Epigenetic Targeting of Histone Deacetylases in Diagnostics and Treatment of Depression
Abstract
:1. Introduction
2. Histone Acetylation
3. Histone Deacetylase (HDAC) Families and Classes
4. HDAC and Depression
5. HDAC and the Hypothalamic-Pituitary-Adrenal (HPA) Axis
6. HDAC and Brain-Derived Neurotrophic Factor
7. HDAC and Neuronal Plasticity
8. Molecular Diagnosis of Depression: An Epigenetic Perspective
9. Molecular Therapeutics of Depression: An Epigenetic Perspective
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed.; American Psychiatric Association: Arlington, VA, USA, 2013. [Google Scholar]
- Burcusa, S.L.; Iacono, W.G. Risk for recurrence in depression. Clin. Psychol. Rev. 2007, 27, 959–985. [Google Scholar] [CrossRef] [Green Version]
- Liu, Q.; He, H.; Yang, J.; Feng, X.; Zhao, F.; Lyu, J. Changes in the global burden of depression from 1990 to 2017: Findings from the Global Burden of Disease study. J. Psychiatry Res. 2020, 126, 134–140. [Google Scholar] [CrossRef] [PubMed]
- Cipriani, A.; Furukawa, T.A.; Salanti, G.; Chaimani, A.; Atkinson, L.Z.; Ogawa, Y.; Levcht, S.; Ruhe, H.G.; Turner, E.H.; Higgins, J.P.T.; et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. Lancet 2018, 391, 1357–1366. [Google Scholar] [CrossRef] [Green Version]
- Calabro, M.; Fabbri, C.; Kasper, S.; Zohar, J.; Souery, D.; Montgomery, S.; Albani, D.; Forloni, G.; Ferentinos, P.; Rujescu, D.; et al. Research Domain Criteria (RDoC): A Perspective to Probe the Biological Background behind Treatment Efficacy in Depression. Curr. Med. Chem. 2021, 28, 1–23. [Google Scholar] [CrossRef] [PubMed]
- Insel, T.; Cuthbert, B.; Garvey, M.; Heinssen, R.; Pine, D.S.; Quinn, K.; Sanislow, C.; Wang, P. Research Domain Criteria (RDoC): Toward a New Classification Framework for Research on Mental Disorders. Am. J. Psychiatry 2010, 167, 748–751. [Google Scholar] [CrossRef] [Green Version]
- Bruckl, T.M.; Spoormaker, V.I.; Samann, P.G.; Brem, A.-K.; Henco, L.; Czamara, D.; Elbau, I.; Grandi, N.C.; Jollans, L.; Kuhnel, A.; et al. The biological classification of mental disorders (BeCOME) study: A protocol for an observational deep-phenotyping study for the identification of biological subtypes. BMC Psychiatry 2020, 20, 213. [Google Scholar] [CrossRef]
- Krishnan, V.; Nestler, E.J. The molecular neurobiology of depression. Nature 2008, 455, 894–902. [Google Scholar] [CrossRef]
- Hasler, G. Pathophysiology of depression: Do we have any solid evidence of interest to clinicians? World Psychiatry 2010, 9, 155–161. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Krishnan, V.; Nestler, E.J. Linking Molecules to Mood: New Insight Into the Biology of Depression. Am. J. Psychiatry 2010, 167, 1305–1320. [Google Scholar] [CrossRef] [Green Version]
- Schlaepfer, T.E.; Cohen, M.X.; Frick, C.; Kosel, M.M.; Brodesser, D.; Axmacher, N.; Joe, A.Y.; Kreft, M.; Lenartz, D.; Sturm, V. Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression. Neuropsychopharmacology 2007, 33, 368–377. [Google Scholar] [CrossRef]
- Price, J.L.; Drevets, W.C. Neural circuits underlying the pathophysiology of mood disorders. Trends Cogn. Sci. 2012, 16, 61–71. [Google Scholar] [CrossRef]
- Clapp, M.; Aurora, N.; Herrera, L.; Bhatia, M.; Wilen, E.; Wakefield, S. Gut Microbiota’s Effect on Mental Health: The Gut-Brain Axis. Clin. Pract. 2017, 7, 131–136. [Google Scholar] [CrossRef] [PubMed]
- Wallace, C.J.K.; Milev, R. The effects of probiotics on depressive symptoms in humans: A systematic review. Ann. Gen. Psychiatry 2017, 16, 14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Black, C.N.; Bot, M.; Scheffer, P.G.; Penninx, B.W.J.H. Oxidative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort. Psychol. Med. 2017, 47, 936–948. [Google Scholar] [CrossRef] [Green Version]
- Navarrete, F.; Garcia-Gutierrez, M.S.; Jurado-Barba, R.; Rubio, G.; Gasparyan, A.; Austrich-Olivares, A.; Manzanares, J. Endocannabinoid System Components as Potential Biomarkers in Psychiatry. Front. Psychiatry 2020, 11, 315. [Google Scholar] [CrossRef] [PubMed]
- Kennis, M.; Gerritsen, L.; Van Dalen, M.; Williams, A.; Cuijpers, P.; Bockting, C. Prospective biomarkers of major depressive disorder: A systematic review and meta-analysis. Mol. Psychiatry 2020, 25, 321–338. [Google Scholar] [CrossRef] [Green Version]
- Opel, N.; Cearns, M.; Clark, S.; Toben, C.; Grotegerd, D.; Heindel, W.; Kugel, H.; Teuber, A.; Minnerup, H.; Berger, K.; et al. Large-scale evidence for an association between low-grade peripheral inflammation and brain structural alterations in major depression in the BiDirect study. J. Psychiatry Neurosci. 2019, 44, 423–431. [Google Scholar] [CrossRef] [Green Version]
- Green, C.; Shen, X.; Stevenson, A.J.; Conole, E.L.; Harris, M.A.; Barbu, M.C.; Hawkins, E.L.; Adams, M.J.; Hillary, R.F.; Lawrie, S.M.; et al. Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder. Brain Behav. Immun. 2021, 92, 39–48. [Google Scholar] [CrossRef]
- Sullivan, P.F.; Neale, M.C.; Kendler, K.S. Genetic Epidemiology of Major Depression: Review and Meta-Analysis. Am. J. Psychiatry 2000, 157, 1552–1562. [Google Scholar] [CrossRef]
- Bosker, F.J.; Hartman, C.A.; Nolte, I.M.; Prins, B.P.; Terpstra, P.; Posthuma, D.; van Veen, T.; Willemsen, G.; DeRijk, R.H.; de Geus, E.J.; et al. Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol. Psychiatry 2010, 16, 516–532. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wray, N.R.; Pergadia, M.L.; Blackwood, D.H.R.; Penninx, B.W.J.H.; Gordon, S.D.; Nyholt, D.R.; Ripke, S.; MacIntyre, D.J.; McGhee, K.A.; Maclean, A.W.; et al. Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned. Mol. Psychiatry 2010, 17, 36–48. [Google Scholar] [CrossRef] [Green Version]
- Uher, R.; Investigators, G.; Investigators, M.; Investigators, S.D. Common Genetic Variation and Antidepressant Efficacy in Major Depressive Disorder: A Meta-Analysis of Three Genome-Wide Pharmacogenetic Studies. Am. J. Psychiatry 2013, 170, 207–217. [Google Scholar]
- Cai, N.; Bigdeli, T.B.; Kretzschmar, W.; Li, Y.; Liang, J.; Song, L.; Hu, J.; Li, Q.; Jin, W.; Hu, Z.; et al. Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature 2015, 523, 588–591. [Google Scholar] [CrossRef] [PubMed]
- Okbay, A.; Baselmans, B.M.L.; De Neve, J.E.; Turley, P.; Nivard, M.G.; Fontana, M.A.; Meddens, S.F.W.; Linner, R.K.; Rietveld, C.A.; Derringer, J.; et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat. Genet. 2016, 48, 624–633. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hyde, C.L.; Nagle, M.W.; Tian, C.; Chen, X.; Paciga, S.A.; Wendland, J.R.; Tung, J.Y.; Hinds, D.A.; Perlis, R.H.; Winslow, A.R. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nat. Genet. 2016, 48, 1031–1036. [Google Scholar] [CrossRef] [PubMed]
- Lewis, C. Mega-Analysis of Genome-Wide Association Studies in Major Depressive Disorder: Mdd Working Group of the Psychiatric Genomics Consortium. Eur. Neuropsychopharm. 2017, 27, S119. [Google Scholar]
- Howard, D.M.; Adams, M.J.; Shirali, M.; Clarke, T.K.; Marioni, R.E.; Davies, G.; Coleman, J.R.I.; Alloza, C.; Shen, X.Y.; Barbu, M.C.; et al. Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways. Nat. Commun. 2018, 9, 1470. [Google Scholar] [CrossRef] [Green Version]
- Saveanu, R.V.; Nemeroff, C.B. Etiology of Depression: Genetic and Environmental Factors. Psychiatry Clin. N. Am. 2012, 35, 51–71. [Google Scholar] [CrossRef]
- Bruce, M.L. Psychosocial risk factors for depressive disorders in late life. Biol. Psychiatry 2002, 52, 175–184. [Google Scholar] [CrossRef]
- Cheptou, P.O.; Donohue, K. Epigenetics as a new avenue for the role of inbreeding depression in evolutionary ecology. Heredity 2013, 110, 205–206. [Google Scholar] [CrossRef] [Green Version]
- Shapero, B.G.; Black, S.K.; Liu, R.T.; Klugman, J.; Bender, R.E.; Abramson, L.Y.; Alloy, L.B. Stressful Life Events and Depression Symptoms: The Effect of Childhood Emotional Abuse on Stress Reactivity. J. Clin. Psychol. 2014, 70, 209–223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, H.; Kennedy, P.J.; Nestler, E.J. Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation. Neuropsychopharmacology 2013, 38, 124–137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, E.; Tsai, S.-J. Epigenetics and Depression: An Update. Psychiatry Investig. 2019, 16, 654–661. [Google Scholar] [CrossRef] [PubMed]
- Mill, J.; Petronis, A. Molecular studies of major depressive disorder: The epigenetic perspective. Mol. Psychiatry 2007, 12, 799–814. [Google Scholar] [CrossRef] [Green Version]
- O’Donnell, K.J.; Meaney, M.J. Epigenetics, Development, and Psychopathology. Annu. Rev. Clin. Psychol. 2020, 16, 327–350. [Google Scholar] [CrossRef] [Green Version]
- Meaney, M.J.; Ferguson-Smith, A.C. Epigenetic regulation of the neural transcriptome: The meaning of the marks. Nat. Neurosci. 2010, 13, 1313–1318. [Google Scholar] [CrossRef]
- Ciuculete, D.M.; Voisin, S.; Kular, L.; Jonsson, J.; Rask-Andersen, M.; Mwinyi, J.; Schioth, H.B. meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes. Clin. Epigenetics 2020, 12, 99. [Google Scholar] [CrossRef]
- Wade, P.A.; Pruss, D.; Wolffe, A.P. Histone acetylation: Chromatin in action. Trends Biochem. Sci. 1997, 22, 128–132. [Google Scholar] [CrossRef]
- Roth, S.Y.; Denu, J.M.; Allis, C.D. Histone Acetyltransferases. Annu. Rev. Biochem. 2001, 70, 81–120. [Google Scholar] [CrossRef]
- Marks, P.A.; Miller, T.; Richon, V.M. Histone deacetylases. Curr. Opin. Pharmacol. 2003, 3, 344–351. [Google Scholar] [CrossRef]
- Narita, T.; Weinert, B.T.; Choudhary, C. Functions and mechanisms of non-histone protein acetylation. Nat. Rev. Mol. Cell Bio. 2019, 20, 156–174. [Google Scholar] [CrossRef] [PubMed]
- Seto, E.; Yoshida, M. Erasers of Histone Acetylation: The Histone Deacetylase Enzymes. Cold Spring Harb. Perspect. Biol. 2014, 6, a018713. [Google Scholar] [CrossRef] [Green Version]
- Taunton, J.; Hassig, C.A.; Schreiber, S.L. A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p. Science 1996, 272, 408–411. [Google Scholar] [CrossRef] [PubMed]
- Ayer, D.E. Histone deacetylases: Transcriptional repression with SINers and NuRDs. Trends Cell Biol. 1999, 9, 193–198. [Google Scholar] [CrossRef]
- Wen, Y.D.; Perissi, V.; Staszewski, L.M.; Yang, W.M.; Krones, A.; Glass, C.K.; Rosenfeld, M.G.; Seto, E. The histone deacetylase-3 complex contains nuclear receptor corepressors. Proc. Natl. Acad. Sci. USA 2000, 97, 7202–7207. [Google Scholar] [CrossRef] [Green Version]
- Hu, E.; Chen, Z.X.; Fredrickson, T.; Zhu, Y.; Kirkpatrick, R.; Zhang, G.-F.; Johanson, K.; Sung, C.-M.; Liu, R.G.; Winkler, J. Cloning and Characterization of a Novel Human Class I Histone Deacetylase That Functions as a Transcription Repressor. J. Biol. Chem. 2000, 275, 15254–15264. [Google Scholar] [CrossRef] [Green Version]
- Grozinger, C.M.; Hassig, C.A.; Schreiber, S.L. Three proteins define a class of human histone deacetylases related to yeast Hda1p. Proc. Natl. Acad. Sci. USA 1999, 96, 4868–4873. [Google Scholar] [CrossRef] [Green Version]
- Muslin, A.J.; Xing, H.M. 14-3-3 proteins: Regulation of subcellular localization by molecular interference. Cell. Signal 2000, 12, 703–709. [Google Scholar] [CrossRef]
- Grozinger, C.M.; Schreiber, S.L. Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization. Proc. Natl. Acad. Sci. USA 2000, 97, 7835–7840. [Google Scholar] [CrossRef] [Green Version]
- Wang, A.H.; Kruhlak, M.J.; Wu, J.; Bertos, N.R.; Vezmar, M.; Posner, B.I.; Bazett-Jones, D.P.; Yang, X.-J. Regulation of Histone Deacetylase 4 by Binding of 14-3-3 Proteins. Mol. Cell. Biol. 2000, 20, 6904–6912. [Google Scholar] [CrossRef] [Green Version]
- McKinsey, T.A.; Zhang, C.L.; Olson, E.N. Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5. Proc. Natl. Acad. Sci. USA 2000, 97, 14400–14405. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kao, H.-Y.; Downes, M.; Ordentlich, P.; Evans, R.M. Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression. Gene Dev. 2000, 14, 55–66. [Google Scholar]
- Zhang, H.; Okada, S.; Hatano, M.; Okabe, S.; Tokuhisa, T. A new functional domain of Bcl6 family that recruits histone deacetylases. Biochim. Biophys. Acta (BBA) Mol. Cell Res. 2001, 1540, 188–200. [Google Scholar] [CrossRef] [Green Version]
- Gao, L.; Cueto, M.A.; Asselbergs, F.; Atadja, P. Cloning and Functional Characterization of HDAC11, a Novel Member of the Human Histone Deacetylase Family. J. Biol. Chem. 2002, 277, 25748–25755. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brachmann, C.B.; Sherman, J.M.; Devine, S.E.; Cameron, E.E.; Pillus, L.; Boeke, J.D. The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell-cycle progression, and chromosome stability. Genes Dev. 1995, 9, 2888–2902. [Google Scholar] [CrossRef] [Green Version]
- Frye, R.A. Characterization of Five Human cDNAs with Homology to the Yeast SIR2 Gene: Sir2-like Proteins (Sirtuins) Metabolize NAD and May Have Protein ADP-Ribosyltransferase Activity. Biochem. Biophys. Res. Commun. 1999, 260, 273–279. [Google Scholar] [CrossRef] [PubMed]
- Du, J.; Zhou, Y.; Su, X.; Yu, J.J.; Khan, S.; Jiang, H.; Kim, J.; Woo, J.; Choi, B.H.; He, B.; et al. Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase. Science 2011, 334, 806–809. [Google Scholar] [CrossRef] [Green Version]
- LaPlant, Q.; Vialou, V.; Covington, H.E., 3rd; Dumitriu, D.; Feng, J.; Warren, B.L.; Maze, I.; Dietz, D.M.; Watts, E.L.; Iniguez, S.D.; et al. Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat. Neurosci. 2010, 13, 1137–1143. [Google Scholar] [CrossRef] [Green Version]
- Hodes, G.E.; Pfau, M.L.; Purushothaman, I.; Ahn, H.F.; Golden, S.A.; Christoffel, D.J.; Magida, J.; Brancato, A.; Takahashi, A.; Flanigan, M.E.; et al. Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress. J. Neurosci. 2015, 35, 16362–16376. [Google Scholar] [CrossRef]
- Han, L.K.M.; Aghajani, M.; Clark, S.L.; Chan, R.F.; Hattab, M.W.; Shabalin, A.A.; Zhao, M.; Kumar, G.; Xie, L.Y.; Jansen, R.; et al. Epigenetic Aging in Major Depressive Disorder. Am. J. Psychiatry 2018, 175, 774–782. [Google Scholar] [CrossRef] [Green Version]
- Covington, H.E.; Maze, I.; LaPlant, Q.C.; Vialou, V.F.; Ohnishi, Y.N.; Berton, O.; Fass, D.M.; Renthal, W.; Rush, A.J.; Wu, E.Y.; et al. Antidepressant Actions of Histone Deacetylase Inhibitors. J. Neurosci. 2009, 29, 11451–11460. [Google Scholar] [CrossRef] [PubMed]
- Covington, H.E.; Vialou, V.F.; LaPlant, Q.; Ohnishi, Y.N.; Nestler, E.J. Hippocampal-dependent antidepressant-like activity of histone deacetylase inhibition. Neurosci. Lett. 2011, 493, 122–126. [Google Scholar] [CrossRef] [Green Version]
- Covington, H.E.; Maze, I.; Vialou, V.; Nestler, E.J. Antidepressant action of HDAC inhibition in the prefrontal cortex. Neuroscience 2015, 298, 329–335. [Google Scholar] [CrossRef] [Green Version]
- Schroeder, F.A.; Lin, C.L.; Crusio, W.E.; Akbarian, S. Antidepressant-Like Effects of the Histone Deacetylase Inhibitor, Sodium Butyrate, in the Mouse. Biol. Psychiatry 2007, 62, 55–64. [Google Scholar] [CrossRef] [PubMed]
- Tsankova, N.M.; Berton, O.; Renthal, W.; Kumar, A.; Neve, R.L.; Nestler, E.J. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat. Neurosci. 2006, 9, 519–525. [Google Scholar] [CrossRef]
- Hobara, T.; Uchida, S.; Otsuki, K.; Matsubara, T.; Funato, H.; Matsuo, K.; Suetsugi, M.; Watanabe, Y. Altered gene expression of histone deacetylases in mood disorder patients. J. Psychiatry Res. 2010, 44, 263–270. [Google Scholar] [CrossRef]
- Singh, H.; Wray, N.; Schappi, J.M.; Rasenick, M.M. Disruption of lipid-raft localized Galphas/tubulin complexes by antidepressants: A unique feature of HDAC6 inhibitors, SSRI and tricyclic compounds. Neuropsychopharmacology 2018, 43, 1481–1491. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Singh, H.; Chmura, J.; Bhaumik, R.; Pandey, G.N.; Rasenick, M.M. Membrane-Associated α-Tubulin Is Less Acetylated in Postmortem Prefrontal Cortex from Depressed Subjects Relative to Controls: Cytoskeletal Dynamics, HDAC6, and Depression. J. Neurosci. 2020, 40, 4033–4041. [Google Scholar] [CrossRef]
- Borba, L.A.; Broseghini, L.D.; Manosso, L.M.; de Moura, A.B.; Botelho, M.E.M.; Arent, C.O.; Behenck, J.P.; Hilsendeger, A.; Kammer, L.H.; Valvassori, S.S.; et al. Environmental enrichment improves lifelong persistent behavioral and epigenetic changes induced by early-life stress. J. Psychiatry Res. 2021, 138, 107–116. [Google Scholar] [CrossRef]
- Herskovits, A.Z.; Guarente, L. SIRT1 in Neurodevelopment and Brain Senescence. Neuron 2014, 81, 471–483. [Google Scholar] [CrossRef] [Green Version]
- Michan, S.; Li, Y.; Chou, M.M.; Parrella, E.; Ge, H.; Long, J.M.; Allard, J.S.; Lewis, K.; Miller, M.; Xu, W.; et al. SIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity. J. Neurosci. 2010, 30, 9695–9707. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kishi, T.; Yoshimura, R.; Kitajima, T.; Okochi, T.; Okumura, T.; Tsunoka, T.; Yamanouchi, Y.; Kinoshita, Y.; Kawashima, K.; Fukuo, Y.; et al. SIRT1 gene is associated with major depressive disorder in the Japanese population. J. Affect. Disord. 2010, 126, 167–173. [Google Scholar] [CrossRef] [PubMed]
- Abe-Higuchi, N.; Uchida, S.; Yamagata, H.; Higuchi, F.; Hobara, T.; Hara, K.; Kobayashi, A.; Watanabe, Y. Hippocampal Sirtuin 1 Signaling Mediates Depression-like Behavior. Biol. Psychiatry 2016, 80, 815–826. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, H.-D.; Hesterman, J.; Call, T.; Magazu, S.; Keeley, E.; Armenta, K.; Kronman, H.; Neve, R.L.; Nestler, E.J.; Ferguson, D. SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens. J. Neurosci. 2016, 36, 8441–8452. [Google Scholar] [CrossRef]
- Yang, L.; Zhao, Y.; Wang, Y.; Liu, L.; Zhang, X.; Li, B.; Cui, R. The Effects of Psychological Stress on Depression. Curr. Neuropharmacol. 2015, 13, 494–504. [Google Scholar] [CrossRef] [Green Version]
- Murgatroyd, C.; Spengler, D. Epigenetics of Early Child Development. Front. Psychiatry 2011, 2, 16. [Google Scholar] [CrossRef] [Green Version]
- Sandi, C.; Haller, J. Stress and the social brain: Behavioural effects and neurobiological mechanisms. Nat. Rev. Neurosci. 2015, 16, 290–304. [Google Scholar] [CrossRef] [Green Version]
- McEwen, B.S.; Bowles, N.P.; Gray, J.D.; Hill, M.N.; Hunter, R.G.; Karatsoreos, I.N.; Nasca, C. Mechanisms of stress in the brain. Nat. Neurosci. 2015, 18, 1353–1363. [Google Scholar] [CrossRef]
- Godoy, L.D.; Rossignoli, M.T.; Delfino-Pereira, P.; Garcia-Cairasco, N.; de Lima Umeoka, E.H. A Comprehensive Overview on Stress Neurobiology: Basic Concepts and Clinical Implications. Front. Behav. Neurosci. 2018, 12, 127. [Google Scholar] [CrossRef] [Green Version]
- Paul, S.; Jeon, W.K.; Bizon, J.L.; Han, J.S. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment. Front. Aging Neurosci. 2015, 7, 43. [Google Scholar] [CrossRef] [Green Version]
- Murgatroyd, C.; Spengler, D. Epigenetic programming of the HPA axis: Early life decides. Stress 2011, 14, 581–589. [Google Scholar] [CrossRef] [PubMed]
- Stankiewicz, A.M.; Swiergiel, A.H.; Lisowski, P. Epigenetics of stress adaptations in the brain. Brain Res. Bull. 2013, 98, 76–92. [Google Scholar] [CrossRef] [Green Version]
- Klengel, T.; Binder, E.B. Epigenetics of Stress-Related Psychiatric Disorders and Gene x Environment Interactions. Neuron 2015, 86, 1343–1357. [Google Scholar] [CrossRef] [Green Version]
- Levine, A.; Worrell, T.R.; Zimnisky, R.; Schmauss, C. Early life stress triggers sustained changes in histone deacetylase expression and histone H4 modifications that alter responsiveness to adolescent antidepressant treatment. Neurobiol. Dis. 2012, 45, 488–498. [Google Scholar] [CrossRef] [Green Version]
- Tesone-Coelho, C.; Morel, L.J.; Bhatt, J.; Estevez, L.; Naudon, L.; Giros, B.; Zwiller, J.; Dauge, V. Vulnerability to opiate intake in maternally deprived rats: Implication of MeCP2 and of histone acetylation. Addict. Biol. 2013, 20, 120–131. [Google Scholar] [CrossRef] [PubMed]
- Murgatroyd, C.; Patchev, A.V.; Wu, Y.; Micale, V.; Bockmuhl, Y.; Fischer, D.; Holsboer, F.; Wotjak, C.T.; Almeida, O.F.; Spengler, D. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat. Neurosci. 2009, 12, 1559–1566. [Google Scholar] [CrossRef] [PubMed]
- Neumann, I.D.; Landgraf, R. Balance of brain oxytocin and vasopressin: Implications for anxiety, depression, and social behaviors. Trends Neurosci. 2012, 35, 649–659. [Google Scholar] [CrossRef] [PubMed]
- Zhang, T.Y.; Labonte, B.; Wen, X.L.; Turecki, G.; Meaney, M.J. Epigenetic mechanisms for the early environmental regulation of hippocampal glucocorticoid receptor gene expression in rodents and humans. Neuropsychopharmacology 2013, 38, 111–123. [Google Scholar] [CrossRef] [Green Version]
- Seo, M.K.; Kim, S.G.; Seog, D.H.; Bahk, W.M.; Kim, S.H.; Park, S.W.; Lee, J.G. Effects of Early Life Stress on Epigenetic Changes of the Glucocorticoid Receptor 17 Promoter during Adulthood. Int. J. Mol. Sci. 2020, 21, 6331. [Google Scholar] [CrossRef]
- Nagahara, A.H.; Tuszynski, M.H. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat. Rev. Drug Discov. 2011, 10, 209–219. [Google Scholar] [CrossRef]
- Hing, B.; Sathyaputri, L.; Potash, J.B. A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder. Am. J. Med. Genet. B 2018, 177, 143–167. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Misztak, P.; Panczyszyn-Trzewik, P.; Nowak, G.; Sowa-Kucma, M. Epigenetic marks and their relationship with BDNF in the brain of suicide victims. PLoS ONE 2020, 15, e0239335. [Google Scholar] [CrossRef] [PubMed]
- Chen, K.-W.; Chen, L.Y. Epigenetic Regulation of BDNF Gene during Development and Diseases. Int. J. Mol. Sci. 2017, 18, 571. [Google Scholar] [CrossRef] [PubMed]
- Zheng, Y.; Fan, W.D.; Zhang, X.Q.; Dong, E.B. Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus. Epigenetics 2016, 11, 150–162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Seo, M.K.; Ly, N.N.; Lee, C.H.; Cho, H.Y.; Choi, C.M.; Nhu, L.H.; Lee, J.G.; Lee, B.J.; Kim, G.M.; Yoon, B.J.; et al. Early life stress increases stress vulnerability through BDNF gene epigenetic changes in the rat hippocampus. Neuropharmacology 2016, 105, 388–397. [Google Scholar] [CrossRef]
- Su, C.L.; Su, C.W.; Hsiao, Y.H.; Gean, P.W. Epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression. J. Psychiatry Res. 2016, 76, 101–110. [Google Scholar] [CrossRef]
- Gassen, N.C.; Fries, G.R.; Zannas, A.S.; Hartmann, J.; Zschocke, J.; Hafner, K.; Carrillo-Roa, T.; Steinbacher, J.; Preissinger, S.N.; Hoeijmakers, L.; et al. Chaperoning epigenetics: FKBP51 decreases the activity of DNMT1 and mediates epigenetic effects of the antidepressant paroxetine. Sci. Signal. 2015, 8, ra119. [Google Scholar] [CrossRef]
- Varela, R.B.; Resende, W.R.; Dal-Pont, G.C.; Gava, F.F.; Tye, S.J.; Quevedo, J.; Valvassori, S.S. HDAC inhibitors reverse mania-like behavior and modulate epigenetic regulatory enzymes in an animal model of mania induced by Ouabain. Pharmacol. Biochem. Behav. 2020, 193, 172917. [Google Scholar] [CrossRef]
- Zocchi, L.; Sassone-Corsi, P. SIRT1-mediated deacetylation of MeCP2 contributes to BDNF expression. Epigenetics 2012, 7, 695–700. [Google Scholar] [CrossRef] [Green Version]
- Duman, R.S.; Aghajanian, G.K.; Sanacora, G.; Krysta, J.H. Synaptic plasticity and depression: New insights from stress and rapid-acting antidepressants. Nat. Med. 2016, 22, 238–249. [Google Scholar] [CrossRef] [Green Version]
- Uchida, S.; Yamagata, H.; Seki, T.; Watanabe, Y. Epigenetic mechanisms of major depression: Targeting neuronal plasticity. Psychiatry Clin. Neurosci. 2018, 72, 212–227. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pena, C.J.; Bagot, R.C.; Labonte, B.; Nestler, E.J. Epigenetic Signaling in Psychiatric Disorders. J. Mol. Biol. 2014, 426, 3389–3412. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Labonte, B.; Engmann, O.; Purushothaman, I.; Menard, C.; Wang, J.S.; Tan, C.F.; Scarpa, J.R.; Moy, G.; Loh, Y.H.E.; Cahill, M.; et al. Sex-specific transcriptional signatures in human depression. Nat. Med. 2017, 23, 1102–1111. [Google Scholar] [CrossRef] [PubMed]
- de Kloet, E.R.; Oitzl, M.S.; Joels, M. Stress and cognition: Are corticosteroids good or bad guys? Trends Neurosci. 1999, 22, 422–426. [Google Scholar] [CrossRef]
- Guan, Z.H.; Giustetto, M.; Lomvardas, S.; Kim, J.H.; Miniaci, M.C.; Schwartz, J.H.; Thanos, D.; Kandel, E.R. Integration of Long-Term-Memory-Related Synaptic Plasticity Involves Bidirectional Regulation of Gene Expression and Chromatin Structure. Cell 2002, 111, 483–493. [Google Scholar] [CrossRef] [Green Version]
- Levenson, J.M.; O’Riordan, K.J.; Brown, K.D.; Trinh, M.A.; Molfese, D.L.; Sweatt, J.D. Regulation of Histone Acetylation during Memory Formation in the Hippocampus. J. Biol. Chem. 2004, 279, 40545–40559. [Google Scholar] [CrossRef] [Green Version]
- Guan, J.-S.; Haggarty, S.J.; Giacometti, E.; Dannenberg, J.-H.; Joseph, N.; Gao, J.; Nieland, T.J.F.; Zhou, Y.; Wang, X.; Mazitschek, R.; et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009, 459, 55–60. [Google Scholar] [CrossRef]
- Bolger, T.A.; Yao, T.P. Intracellular trafficking of histone deacetylase 4 regulates neuronal cell death. J. Neurosci. 2005, 25, 9544–9553. [Google Scholar] [CrossRef] [Green Version]
- Chen, B.; Cepko, C.L. HDAC4 Regulates Neuronal Survival in Normal and Diseased Retinas. Science 2009, 323, 256–259. [Google Scholar] [CrossRef] [Green Version]
- Sando, R.; Gounko, N.; Pieraut, S.; Liao, L.J.; Yates, J.; Maximov, A. HDAC4 Governs a Transcriptional Program Essential for Synaptic Plasticity and Memory. Cell 2012, 151, 821–834. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, M.S.; Akhtar, M.W.; Adachi, M.; Mahgoub, M.; Bassel-Duby, R.; Kavalali, E.T.; Olson, E.N.; Monteggia, L.M. An Essential Role for Histone Deacetylase 4 in Synaptic Plasticity and Memory Formation. J. Neurosci. 2012, 32, 10879–10886. [Google Scholar] [CrossRef] [Green Version]
- Campbell, R.R.; Kramar, E.A.; Pham, L.; Beardwood, J.H.; Augustynski, A.S.; Lopez, A.J.; Chitnis, O.S.; Delima, G.; Banihani, J.; Matheos, D.P.; et al. HDAC3 Activity within the Nucleus Accumbens Regulates Cocaine-Induced Plasticity and Behavior in a Cell-Type-Specific Manner. J. Neurosci. 2021, 41, 2814–2827. [Google Scholar] [CrossRef] [PubMed]
- Schmaal, L.; Pozzi, E.; Ho, T.C.; van Velzen, L.S.; Veer, I.M.; Opel, N.; Van Someren, E.J.W.; Han, L.K.M.; Aftanas, L.; Aleman, A.; et al. ENIGMA MDD: Seven years of global neuroimaging studies of major depression through worldwide data sharing. Transl. Psychiatry 2020, 10, 172. [Google Scholar] [CrossRef]
- Erjavec, G.N.; Sagud, M.; Perkovic, M.N.; Strac, D.S.; Konjevod, M.; Tudor, L.; Uzun, S.; Pivac, N. Depression: Biological markers and treatment. Prog. Neuro Psychopharmacol. Biol. Psychiatry 2021, 105, 110139. [Google Scholar] [CrossRef]
- Gadad, B.S.; Jha, M.K.; Czysz, A.; Furman, J.L.; Mayes, T.L.; Emslie, M.P.; Trivedi, M.H. Peripheral biomarkers of major depression and antidepressant treatment response: Current knowledge and future outlooks. J. Affect. Disord. 2018, 233, 3–14. [Google Scholar] [CrossRef] [PubMed]
- Le-Niculescu, H.; Roseberry, K.; Gill, S.S.; Levey, D.F.; Phalen, P.L.; Mullen, J.; Williams, A.; Bhairo, S.; Voegtline, T.; Davis, H.; et al. Precision medicine for mood disorders: Objective assessment, risk prediction, pharmacogenomics, and repurposed drugs. Mol. Psychiatry 2021, 1–29. [Google Scholar] [CrossRef]
- Himmerich, H.; Milenovic, S.; Fulda, S.; Plumakers, B.; Sheldrick, A.J.; Michel, T.M.; Kircher, T.; Rink, L. Regulatory T cells increased while IL-1 beta decreased during antidepressant therapy. J. Psychiatr. Res. 2010, 44, 1052–1057. [Google Scholar] [CrossRef] [PubMed]
- Cattaneo, A.; Gennarelli, M.; Uher, R.; Breen, G.; Farmer, A.; Aitchison, K.J.; Craig, I.W.; Anacker, C.; Zunsztain, P.A.; McGuffin, P.; et al. Candidate Genes Expression Profile Associated with Antidepressants Response in the GENDEP Study: Differentiating between Baseline ‘Predictors’ and Longitudinal ‘Targets’. Neuropsychopharmacology 2013, 38, 377–385. [Google Scholar] [CrossRef]
- Cattaneo, A.; Ferrari, C.; Uher, R.; Bocchio-Chiavetto, L.; Riva, M.A.; Pariante, C.M. Absolute Measurements of Macrophage Migration Inhibitory Factor and Interleukin-1-beta mRNA Levels Accurately Predict Treatment Response in Depressed Patients. Int. J. Neuropsychoph. 2016, 19, pyw045. [Google Scholar] [CrossRef] [Green Version]
- Belzeaux, R.; Lin, R.X.; Ju, C.; Chay, M.A.; Fiori, L.M.; Lutz, P.E.; Turecki, G. Transcriptomic and epigenomic biomarkers of antidepressant response. J. Affect. Disord. 2018, 233, 36–44. [Google Scholar] [CrossRef]
- Le-Niculescu, H.; Kurian, S.M.; Yehyawi, N.; Dike, C.; Patel, S.D.; Edenberg, H.J.; Tsuang, M.T.; Salomon, D.R.; Nurnberger, J.I., Jr.; Niculescu, A.B. Identifying blood biomarkers for mood disorders using convergent functional genomics. Mol. Psychiatry 2009, 14, 156–174. [Google Scholar] [CrossRef] [PubMed]
- Buch, A.M.; Liston, C. Dissecting diagnostic heterogeneity in depression by integrating neuroimaging and genetics. Neuropsychopharmacology 2021, 46, 156–175. [Google Scholar] [CrossRef] [PubMed]
- Miller, E.K.; Cohen, J.D. An Integrative Theory of Prefrontal Cortex Function. Annu. Rev. Neurosci. 2001, 24, 167–202. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mueller, T.M.; Meador-Woodruff, J.H. Post-translational protein modifications in schizophrenia. NPJ Schizophr. 2020, 6, 1–16. [Google Scholar] [CrossRef]
- Jovanova, O.S.; Nedeljkovic, I.; Spieler, D.; Walker, R.M.; Liu, C.Y.; Luciano, M.; Bressler, J.; Brody, J.; Drake, A.J.; Evans, K.L.; et al. DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons Meta-analysis of Multiethnic Epigenome-wide Studies. JAMA Psychiatry 2018, 75, 949–959. [Google Scholar] [CrossRef] [Green Version]
- Li, M.; D’Arcy, C.; Li, X.; Zhang, T.; Joober, R.; Meng, X. What do DNA methylation studies tell us about depression? A systematic review. Transl. Psychiatry 2019, 9, 68. [Google Scholar] [CrossRef] [Green Version]
- Lopez, J.P.; Mamdani, F.; Labonte, B.; Beaulieu, M.M.; Yang, J.P.; Berlim, M.T.; Ernst, C.; Turecki, G. Epigenetic regulation of BDNF expression according to antidepressant response. Mol. Psychiatry 2013, 18, 398–399. [Google Scholar] [CrossRef] [Green Version]
- Iga, J.; Ueno, S.; Yamauchi, K.; Numata, S.; Kinouchi, S.; Tayoshi-Shibuya, S.; Song, H.W.; Ohmori, T. Altered HDAC5 and CREB mRNA expressions in the peripheral leukocytes of major depression. Prog. Neuro Psychopharmacol. Biol. Psychiatry 2007, 31, 628–632. [Google Scholar] [CrossRef]
- Nasca, C.; Bigio, B.; Lee, F.S.; Young, S.P.; Kautz, M.M.; Albright, A.; Beasley, J.; Millington, D.S.; Mathé, A.A.; Kocsis, J.H.; et al. Acetyl-l-carnitine deficiency in patients with major depressive disorder. Proc. Natl. Acad. Sci. USA 2018, 115, 8627–8632. [Google Scholar] [CrossRef] [Green Version]
- Wey, H.-Y.; Wang, C.; Schroeder, F.A.; Logan, J.; Price, J.C.; Hooker, J.M. Kinetic Analysis and Quantification of [11C]Martinostat for in Vivo HDAC Imaging of the Brain. ACS Chem. Neurosci. 2015, 6, 708–715. [Google Scholar] [CrossRef] [Green Version]
- Wey, H.Y.; Gilbert, T.M.; Zurcher, N.R.; She, A.; Bhanot, A.; Taillon, B.D.; Schroeder, F.A.; Wang, C.; Haggarty, S.J.; Hooker, J.M. Insights into neuroepigenetics through human histone deacetylase PET imaging. Sci. Transl. Med. 2016, 8, 351ra106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gilbert, T.M.; Zürcher, N.R.; Wu, C.J.; Bhanot, A.; Hightower, B.G.; Kim, M.; Albrecht, D.S.; Wey, H.-Y.; Schroeder, F.A.; Rodriguez-Thompson, A.; et al. PET neuroimaging reveals histone deacetylase dysregulation in schizophrenia. J. Clin. Investig. 2019, 129, 364–372. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tseng, C.-E.J.; Gilbert, T.M.; Catanese, M.C.; Hightower, B.G.; Peters, A.T.; Parmar, A.J.; Kim, M.; Wang, C.; Roffman, J.L.; Brown, H.E.; et al. In vivo human brain expression of histone deacetylases in bipolar disorder. Transl. Psychiatry 2020, 10, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Toth, M. Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain. Annu. Rev. Pharmacol. Toxicol. 2021, 61, 181–201. [Google Scholar] [CrossRef] [PubMed]
- Elliott, E.; Ezra-Nevo, G.; Regev, L.; Neufeld-Cohen, A.; Chen, A. Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice. Nat. Neurosci. 2010, 13, 1351–1353. [Google Scholar] [CrossRef]
- Ookubo, M.; Kanai, H.; Aoki, H.; Yamada, N. Antidepressants and mood stabilizers effects on histone deacetylase expression in C57BL/6 mice: Brain region specific changes. J. Psychiatry Res. 2013, 47, 1204–1214. [Google Scholar] [CrossRef]
- Deussing, J.M.; Jakovcevski, M. Histone Modifications in Major Depressive Disorder and Related Rodent Models. Adv. Exp. Med. Biol. 2017, 978, 169–183. [Google Scholar] [CrossRef]
- Fuchikami, M.; Yamamoto, S.; Morinobu, S.; Okada, S.; Yamawaki, Y.; Yamawaki, S. The potential use of histone deacetylase inhibitors in the treatment of depression. Prog. Neuro Psychopharmacol. Biol. Psychiatry 2016, 64, 320–324. [Google Scholar] [CrossRef] [Green Version]
- Uchida, S.; Hara, K.; Kobayashi, A.; Otsuki, K.; Yamagata, H.; Hobara, T.; Suzuki, T.; Miyata, N.; Watanabe, Y. Epigenetic Status of Gdnf in the Ventral Striatum Determines Susceptibility and Adaptation to Daily Stressful Events. Neuron 2011, 69, 359–372. [Google Scholar] [CrossRef] [Green Version]
- Golden, S.A.; Christoffel, D.J.; Heshmati, M.; Hodes, G.E.; Magida, J.; Davis, K.; Cahill, M.E.; Dias, C.; Ribeiro, E.; Ables, J.L.; et al. Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression. Nat. Med. 2013, 19, 337–344. [Google Scholar] [CrossRef] [Green Version]
- Han, A.; Sung, Y.-B.; Chung, S.-Y.; Kwon, M.-S. Possible additional antidepressant-like mechanism of sodium butyrate: Targeting the hippocampus. Neuropharmacology 2014, 81, 292–302. [Google Scholar] [CrossRef]
- Sada, N.; Fujita, Y.; Mizuta, N.; Ueno, M.; Furukawa, T.; Yamashita, T. Inhibition of HDAC increases BDNF expression and promotes neuronal rewiring and functional recovery after brain injury. Cell Death Dis. 2020, 11, 1–15. [Google Scholar] [CrossRef] [PubMed]
- Athira, K.V.; Madhana, R.M.; Bais, A.K.; Singh, V.B.; Malik, A.; Sinha, S.; Lahkar, M.; Kumar, P.; Samudrala, P.K. Cognitive Improvement by Vorinostat through Modulation of Endoplasmic Reticulum Stress in a Corticosterone-Induced Chronic Stress Model in Mice. ACS Chem. Neurosci. 2020, 11, 2649–2657. [Google Scholar] [CrossRef]
- Ershadi, A.S.B.; Amini-Khoei, H.; Hosseini, M.-J.; Dehpour, A.R. SAHA Improves Depressive Symptoms, Cognitive Impairment and Oxidative Stress: Rise of a New Antidepressant Class. Neurochem. Res. 2021, 46, 1252–1263. [Google Scholar] [CrossRef] [PubMed]
- Vinarskaya, A.K.; Balaban, P.M.; Roshchin, M.V.; Zuzina, A.B. Sodium butyrate as a selective cognitive enhancer for weak or impaired memory. Neurobiol. Learn. Mem. 2021, 180, 107414. [Google Scholar] [CrossRef] [PubMed]
- Prince, H.M.; Bishton, M.J.; Harrison, S.J. Clinical Studies of Histone Deacetylase Inhibitors. Clin. Cancer Res. 2009, 15, 3958–3969. [Google Scholar] [CrossRef] [Green Version]
- Subramanian, S.; Bates, S.E.; Wright, J.J.; Espinoza-Delgado, I.; Piekarz, R.L. Clinical Toxicities of Histone Deacetylase Inhibitors. Pharmaceuticals 2010, 3, 2751–2767. [Google Scholar] [CrossRef] [Green Version]
- Majchrzak-Celinska, A.; Warych, A.; Szoszkiewicz, M. Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing. Genes 2021, 12, 208. [Google Scholar] [CrossRef]
- Karnib, N.; El-Ghandour, R.; El Hayek, L.; Nasrallah, P.; Khalifeh, M.; Barmo, N.; Jabre, V.; Ibrahim, P.; Bilen, M.; Stephan, J.; et al. Lactate is an antidepressant that mediates resilience to stress by modulating the hippocampal levels and activity of histone deacetylases. Neuropsychopharmacology 2019, 44, 1152–1162. [Google Scholar] [CrossRef]
- Wang, J.; Hodes, G.E.; Zhang, H.; Zhang, S.; Zhao, W.; Golden, S.A.; Bi, W.; Menard, C.; Kana, V.; Leboeuf, M.; et al. Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice. Nat. Commun. 2018, 9, 477. [Google Scholar] [CrossRef] [Green Version]
Class | Protein (S. cerevisiae) | Protein (Human) | Subcellular Localization |
---|---|---|---|
Class I | Rpd3 | HDAC1 | Nucleus |
HDAC2 | Nucleus | ||
HDAC3 | Nucleus | ||
HDAC8 | Nucleus | ||
Class IIa | Hda1 | HDAC4 | Nucleus/cytoplasm |
HDAC5 | Nucleus/cytoplasm | ||
HDAC7 | Nucleus/cytoplasm | ||
HDAC9 | Nucleus/cytoplasm | ||
Class IIb | Hda1 | HDAC6 | Cytoplasm |
HDAC10 | Cytoplasm | ||
Class IV | Hos3 | HDAC11 | Nucleus/cytoplasm |
Class III | Sir2 | SIRT1 | Nucleus/cytoplasm |
SIRT2 | Nucleus/cytoplasm | ||
SIRT3 | Nucleus/mitochondria | ||
SIRT4 | Mitochondria | ||
SIRT5 | Mitochondria | ||
SIRT6 | Nucleus | ||
SIRT7 | Nucleus |
HDAC Inhibitor | Animal Model | Measurement of Antidepressant Effect | Molecular Mechanisms of Action | Ref. |
---|---|---|---|---|
MS-275 | Chronic social defeat stress | Social avoidance, sucrose preference, FST | acH3 ↑ in the NAc | [62] |
Chronic social defeat stress | Sucrose preference test, social avoidance (combined with social enrichment) | acH3 ↑ in the hippocampus | [63] | |
Chronic social defeat stress | Social avoidance, FST | acH3 ↑ in the mPFC | [64] | |
Chronic social defeat stress | Social avoidance | Rac1 ↑ in the NAc synapse structural plasticity normalization | [141] | |
SAHA | Chronic social defeat stress | Social avoidance, sucrose preference, FST | acH3 ↑ in the NAc | [62] |
Chronic unpredictable mild stress | Social interaction, sucrose preference test, novelty-suppressed test, FST | HDAC2 inhibition, Gdnf ↑ in the NAc | [140] | |
Sodium butyrate | Behavioral despair paradigm | TST | acH3 ↑ in the hippocampus, Bdnf↑ in the frontal cortex | [65] |
Chronic social defeat stress | Social avoidance | HDAC5 inhibition, acH3 ↑ in Bdnf gene P3, P4 promotor | [66] | |
Chronic restraint stress | Sucrose preference test, Light/dark test, TST, FST | HDAC2 ↑, pCREB ↑, AcH3 ↑, BDNF ↑ in the hippocampus | [142] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Park, H.-S.; Kim, J.; Ahn, S.H.; Ryu, H.-Y. Epigenetic Targeting of Histone Deacetylases in Diagnostics and Treatment of Depression. Int. J. Mol. Sci. 2021, 22, 5398. https://doi.org/10.3390/ijms22105398
Park H-S, Kim J, Ahn SH, Ryu H-Y. Epigenetic Targeting of Histone Deacetylases in Diagnostics and Treatment of Depression. International Journal of Molecular Sciences. 2021; 22(10):5398. https://doi.org/10.3390/ijms22105398
Chicago/Turabian StylePark, Hyun-Sun, Jongmin Kim, Seong Hoon Ahn, and Hong-Yeoul Ryu. 2021. "Epigenetic Targeting of Histone Deacetylases in Diagnostics and Treatment of Depression" International Journal of Molecular Sciences 22, no. 10: 5398. https://doi.org/10.3390/ijms22105398