Abstract
The circadian clock governs multiple biological functions at the molecular level and plays an essential role in providing temporal diversity of behavior and physiology including neuronal activity. Studies spanning the past two decades have deciphered the molecular mechanisms of the circadian clock, which appears to operate as an essential interface in linking cellular metabolism to epigenetic control. Accumulating evidence illustrates that disruption of circadian rhythms through jet lag, shift work, and temporary irregular life-style could lead to depression-like symptoms. Remarkably, abnormal neuronal activity and depression-like behavior appear in animals lacking elements of the molecular clock. Recent studies demonstrate that neuronal and synaptic gene induction is under epigenetic control, and robust epigenetic remodeling is observed under depression and related psychiatric disorders. Thus, the intertwined links between the circadian clock and epigenetics may point to novel approaches for antidepressant treatments, epigenetic therapy, and chronotherapy. In this chapter we summarize how the circadian clock is involved in neuronal functions and depressive-like behavior and propose that potential strategies for antidepressant therapy by incorporating circadian genomic and epigenetic rewiring of neuronal signaling pathways.
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References
Abe-Higuchi N et al (2016) Hippocampal Sirtuin 1 signaling mediates depression-like behavior. Biol Psychiatry 80:815–826. https://doi.org/10.1016/j.biopsych.2016.01.009
Aguilar-Arnal L, Katada S, Orozco-Solis R, Sassone-Corsi P (2015) NAD(+)-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1. Nat Struct Mol Biol 22:312–318. https://doi.org/10.1038/nsmb.2990
Asher G, Sassone-Corsi P (2015) Time for food: the intimate interplay between nutrition, metabolism, and the circadian clock. Cell 161:84–92. https://doi.org/10.1016/j.cell.2015.03.015
Bellet MM, Vawter MP, Bunney BG, Bunney WE, Sassone-Corsi P (2011) Ketamine influences CLOCK:BMAL1 function leading to altered circadian gene expression. PLoS One 6:e23982. https://doi.org/10.1371/journal.pone.0023982
Benedetti F, Smeraldi E (2009) Neuroimaging and genetics of antidepressant response to sleep deprivation: implications for drug development. Curr Pharm Des 15:2637–2649
Benito E et al (2015) HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models. J Clin Invest 125:3572–3584. https://doi.org/10.1172/jci79942
Berger SL, Sassone-Corsi P (2016) Metabolic signaling to chromatin. Cold Spring Harb Perspect Biol 8(11):a019463. https://doi.org/10.1101/cshperspect.a019463
Berson DM, Dunn FA, Takao M (2002) Phototransduction by retinal ganglion cells that set the circadian clock. Science 295:1070–1073. https://doi.org/10.1126/science.1067262
Bigio B, Mathe AA, Sousa VC, Zelli D, Svenningsson P, McEwen BS, Nasca C (2016) Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: implications for treatment resistance. Proc Natl Acad Sci U S A 113:7906–7911. https://doi.org/10.1073/pnas.1603111113
Borrelli E, Nestler EJ, Allis CD, Sassone-Corsi P (2008) Decoding the epigenetic language of neuronal plasticity. Neuron 60:961–974. https://doi.org/10.1016/j.neuron.2008.10.012
Bunney BG, Bunney WE (2013) Mechanisms of rapid antidepressant effects of sleep deprivation therapy: clock genes and circadian rhythms. Biol Psychiatry 73:1164–1171. https://doi.org/10.1016/j.biopsych.2012.07.020
Chawla S, Vanhoutte P, Arnold FJ, Huang CL, Bading H (2003) Neuronal activity-dependent nucleocytoplasmic shuttling of HDAC4 and HDAC5. J Neurochem 85:151–159
Choi M et al (2015) Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats. Proc Natl Acad Sci U S A 112:15755–15760. https://doi.org/10.1073/pnas.1513913112
Covington HE 3rd et al (2009) Antidepressant actions of histone deacetylase inhibitors. J Neurosci 29:11451–11460. https://doi.org/10.1523/jneurosci.1758-09.2009
Covington HE 3rd, Vialou VF, LaPlant Q, Ohnishi YN, Nestler EJ (2011) Hippocampal-dependent antidepressant-like activity of histone deacetylase inhibition. Neurosci Lett 493:122–126
Dallaspezia S, Benedetti F (2011) Chronobiological therapy for mood disorders. Expert Rev Neurother 11:961–970. https://doi.org/10.1586/ern.11.61
Dallaspezia S, Suzuki M, Benedetti F (2015) Chronobiological therapy for mood disorders. Curr Psychiatry Rep 17:95. https://doi.org/10.1007/s11920-015-0633-6
Deussing JM, Jakovcevski M (2017) Histone modifications in major depressive disorder and related rodent models. Adv Exp Med Biol 978:169–183. https://doi.org/10.1007/978-3-319-53889-1_9
Doi M, Hirayama J, Sassone-Corsi P (2006) Circadian regulator CLOCK is a histone acetyltransferase. Cell 125:497–508. https://doi.org/10.1016/j.cell.2006.03.033
Erburu M, Munoz-Cobo I, Diaz-Perdigon T, Mellini P, Suzuki T, Puerta E, Tordera RM (2017) SIRT2 inhibition modulate glutamate and serotonin systems in the prefrontal cortex and induces antidepressant-like action. Neuropharmacology 117:195–208. https://doi.org/10.1016/j.neuropharm.2017.01.033
Ezagouri S et al (2019) Physiological and molecular dissection of daily variance in exercise capacity. Cell Metab 30:78–91.e74. https://doi.org/10.1016/j.cmet.2019.03.012
Fuchikami M, Morinobu S, Kurata A, Yamamoto S, Yamawaki S (2009) Single immobilization stress differentially alters the expression profile of transcripts of the brain-derived neurotrophic factor (BDNF) gene and histone acetylation at its promoters in the rat hippocampus. Int J Neuropsychopharmacol 12:73–82. https://doi.org/10.1017/s1461145708008997
Gallegos DA, Chan U, Chen LF, West AE (2018) Chromatin regulation of neuronal maturation and plasticity. Trends Neurosci 41:311–324. https://doi.org/10.1016/j.tins.2018.02.009
Germain A, Kupfer DJ (2008) Circadian rhythm disturbances in depression human. Psychopharmacology 23:571–585. https://doi.org/10.1002/hup.964
Greco CM, Sassone-Corsi P (2018) Circadian blueprint of metabolic pathways in the brain. Nature Rev Neurosci 20:71–82. https://doi.org/10.1038/s41583-018-0096-y
Green CB, Takahashi JS, Bass J (2008) The meter of metabolism. Cell 134:728–742. https://doi.org/10.1016/j.cell.2008.08.022
Han A, Sung Y-B, Chung S-Y, Kwon M-S (2014) Possible additional antidepressant-like mechanism of sodium butyrate: Targeting the hippocampus. Neuropharmacology 81:292–302
Hinwood M, Tynan RJ, Day TA, Walker FR (2011) Repeated social defeat selectively increases deltaFosB expression and histone H3 acetylation in the infralimbic medial prefrontal cortex. Cerebral Cortex (New York, NY: 1991) 21:262–271. https://doi.org/10.1093/cercor/bhq080
Jiang WG et al (2013) Hippocampal CLOCK protein participates in the persistence of depressive-like behavior induced by chronic unpredictable stress. Psychopharmacology 227:79–92. https://doi.org/10.1007/s00213-012-2941-4
Katada S, Sassone-Corsi P (2010) The histone methyltransferase MLL1 permits the oscillation of circadian gene expression. Nat Struct Mol Biol 17:1414–1421. https://doi.org/10.1038/nsmb.1961
Kenworthy CA, Sengupta A, Luz SM, Ver Hoeve ES, Meda K, Bhatnagar S, Abel T (2014) Social defeat induces changes in histone acetylation and expression of histone modifying enzymes in the ventral hippocampus, prefrontal cortex, and dorsal raphe nucleus. Neuroscience 264:88–98. https://doi.org/10.1016/j.neuroscience.2013.01.024
Khalifeh AH (2017) The effect of chronotherapy on depressive symptoms. Evidence-based practice. Saudi Med J 38:457–464. https://doi.org/10.15537/smj.2017.5.18062
Koike N, Yoo SH, Huang HC, Kumar V, Lee C, Kim TK, Takahashi JS (2012) Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science 338:349–354. https://doi.org/10.1126/science.1226339
Landgraf D, Long JE, Proulx CD, Barandas R, Malinow R, Welsh DK (2016) Genetic disruption of circadian rhythms in the suprachiasmatic nucleus causes helplessness, behavioral despair, and anxiety-like. Behavior in Mice Biol Psychiatry 80:827–835. https://doi.org/10.1016/j.biopsych.2016.03.1050
Lee IT et al (2015) Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms. Neuron 85:1086–1102. https://doi.org/10.1016/j.neuron.2015.02.006
LeGates TA, Fernandez DC, Hattar S (2014) Light as a central modulator of circadian rhythms, sleep and affect nature reviews. Neuroscience 15:443–454. https://doi.org/10.1038/nrn3743
Li JZ et al (2013) Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. Proc Natl Acad Sci U S A 110:9950–9955. https://doi.org/10.1073/pnas.1305814110
Lin H, Geng X, Dang W, Wu B, Dai Z, Li Y, Yang Y, Zhang H, Shi J (2012) Molecular mechanisms associated with the antidepressant effects of the class I histone deacetylase inhibitor MS-275 in the rat ventrolateral orbital cortex. Brain Res 1447:119–125
Lockley SW, Brainard GC, Czeisler CA (2003) High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light. J Clin Endocrinol Metab 88:4502–4505. https://doi.org/10.1210/jc.2003-030570
Lyall LM et al (2018) Association of disrupted circadian rhythmicity with mood disorders, subjective wellbeing, and cognitive function: a cross-sectional study of 91 105 participants from the UK biobank the lancet psychiatry. Lancet Psychiatry 5(6):507–514. https://doi.org/10.1016/s2215-0366(18)30139-1
Mahan AL, Mou L, Shah N, Hu JH, Worley PF, Ressler KJ (2012) Epigenetic modulation of Homer1a transcription regulation in amygdala and hippocampus with pavlovian fear conditioning. J Neurosci 32:4651–4659. https://doi.org/10.1523/jneurosci.3308-11.2012
Mahgoub M, Monteggia LM (2013) Epigenetics and psychiatry. Neurotherapeutics : The Journal of the American Society for Experimental Neurotherapeutics 10:734–741. https://doi.org/10.1007/s13311-013-0213-6
Masri S, Sassone-Corsi P (2014) Sirtuins and the circadian clock: bridging chromatin and metabolism. Sci Signal 7:re6
Masri S, Sassone-Corsi P (2018) The emerging link between cancer, metabolism, and circadian rhythms. Nat Med 24:1795–1803. https://doi.org/10.1038/s41591-018-0271-8
Mongrain V, La Spada F, Curie T, Franken P (2011) Sleep loss reduces the DNA-binding of BMAL1, CLOCK, and NPAS2 to specific clock genes in the mouse cerebral cortex. PLoS One 6:e26622. https://doi.org/10.1371/journal.pone.0026622
Montagud-Romero S et al (2016) Up-regulation of histone acetylation induced by social defeat mediates the conditioned rewarding effects of cocaine. Prog Neuro-Psychopharmacol Biol Psychiatry 70:39–48. https://doi.org/10.1016/j.pnpbp.2016.04.016
Nagy C, Vaillancourt K, Turecki G (2018) A role for activity-dependent epigenetics in the development and treatment of major depressive disorder. Genes Brain Behav 17:e12446. https://doi.org/10.1111/gbb.12446
Nakahata Y et al (2008) The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134:329–340. https://doi.org/10.1016/j.cell.2008.07.002
Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P (2009) Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324:654–657
Nasca C et al (2013) L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. Proc Natl Acad Sci U S A 110:4804–4809. https://doi.org/10.1073/pnas.1216100110
Ohdo S (2010) Chronotherapeutic strategy: rhythm monitoring, manipulation and disruption. Adv Drug Deliv Rev 62:859–875. https://doi.org/10.1016/j.addr.2010.01.006
Orozco-Solis R et al (2017) A circadian genomic signature common to ketamine and sleep deprivation in the anterior cingulate cortex. Biol Psychiatry 82:351–360. https://doi.org/10.1016/j.biopsych.2017.02.1176
Panda S (2016) Circadian physiology of metabolism. Science 354:1008–1015. https://doi.org/10.1126/science.aah4967
Patke A, Murphy PJ, Onat OE, Krieger AC, Ozcelik T, Campbell SS, Young MW (2017) Mutation of the human circadian clock gene CRY1 in familial delayed sleep phase disorder. Cell 169:203–215.e213. https://doi.org/10.1016/j.cell.2017.03.027
Ramsey KM et al (2009) Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324:651–654. https://doi.org/10.1126/science.1171641
Rosenthal NE et al (1984) Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy Archives of general psychiatry 41:72–80
Sato S, Sassone-Corsi P (2019) Circadian and epigenetic control of depression-like behaviors. Curr Opin Behav Sci 25:15–22. https://doi.org/10.1016/j.cobeha.2018.05.010
Sato S et al (2017) Circadian reprogramming in the liver identifies metabolic pathways of aging. Cell 170:664–677. e611. https://doi.org/10.1016/j.cell.2017.07.042
Sato S et al (2019) Time of exercise specifies the impact on muscle metabolic pathways and systemic energy homeostasis. Cell Metab 30(1):92–110.e4. https://doi.org/10.1016/j.cmet.2019.03.013
Sato S, Bunney BG, Vawter MP, Bunney WE, Sassone-Corsi P (2020) Homer1a undergoes bimodal transcriptional regulation by CREB and the circadian clock. Neuroscience 434:161–170. https://doi.org/10.1016/j.neuroscience.2020.03.031
Schmauss C (2015) An HDAC-dependent epigenetic mechanism that enhances the efficacy of the antidepressant drug fluoxetine. Sci Rep 5(1)
Schroeder FA, Lin CL, Crusio WE, Akbarian S (2007) Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. Biol Psychiatry 62(1):55–64
Shen EY et al (2016) Neuronal deletion of Kmt2a/Mll1 histone methyltransferase in ventral striatum is associated with defective spike-timing-dependent striatal synaptic plasticity, altered response to dopaminergic drugs, and increased anxiety. Neuropsychopharmacology 41:3103–3113. https://doi.org/10.1038/npp.2016.144
Shimazu T et al (2013) Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339:211–214. https://doi.org/10.1126/science.1227166
Sleiman SF et al (2016) Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body beta-hydroxybutyrate. eLife 5:e15092. https://doi.org/10.7554/eLife.15092
Takahashi JS (2017) Transcriptional architecture of the mammalian circadian clock nature reviews. Genetics 18:164–179. https://doi.org/10.1038/nrg.2016.150
Tognini P et al (2017) Distinct circadian signatures in liver and gut clocks revealed by ketogenic. Diet Cell Metab 26(523–538):e525. https://doi.org/10.1016/j.cmet.2017.08.015
Top D, Young MW (2017) Coordination between differentially regulated circadian clocks generates rhythmic behavior. Cold Spring Harb Perspect Biol 10(7):a033589. https://doi.org/10.1101/cshperspect.a033589
Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525. https://doi.org/10.1038/nn1659
Uchida S, Hara K, Kobayashi A, Otsuki K, Yamagata H, Hobara T, Suzuki T, Miyata N, Watanabe Y (2011) Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events. Neuron 69(2):359–372
Wang J et al (2018) Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice. Nat Commun 9:477. https://doi.org/10.1038/s41467-017-02794-5
Wray NR et al (2018) Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet 50:668–681. https://doi.org/10.1038/s41588-018-0090-3
Yamawaki Y, Fuchikami M, Morinobu S, Segawa M, Matsumoto T, Yamawaki S (2012) Antidepressant-like effect of sodium butyrate (HDAC inhibitor) and its molecular mechanism of action in the rat hippocampus. World J Biol Psychiatry 13(6):458–467
Zaki NFW, Spence DW, BaHammam AS, Pandi-Perumal SR, Cardinali DP, Brown GM (2018) Chronobiological theories of mood disorder. Eur Arch Psychiatry Clin Neurosci 268:107–118. https://doi.org/10.1007/s00406-017-0835-5
Zhang Y, Liu C, Zhao Y, Zhang X, Li B, Cui R (2015) The effects of calorie restriction in depression and potential mechanisms. Curr Neuropharmacol 13:536–542
Acknowledgments
We are grieved by the unexpected loss of Prof. Paolo Sassone-Corsi. It has been an honor and pleasure to have had the opportunity to work with him on this book chapter. We thank all the members of the Sassone-Corsi lab for useful discussions and support. S.S. is supported by the Brain & Behavioral Research Foundation (NARSAD Young Investigator Grant 28681).
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Sato, S., Sassone-Corsi, P. (2021). Linking Depression to Epigenetics: Role of the Circadian Clock. In: Engmann, O., Brancaccio, M. (eds) Circadian Clock in Brain Health and Disease. Advances in Experimental Medicine and Biology, vol 1344. Springer, Cham. https://doi.org/10.1007/978-3-030-81147-1_3
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