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Perinatal Programming of Neurodevelopment: Epigenetic Mechanisms and the Prenatal Shaping of the Brain

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Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 10))

Abstract

The recent years have witnessed an exponential growth in the knowledge of epigenetic mechanisms, and piling evidence now links DNA methylation and histone modifications with a wide range of physiological processes from embryonic development to memory formation and behavior. Not surprisingly, deregulation of epigenetic modifications is associated with human diseases as well.

An important feature of epigenetics is the ability of transducing environmental input into biological signaling, mainly by modulation of the transcriptome in response to a particular scenario. This characteristic generates developmental plasticity and allows the manifestation of a variety of phenotypes from the same genome.

The early-life years represent a period of particular susceptibility to epigenetic alteration, as active changes in DNA methylation and histone marks are occurring as part of developmental programs and in response to environmental cues, which notably include psychosocial stimulation and maternal behavior. Memory formation and storage, response to stress in adult life, behavior, and manifestation of neurodegenerative conditions can all be imprinted in the organism by epigenetic modifications that contribute to shape the brain during prenatal or early postnatal life. Moreover, if these epigenetic alterations are preserved in the germ line, changes induced in one generation are likely inherited by future offspring. Programming by transgenerational inheritance thus represents a central mechanism by which environmental conditions may influence disease risk across multiple generations.

As novel techniques emerge and as genome-wide profiling of disease-associated methylomes is achieved, epigenetic marks open a new source for biomarker discovery.

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References

  • Adalsteinsson BT, Gudnason H, Aspelund T, Harris TB, Launer LJ, Eiriksdottir G, Smith AV, Gudnason V (2012) Heterogeneity in white blood cells has potential to confound DNA methylation measurements. PloS ONE 7:e46705

    CAS  PubMed Central  PubMed  Google Scholar 

  • Akbarian S, Huang HS (2009) Epigenetic regulation in human brain-focus on histone lysine methylation. Biol Psychiatry 65:198–203

    CAS  PubMed Central  PubMed  Google Scholar 

  • Allis CD, Jenuwein T, Reinberg D (2006) Overview and concepts. In: Allis CD, Jenuwein T, Reinberg D (eds) Epigenetics. Cold Spring Harbor Laboratory, New York, pp 23–61

    Google Scholar 

  • Anglim PP, Alonzo TA, Laird-Offringa IA (2008) DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update. Mol Cancer 7:81

    PubMed Central  PubMed  Google Scholar 

  • Anway MD, Skinner MK (2006) Epigenetic transgenerational actions of endocrine disruptors. Endocrinology 147:S43–S49

    CAS  PubMed  Google Scholar 

  • Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308:1466–1469

    CAS  PubMed  Google Scholar 

  • Anway MD, Leathers C, Skinner MK (2006) Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology 147:5515–5523

    CAS  PubMed  Google Scholar 

  • Bale TL, Vale WW (2004) CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol 44:525–557

    CAS  PubMed  Google Scholar 

  • Ballas N, Battaglioli E, Atouf F, Andres ME, Chenoweth J, Anderson ME, Burger C, Moniwa M, Davie JR, Bowers WJ, Federoff HJ, Rose DW, Rosenfeld MG, Brehm P, Mandel G (2001) Regulation of neuronal traits by a novel transcriptional complex. Neuron 31:353–365

    CAS  PubMed  Google Scholar 

  • Barker DJ, Clark PM (1997) Fetal undernutrition and disease in later life. Rev Reprod 2:105–112

    CAS  PubMed  Google Scholar 

  • Beck S, Olek A, Walter J (1999) From genomics to epigenomics: a loftier view of life. Nat Biotechnol 17:1144

    CAS  PubMed  Google Scholar 

  • Belinsky SA, Klinge DM, Dekker JD, Smith MW, Bocklage TJ, Gilliland FD, Crowell RE, Karp DD, Stidley CA, Picchi MA (2005) Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin Cancer Res 11:6505–6511

    CAS  PubMed  Google Scholar 

  • Berube NG (2011) ATRX in chromatin assembly and genome architecture during development and disease. Biochem Cell Biol 89:435–444

    CAS  PubMed  Google Scholar 

  • Bilang-Bleuel A, Ulbricht S, Chandramohan Y, De Carli S, Droste SK, Reul JM (2005) Psychological stress increases histone H3 phosphorylation in adult dentate gyrus granule neurons: involvement in a glucocorticoid receptor-dependent behavioural response. Euro J Neurosci 22:1691–1700

    Google Scholar 

  • Binder E, Droste SK, Ohl F, Reul JM (2004) Regular voluntary exercise reduces anxiety-related behaviour and impulsiveness in mice. Behav Brain Res 155:197–206

    PubMed  Google Scholar 

  • Caldji C, Tannenbaum B, Sharma S, Francis D, Plotsky PM, Meaney MJ (1998) Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc Natl Acad Sci U S A 95:5335–5340

    CAS  PubMed Central  PubMed  Google Scholar 

  • Caldji C, Francis D, Sharma S, Plotsky PM, Meaney MJ (2000) The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat. Neuropsychopharmacology 22:219–229

    CAS  PubMed  Google Scholar 

  • Caldji C, Diorio J, Meaney MJ (2003) Variations in maternal care alter GABA(A) receptor subunit expression in brain regions associated with fear. Neuropsychopharmacology 28:1950–1959

    CAS  PubMed  Google Scholar 

  • Caldji C, Hellstrom IC, Zhang TY, Diorio J, Meaney MJ (2011) Environmental regulation of the neural epigenome. FEBS Lett 585:2049–2058

    CAS  PubMed  Google Scholar 

  • Cassidy SB, Schwartz S, Miller JL, Driscoll DJ (2012) Prader-Willi syndrome. Genet Med 14:10–26

    CAS  PubMed  Google Scholar 

  • Champagne FA, Meaney MJ (2006) Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model. Biol Psychiatry 59:1227–1235

    CAS  PubMed  Google Scholar 

  • Champagne FA, Weaver IC, Diorio J, Sharma S, Meaney MJ (2003) Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area. Endocrinology 144:4720–4724

    CAS  PubMed  Google Scholar 

  • Chandramohan Y, Droste SK, Reul JM (2007) 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 101:815–828

    CAS  PubMed  Google Scholar 

  • Chong JA, Tapia-Ramirez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD, Mandel G (1995) REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 80:949–957

    CAS  PubMed  Google Scholar 

  • Chugani HT, Behen ME, Muzik O, Juhasz C, Nagy F, Chugani DC (2001) Local brain functional activity following early deprivation: a study of postinstitutionalized Romanian orphans. Neuroimage 14:1290–1301

    CAS  PubMed  Google Scholar 

  • Cohen FE, Prusiner SB (1998) Pathologic conformations of prion proteins. Annu Rev Biochem 67:793–819

    CAS  PubMed  Google Scholar 

  • Crick F (1970) Central dogma of molecular biology. Nature 227:561–563

    CAS  PubMed  Google Scholar 

  • Crosio C, Cermakian N, Allis CD, Sassone-Corsi P (2000) Light induces chromatin modification in cells of the mammalian circadian clock. Nat Neurosci 3:1241–1247

    CAS  PubMed  Google Scholar 

  • Crosio C, Heitz E, Allis CD, Borrelli E, Sassone-Corsi P (2003) Chromatin remodeling and neuronal response: multiple signaling pathways induce specific histone H3 modifications and early gene expression in hippocampal neurons. J Cell Sci 116:4905–4914

    CAS  PubMed  Google Scholar 

  • Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909

    CAS  PubMed  Google Scholar 

  • Davies MN, Volta M, Pidsley R, Lunnon K, Dixit A, Lovestone S, Coarfa C, Harris RA, Milosavljevic A, Troakes C, Al-Sarraj S, Dobson R, Schalkwyk LC, Mill J (2012) Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol 13:R43

    CAS  PubMed Central  PubMed  Google Scholar 

  • Day JJ, Childs D, Guzman-Karlsson MC, Kibe M, Moulden J, Song E, Tahir A, Sweatt JD (2013) DNA methylation regulates associative reward learning. Nat Neurosci 16:1445–1452

    CAS  PubMed Central  PubMed  Google Scholar 

  • de Kloet ER, Karst H, Joels M (2008) Corticosteroid hormones in the central stress response: quick-and-slow. Front Neuroendocrinol 29:268–272

    CAS  PubMed  Google Scholar 

  • Denenberg VH (1964) Critical periods, stimulus input, and emotional reactivity: a theory of infantile stimulation. Psychol Rev 71:335–351

    CAS  PubMed  Google Scholar 

  • Desplats P, Spencer B, Coffee E, Patel P, Michael S, Patrick C, Adame A, Rockenstein E, Masliah E (2011) Alpha-synuclein sequesters Dnmt1 from the nucleus: a novel mechanism for epigenetic alterations in Lewy body diseases. J Biol Chem 286:9031–9037

    CAS  PubMed Central  PubMed  Google Scholar 

  • Desplats P, Spencer B, Crews L, Patel P, Morvinski-Friedmann D, Kosberg K, Roberts S, Patrick C, Winner B, Winkler J, Masliah E (2012) Alpha-synuclein induces alterations in adult neurogenesis in Parkinson’s disease models via p53-mediated repression of Notch1. J Biol Chem 287:31691–31702

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dolinoy DC, Huang D, Jirtle RL (2007a) Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci U S A 104:13056–13061

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dolinoy DC, Weidman JR, Jirtle RL (2007b) Epigenetic gene regulation: linking early developmental environment to adult disease. Reprod Toxicol 23:297–307

    CAS  PubMed  Google Scholar 

  • Entringer S, Buss C, Kumsta R, Hellhammer DH, Wadhwa PD, Wust S (2009) Prenatal psychosocial stress exposure is associated with subsequent working memory performance in young women. Behav Neurosci 123:886–893

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fenoglio KA, Brunson KL, Avishai-Eliner S, Stone BA, Kapadia BJ, Baram TZ (2005) Enduring, handling-evoked enhancement of hippocampal memory function and glucocorticoid receptor expression involves activation of the corticotropin-releasing factor type 1 receptor. Endocrinology 146:4090–4096

    CAS  PubMed Central  PubMed  Google Scholar 

  • Field T, Diego M, Hernandez-Reif M, Vera Y, Gil K, Schanberg S, Kuhn C, Gonzalez-Garcia A (2004) Prenatal maternal biochemistry predicts neonatal biochemistry. Int J Neurosci 114:933–945

    CAS  PubMed  Google Scholar 

  • Foley DL, Craig JM, Morley R, Olsson CA, Dwyer T, Smith K, Saffery R (2009) Prospects for epigenetic epidemiology. Am J Epidemiol 169:389–400

    PubMed Central  PubMed  Google Scholar 

  • Franchini DM, Schmitz KM, Petersen-Mahrt SK (2012) 5-Methylcytosine DNA demethylation: more than losing a methyl group. Annu Rev Genet 46:419–441

    CAS  PubMed  Google Scholar 

  • Francis D, Diorio J, Liu D, Meaney MJ (1999) Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155–1158

    CAS  PubMed  Google Scholar 

  • Fride E, Dan Y, Gavish M, Weinstock M (1985) Prenatal stress impairs maternal behavior in a conflict situation and reduces hippocampal benzodiazepine receptors. Life Sci 36:2103–2109

    CAS  PubMed  Google Scholar 

  • Galobardes B, Davey Smith G, Jeffreys M, McCarron P (2006) Childhood socioeconomic circumstances predict specific causes of death in adulthood: the Glasgow student cohort study. J Epidemiol Community Health 60:527–529

    PubMed Central  PubMed  Google Scholar 

  • Gavin DP, Akbarian S (2012) Epigenetic and post-transcriptional dysregulation of gene expression in schizophrenia and related disease. Neurobiol Dis 46:255–262

    CAS  PubMed  Google Scholar 

  • Grayson DR, Guidotti A (2013) The dynamics of DNA methylation in schizophrenia and related psychiatric disorders. Neuropsychopharmacology 38:138–166

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro ML, Persico A, Pericak-Vance MA (2009) Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med 7:62

    PubMed Central  PubMed  Google Scholar 

  • Grillo E, Villard L, Clarke A, Ben Zeev B, Pineda M, Bahi-Buisson N, Hryniewiecka-Jaworska A, Bienvenu T, Armstrong J, Roche-Martinez A, Mari F, Veneselli E, Russo S, Vignoli A, Pini G, Djuric M, Bisgaard AM, Mejaski Bosnjak V, Polgar N, Cogliati F, Ravn K, Pintaudi M, Melegh B, Craiu D, Djukic A, Renieri A (2012) Rett networked database: an integrated clinical and genetic network of Rett syndrome databases. Hum Mutat 33:1031–1036

    CAS  PubMed  Google Scholar 

  • Grozinger CM, Schreiber SL (2002) Deacetylase enzymes: biological functions and the use of small-molecule inhibitors. Chem Biol 9:3–16

    CAS  PubMed  Google Scholar 

  • Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai LH (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459:55–60

    CAS  PubMed Central  PubMed  Google Scholar 

  • Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK (2010) Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS ONE 5

    Google Scholar 

  • He Q, Chen HY, Bai EQ, Luo YX, Fu RJ, He YS, Jiang J, Wang HQ (2010) Development of a multiplex MethyLight assay for the detection of multigene methylation in human colorectal cancer. Cancer Genet Cytogenet 202:1–10

    CAS  PubMed  Google Scholar 

  • He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y, Li X, Dai Q, Song CX, Zhang K, He C, Xu GL (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333:1303–1307

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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. Cereb Cortex 21:262–271

    PubMed  Google Scholar 

  • Hirsch EC, Hunot S, Faucheux B, Agid Y, Mizuno Y, Mochizuki H, Tatton WG, Tatton N, Olanow WC (1999) Dopaminergic neurons degenerate by apoptosis in Parkinson’s disease. Mov Disord 14:383–385

    CAS  PubMed  Google Scholar 

  • Huang Y, Myers SJ, Dingledine R (1999) Transcriptional repression by REST: recruitment of Sin3A and histone deacetylase to neuronal genes. Nat Neurosci 2:867–872

    CAS  PubMed  Google Scholar 

  • Huizink AC, Mulder EJ, Buitelaar JK (2004) Prenatal stress and risk for psychopathology: specific effects or induction of general susceptibility? Psychol Bull 130:115–142

    PubMed  Google Scholar 

  • Hunter RG, McCarthy KJ, Milne TA, Pfaff DW, McEwen BS (2009) Regulation of hippocampal H3 histone methylation by acute and chronic stress. Proc Natl Acad Sci U S A 106:20912–20917

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ito S, D’Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y (2010) Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466:1129–1133

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300–1303

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jana NR (2012) Understanding the pathogenesis of Angelman syndrome through animal models. Neural Plast 2012:710943

    PubMed Central  PubMed  Google Scholar 

  • Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    CAS  PubMed  Google Scholar 

  • Jiang Y, Langley B, Lubin FD, Renthal W, Wood MA, Yasui DH, Kumar A, Nestler EJ, Akbarian S, Beckel-Mitchener AC (2008) Epigenetics in the nervous system. J Neurosci 28:11753–11759

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kaplan GA, Turrell G, Lynch JW, Everson SA, Helkala EL, Salonen JT (2001) Childhood socioeconomic position and cognitive function in adulthood. Int J Epidemiol 30:256–263

    CAS  PubMed  Google Scholar 

  • Kim FJ, Battini JL, Manel N, Sitbon M (2004a) Emergence of vertebrate retroviruses and envelope capture. Virology 318:183–191

    CAS  PubMed  Google Scholar 

  • Kim H, Kwon YM, Kim JS, Lee H, Park JH, Shim YM, Han J, Park J, Kim DH (2004b) Tumor-specific methylation in bronchial lavage for the early detection of non-small-cell lung cancer. J Clin Oncol 22:2363–2370

    CAS  PubMed  Google Scholar 

  • Kim HS, Kim EM, Kim NJ, Chang KA, Choi Y, Ahn KW, Lee JH, Kim S, Park CH, Suh YH (2004c) Inhibition of histone deacetylation enhances the neurotoxicity induced by the C-terminal fragments of amyloid precursor protein. J Neurosci Res 75:117–124

    CAS  PubMed  Google Scholar 

  • Kornberg RD (1974) Chromatin structure: a repeating unit of histones and DNA. Science 184:868–871

    CAS  PubMed  Google Scholar 

  • Korosi A, Shanabrough M, McClelland S, Liu ZW, Borok E, Gao XB, Horvath TL, Baram TZ (2010) Early-life experience reduces excitation to stress-responsive hypothalamic neurons and modulate the programming the expression of corticotropin-releasing hormone. J Neurosci 30:703–713

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929–930

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kuo MH, Allis CD (1998) Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays 20:615–626

    CAS  PubMed  Google Scholar 

  • Lattal KM, Wood MA (2013) Epigenetics and persistent memory: implications for reconsolidation and silent extinction beyond the zero. Nat Neurosci 16:124–129

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee DY, Hayes JJ, Pruss D, Wolffe AP (1993) A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72:73–84

    CAS  PubMed  Google Scholar 

  • Lehnen H, Zechner U, Haaf T (2013) Epigenetics of gestational diabetes mellitus and offspring health: the time for action is in early stages of life. Mol Hum Reprod 19:415–422

    PubMed Central  PubMed  Google Scholar 

  • Levenson JM, Sweatt JD (2005) Epigenetic mechanisms in memory formation. Nat Rev Neurosci 6:108–118

    CAS  PubMed  Google Scholar 

  • Levenson JM, O’Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD (2004) Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 279:40545–40559

    CAS  PubMed  Google Scholar 

  • Levine S (1970) The pituitary-adrenal system and the developing brain. Prog Brain Res 32:79–85

    CAS  PubMed  Google Scholar 

  • Levine S (1994) The ontogeny of the hypothalamic-pituitary-adrenal axis. The influence of maternal factors. Ann N Y Acad Sci 746:275–288 (discussion 289–293)

    CAS  PubMed  Google Scholar 

  • Levy OA, Malagelada C, Greene LA (2009) Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Apoptosis 14:478–500

    PubMed Central  PubMed  Google Scholar 

  • Li L, Suzuki T, Mori N, Greengard P (1993) Identification of a functional silencer element involved in neuron-specific expression of the synapsin I gene. Proc Natl Acad Sci U S A 90:1460–1464

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277:1659–1662

    CAS  PubMed  Google Scholar 

  • Liu J, Chen J, Ehrlich S, Walton E, White T, Perrone-Bizzozero N, Bustillo J, Turner JA, Calhoun VD (2013) Methylation patterns in whole blood correlate with symptoms in schizophrenia patients. Schizophr Bull 40:769–776

    PubMed  Google Scholar 

  • Lubin FD, Roth TL, Sweatt JD (2008) Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci 28:10576–10586

    CAS  PubMed Central  PubMed  Google Scholar 

  • Magistri M, Faghihi MA, St Laurent G, 3rd, Wahlestedt C (2012) Regulation of chromatin structure by long noncoding RNAs: focus on natural antisense transcripts. Trends Genet 28:389–396

    CAS  PubMed Central  PubMed  Google Scholar 

  • Malvaez M, McQuown SC, Rogge GA, Astarabadi M, Jacques V, Carreiro S, Rusche JR, Wood MA (2013) HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. Proc Natl Acad Sci U S A 110:2647–2652

    CAS  PubMed Central  PubMed  Google Scholar 

  • Manning-Courtney P, Murray D, Currans K, Johnson H, Bing N, Kroeger-Geoppinger K, Sorensen R, Bass J, Reinhold J, Johnson A, Messerschmidt T (2013) Autism spectrum disorders. Curr Probl Pediatr Adolesc Health Care 43:2–11

    PubMed  Google Scholar 

  • Martinotti G, Di Iorio G, Marini S, Ricci V, De Berardis D, Di Giannantonio M (2012) Nerve growth factor and brain-derived neurotrophic factor concentrations in schizophrenia: a review. J Biol Regul Homeost Agents 26:347–356

    CAS  PubMed  Google Scholar 

  • Masliah E, Mallory M, Hansen L, DeTeresa R, Alford M, Terry R (1994) Synaptic and neuritic alterations during the progression of Alzheimer’s disease. Neurosci Lett 174:67–72

    CAS  PubMed  Google Scholar 

  • Masliah E, Dumaop W, Galasko D, Desplats P (2013) Distinctive patterns of DNA methylation associated with Parkinson disease: Identification of concordant epigenetic changes in brain and peripheral blood leukocytes. Epigenetics 8:1030–1038

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mastroeni D, McKee A, Grover A, Rogers J, Coleman PD (2009) Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer’s disease. PloS ONE 4:e6617

    PubMed Central  PubMed  Google Scholar 

  • Mastroeni D, Grover A, Delvaux E, Whiteside C, Coleman PD, Rogers J (2010) Epigenetic changes in Alzheimer’s disease: decrements in DNA methylation. Neurobiol Aging 31:2025–2037

    CAS  PubMed Central  PubMed  Google Scholar 

  • McClelland SKA, Cope J, Ivy A, Baram T (2011) Emerging roles of epigenetic mechanisms in the enduring effects of neonatal stress and experience on lerning and memory. Neurobiol Learn Mem 96:79–88

    PubMed Central  PubMed  Google Scholar 

  • McEwen BS (2007) Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 87:873–904

    PubMed  Google Scholar 

  • McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonte B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12:342–348

    CAS  PubMed Central  PubMed  Google Scholar 

  • McManus MT, Sharp PA (2002) Gene silencing in mammals by small interfering RNAs. Nat Rev Genet 3:737–747

    CAS  PubMed  Google Scholar 

  • Meaney MJ (2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24:1161–1192

    CAS  PubMed  Google Scholar 

  • Meaney MJ (2010) Epigenetics and the biological definition of gene x environment interactions. Child Dev 81:41–79

    PubMed  Google Scholar 

  • Meaney MJ, Mitchell JB, Aitken DH, Bhatnagar S, Bodnoff SR, Iny LJ, Sarrieau A (1991) The effects of neonatal handling on the development of the adrenocortical response to stress: implications for neuropathology and cognitive deficits in later life. Psychoneuroendocrinology 16:85–103

    CAS  PubMed  Google Scholar 

  • Meaney MJ, Aitken DH, van Berkel C, Bhatnagar S, Sapolsky RM (1988) Effect of neonatal handling on age-related impairments associated with the hippocampus. Science 239:766–768

    CAS  PubMed  Google Scholar 

  • Meany MDJ, Donaldson L, Yau J, Chapman K, Seckl J (2000) Handling alters the expression of messenger RNAs for AP-2, NGFI-A and NGFI-B in the hippocampus of neonatal rats. J Neuroscience 20:3936–3945

    Google Scholar 

  • Medstrand P, van de Lagemaat LN, Dunn CA, Landry JR, Svenback D, Mager DL (2005) Impact of transposable elements on the evolution of mammalian gene regulation. Cytogenet Genome Res 110:342–352

    CAS  PubMed  Google Scholar 

  • Mehta D, Klengel T, Conneely KN, Smith AK, Altmann A, Pace TW, Rex-Haffner M, Loeschner A, Gonik M, Mercer KB, Bradley B, Muller-Myhsok B, Ressler KJ, Binder EB (2013) Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc Natl Acad Sci U S A 110:8302–8307

    CAS  PubMed Central  PubMed  Google Scholar 

  • Meng H, Joyce AR, Adkins DE, Basu P, Jia Y, Li G, Sengupta TK, Zedler BK, Murrelle EL, van den Oord EJ (2010) A statistical method for excluding non-variable CpG sites in high-throughput DNA methylation profiling. BMC Bioinformatics 11:227

    PubMed Central  PubMed  Google Scholar 

  • Millan MJ (2013) An epigenetic framework for neurodevelopmental disorders: from pathogenesis to potential therapy. Neuropharmacology 68:2–82

    CAS  PubMed  Google Scholar 

  • Moore CL, Power KL (1986) Prenatal stress affects mother-infant interaction in Norway rats. Dev Psychobiol 19:235–245

    CAS  PubMed  Google Scholar 

  • Morgan HD, Santos F, Green K, Dean W, Reik W (2005) Epigenetic modulation of programming in mammals. Hum Mol Genet 14 (Spec No 1):R47–R58

    CAS  PubMed  Google Scholar 

  • Mulligan CJ, D’Errico NC, Stees J, Hughes DA (2012) Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics 7:853–857

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nagahara AH, Tuszynski MH (2011) Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 10:209–219

    CAS  PubMed  Google Scholar 

  • Nagarajan RP, Hogart AR, Gwye Y, Martin MR, LaSalle JM (2006) Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics 1:e1–e11

    PubMed Central  PubMed  Google Scholar 

  • Nan X, Campoy FJ, Bird A (1997) MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell 88:471–481

    CAS  PubMed  Google Scholar 

  • Naruse Y, Aoki T, Kojima T, Mori N (1999) Neural restrictive silencer factor recruits mSin3 and histone deacetylase complex to repress neuron-specific target genes. Proc Natl Acad Sci U S A 96:13691–13696

    CAS  PubMed Central  PubMed  Google Scholar 

  • Naruse Y, Oh-hashi K, Iijima N, Naruse M, Yoshioka H, Tanaka M (2004) Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation. Mol Cell Biol 24:6278–6287

    CAS  PubMed Central  PubMed  Google Scholar 

  • Naumova OY, Lee M, Koposov R, Szyf M, Dozier M, Grigorenko EL (2012) Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents. Dev Psychopathol 24:143–155

    PubMed Central  PubMed  Google Scholar 

  • Nelson CA 3rd, Zeanah CH, Fox NA, Marshall PJ, Smyke AT, Guthrie D (2007) Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project. Science 318:1937–1940

    CAS  PubMed  Google Scholar 

  • Nilsson EE, Anway MD, Stanfield J, Skinner MK (2008) Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease. Reproduction 135:713–721

    CAS  PubMed  Google Scholar 

  • Nilsson E, Larsen G, Manikkam M, Guerrero-Bosagna C, Savenkova MI, Skinner MK (2012) Environmentally induced epigenetic transgenerational inheritance of ovarian disease. PLoS ONE 7:e36129

    CAS  PubMed Central  PubMed  Google Scholar 

  • O’Connor TG, Rutter M (2000) Attachment disorder behavior following early severe deprivation: extension and longitudinal follow-up. English and Romanian adoptees study team. J Am Acad Child Adolesc Psychiatry 39:703–712

    PubMed  Google Scholar 

  • Okano M, Xie S, Li E (1998) Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 19:219–220

    CAS  PubMed  Google Scholar 

  • Perkins A, Lehmann C, Lawrence RC, Kelly SJ (2013) Alcohol exposure during development: Impact on the epigenome. Int J Dev Neurosci 31:391–397

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perry M, Chalkley R (1982) Histone acetylation increases the solubility of chromatin and occurs sequentially over most of the chromatin. A novel model for the biological role of histone acetylation. J Biol Chem 257:7336–7347

    CAS  PubMed  Google Scholar 

  • Plotsky PM, Meaney MJ (1993) Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Brain Res Mol Brain Res 18:195–200

    CAS  PubMed  Google Scholar 

  • Plotsky PM, Cunningham ET Jr, Widmaier EP (1989) Catecholaminergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion. Endocr Rev 10:437–458

    CAS  PubMed  Google Scholar 

  • Ramchandani S, Bhattacharya SK, Cervoni N, Szyf M (1999) DNA methylation is a reversible biological signal. Proc Natl Acad Sci U S A 96:6107–6112

    CAS  PubMed Central  PubMed  Google Scholar 

  • Razin A (1998) CpG methylation, chromatin structure and gene silencing-a three-way connection. Embo J 17:4905–4908

    CAS  PubMed Central  PubMed  Google Scholar 

  • Razin A, Riggs AD (1980) DNA methylation and gene function. Science 210:604–610

    CAS  PubMed  Google Scholar 

  • Reik W, Walter J (2001) Genomic imprinting: parental influence on the genome. Nat Rev Genet 2:21–32

    CAS  PubMed  Google Scholar 

  • Reinius LE, Acevedo N, Joerink M, Pershagen G, Dahlen SE, Greco D, Soderhall C, Scheynius A, Kere J (2012) Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility. PloS ONE 7:e41361

    CAS  PubMed Central  PubMed  Google Scholar 

  • Riggs ADM, Martienssen RA, Russo VEA (1996) Introduction in epigenetic mechanisms of gene regulation. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 1–4 (ed, V.E.A. Russo et al.)

    Google Scholar 

  • Roth SY, Denu JM, Allis CD (2001) Histone acetyltransferases. Annu Rev Biochem 70:81–120

    CAS  PubMed  Google Scholar 

  • Roth TL, Lubin FD, Funk AJ, Sweatt JD (2009) Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry 65:760–769

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shorter J, Lindquist S (2005) Prions as adaptive conduits of memory and inheritance. Nat Rev Genet 6:435–450

    CAS  PubMed  Google Scholar 

  • Shulha HP, Cheung I, Whittle C, Wang J, Virgil D, Lin CL, Guo Y, Lessard A, Akbarian S, Weng Z (2012) Epigenetic signatures of autism: trimethylated H3K4 landscapes in prefrontal neurons. Arch Gen Psychiatry 69:314–324

    CAS  PubMed  Google Scholar 

  • Siegmund KD, Connor CM, Campan M, Long TI, Weisenberger DJ, Biniszkiewicz D, Jaenisch R, Laird PW, Akbarian S (2007) DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS ONE 2:e895

    PubMed Central  PubMed  Google Scholar 

  • Skinner MK (2011) Environmental epigenetic transgenerational inheritance and somatic epigenetic mitotic stability. Epigenetics 6:838–842

    CAS  PubMed  Google Scholar 

  • Skinner MK, Anway MD, Savenkova MI, Gore AC, Crews D (2008) Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior. PloS ONE 3:e3745

    PubMed Central  PubMed  Google Scholar 

  • Skinner MK, Manikkam M, Guerrero-Bosagna C (2010) Epigenetic transgenerational actions of environmental factors in disease etiology. Trends Endocrinol Metab 21:214–222

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stankiewicz AM, Swiergiel AH, Lisowski P (2013) Epigenetics of stress adaptations in the brain. Brain Res Bull 98C:76–92

    Google Scholar 

  • Szwagierczak A, Bultmann S, Schmidt CS, Spada F, Leonhardt H (2010) Sensitive enzymatic quantification of 5-hydroxymethylcytosine in genomic DNA. Nucleic Acids Res 38:e181

    PubMed Central  PubMed  Google Scholar 

  • Szyf M, Weaver IC, Champagne FA, Diorio J, Meaney MJ (2005) Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat. Front Neuroendocrinol 26:139–162

    CAS  PubMed  Google Scholar 

  • Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tehranifar P, Wu HC, Fan X, Flom JD, Ferris JS, Cho YH, Gonzalez K, Santella RM, Terry MB (2013) Early life socioeconomic factors and genomic DNA methylation in mid-life. Epigenetics 8:23–27

    CAS  PubMed Central  PubMed  Google Scholar 

  • Terry MB, Delgado-Cruzata L, Vin-Raviv N, Wu HC, Santella RM (2011) DNA methylation in white blood cells: association with risk factors in epidemiologic studies. Epigenetics 6:828–837

    CAS  PubMed Central  PubMed  Google Scholar 

  • Torregrossa MM, Taylor JR (2013) Learning to forget: manipulating extinction and reconsolidation processes to treat addiction. Psychopharmacology (Berl) 226:659–672

    CAS  Google Scholar 

  • Tsankova N, Renthal W, Kumar A, Nestler EJ (2007) Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 8:355–367

    CAS  PubMed  Google Scholar 

  • Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439:811–816

    CAS  PubMed  Google Scholar 

  • Uno H, Tarara R, Else JG, Suleman MA, Sapolsky RM (1989) Hippocampal damage associated with prolonged and fatal stress in primates. J Neurosci 9:1705–1711

    CAS  PubMed  Google Scholar 

  • Urdinguio RG, Sanchez-Mut JV, Esteller M (2009) Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies. Lancet Neurol 8:1056–1072

    CAS  PubMed  Google Scholar 

  • Valinluck V, Sowers LC (2007) Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res 67:946–950

    CAS  PubMed  Google Scholar 

  • Vallee M, MacCari S, Dellu F, Simon H, Le Moal M, Mayo W (1999) 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 11:2906–2916

    CAS  PubMed  Google Scholar 

  • Van den Bergh BR, Mulder EJ, Mennes M, Glover V (2005) Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review. Neurosci Biobehav Rev 29:237–258

    PubMed  Google Scholar 

  • Van den Hove DL, Steinbusch HW, Scheepens A, Van deBWD, Kooiman LA, Boosten BJ, Prickaerts J, Blanco CE (2006) Prenatal stress and neonatal rat brain development. Neuroscience 137:145–155

    CAS  PubMed  Google Scholar 

  • Vaquero A, Loyola A, Reinberg D (2003) The constantly changing face of chromatin. Sci Aging Knowledge Environ 2003:RE4

    PubMed  Google Scholar 

  • Waddington CH (1942) The epigenotype. Endeavour 1:18–20

    Google Scholar 

  • Wadhwa PD, Sandman CA, Porto M, Dunkel-Schetter C, Garite TJ (1993) The association between prenatal stress and infant birth weight and gestational age at birth: a prospective investigation. Am J Obstet Gynecol 169:858–865

    CAS  PubMed  Google Scholar 

  • Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854

    CAS  PubMed  Google Scholar 

  • Weaver IC, Champagne FA, Brown SE, Dymov S, Sharma S, Meaney MJ, Szyf M (2005) Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J Neurosci 25:11045–11054

    CAS  PubMed  Google Scholar 

  • Weaver IC, DiAlessio AC, Brown SE, Hellstrom IC, Dymov S, Diorio J et al (2007) The trasncription factor NGFI-A mediates epigenetic programming: Altering epigenetic marking through immediate early genes. J Neurosci 27:1756–1768

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weber M, Hellmann I, Stadler MB, Ramos L, Paabo S, Rebhan M, Schubeler D (2007) Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 39:457–466

    CAS  PubMed  Google Scholar 

  • Weinstock M (2001) Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 65:427–451

    CAS  PubMed  Google Scholar 

  • Wilkinson MB, Xiao G, Kumar A, LaPlant Q, Renthal W, Sikder D, Kodadek TJ, Nestler EJ (2009) Imipramine treatment and resiliency exhibit similar chromatin regulation in the mouse nucleus accumbens in depression models. J Neurosci 29:7820–7832

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson RS, Schneider JA, Boyle PA, Arnold SE, Tang Y, Bennett DA (2007) Chronic distress and incidence of mild cognitive impairment. Neurology 68:2085–2092

    CAS  PubMed  Google Scholar 

  • Yamada K, Mizuno M, Nabeshima T (2002) Role for brain-derived neurotrophic factor in learning and memory. Life Sci 70:735–744

    CAS  PubMed  Google Scholar 

  • Zuena AR, Mairesse J, Casolini P, Cinque C, Alema GS, Morley-Fletcher S, Chiodi V, Spagnoli LG, Gradini R, Catalani A, Nicoletti F, Maccari S (2008) Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats. PLoS ONE 3:e2170

    PubMed Central  PubMed  Google Scholar 

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Desplats, P. (2015). Perinatal Programming of Neurodevelopment: Epigenetic Mechanisms and the Prenatal Shaping of the Brain. In: Antonelli, M. (eds) Perinatal Programming of Neurodevelopment. Advances in Neurobiology, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1372-5_16

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