexpression of SIRT1 in the BNST reversed chronic stress-induced anxiety-like behaviors, downregulated CRF upregulation, and normalized CRF neuronal hyperactivity. Mechanistically, SIRT1 enhanced glucocorticoid receptor (GR)-mediated CRF transcriptional repression through directly interacting with and deacetylating the GR co-chaperone FKBP5 to induce its dissociation from the GR, ultimately downregulating CRF. Together, this study unravels an important cellular and molecular mechanism highlighting an anxiolytic role for SIRT1 in the mouse BNST, which may open up new therapeutic avenues for treating stress-related anxiety disorders.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Anxiety-like behaviors accompanied by increased corticotropin-releasing factor (CRF) and decreased SIRT1 expression in the BNST of chronic unpredictable mild stress (CUMS)-exposed mice.
Fig. 2: Pharmacologically activating SIRT1 or viral-mediated local overexpression of SIRT1 in the BNST reverses the anxiety phenotype of CUMS mice.
Fig. 3: Downregulation of CRF is required for the anxiolytic phenotype induced by SIRT1 overexpression.
Fig. 4: SIRT1 overexpression normalizes the hyperactivity of CRF neurons in the BNST of chronically stressed mice, which are recruited during anxiogenic behaviors.
Fig. 5: SIRT1 enhances GRα-mediated transcriptional repression of CRF.
Fig. 6: SIRT1 promotes FKBP5 deacetylation to facilitate its dissociation from GR.

Similar content being viewed by others

References

  1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:593–602.

    PubMed  Google Scholar 

  2. Joels M, Baram TZ. The neuro-symphony of stress. Nat Rev Neurosci. 2009;10:459–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Lucassen PJ, Pruessner J, Sousa N, Almeida OF, Van Dam AM, Rajkowska G, et al. Neuropathology of stress. Acta Neuropathol. 2014;127:109–35.

    CAS  PubMed  Google Scholar 

  4. Gao J, Wang WY, Mao YW, Graff J, Guan JS, Pan L, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature. 2010;466:1105–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Michan S, Li Y, Chou MM, Parrella E, Ge H, Long JM, et al. SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci. 2010;30:9695–707.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Herskovits AZ, Guarente L. SIRT1 in neurodevelopment and brain senescence. Neuron. 2014;81:471–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Kim HD, Hesterman J, Call T, Magazu S, Keeley E, Armenta K, et al. SIRT1 mediates depression-like behaviors in the nucleus accumbens. J Neurosci. 2016;36:8441–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Abe-Higuchi N, Uchida S, Yamagata H, Higuchi F, Hobara T, Hara K, et al. Hippocampal sirtuin 1 signaling mediates depression-like behavior. Biol Psychiatry. 2016;80:815–26.

    CAS  PubMed  Google Scholar 

  9. Lei Y, Wang J, Wang D, Li C, Liu B, Fang X, et al. SIRT1 in forebrain excitatory neurons produces sexually dimorphic effects on depression-related behaviors and modulates neuronal excitability and synaptic transmission in the medial prefrontal cortex. Mol Psychiatry. 2020;25:1094–111.

    CAS  PubMed  Google Scholar 

  10. Yu D, Homiack DR, Sawyer EJ, Schrader LA. BK channel deacetylation by SIRT1 in dentate gyrus regulates anxiety and response to stress. Commun Biol. 2018;1:82–95.

    PubMed  PubMed Central  Google Scholar 

  11. Libert S, Pointer K, Bell EL, Das A, Cohen DE, Asara JM, et al. SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive. Cell. 2011;147:1459–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhou C, Wu Y, Ding X, Shi N, Cai Y, Pan ZZ. SIRT1 decreases emotional pain vulnerability with associated CaMKIIalpha deacetylation in central amygdala. J Neurosci. 2020;40:2332–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Marcinkiewcz CA, Mazzone CM, D’Agostino G, Halladay LR, Hardaway JA, DiBerto JF, et al. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature. 2016;537:97–101.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Choi DC, Furay AR, Evanson NK, Ostrander MM, Ulrich-Lai YM, Herman JP. Bed nucleus of the stria terminalis subregions differentially regulate hypothalamic-pituitary-adrenal axis activity: implications for the integration of limbic inputs. J Neurosci. 2007;27:2025–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Duvarci S, Bauer EP, Pare D. The bed nucleus of the stria terminalis mediates inter-individual variations in anxiety and fear. J Neurosci. 2009;29:10357–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Kim SY, Adhikari A, Lee SY, Marshel JH, Kim CK, Mallory CS, et al. Diverging neural pathways assemble a behavioural state from separable features in anxiety. Nature. 2013;496:219–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Henckens M, Printz Y, Shamgar U, Dine J, Lebow M, Drori Y, et al. CRF receptor type 2 neurons in the posterior bed nucleus of the stria terminalis critically contribute to stress recovery. Mol Psychiatry. 2017;22:1691–1700.

    CAS  PubMed  Google Scholar 

  18. Hu P, Liu J, Maita I, Kwok C, Gu E, Gergues MM, et al. Chronic stress induces maladaptive behaviors by activating corticotropin-releasing hormone signaling in the mouse oval bed nucleus of the stria terminalis. J Neurosci. 2020;40:2519–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Willner P. The chronic mild stress (CMS) model of depression: history, evaluation and usage. Neurobiol Stress. 2017;6:78–93.

    PubMed  Google Scholar 

  20. Daniel SE, Rainnie DG. Stress modulation of opposing circuits in the bed nucleus of the stria terminalis. Neuropsychopharmacology. 2016;41:103–25.

    PubMed  Google Scholar 

  21. Muglia LJ, Jacobson L, Luedke C, Vogt SK, Schaefer ML, Dikkes P, et al. Corticotropin-releasing hormone links pituitary adrenocorticotropin gene expression and release during adrenal insufficiency. J Clin Invest. 2000;105:1269–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Young CE, Tong Q. Corticotropin releasing hormone signaling in the bed nuclei of the stria terminalis as a link to maladaptive behaviors. Front Neurosci. 2021;15:642379.

    PubMed  PubMed Central  Google Scholar 

  23. Binder EB. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology. 2009;34:S186–195.

    CAS  PubMed  Google Scholar 

  24. Touma C, Gassen NC, Herrmann L, Cheung-Flynn J, Bull DR, Ionescu IA, et al. FK506 binding protein 5 shapes stress responsiveness: modulation of neuroendocrine reactivity and coping behavior. Biol Psychiatry. 2011;70:928–36.

    CAS  PubMed  Google Scholar 

  25. Li H, Su P, Lai TK, Jiang A, Liu J, Zhai D, et al. The glucocorticoid receptor-FKBP51 complex contributes to fear conditioning and posttraumatic stress disorder. J Clin Invest. 2020;130:877–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Hausl AS, Balsevich G, Gassen NC, Schmidt MV. Focus on FKBP51: a molecular link between stress and metabolic disorders. Mol Metab. 2019;29:170–81.

    PubMed  PubMed Central  Google Scholar 

  27. Hu P, Maita I, Phan ML, Gu E, Kwok C, Dieterich A, et al. Early-life stress alters affective behaviors in adult mice through persistent activation of CRH-BDNF signaling in the oval bed nucleus of the stria terminalis. Transl Psychiatry. 2020;10:396.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Samuels BA, Anacker C, Hu A, Levinstein MR, Pickenhagen A, Tsetsenis T, et al. 5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response. Nat Neurosci. 2015;18:1606–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. File SE, Seth P. A review of 25 years of the social interaction test. Eur J Pharm. 2003;463:35–53.

    CAS  Google Scholar 

  30. Kaidanovich-Beilin O, Lipina T, Vukobradovic I, Roder J, Woodgett JR. Assessment of social interaction behaviors. J Vis Exp. 2011;25:2473.

    Google Scholar 

  31. Qi XR, Zhao J, Liu J, Fang H, Swaab DF, Zhou JN. Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders. Cereb Cortex. 2015;25:75–83.

    PubMed  Google Scholar 

  32. Hu P, Liu J, Zhao J, Qi XR, Qi CC, Lucassen PJ, et al. All-trans retinoic acid-induced hypothalamus-pituitary-adrenal hyperactivity involves glucocorticoid receptor dysregulation. Transl Psychiatry. 2013;3:e336.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Liang B, Zhang L, Barbera G, Fang W, Zhang J, Chen X, et al. Distinct and dynamic ON and OFF neural ensembles in the prefrontal cortex code social exploration. Neuron 2018;100:700–14 e709.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Chen P, Lou S, Huang ZH, Wang Z, Shan QH, Wang Y, et al. Prefrontal cortex corticotropin-releasing factor neurons control behavioral style selection under challenging situations. Neuron 2020;106:301–15 e307.

    CAS  PubMed  Google Scholar 

  35. Zhang X, Lei B, Yuan Y, Zhang L, Hu L, Jin S, et al. Brain control of humoral immune responses amenable to behavioural modulation. Nature. 2020;581:204–8.

    CAS  PubMed  Google Scholar 

  36. Zhou P, Resendez SL, Rodriguez-Romaguera J, Jimenez JC, Neufeld SQ, Giovannucci A, et al. Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data. Elife. 2018;7:1–37.

    CAS  Google Scholar 

  37. Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, et al. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science. 2006;311:864–8.

    CAS  PubMed  Google Scholar 

  38. Herman JP, Schafer MK, Thompson RC, Watson SJ. Rapid regulation of corticotropin-releasing hormone gene transcription in vivo. Mol Endocrinol. 1992;6:1061–9.

    CAS  PubMed  Google Scholar 

  39. van der Laan S, de Kloet ER, Meijer OC. Timing is critical for effective glucocorticoid receptor mediated repression of the cAMP-induced CRH gene. PLoS One. 2009;4:e4327.

    PubMed  PubMed Central  Google Scholar 

  40. Yamamori E, Iwasaki Y, Taguchi T, Nishiyama M, Yoshida M, Asai M, et al. Molecular mechanisms for corticotropin-releasing hormone gene repression by glucocorticoid in BE(2)C neuronal cell line. Mol Cell Endocrinol. 2007;264:142–8.

    CAS  PubMed  Google Scholar 

  41. Malkoski SP, Dorin RI. Composite glucocorticoid regulation at a functionally defined negative glucocorticoid response element of the human corticotropin-releasing hormone gene. Mol Endocrinol. 1999;13:1629–44.

    CAS  PubMed  Google Scholar 

  42. Scammell JG, Denny WB, Valentine DL, Smith DF. Overexpression of the FK506-binding immunophilin FKBP51 is the common cause of glucocorticoid resistance in three New World primates. Gen Comp Endocrinol. 2001;124:152–65.

    CAS  PubMed  Google Scholar 

  43. Liu T, Lin YH, Leng W, Jung SY, Zhang H, Deng M, et al. A divergent role of the SIRT1-TopBP1 axis in regulating metabolic checkpoint and DNA damage checkpoint. Mol Cell. 2014;56:681–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Yu J, Qin B, Wu F, Qin S, Nowsheen S, Shan S, et al. Regulation of serine-threonine kinase akt activation by NAD(+)-dependent deacetylase SIRT7. Cell Rep. 2017;18:1229–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Yang XJ. The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases. Nucleic Acids Res. 2004;32:959–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Lv Y, Chen P, Shan QH, Qin XY, Qi XH, Zhou JN. Regulation of cued fear expression via corticotropin-releasing-factor neurons in the ventral anteromedial thalamic nucleus. Neurosci Bull. 2021;37:217–28.

    CAS  PubMed  Google Scholar 

  47. Wang T, Ma YN, Zhang CC, Liu X, Sun YX, Wang HL, et al. The nucleus accumbens CRH-CRHR1 system mediates early-life stress-induced sleep disturbance and dendritic atrophy in the adult mouse. Neurosci Bull. 2023;39:41–56.

    CAS  PubMed  Google Scholar 

  48. Hausl AS, Brix LM, Hartmann J, Pohlmann ML, Lopez JP, Menegaz D, et al. The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus of male mice. Mol Psychiatry. 2021;26:3060–76.

    PubMed  PubMed Central  Google Scholar 

  49. Engelhardt C, Tang F, Elkhateib R, Bordes J, Brix LM, van Doeselaar L, et al. FKBP51 in the oval bed nucleus of the stria terminalis regulates anxiety-like behavior. eNeuro. 2021;8:0425–0421.

    Google Scholar 

  50. Hartmann J, Bajaj T, Klengel C, Chatzinakos C, Ebert T, Dedic N, et al. Mineralocorticoid receptors dampen glucocorticoid receptor sensitivity to stress via regulation of FKBP5. Cell Rep. 2021;35:109185.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010;5:253–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Jimenez JC, Su K, Goldberg AR, Luna VM, Biane JS, Ordek G, et al. Anxiety cells in a hippocampal-hypothalamic circuit. Neuron. 2018;97:670–83 e676.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Leonardo ED, Hen R. Genetics of affective and anxiety disorders. Annu Rev Psychol. 2006;57:117–37.

    CAS  PubMed  Google Scholar 

  54. Wang L, Shen M, Jiang C, Ma L, Wang F. Parvalbumin interneurons of central amygdala regulate the negative affective states and the expression of corticotrophin-releasing hormone during morphine withdrawal. Int J Neuropsychopharmacol. 2016;19:pyw060.

    PubMed  PubMed Central  Google Scholar 

  55. Soden ME, Yee JX, Cuevas B, Rastani A, Elum J, Zweifel LS. Distinct encoding of reward and aversion by peptidergic BNST inputs to the VTA. Front Neural Circuits. 2022;16:918839.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Dabrowska J, Martinon D, Moaddab M, Rainnie DG. Targeting corticotropin-releasing factor projections from the oval nucleus of the bed nucleus of the stria terminalis using cell-type specific neuronal tracing studies in mouse and rat brain. J Neuroendocrinol. 2016;28. https://doi.org/10.1111/jne.12442.

  57. Giardino WJ, Eban-Rothschild A, Christoffel DJ, Li SB, Malenka RC, de Lecea L. Parallel circuits from the bed nuclei of stria terminalis to the lateral hypothalamus drive opposing emotional states. Nat Neurosci. 2018;21:1084–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Nguyen AQ, Dela Cruz JA, Sun Y, Holmes TC, Xu X. Genetic cell targeting uncovers specific neuronal types and distinct subregions in the bed nucleus of the stria terminalis. J Comp Neurol. 2016;524:2379–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Gray JM, Vecchiarelli HA, Morena M, Lee TT, Hermanson DJ, Kim AB, et al. Corticotropin-releasing hormone drives anandamide hydrolysis in the amygdala to promote anxiety. J Neurosci. 2015;35:3879–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Reyes BAS, Carvalho AF, Szot P, Kalamarides DJ, Wang Q, Kirby LG, et al. Cortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion. Exp Neurol. 2017;292:179–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Natividad LA, Buczynski MW, Herman MA, Kirson D, Oleata CS, Irimia C, et al. Constitutive increases in amygdalar corticotropin-releasing factor and fatty acid amide hydrolase drive an anxious phenotype. Biol Psychiatry. 2017;82:500–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Henckens MJ, Deussing JM, Chen A. Region-specific roles of the corticotropin-releasing factor-urocortin system in stress. Nat Rev Neurosci. 2016;17:636–51.

    CAS  PubMed  Google Scholar 

  63. Ramot A, Jiang Z, Tian JB, Nahum T, Kuperman Y, Justice N, et al. Hypothalamic CRFR1 is essential for HPA axis regulation following chronic stress. Nat Neurosci. 2017;20:385–8.

    CAS  PubMed  Google Scholar 

  64. Sink KS, Walker DL, Freeman SM, Flandreau EI, Ressler KJ, Davis M. Effects of continuously enhanced corticotropin releasing factor expression within the bed nucleus of the stria terminalis on conditioned and unconditioned anxiety. Mol Psychiatry. 2013;18:308–19.

    CAS  PubMed  Google Scholar 

  65. Silberman Y, Winder DG. Emerging role for corticotropin releasing factor signaling in the bed nucleus of the stria terminalis at the intersection of stress and reward. Front Psychiatry. 2013;4:1–12.

    Google Scholar 

  66. Zhou JN, Hofman MA, Gooren LJ, Swaab DF. A sex difference in the human brain and its relation to transsexuality. Nature. 1995;378:68–70.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Prof.Dr. Paul J. Lucassen (University of Amsterdam, The Netherlands) for editing the manuscript and providing helpful suggestions; Dr. Troy A. Roepke (Rutgers University, NJ, USA), Dr. Tao Zhang (Johns Hopkins University School of Medicine, MD, USA), Dr. Li-Feng Zhang (PKU-Nanjing Institute of Translational Medicine, Nanjing, China), and Prof. Guang-Hui Wang (Soochow University, Suzhou, China), for technical consultation; and thank Mr. Zhen-Bang Liu; Dr. Hui Fang; Dr. Chuan Huang; Dr. Xin-Ya Qin; Dr. Chen-Wei Wang; Dr. Gao Wu; (all from USTC); Mr. Meng-Cheng Huang (Shanghai Applied Protein Technology Co. Ltd, Shanghai, China); and Dr. Hui Gong (Huazhong University of Science and Technology, Wuhan, China) for technical support. We thank Dr. Wu Zhang and Mr. Hong-Jun Liu from Brain VTA ltd (Wuhan, China) for consultation of virus information. We thank Dr. Minmin Luo (NIBS Institute, Beijing, China) for providing the Ai14-reporter mice line. We also thank Dr. Yan-Yan Su from Anhui Medical University for graphical assistance.

Funding

This work was supported by National Science Foundation of China (Grant No. 32030046; 32000716; 82271554; 82201671), the Strategic Priority Research Program of the Chinese Academy of Science (Grant No. XDB32020200), the National Key R&D Program of China (Grant No. 2022ZD0205202), the Key Direction Cultivation Funding from the University of Science and Technology of China (Grant No. WK3460000007).

Author information

Author notes

  1. These authors contributed equally: Pu Hu, Yu Wang.

Authors and Affiliations

  1. Hefei National Research Center for Physical Sciences at the Microscale, Chinese Academy of Sciences Key Laboratory of Brain Function and Diseases, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, PR China

    Pu Hu, Xiu-Hong Qi, Xiao Ma, Yu-Peng Yang & Zhi Zhang

  2. Institute of Brain Science, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China

    Yu Wang, Qing-Hong Shan, Peng Chen & Jiang-Ning Zhou

  3. National Engineering Laboratory for Brain-inspired Intelligence Technology and Application, School of Information Science and Technology, University of Science and Technology of China, Hefei, 230026, Anhui, China

    Zhao-Huan Huang

  4. Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, 230026, China

    Zhao-Huan Huang

  5. Department of Neuropsychiatric Disorders, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands

    Dick F. Swaab

  6. Department of Psychology, Rutgers University, Piscataway, NJ, 08854, USA

    Benjamin A. Samuels

  7. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200072, PR China

    Jiang-Ning Zhou

Authors
  1. Pu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiu-Hong Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing-Hong Shan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhao-Huan Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiao Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yu-Peng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dick F. Swaab
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Benjamin A. Samuels
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jiang-Ning Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PH and JNZ conceptualized the study. PH and YW designed experiments. PH and YW conducted experiments and analyzed data. XHQ helped with cell culture and molecular experiments and analyzed data. QHS helped with electrophysiological recording and calcium imaging data analysis. ZHH and PC contributed reagents and provided transgenic mice line. XM helped with calcium imaging data analysis. YPY and ZZ contributed reagents and provided helpful suggestions to the manuscript. PH wrote the paper together with JNZ with inputs from all co-authors. DFS, BAS and ZZ edited and revised the manuscript and provided helpful suggestions. All authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Pu Hu or Jiang-Ning Zhou.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, P., Wang, Y., Qi, XH. et al. SIRT1 in the BNST modulates chronic stress-induced anxiety of male mice via FKBP5 and corticotropin-releasing factor signaling. Mol Psychiatry 28, 5101–5117 (2023). https://doi.org/10.1038/s41380-023-02144-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-023-02144-6

Search

Advanced search

Quick links