Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-26T09:04:48.730Z Has data issue: false hasContentIssue false

Understanding the epigenetics of neurodevelopmental disorders and DOHaD

Published online by Cambridge University Press:  24 February 2015

T. Kubota*
Affiliation:
Department of Epigenetic Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
K. Miyake
Affiliation:
Department of Epigenetic Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
N. Hariya
Affiliation:
Department of Epigenetic Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
K. Mochizuki
Affiliation:
Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, Faculty of Medicine, University of Yamanashi, Kofu, Japan
*
*Address for correspondence: T. Kubota, Department of Epigenetic Medicine, Fuculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. (Email: takeot@yamanashi.ac.jp)

Abstract

The Developmental Origins of Health and Disease (DOHaD) hypothesis refers to the concept that ‘malnutrition during the fetal period induces a nature of thrift in fetuses, such that they have a higher change of developing non-communicable diseases, such as obesity and diabetes, if they grow up in the current well-fed society.’ Epigenetics is a chemical change in DNA and histones that affects how genes are expressed without alterations of DNA sequences. Several lines of evidence suggest that malnutrition during the fetal period alters the epigenetic expression status of metabolic genes in the fetus and that this altered expression can persist, and possibly lead to metabolic disorders. Similarly, mental stress during the neonatal period can alter the epigenetic expression status of neuronal genes in neonates. Moreover, such environmental, stress-induced, epigenetic changes are transmitted to the next generation via an acquired epigenetic status in sperm. The advantage of epigenetic modifications over changes in genetic sequences is their potential reversibility; thus, epigenetic alterations are potentially reversed with gene expression. Therefore, we potentially establish ‘preemptive medicine,’ that, in combination with early detection of abnormal epigenetic status and early administration of epigenetic-restoring drugs may prevent the development of disorders associated with the DOHaD.

Type
Review
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Inoue, K, Kanai, M, Tanabe, Y, et al. Prenatal interphase FISH diagnosis of PLP1 duplication associated with Pelizaeus–Merzbacher disease. Prenat Diagn. 2001; 21, 11331136.Google Scholar
2. Reiner, O, Carrozzo, R, Shen, Y, et al. Isolation of a Miller-Dieker lissencephaly gene containing g protein beta-subunit-like repeats. Nature. 1993; 364, 717721.Google Scholar
3. Bi, W, Sapir, T, Shchelochkov, OA, et al. Increased LIS1 expression affects human and mouse brain development. Nat Genet. 2009; 41, 168177.CrossRefGoogle ScholarPubMed
4. Online Mendelian Inheritance in Man (OMIM): #118220. Retrieved 31 January 2015 from http://www ncbi nlm nih gov/entrez/ Google Scholar
5. Obi, T, Nishioka, K, Ross, OA, et al. Clinicopathologic study of a SNCA gene duplication patient with Parkinson disease and dementia. Neurology. 2008; 70, 238241.Google Scholar
6. Waddington, CH. Epigenotype. Endeavour. 1942; 1, 1820.Google Scholar
7. Sharma, S, Kelly, TK, Jones, PA. Epigenetics in cancer. Carcinogenesis. 2010; 31, 2736.Google Scholar
8. Kubota, T, Das, S, Christian, SL, et al. Methylation-specific PCR simplifies imprinting analysis. Nat Genet. 1997; 16, 1617.CrossRefGoogle ScholarPubMed
9. Nicholls, RD, Saitoh, S, Horsthemke, B. Imprinting in Prader-Willi and Angelman syndromes. Trends Genet. 1998; 14, 194200.Google Scholar
10. Duker, AL, Ballif, BC, Bawle, EV, et al. Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader-Willi syndrome. Eur J Hum Genet. 2010; 18, 11961201.Google Scholar
11. Runte, M, Kroisel, PM, Gillessen-Kaesbach, G, et al. SNURF-SNRPN and UBE3A transcript levels in patients with Angelman syndrome. Hum Genet. 2004; 114, 553561.Google Scholar
12. Kubota, T, Saitoh, S, Matsumoto, T, et al. Excess functional copy of allele at chromosomal region 11p15 may cause Wiedemann-Beckwith (EMG) syndrome. Am J Med Genet. 1994; 49, 378383.CrossRefGoogle ScholarPubMed
13. Gene Reviews (internet): Beckwith-Wiedemann syndrome. Retrieved 31 January 2015 from http://www.ncbi.nlm.nih.gov/books/NBK1394/ Google Scholar
14. Kubota, T, Wakui, K, Nakamura, T, et al. Proportion of the cells with functional X disomy is associated with the severity of mental retardation in mosaic ring X Turner syndrome females. Cytogenet Genome Res. 2002; 99, 276284.CrossRefGoogle ScholarPubMed
15. Kubota, T, Nonoyama, S, Tonoki, H, et al. A new assay for the analysis of X-chromosome inactivation based on methylation-specific PCR. Hum Genet. 1999; 104, 4955.Google Scholar
16. Sasaki, H, Matsui, Y. Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet. 2008; 9, 129140.CrossRefGoogle ScholarPubMed
17. Sakashita, K, Koike, K, Kinoshita, T, et al. Dynamic DNA methylation change in the CpG island region of p15 during human myeloid development. J Clin Invest. 2001; 108, 11951204.CrossRefGoogle ScholarPubMed
18. Lillycrop, KA, Phillips, ES, Jackson, AA, Hanson, MA, Burdge, GC. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr. 2005; 135, 13821386.Google Scholar
19. Lillycrop, KA, Phillips, ES, Torrens, C, et al. Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring. Br J Nutr. 2008; 100, 278282.CrossRefGoogle ScholarPubMed
20. Weaver, IC, Cervoni, N, Champagne, FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004; 7, 847854.Google Scholar
21. Nolen, LD, Gao, S, Han, Z, et al. X chromosome reactivation and regulation in cloned embryos. Dev Biol. 2005; 279, 525540.Google Scholar
22. Okano, M, Bell, DW, Haber, DA, et al. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999; 99, 247257.Google Scholar
23. Shirohzu, H, Kubota, T, Kumazawa, A, et al. Three novel DNMT3B mutations in Japanese patients with ICF syndrome. Am J Med Genet. 2002; 112, 3137.CrossRefGoogle ScholarPubMed
24. Kubota, T, Furuumi, H, Kamoda, T, et al. ICF syndrome in a girl with DNA hypomethylation but without detectable DNMT3B mutation. Am J Med Genet. A. 2004; 129, 290293.Google Scholar
25. Tatton-Brown, K, Seal, S, Ruark, E, et al. Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability. Nat Genet. 2014; 46, 385388.Google Scholar
26. Amir, RE, Van den Veyver, IB, Wan, M, et al. Rett syndrome is caused by mutations in X-linked MECP2 encoding methyl-CpG-binding protein 2. Nat Genet. 1999; 23, 185188.Google Scholar
27. Chunshu, Y, Endoh, K, Soutome, M, et al. A patient with classic Rett syndrome with a novel mutation in MECP2 exon 1. Clin Genet. 2006; 70, 530531.Google Scholar
28. Miyake, K, Hirasawa, T, Soutome, M, et al. The protocadherins, PCDHB1 and PCDH7, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome. BMC Neurosci. 2011; 12, 81.Google Scholar
29. Lumey, LH. Decreased birthweights in infants after maternal in utero exposure to the Dutch famine of 1944-1945. Paediatr Perinat Epidemiol. 1992; 6, 240253.CrossRefGoogle Scholar
30. Painter, RC, de Rooij, SR, Bossuyt, PM, et al. Early onset of coronary artery disease after prenatal exposure to the Dutch famine. Am J Clin Nutr. 2006; 84, 322327.Google Scholar
31. St Clair, D, Xu, M, Wang, P, et al. Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. JAMA. 2005; 294, 557562.Google Scholar
32. Gluckman, PD, Seng, CY, Fukuoka, H, Beedle, AS, Hanson, MA. Low birthweight and subsequent obesity in Japan. Lancet. 2007; 369, 10811082.Google Scholar
33. Tobi, EW, Lumey, LH, Talens, RP, et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009; 18, 40464053.Google Scholar
34. Lim, D, Bowdin, SC, Tee, L. Clinical and molecular genetic features of Beckwith-Wiedemann syndrome associated with assisted reproductive technologies. Hum Reprod. 2009; 24, 741747.CrossRefGoogle ScholarPubMed
35. Tee, L, Lim, DH, Dias, RP, et al. Epimutation profiling in Beckwith-Wiedemann syndrome: relationship with assisted reproductive technology. Clin Epigenetics. 2013; 5, 23.Google Scholar
36. McGowan, PO, Sasaki, A, D’Alessio, AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009; 12, 342348.Google Scholar
37. Murgatroyd, C, Patchev, AV, Wu, Y, et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci. 2009; 12, 15591566.Google Scholar
38. Kim, YS, Leventhal, BL, Koh, YJ, et al. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry. 2011; 168, 904912.Google Scholar
39. Tsankova, NM, Berton, O, Renthal, W, et al. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci. 2006; 9, 519525.Google Scholar
40. Jessberger, S, Nakashima, K, Clemenson, GD Jr, et al. Epigenetic modulation of seizure-induced neurogenesis and cognitive decline. J Neurosci. 2007; 27, 59675975.Google Scholar
41. Dong, E, Nelson, M, Grayson, DR, Costa, E, Guidotti, A. Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation. Proc Natl Acad Sci USA. 2008; 105, 1361413619.Google Scholar
42. Dong, E, Chen, Y, Gavin, DP, Grayson, DR, Guidotti, A. Valproate induces DNA demethylation in nuclear extracts from adult mouse brain. Epigenetics. 2010; 5, 730735.Google Scholar
43. Wang, Q, Xu, X, Li, J, et al. Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells. Cell Res. 2011; 21, 14241435.CrossRefGoogle ScholarPubMed
44. Ma, DK, Jang, MH, Guo, JU, et al. Neuronal activity–induced gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science. 2009; 323, 10741077.Google Scholar
45. Breitling, LP, Yang, R, Korn, B, Burwinkel, B, Brenner, H. Tobacco-smoking-related differential DNA methylation: 27 K discovery and replication. Am J Hum Genet. 2011; 88, 450457.Google Scholar
46. Shenker, NS, Polidoro, S, van Veldhoven, K, et al. Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Hum Mol Genet. 2013; 22, 843851.Google Scholar
47. Waterland, RA, Jirtle, RL. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003; 23, 52935300.Google Scholar
48. Rimland, B. Controversies in the treatment of autistic children: vitamin and drug therapy. J Child Neurol. 1988; 3(Suppl.), S68S72.CrossRefGoogle ScholarPubMed
49. James, SJ, Cutler, P, Melnyk, S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004; 80, 16111617.Google Scholar
50. Moretti, P, Sahoo, T, Hyland, K, et al. Cerebral folate deficiency with developmental delay; autism; and response to folinic acid. Neurology. 2005; 64, 10881090.Google Scholar
51. Kucharski, R, Maleszka, J, Foret, S, Maleszka, R. Nutritional control of reproductive status in honeybees via DNA methylation. Science. 2008; 319, 18271830.Google Scholar
52. Yaoi, T, Itoh, K, Nakamura, K, et al. Genome-wide analysis of epigenomic alterations in fetal mouse forebrain after exposure to low doses of bisphenol A. Biochem Biophys Res Commun. 2008; 376, 563567.Google Scholar
53. Gore, AC, Walker, DM, Zama, AM, Armenti, AE, Uzumcu, M. Early life exposure to endocrine-disrupting chemicals causes lifelong molecular reprogramming of the hypothalamus and premature reproductive aging. Mol Endocrinol. 2011; 25, 21572168.Google Scholar
54. Ma, DK, Jang, MH, Guo, JU, et al. Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science. 2009; 323, 10741077.Google Scholar
55. Ling, C, Rönn, T. Epigenetic adaptation to regular exercise in humans. Drug Discov Today. 2014; 19, 10151018.Google Scholar
56. Kondo, M, Gray, LJ, Pelka, GJ, et al. Environmental enrichment ameliorates a motor coordination deficit in a mouse model of Rett syndrome-Mecp2 gene dosage effects and BDNF expression. Eur J Neurosci. 2008; 27, 33423350.Google Scholar
57. Lonetti, G, Angelucci, A, Morando, L, et al. Early environmental enrichment moderates the behavioral and synaptic phenotype of MeCP2 null mice. Biol Psychiatry. 2010; 67, 657665.Google Scholar
58. Nag, N, Moriuchi, JM, Peitzman, CG, et al. Environmental enrichment alters locomotor behaviour and ventricular volume in MeCP2 1lox mice. Behav Brain Res. 2009; 196, 4448.CrossRefGoogle ScholarPubMed
59. Kerr, B, Silva, PA, Walz, K, Young, JI. Unconventional transcriptional response to environmental enrichment in a mouse model of Rett syndrome. PLoS One. 2010; 5, e11534.Google Scholar
60. Luikenhuis, S, Giacometti, E, Beard, CF, Jaenisch, R. Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci USA. 2004; 101, 60336038.Google Scholar
61. Guy, J, Gan, J, Selfridge, J, Cobb, S, Bird, A. Reversal of neurological defects in a mouse model of Rett syndrome. Science. 2007; 315, 11431147.Google Scholar
62. Lioy, DT, Garg, SK, Monaghan, CE, et al. A role for glia in the progression of Rett’s syndrome. Nature. 2011; 475, 497500.Google Scholar
63. Vecsler, M, Simon, AJ, Amariglio, N, Rechavi, G, Gak, E. MeCP2 deficiency downregulates specific nuclear proteins that could be partially recovered by valproic acid in vitro. Epigenetics. 2010; 5, 6167.Google Scholar
64. Abel, T, Zukin, RS. Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol. 2008; 8, 5764.Google Scholar
65. Cassel, S, Carouge, D, Gensburger, C, et al. Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain. Mol Pharmacol. 2006; 70, 487492.Google Scholar
66. Popp, C, Dean, W, Feng, S, et al. Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature. 2011; 463, 11011105.CrossRefGoogle Scholar
67. Daxinger, L, Whitelaw, E. Transgenerational epigenetic inheritance: more questions than answers. Genome Res. 2010; 20, 16231628.CrossRefGoogle ScholarPubMed
68. Horsthemke, B. Heritable germline epimutations in humans. Nat Genet. 2007; 39, 573574.Google Scholar
69. Rakyan, VK, Chong, S, Champ, ME, et al. Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci USA. 2003; 100, 25382543.Google Scholar
70. Relton, CL, Davey Smith, G. Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int J Epidemiol. 2012; 41, 161176.Google Scholar
71. Kappeler, L, Meaney, MJ. Epigenetics and parental effects. Bioessays. 2010; 32, 818827.Google Scholar
72. Waterland, RA, Travisano, M, Tahiliani, KG. Diet-induced hypermethylation at agouti viable yellow is not inherited transgenerationally through the female. FASEB J. 2007; 21, 33803385.Google Scholar
73. Anway, MD, Cupp, AS, Uzumcu, M, Skinner, MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005; 308, 14661469, Erratum in: Science. 2010; 328, 690.Google Scholar
74. Manikkam, M, Tracey, R, Guerrero-Bosagna, C, Skinner, MK. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One. 2013; 8, e55387.CrossRefGoogle ScholarPubMed
75. Seong, KH, Li, D, Shimizu, H, Nakamura, R, Ishii, S. Inheritance of stress-induced, ATF-2-dependent epigenetic change. Cell. 2011; 145, 10491061.Google Scholar
76. Franklin, TB, Russig, H, Weiss, IC, et al. Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry. 2010; 68, 408415.Google Scholar
77. Champagne, FA, Weaver, IC, Diorio, J, et al. Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology. 2006; 147, 29092915.Google Scholar
78. Martínez, D, Pentinat, T, Ribó, S, et al. In utero undernutrition in male mice programs liver lipid metabolism in the second-generation offspring involving altered lxra DNA methylation. Cell Metab. 2014; 19, 941951.Google Scholar
79. Jones, B. Epigenetics: transgenerational effects of in utero malnutrition. Nat Rev Genet. 2014; 15, 364.Google Scholar
80. Xu, C, Spragni, E, Jacques, V, Rsche, JR, Gottesfeld, JM. Improved histone deacetylase inhibitors as therapeutics for the neurodegenerative disease Friedreich’s ataxia: a new synthetic route. Pharmaceuticals. 2011; 4, 15781590.Google Scholar
81. leiman, SF, Berlin, J, Basso, M, et al. Histone deacetylase inhibitors and mitramycin a impact a similar neuroprotective pathway at a crossroad between cancer and neurodegeneration. Pharmaceuticals. 2011; 4, 11831185.Google Scholar
82. Wiers, CE. Methylation and the human brain: towards a new discipline of imaging epigenetics. Eur Arch Psychiatry Clin Neurosci. 2012; 262, 271273.Google Scholar
83. Lista, S, Garaci, FG, Toschi, N, Hampel, H. Imaging epigenetics in Alzheimer’s disease. Curr Pharm Des. 2013; 19, 63936415.Google Scholar
84. Wang, Y, Zhang, YL, Hennig, K, et al. Class I HDAC imaging using [(3)H]CI-994 autoradiography. Epigenetics. 2013; 8, 756764.Google Scholar
85. Wang, C, Schroeder, FA, Hooker, JM. Visualizing epigenetics: current advances and advantages in HDAC PET imaging techniques. Neuroscience. 2014; 264, 186197.Google Scholar