Stress and anxiety across the lifespan: Structural plasticity and epigenetic regulation

Epigenomics

Volumn 5, Issue 2, 2013, Pages 177-194

  Hunter, Richard G ^a,b   McEwen, Bruce S ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

^b UNIVERSITY OF MASSACHUSETTS BOSTON   (United States)

Author keywords

adolescence; adulthood; aging; DNA methylation; early life; histone modification; ncRNA

Indexed keywords

ANTIDEPRESSANT AGENT; BRAIN DERIVED NEUROTROPHIC FACTOR; COCAINE; CORTICOTROPIN; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3A; EARLY GROWTH RESPONSE FACTOR 1; GLUCOCORTICOID; GLUTAMATE DECARBOXYLASE 67; GLUTAMIC ACID; METHYL CPG BINDING PROTEIN 2; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PRODYNORPHIN; REELIN; VINCLOZOLIN; ZEBULARINE;

ADOLESCENCE; ADULTHOOD; AGING; ANXIETY; BRAIN DEVELOPMENT; BRAIN FUNCTION; BRAIN REGION; CHRONIC STRESS; COGNITIVE DEVELOPMENT; COGNITIVE THERAPY; DENTATE GYRUS; DISEASE PREDISPOSITION; DNA METHYLATION; EARLY LIFE STRESS; EPIGENETICS; FEAR; GENOMIC INSTABILITY; HIPPOCAMPUS; HISTONE ACETYLATION; HISTONE MODIFICATION; HOME ENVIRONMENT; HUMAN; IMMOBILIZATION STRESS; LIFESPAN; LOCUS OF CONTROL; MATERNAL BEHAVIOR; MATERNAL CARE; MEMORY CONSOLIDATION; MOOD; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NEUROTRANSMITTER RELEASE; NONHUMAN; PERSONAL EXPERIENCE; POSTTRAUMATIC STRESS DISORDER; PREFRONTAL CORTEX; PRENATAL STRESS; PRIORITY JOURNAL; REVIEW; SENSORY STIMULATION; SPATIAL LEARNING; SPATIAL MEMORY; STRESS; TRANSCRIPTION INITIATION;

ANXIETY; BRAIN; DNA TRANSPOSABLE ELEMENTS; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; HUMANS; NEURONAL PLASTICITY; STRESS, PSYCHOLOGICAL;

EID: 84876141686     PISSN: 17501911     EISSN: 1750192X     Source Type: Journal    
DOI: 10.2217/epi.13.8     Document Type: Review

References (204)

1. Lupien SJ, McEwen BS, Gunnar MR, Heim C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat. Rev. Neurosci. 10(6), 434-445 (2009).
2. McEwen BS, Gianaros PJ. Central role of the brain in stress and adaptation: links to socioeconomic status, health, and disease. Ann. NY Acad. Sci. 1186, 190-222 (2010).
3. McEwen BS, Eiland L, Hunter RG, Miller MM. Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress. Neuropharmacology 62(1), 3-12 (2012).
4. McEwen BS. Stress, sex, and neural adaptation to a changing environment: mechanisms of neuronal remodeling. Ann. NY Acad. Sci. 1204(Suppl.), E38-E59 (2010).
5. Bennett E, Diamond M, Krech D, Rosenzweig M. Chemical and anatomical plasticity of brain. Science 146, 610-619 (1964).
6. Erickson KI, Voss MW, Prakash RS et al. Exercise training increases size of hippocampus and improves memory. Proc. Natl Acad. Sci. USA 108(7), 3017-3022 (2011).
7. Wang X, Merzenich MM, Sameshima K, Jenkins WM. Remodelling of hand representation in adult cortex determined by timing of tactile stimulation. Nature 378, 71-75 (1995).
8. Draganski B, Gaser C, Kempermann G et al. Temporal and spatial dynamics of brain structure changes during extensive learning. J. Neurosci. 26(23), 6314-6317 (2006).
9. Bezzola L, Merillat S, Gaser C, Jancke L. Training-induced neural plasticity in golf novices. J. Neurosci. 31(35), 12444-12448 (2011).
10. McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol. Rev. 87, 873-904 (2007). (Pubitemid 47086281)
11. McEwen BS. Stress and hippocampal plasticity. Annu. Rev. Neurosci. 22, 105-122 (1999). (Pubitemid 29144882)
12. Bloss EB, Janssen WG, McEwen BS, Morrison JH. Interactive effects of stress and aging on structural plasticity in the prefrontal cortex. J. Neurosci. 30(19), 6726-6731 (2010).
13. Vyas A, Mitra R, Rao BSS, Chattarji S. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J. Neurosci. 22, 6810-6818 (2002). (Pubitemid 35386438)
14. Roozendaal B, McEwen BS, Chattarji S. Stress, memory and the amygdala. Nat. Rev. Neurosci. 10, 423-433 (2009).
15. McEwen BS, Gianaros PJ. Stress- and allostasis-induced brain plasticity. Annu. Rev. Med. 62, 431-445 (2011).
16. Pruessner JC, Baldwin MW, Dedovic K et al. Self-esteem, locus of control, hippocampal volume, and cortisol regulation in young and old adulthood. NeuroImage 28, 815-826 (2005). (Pubitemid 41713617)
17. Gurvits TV, Shenton ME, Hokama H et al. Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. Biol. Psychiatry 40, 1091-1099 (1996). (Pubitemid 26400873)
18. Cho K. Chronic 'jet lag' produces temporal lobe atrophy and spatial cognitive deficits. Nat. Neurosci. 4, 567-568 (2001). (Pubitemid 32507369)
19. Davidson RJ, McEwen BS. Social influences on neuroplasticity: stress and interventions to promote well-being. Nat. Neurosci. 15(5), 689-695 (2012).
20. Holzel BK, Carmody J, Evans KC et al. Stress reduction correlates with structural changes in the amygdala. Soc. Cogn. Affect. Neurosci. 5(1), 11-17 (2009).
21. Stahl SM. Psychotherapy as an epigenetic 'drug': psychiatric therapeutics target symptoms linked to malfunctioning brain circuits with psychotherapy as well as with drugs. J. Clin. Pharm. Ther. 37(3), 249-253 (2012).
22. McEwen BS. Protective and damaging effects of stress mediators. N. Engl. J. Med. 338, 171-179 (1998).
23. Nugent BM, McCarthy MM. Epigenetic underpinnings of developmental sex differences in the brain. Neuroendocrinology 93(3), 150-158 (2011).
24. Hoffmann A, Spengler D. The lasting legacy of social stress on the epigenome of the hypothalamic-pituitary-adrenal axis. Epigenomics 4(4), 431-444 (2012).
25. Bale TL. Sex differences in prenatal epigenetic programming of stress pathways. Stress 14(4), 348-356 (2011).
26. Maccari S, Morley-Fletcher S. Effects of prenatal restraint stress on the hypothalamus-pituitary-adrenal axis and related behavioural and neurobiological alterations. Psychoneuroendocrinology 32, S10-S15 (2007). (Pubitemid 47211641)
27. Francis DD, Diorio J, Plotsky PM, Meaney MJ. Environmental enrichment reverses the effects of maternal separation on stress reactivity. J. Neurosci. 22, 7840-7843 (2002). (Pubitemid 35379088)
28. Plotsky PM, Thrivikraman KV, Nemeroff CB, Caldji C, Sharma S, Meaney MJ. Long-term consequences of neonatal rearing on central corticotropin-releasing factor systems in adult male rat offspring. Neuropsychopharmacology 30, 2192-2204 (2005). (Pubitemid 41643970)
29. Eiland L, McEwen BS. Early life stress followed by subsequent adult chronic stress potentiates anxiety and blunts hippocampal structural remodeling. Hippocampus 22(1), 82-91 (2012).
30. Caldji C, Diorio J, Meaney MJ. Variations in maternal care in infancy regulate the development of stress reactivity. Biol. Psychiat. 48, 1164-1174 (2000). (Pubitemid 32008442)
31. Akers KG, Yang Z, Delvecchio DP et al. Social competitiveness and plasticity of neuroendocrine function in old age: influence of neonatal novelty exposure and maternal care reliability. PLoS ONE 3(7), e2840 (2008).
32. Tang AC, Reeb-Sutherland BC, Yang Z, Romeo RD, McEwen BS. Neonatal novelty-induced persistent enhancement in offspring spatial memory and the modulatory role of maternal self-stress regulation. J. Neurosci. 31(14), 5348-5352 (2011).
33. Francis D, Diorio J, Liu D, Meaney MJ. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286, 1155-1158 (1999).
34. Weaver ICG, Cervoni N, Champagne FA et al. Epigenetic programming by maternal behavior. Nat. Neurosci. 7, 847-854 (2004). (Pubitemid 38989508)
35. Kaufman D, Smith ELP, Gohil BC et al. Early appearance of the metabolic syndrome in socially reared bonnet macaques. J. Clin. Endocrinol. Metab. 90, 404-408 (2005). (Pubitemid 40116688)
36. Kaufman D, Banerji MA, Shorman I et al. Early-life stress and the development of obesity and insulin resistance in juvenile bonnet macaques. Diabetes 56, 1-5 (2007).
37. Mcgowan PO, Sasaki A, D'alessio AC et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat. Neurosci. 12, 241-243 (2009).
38. Danese A, McEwen BS. Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol. Behav. 106(1), 29-39 (2012).
39. Entringer S, Epel ES, Kumsta R et al. Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proc. Natl Acad. Sci. USA 108(33), E513-E518 (2011).
40. Shonkoff JP, Boyce WT, McEwen BS. Neuroscience, molecular biology, and the childhood roots of health disparities. JAMA 301, 2252-2259 (2009).
41. Anda RF, Butchart A, Felitti VJ, Brown DW. Building a framework for global surveillance of the public health implications of adverse childhood experiences. Am. J. Prev. Med. 39(1), 93-98 (2010).
42. Evans GW, Gonnella C, Marcynyszyn LA, Gentile L, Salpekar N. The role of chaos in poverty and children's socioemotional adjustment. Psychol. Sci. 16, 560-565 (2004). (Pubitemid 41186750)
43. Lupien SJ, Parent S, Evans AC et al. Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth. Proc. Natl Acad. Sci. USA 108(34), 14324-14329 (2011).
44. Farah MJ, Shera DM, Savage JH et al. Childhood poverty: Specific associations with neurocognitive development. Brain Res. 1110, 166-174 (2006). (Pubitemid 44344609)
45. Danese A, McEwen BS. Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol. Behav. 106(1), 29-39 (2011).
46. Hart B, Risley TR. Meaningful Differences in the Everyday Experience of Young American Children. Brookes Publishing Company, MD, USA (1995).
47. Pesonen AK, Raikkonen K. The lifespan consequences of early life stress. Physiol. Behav. 106(5), 722-727 (2012).
48. Roseboom TJ, Painter RC, van Abeelen AF, Veenendaal MV, De Rooij SR. Hungry in the womb: what are the consequences? Lessons from the Dutch famine. Maturitas 70(2), 141-145 (2011).
49. Heijmans BT, Tobi EW, Stein AD et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl Acad. Sci. USA 105(44), 17046-17049 (2008).
50. Yehuda R, Bell A, Bierer LM, Schmeidler J. Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors. J. Psychiatr. Res. 42(13), 1104-1111 (2008).
51. Yehuda R, Bierer LM. Transgenerational transmission of cortisol and PTSD risk. Prog. Brain Res. 167, 121-135 (2008).
52. Francis DD, Meaney MJ. Maternal care and the development of stress responses. Curr. Opin. Neurobiol. 9(1), 128-134 (1999). (Pubitemid 29084099)
53. Wosiski-Kuhn M, Stranahan AM. Opposing effects of positive and negative stress on hippocampal plasticity over the lifespan. Ageing Res. Rev. 11(3), 399-403 (2012).
54. Wosiski-Kuhn M, Stranahan AM. Opposing effects of positive and negative stress on hippocampal plasticity over the lifespan. Ageing Res. Rev. 11(3), 399-403 (2011).
55. Koenig JI, Walker CD, Romeo RD, Lupien SJ. Effects of stress across the lifespan. Stress 14(5), 475-480 (2011).
56. Vallee M, Maccari S, Dellu F, Simon H, Le Moal M, Mayo W. Long-term effects of prenatal stress and postnatal handling on age-related glucocorticoid secretion and cognitive performance: a longitudinal study in the rat. Eur. J. Neurosci. 11(8), 2906-2916 (1999). (Pubitemid 29364207)
57. Vallee M, Mayo W, Dellu F, Le Moal M, Simon H, Maccari S. Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: correlation with stress-induced corticosterone secretion. J. Neurosci. 17(7), 2626-2636 (1997). (Pubitemid 27137428)
58. Seckl Jr. Glucocorticoids, developmental 'programming' and the risk of affective dysfunction. Prog. Brain Res. 167, 17-34 (2008). (Pubitemid 350123222)
59. Cratty MS, Ward HE, Johnson EA, Azzaro AJ, Birkle DL. Prenatal stress increases corticotropin-releasing factor (CRF) content and release in rat amygdala minces. Brain Res. 675(1-2), 297-302 (1995).
60. Murmu MS, Salomon S, Biala Y, Weinstock M, Braun K, Bock J. Changes of spine density and dendritic complexity in the prefrontal cortex in offspring of mothers exposed to stress during pregnancy. Eur. J. Neurosci. 24(5), 1477-1487 (2006). (Pubitemid 44401670)
61. Lemaire V, Koehl M, Le Moal M, Abrous DN. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc. Natl Acad. Sci. USA 97(20), 11032-11037 (2000).
62. Coe CL, Kramer M, Czeh B et al. Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys. Biol. Psychiatry 54(10), 1025-1034 (2003). (Pubitemid 37415037)
63. Fujioka T, Sakata Y, Yamaguchi K, Shibasaki T, Kato H, Nakamura S. The effects of prenatal stress on the development of hypothalamic paraventricular neurons in fetal rats. Neuroscience 92(3), 1079-1088 (1999). (Pubitemid 29287552)
64. Fujioka A, Fujioka T, Ishida Y, Maekawa T, Nakamura S. Differential effects of prenatal stress on the morphological maturation of hippocampal neurons. Neuroscience 141(2), 907-915 (2006). (Pubitemid 44066657)
65. Fujioka T, Fujioka A, Tan N et al. Mild prenatal stress enhances learning performance in the non-adopted rat offspring. Neuroscience 103(2), 301-307 (2001). (Pubitemid 32201917)
66. Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J. Neurosci. 28(36), 9055-9065 (2008).
67. Morgan CP, Bale TL. Early prenatal stress epigenetically programs dysmasculinization in second-generation offspring via the paternal lineage. J. Neurosci. 31(33), 11748-11755 (2011).
68. Oberlander TF, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin AM. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3(2), 97-106 (2008).
69. Jensen Pena C, Monk C, Champagne FA. Epigenetic effects of prenatal stress on 11beta-hydroxysteroid dehydrogenase-2 in the placenta and fetal brain. PLoS ONE 7(6), e39791 (2012).
70. Marsit CJ, Maccani MA, Padbury JF, Lester BM. Placental 11-beta hydroxysteroid dehydrogenase methylation is associated with newborn growth and a measure of neurobehavioral outcome. PLoS ONE 7(3), e33794 (2012).
71. Matrisciano F, Tueting P, Dalal I et al. Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology doi:http://dx.doi.org/10. 1016/j. bbr.2011.03.031 (2012) (Epub ahead of print).
72. Brown AS. The environment and susceptibility to schizophrenia. Prog. Neurobiol. 93(1), 23-58 (2011).
73. Koenig JI, Kirkpatrick B, Lee P. Glucocorticoid hormones and early brain development in schizophrenia. Neuropsychopharmacology 27(2), 309-318 (2002). (Pubitemid 34686982)
74. Lemaire V, Lamarque S, Le Moal M, Piazza PV, Abrous DN. Postnatal stimulation of the pups counteracts prenatal stress-induced deficits in hippocampal neurogenesis. Biol. Psychiatry 59(9), 786-792 (2006).
75. Dicorcia JA, Tronick E. Quotidian resilience: exploring mechanisms that drive resilience from a perspective of everyday stress and coping. Neurosci. Biobehav. Rev. 35(7), 1593-1602 (2011).
76. Francis D, Diorio J, Liu D, Meaney MJ. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286(5442), 1155-1158 (1999).
77. Champagne FA, Francis DD, Mar A, Meaney MJ. Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol. Behav. 79(3), 359-371 (2003). (Pubitemid 37098279)
78. Liu D, Diorio J, Tannenbaum B et al. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277(5332), 1659-1662 (1997). (Pubitemid 27446227)
79. Champagne DL, Bagot RC, Van Hasselt F et al. Maternal care and hippocampal plasticity. evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J. Neurosci. 28(23), 6037-6045 (2008).
80. Bagot RC, van Hasselt FN, Champagne DL, Meaney MJ, Krugers HJ, Joels M. Maternal care determines rapid effects of stress mediators on synaptic plasticity in adult rat hippocampal dentate gyrus. Neurobiol Learn. Mem. 92(3), 292-300 (2009).
81. Del Giudice M, Ellis BJ, Shirtcliff EA. The Adaptive Calibration Model of stress responsivity. Neurosci. Biobehav. Rev. 35(7), 1562-1592 (2012).
82. Weaver IC, Cervoni N, Champagne FA et al. Epigenetic programming by maternal behavior. Nat. Neurosci. 7(8), 847-854 (2004). (Pubitemid 38989508)
83. Cervoni N, Szyf M. Demethylase activity is directed by histone acetylation. J. Biol. Chem. 276(44), 40778-40787 (2001).
84. Weaver IC, D'alessio AC, Brown SE et al. The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: altering epigenetic marks by immediate-early genes. J. Neurosci. 27(7), 1756-1768 (2007). (Pubitemid 46280071)
85. Turner JD, Muller CP. Structure of the glucocorticoid receptor (NR3C1) gene 5' untranslated region: identification, and tissue distribution of multiple new human exon 1. J. Mol. Endocrinol. 35(2), 283-292 (2005). (Pubitemid 41556176)
86. Mcgowan PO, Sasaki A, D'alessio AC et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat. Neurosci. 12(3), 342-348 (2009).
87. Labonte B, Yerko V, Gross J et al. Differential glucocorticoid receptor exon 1(b), 1(c), and 1(h) expression and methylation in suicide completers with a history of childhood abuse. Biol. Psychiatry 72(1), 41-48 (2012).
88. Alt SR, Turner JD, Klok MD et al. Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed. Psychoneuroendocrinology 35(4), 544-556 (2010).
89. Tyrka AR, Price LH, Marsit C, Walters OC, Carpenter LL. Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: preliminary findings in healthy adults. PLoS ONE 7(1), e30148 (2012).
90. Labonte B, Suderman M, Maussion G et al. Genome-wide epigenetic regulation by early-life traumagenome epigenetic regulation by early-life trauma. Arch. Gen. Psychiatry 69(7), 722-731 (2012).
91. Crudo A, Petropoulos S, Moisiadis VG et al. Prenatal synthetic glucocorticoid treatment changes DNA methylation States in male organ systems: multigenerational effects. Endocrinology 153(7), 3269-3283 (2012).
92. Crews D, Gillette R, Scarpino SV, Manikkam M, Savenkova MI, Skinner MK. Epigenetic transgenerational inheritance of altered stress responses. Proc. Natl Acad. Sci. USA 109(23), 9143-9148 (2012).
93. Skinner MK, Anway MD, Savenkova MI, Gore AC, Crews D. Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior. PLoS ONE 3(11), e3745 (2008).
94. Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK. Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS ONE 5(9), e13100 (2010).
95. Dietz DM, Laplant Q, Watts EL et al. Paternal transmission of stress-induced pathologies. Biol. Psychiatry 70(5), 408-414 (2011).
96. Walker AK, Hawkins G, Sominsky L, Hodgson DM. Transgenerational transmission of anxiety induced by neonatal exposure to lipopolysaccharide: Implications for male and female germ lines. Psychoneuroendocrinology 37(8), 1320-1335 (2012).
97. Franklin TB, Russig H, Weiss IC et al. Epigenetic transmission of the impact of early stress across generations. Biol. Psychiatry 68(5), 408-415 (2010).
98. Liu D, Diorio J, Day JC, Francis DD, Meaney MJ. Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat. Neurosci. 3(8), 799-806 (2000). (Pubitemid 30485705)
99. Eiland L, Ramroop J, Hill MN, Manley J, McEwen BS. Chronic juvenile stress produces corticolimbic dendritic architectural remodeling and modulates emotional behavior in male and female rats. Psychoneuroendocrinology 37(1), 39-47 (2011).
100. Liu D, Caldji C, Sharma S, Plotsky PM, Meaney MJ. Influence of neonatal rearing conditions on stress-induced adrenocorticotropin responses and norepinepherine release in the hypothalamic paraventricular nucleus. J. Neuroendocrinol. 12(1), 5-12 (2000). (Pubitemid 30098930)
101. Murgatroyd C, Patchev AV, Wu Y et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat. Neurosci. 12(12), 1559-1566 (2009).
102. Kriaucionis S, Bird A. DNA methylation and Rett syndrome. Hum. Mol. Genet. 12(Suppl. 2), R221-R227 (2003). (Pubitemid 37259336)
103. Martinowich K, Hattori D, Wu H et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302(5646), 890-893 (2003). (Pubitemid 37339633)
104. Chen WG, Chang Q, Lin Y et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302(5646), 885-889 (2003). (Pubitemid 37339632)
105. Roth TL, Lubin FD, Funk AJ, Sweatt JD. Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol. Psychiatry 65(9), 760-769 (2009).
106. Simmons RK, Howard JL, Simpson DN, Akil H, Clinton SM. DNA methylation in the developing hippocampus and amygdala of anxiety-prone versus risk-taking rats. Dev. Neurosci. 34(1), 58-67 (2012).
107. Sturman DA, Moghaddam B. The neurobiology of adolescence: changes in brain architecture, functional dynamics, and behavioral tendencies. Neurosci. Biobehav. Rev. 35(8), 1704-1712 (2011).
108. Mcgorry PD, Purcell R, Goldstone S, Amminger GP. Age of onset and timing of treatment for mental and substance use disorders: implications for preventive intervention strategies and models of care. Curr. Opin. Psychiatry 24(4), 301-306 (2011).
109. Blakemore SJ. Development of the social brain in adolescence. J. R. Soc. Med. 105(3), 111-116 (2012).
110. Gunnar MR, Wewerka S, Frenn K, Long JD, Griggs C. Developmental changes in hypothalamus-pituitary-adrenal activity over the transition to adolescence: normative changes and associations with puberty. Dev. Psychopathol. 21(1), 69-85 (2009).
111. Romeo RD, Karatsoreos IN, McEwen BS. Pubertal maturation and time of day differentially affect behavioral and neuroendocrine responses following an acute stressor. Horm. Behav. 50(3), 463-468 (2006). (Pubitemid 44215888)
112. Romeo RD, Bellani R, Karatsoreos IN et al. Stress history and pubertal development interact to shape hypothalamic-pituitary-adrenal axis plasticity. Endocrinology 147(4), 1664-1674 (2006).
113. Isgor C, Kabbaj M, Akil H, Watson SJ. Delayed effects of chronic variable stress during peripubertal-juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats. Hippocampus 14(5), 636-648 (2004). (Pubitemid 39107017)
114. Trollope AF, Gutierrez-Mecinas M, Mifsud KR, Collins A, Saunderson EA, Reul JM. Stress, epigenetic control of gene expression and memory formation. Exp. Neurol. 233(1), 3-11 (2012).
115. Lein ES, Hawrylycz MJ, Ao N et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445(7124), 168-176 (2007). (Pubitemid 46095716)
116. Zovkic IB, Sweatt JD. Epigenetic Mechanisms in learned fear: implications for PTSD. Neuropsychopharmacology 38(1), 77-93 (2012).
117. Sultan FA, Day JJ. Epigenetic mechanisms in memory and synaptic function. Epigenomics 3(2), 157-181 (2011).
118. Griffith JS, Mahler HR. DNA ticketing theory of memory. Nature 223(5206), 580-582 (1969).
119. Crick F. Memory and molecular turnover. Nature 312(5990), 101 (1984).
120. Holliday R. Is there an epigenetic component in long-term memory? J. Theor. Biol. 200(3), 339-341 (1999). (Pubitemid 29504869)
121. Levenson JM, O'Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD. Regulation of histone acetylation during memory formation in the hippocampus. J. Biol. Chem. 279(39), 40545-40559 (2004). n This and [122] were important firsts in our understanding of the role of epigenetic marks in memory. (Pubitemid 39287646)
122. Miller CA, Sweatt JD. Covalent modification of DNA regulates memory formation. Neuron 53(6), 857-869 (2007). (Pubitemid 46367557)
123. Lubin FD, Roth TL, Sweatt JD. Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J. Neurosci. 28(42), 10576-10586 (2008).
124. Koshibu K, Graff J, Beullens M et al. Protein phosphatase 1 regulates the histone code for long-term memory. J. Neurosci. 29(41), 13079-13089 (2009).
125. Koshibu K, Graff J, Mansuy IM. Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation. Neuroscience 173, 30-36 (2011).
126. Maddox SA, Schafe GE. Epigenetic alterations in the lateral amygdala are required for reconsolidation of a Pavlovian fear memory. Learn. Mem. 18(9), 579-593 (2011).
127. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH. Recovery of learning and memory is associated with chromatin remodelling. Nature 447(7141), 178-182 (2007). (Pubitemid 46763080)
128. Guan JS, Haggarty SJ, Giacometti E et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459(7243), 55-60 (2009).
129. Bredy TW, Wu H, Crego C, Zellhoefer J, Sun YE, Barad M. Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learn. Mem. 14(4), 268-276 (2007). (Pubitemid 46625629)
130. Calfa G, Chapleau CA, Campbell S et al. HDAC activity is required for BDNF to increase quantal neurotransmitter release and dendritic spine density in CA1 pyramidal neurons. Hippocampus 22(7), 1493-1500 (2011).
131. Bilang-Bleuel A, Ulbricht S, Chandramohan Y, De Carli S, Droste SK, Reul JM. Psychological stress increases histone H3 phosphorylation in adult dentate gyrus granule neurons: involvement in a glucocorticoid receptor-dependent behavioural response. Eur. J. Neurosci. 22(7), 1691-1700 (2005). (Pubitemid 41482957)
132. Clayton AL, Rose S, Barratt MJ, Mahadevan LC. Phosphoacetylation of histone H3 on c-fos- and c-jun-associated nucleosomes upon gene activation. EMBO J. 19(14), 3714-3726 (2000). (Pubitemid 30462129)
133. Cheung P, Tanner KG, Cheung WL, Sassone- Corsi P, Denu JM, Allis CD. Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. Mol. Cell 5(6), 905-915 (2000).
134. Crosio C, Heitz E, Allis CD, Borrelli E, Sassone-Corsi P. Chromatin remodeling and neuronal response: multiple signaling pathways induce specific histone H3 modifications and early gene expression in hippocampal neurons. J. Cell Sci. 116(Pt 24), 4905-4914 (2003). (Pubitemid 38016697)
135. Perhaps the first demonstration of the effect of external manipulation on histone modifications in the brain.
136. Chandramohan Y, Droste SK, Arthur JS, Reul JM. The forced swimming-induced behavioural immobility response involves histone H3 phospho-acetylation and c-Fos induction in dentate gyrus granule neurons via activation of the N-methyl-d-aspartate/ extracellular signal-regulated kinase/mitogen-and stress-activated kinase signalling pathway. Eur. J. Neurosci. 27(10), 2701-2713 (2008). (Pubitemid 351781672)
137. Chandramohan Y, Droste SK, Reul JM. Novelty stress induces phospho-acetylation of histone H3 in rat dentate gyrus granule neurons through coincident signalling via the N-methyl-D-aspartate receptor and the glucocorticoid receptor: relevance for c-fos induction. J. Neurochem. 101(3), 815-828 (2007). (Pubitemid 46633323)
138. Collins A, Hill LE, Chandramohan Y, Whitcomb D, Droste SK, Reul JM. Exercise improves cognitive responses to psychological stress through enhancement of epigenetic mechanisms and gene expression in the dentate gyrus. PLoS ONE 4(1), e4330 (2009).
139. Papadopoulos A, Chandramohan Y, Collins A, Droste SK, Nutt DJ, Reul JM. GABAergic control of novelty stress-responsive epigenetic and gene expression mechanisms in the rat dentate gyrus. Eur. Neuropsychopharmacol. 21(4), 316-324 (2011).
140. McEwen BS. Stress and hippocampal plasticity. Annu. Rev. Neurosci. 22, 105-122 (1999). (Pubitemid 29144882)
141. Reul JM, Hesketh SA, Collins A, Mecinas MG. Epigenetic mechanisms in the dentate gyrus act as a molecular switch in hippocampus-associated memory formation. Epigenetics 4(7), 434-439 (2009).
142. Gutierrez-Mecinas M, Trollope AF, Collins A et al. Long-lasting behavioral responses to stress involve a direct interaction of glucocorticoid receptors with ERK1/2-MSK1- Elk-1 signaling. Proc. Natl Acad. Sci. USA 108(33), 13806-13811 (2011).
143. Nestler EJ, Hyman SE. Animal models of neuropsychiatric disorders. Nat. Neurosci. 13(10), 1161-1169 (2010).
144. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat. Neurosci. 9(4), 519-525 (2006).
145. Tsankova NM, Kumar A, Nestler EJ. Histone modifications at gene promoter regions in rat hippocampus after acute and chronic electroconvulsive seizures. J. Neurosci. 24(24), 5603-5610 (2004). (Pubitemid 38812643)
146. Renthal W, Maze I, Krishnan V et al. Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron 56(3), 517-529 (2007). (Pubitemid 350030878)
147. Covington HE, 3rd, Maze I, Laplant QC et al. Antidepressant actions of histone deacetylase inhibitors. J. Neurosci. 29(37), 11451-11460 (2009).
148. Laplant Q, Vialou V, Covington HE 3rd et al. Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat. Neurosci. 13(9), 1137-1143 (2010).
149. 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. 13(11), 1351-1353 (2010).
150. Wilkinson MB, Xiao G, Kumar A et al. Imipramine treatment and resiliency exhibit similar chromatin regulation in the mouse nucleus accumbens in depression models. J. Neurosci. 29(24), 7820-7832 (2009).
151. Covington HE, 3rd, Maze I, Sun H et al. A role for repressive histone methylation in cocaine-induced vulnerability to stress. Neuron 71(4), 656-670 (2011).
152. Maze I, Covington HE 3rd, Dietz DM et al. Essential role of the histone methyltransferase G9a in cocaine-induced plasticity. Science 327(5962), 213-216 (2010).
153. Hunter RG, Mccarthy KJ, Milne TA, Pfaff DW, McEwen BS. Regulation of hippocampal H3 histone methylation by acute and chronic stress. Proc. Natl Acad. Sci. USA 106(49), 20912-20917 (2009).
154. Reed B, Fang N, Mayer-Blackwell B et al. Chromatin alterations in response to forced swimming underlie increased prodynorphin transcription. Neuroscience 220, 109-118 (2012).
155. Mcclintock B. The significance of responses of the genome to challenge. Science 226(4676), 792-801 (1984). (Pubitemid 15200674)
156. Hunter RG, Murakami G, Dewell S et al. Acute stress and hippocampal histone H3 lysine 9 trimethylation, a retrotransposon silencing response. Proc. Natl Acad. Sci. USA 109(43), 17657-17662 (2012).
157. Rusiecki JA, Chen L, Srikantan V et al. DNA methylation in repetitive elements and posttraumatic stress disorder: a case-control study of US military service members. Epigenomics 4(1), 29-40 (2012).
158. Hedges DJ, Belancio VP. Restless genomes humans as a model organism for understanding host-retrotransposable element dynamics. Adv. Genet. 73, 219-262 (2011).
159. Uchida S, Nishida A, Hara K et al. Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated downregulation of the glucocorticoid receptor. Eur. J. Neurosci. 27(9), 2250-2261 (2008). (Pubitemid 351590921)
160. Vreugdenhil E, Verissimo CS, Mariman R et al. MicroRNA 18 and 124a down-regulate the glucocorticoid receptor: implications for glucocorticoid responsiveness in the brain. Endocrinology 150(5), 2220-2228 (2009).
161. Meerson A, Cacheaux L, Goosens KA, Sapolsky RM, Soreq H, Kaufer D. Changes in brain MicroRNAs contribute to cholinergic stress reactions. J. Mol. Neurosci. 40(1-2), 47-55 (2010).
162. Haramati S, Navon I, Issler O et al. MicroRNA as repressors of stress-induced anxiety: the case of amygdalar miR-34. J. Neurosci. 31(40), 14191-14203 (2011).
163. Rinaldi A, Vincenti S, De Vito F et al. Stress induces region specific alterations in microRNAs expression in mice. Behav. Brain Res. 208(1), 265-269 (2010).
164. Babenko O, Golubov A, Ilnytskyy Y, Kovalchuk I, Metz GA. Genomic and Epigenomic responses to chronic stress involve miRNA-mediated programming. PLoS ONE 7(1), e29441 (2012).
165. Mongrain V, Hernandez SA, Pradervand S et al. Separating the contribution of glucocorticoids and wakefulness to the molecular and electrophysiological correlates of sleep homeostasis. Sleep 33(9), 1147-1157 (2010).
166. Rajasethupathy P, Antonov I, Sheridan R et al. A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 149(3), 693-707 (2012).
167. Mccue AD, Nuthikattu S, Reeder SH, Slotkin RK. Gene expression and stress response mediated by the epigenetic regulation of a transposable element small RNA. PLoS Genet. 8(2), e1002474 (2012).
168. Perdiguero E, Sousa-Victor P, Ballestar E, Munoz-Canoves P. Epigenetic regulation of myogenesis. Epigenetics 4(8), 541-550 (2009).
169. Sanosaka T, Namihira M, Nakashima K. Epigenetic mechanisms in sequential differentiation of neural stem cells. Epigenetics 4(2), 89-92 (2009).
170. Sapolsky RM, Krey LC, McEwen BS. Corticosterone receptors decline in a sitespecific manner in the aged rat brain. Brain Res. 289(1-2), 235-240 (1983). (Pubitemid 14222524)
171. Sapolsky RM, Krey LC, McEwen BS. The adrenocortical stress-response in the aged male rat: impairment of recovery from stress. Exp. Gerontol. 18(1), 55-64 (1983). (Pubitemid 13099361)
172. Sapolsky RM, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr. Rev. 7(3), 284-301 (1986).
173. Garrido P. Aging and stress: past hypotheses, present approaches and perspectives. Aging Dis 2(1), 80-99 (2012).
174. Lupien S, Lecours AR, Schwartz G et al. Longitudinal study of basal cortisol levels in healthy elderly subjects: evidence for subgroups. Neurobiol. Aging 17(1), 95-105 (1996). (Pubitemid 26022348)
175. Foy MR, Baudry M, Foy JG, Thompson RF. 17beta-estradiol modifies stress-induced and age-related changes in hippocampal synaptic plasticity. Behav. Neurosci. 122(2), 301-309 (2008). (Pubitemid 351672322)
176. Lee SW, Clemenson GD, Gage FH. New neurons in an aged brain. Behav. Brain Res. 227(2), 497-507 (2012).
177. Burke SN, Barnes CA. Senescent synapses and hippocampal circuit dynamics. Trends Neurosci. 33(3), 153-161 (2010).
178. Heyn H, Li N, Ferreira HJ et al. Distinct DNA methylomes of newborns and centenarians. Proc. Natl Acad. Sci. USA 109(26), 10522-10527 (2012).
179. Dosunmu R, Alashwal H, Zawia NH. Genome-wide expression and methylation profiling in the aged rodent brain due to earlylife Pb exposure and its relevance to aging. Mech. Ageing Dev. 133(6), 435-443 (2012).
180. Thompson RF, Atzmon G, Gheorghe C et al. Tissue-specific dysregulation of DNA methylation in aging. Aging Cell 9(4), 506-518 (2010).
181. Hernandez DG, Nalls MA, Gibbs JR et al. Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum. Mol. Genet. 20(6), 1164-1172 (2011).
182. Numata S, Ye T, Hyde TM et al. DNA methylation signatures in development and aging of the human prefrontal cortex. Am. J. Hum. Genet. 90(2), 260-272 (2012).
183. Rao JS, Keleshian VL, Klein S, Rapoport SI. Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients. Transl. Psychiatry 2, e132 (2012).
184. Anderson RM, Shanmuganayagam D, Weindruch R. Caloric restriction and aging: studies in mice and monkeys. Toxicol. Pathol. 37(1), 47-51 (2009).
185. Chouliaras L, Van Den Hove DL, Kenis G et al. Caloric restriction attenuates age-related changes of DNA methyltransferase 3a in mouse hippocampus. Brain Behav. Immun. 25(4), 616-623 (2010).
186. Patel NV, Finch CE. The glucocorticoid paradox of caloric restriction in slowing brain aging. Neurobiol. Aging 23(5), 707-717 (2002). (Pubitemid 35217697)
187. McEwen BS. Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann. NY Acad. Sci. 933, 265-277 (2001). (Pubitemid 32390122)
188. Szulwach KE, Li X, Li Y et al. 5-hmCmediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat. Neurosci. 14(12), 1607-1616 (2011).
189. Chen H, Dzitoyeva S, Manev H. Effect of aging on 5-hydroxymethylcytosine in the mouse hippocampus. Restor. Neurol. Neurosci. 30(3), 237-245 (2012).
190. Graff J, Rei D, Guan JS et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 483(7388), 222-226 (2012).
191. Zeng Y, Tan M, Kohyama J et al. Epigenetic enhancement of BDNF signaling rescues synaptic plasticity in aging. J. Neurosci. 31(49), 17800-17810 (2011).
192. Peleg S, Sananbenesi F, Zovoilis A et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328(5979), 753-756 (2010).
193. Walker MP, Laferla FM, Oddo SS, Brewer GJ. Reversible epigenetic histone modifications and Bdnf expression in neurons with aging and from a mouse model of Alzheimer's disease. Age (Dordr.) doi:10.1007/ s11357-011-9375-5 (2012) (Epub ahead of print).
194. Castellano JF, Fletcher BR, Kelley-Bell B, Kim DH, Gallagher M, Rapp PR. Age-related memory impairment is associated with disrupted multivariate epigenetic coordination in the hippocampus. PLoS ONE 7(3), e33249 (2012).
195. Doyle JP, Dougherty JD, Heiman M et al. Application of a translational profiling approach for the comparative analysis of CNS cell types. Cell 135(4), 749-762 (2008).
196. Heiman M, Schaefer A, Gong S et al. A translational profiling approach for the molecular characterization of CNS cell types. Cell 135(4), 738-748 (2008).
197. Veenema AH. Early life stress, the development of aggression and neuroendocrine and neurobiological correlates: what can we learn from animal models? Front. Neuroendocrinol. 30(4), 497-518 (2009).
198. Kolber BJ, Wieczorek L, Muglia LJ. Hypothalamic-pituitary-adrenal axis dysregulation and behavioral analysis of mouse mutants with altered glucocorticoid or mineralocorticoid receptor function. Stress 11(5), 321-338 (2008).
199. Zhang D, Yu ZY, Cruz P, Kong Q, Li S, Kone BC. Epigenetics and the control of epithelial sodium channel expression in collecting duct. Kidney Int. 75(3), 260-267 (2009).
200. ENCODE Project Consortium. The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306(5696), 636-640 (2004).
201. Spannhoff A, Hauser AT, Heinke R, Sippl W, Jung M. The emerging therapeutic potential of histone methyltransferase and demethylase inhibitors. ChemMedChem. 4(10), 1568-1582 (2009).
202. Kubicek S, O'Sullivan RJ, August EM et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol. Cell 25(3), 473-481 (2007). (Pubitemid 46206139)
203. Hunter RG. Epigenetic effects of stress and corticosteroids in the brain. Front. Cell. Neurosci. 6, 18 (2012).
204. Magarinõs AM, Mcewen BS, Flügge G, Fuchs E. Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J. Neurosci. 16(10), 3534-3540 (1996). (Pubitemid 26142382)