Long-term genomic and epigenomic dysregulation as a consequence of prenatal alcohol exposure: A model for fetal alcohol spectrum disorders

Frontiers in Genetics

Volumn 5, Issue JUN, 2014, Pages

  Kleiber, Morgan L ^a   Diehl, Eric J ^a   Laufer, Benjamin I ^a   Mantha, Katarzyna ^a   Chokroborty Hoque, Aniruddho ^a   Alberry, Bonnie ^a   Singh, Shiva M ^a  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

Author keywords

DNA methylation; Epigenetics; Fetal alcohol spectrum disorders; Gene expression; Histone modifications; MicroRNA; Mouse models; Neurodevelopment

Indexed keywords

ALCOHOL; MAMMALIAN TARGET OF RAPAMYCIN; MICRORNA; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RETINOIC ACID RECEPTOR; RETINOID X RECEPTOR; UNTRANSLATED RNA;

ADAPTATION; APOPTOSIS; CELL COMMUNICATION; CELL MIGRATION; CELL STRESS; CELL SURVIVAL; DNA METHYLATION; EPIGENETICS; FETAL ALCOHOL SYNDROME; FIRST TRIMESTER PREGNANCY; GENE EXPRESSION; GENOME IMPRINTING; HISTONE MODIFICATION; HUMAN; MOLECULAR PATHOLOGY; MOUSE MODEL; NERVE CELL DIFFERENTIATION; NEURULATION; NONHUMAN; NUCLEAR REPROGRAMMING; PERINATAL PERIOD; PRENATAL EXPOSURE; REVIEW; SECOND TRIMESTER PREGNANCY; SYNAPTIC TRANSMISSION; THIRD TRIMESTER PREGNANCY;

EID: 84906262895     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2014.00161     Document Type: Review

References (100)

1. Allan, A. M., Chynoweth, J., Tyler, L. A., and Caldwell, K. K. (2003). A mouse model of prenatal ethanol exposure using a voluntary drinking paradigm. Alcohol. Clin. Exp. Res . 27, 2009-2016. doi: 10.1097/01.ALC.0000100940.95053.72
2. Barak, A. J., Beckenhauer, H. C., and Tuma, D. J. (1996). Betaine effects on hepatic methionine metabolism elicited by short-term ethanol feeding. Alcohol 13, 483-486. doi: 10.1016/0741-8329(96)00040-7
3. Barski, A., Cuddapah, S., Cui, K., Roh, T. Y., Schones, D. E., Wang, Z., et al. (2007). High-resolution profiling of histone methylations in the human genome. Cell 129, 823-837. doi: 10.1016/j.cell.2007.05.009
4. Bekdash, R. A., Zhang, C., and Sarkar, D. K. (2013). Gestational choline supplementation normalized fetal alcohol-induced alterations in histone modifications, DNA methylation, and proopiomelanocortin (POMC) gene expression in beta-endorphin-producing POMC neurons of the hypothalamus. Alcohol. Clin. Exp. Res . 37, 1133-1142. doi: 10.1111/acer.12082
5. Boehm, S. L. 2nd. Moore, E. M., Walsh, C. D., Gross, C. D., Cavelli, A. M., Gigante, E., et al. (2008). Using drinking in the dark to model prenatal binge-like exposure to ethanol in C57BL/6J mice. Dev. Psychobiol . 50, 566-578. doi: 10.1002/dev.20320
6. Bystron, I., Blakemore, C., and Rakic, P. (2008). Development of the human cerebral cortex: boulder committee revisited. Nat. Rev. Neurosci . 9, 110-122. doi: 10.1038/nrn2252
7. Camarillo, C., and Miranda, R. C. (2008). Ethanol exposure during neurogenesis induces persistent effects on neural maturation: evidence from an ex vivo model of fetal cerebral cortical neuroepithelial progenitor maturation. Gene Expr . 14, 159-171.
8. Chang, G. Q., Karatayev, O., Liang, S. C., Barson, J. R., and Leibowitz, S. F. (2012). Prenatal ethanol exposure stimulates neurogenesis in hypothalamic and limbic peptide systems: possible mechanism for offspring ethanol overconsumption. Neuroscience 222, 417-428. doi: 10.1016/j.neuroscience.2012.05.066
9. Chen, C. P., Kuhn, P., Advis, J. P., and Sarkar, D. K. (2006). Prenatal ethanol exposure alters the expression of period genes governing the circadian function of beta-endorphin neurons in the hypothalamus. J. Neurochem . 97, 1026-1033. doi: 10.1111/j.1471-4159.2006.03839.x
10. Choudhury, M., and Shukla, S. D. (2008). Surrogate alcohols and their metabolites modify histone H3 acetylation: involvement of histone acetyl transferase and histone deacetylase. Alcohol. Clin. Exp. Res . 32, 829-839. doi: 10.1111/j.1530-0277.2008.00630.x
11. Chudley, A. E., Conry, J., Cook, J. L., Loock, C., Rosales, T., and LeBlanc, N. (2005). Fetal alcohol spectrum disorder: canadian guidelines for diagnosis. CMAJ 172, S1-S21. doi: 10.1503/cmaj.1040302
12. Coolen, M., Katz, S., and Bally-Cuif, L. (2013). miR-9: a versatile regulator of neurogenesis. Front. Cell Neurosci . 7:220. doi: 10.3389/fncel.2013.00220
13. Davies, W., Isles, A. R., Humby, T., and Wilkinson, L. S. (2008). What are imprinted genes doing in the brain? Adv. Exp. Med. Biol . 626, 62-70. doi: 10.1007/978-0-387-77576-0_5
14. Dikranian, K., Qin, Y. Q., Labruyere, J., Nemmers, B., and Olney, J. W. (2005). Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures. Brain Res. Dev. Brain Res . 155, 1-13. doi: 10.1016/j.devbrainres.2004.11.005
15. Dobbing, J., and Sands, J. (1979). Comparative aspects of the brain growth spurt. Early Hum. Dev . 3, 79-83. doi: 10.1016/0378-3782(79)90022-7
16. Downing, C., Flink, S., Florez-McClure, M. L., Johnson, T. E., Tabakoff, B., and Kechris, K. J. (2012). Gene expression changes in C57BL/6J and DBA/2J mice following prenatal alcohol exposure. Alcohol. Clin. Exp. Res . 36, 1519-1529. doi: 10.1111/j.1530-0277.2012.01757.x
17. Downing, C., Johnson, T. E., Larson, C., Leakey, T. I., Siegfried, R. N., Rafferty, T. M., et al. (2011). Subtle decreases in DNA methylation and gene expression at the mouse Igf2 locus following prenatal alcohol exposure: effects of a methyl-supplemented diet. Alcohol 45, 65-71. doi: 10.1016/j.alcohol.2010.07.006
18. Earnest, D. J., Chen, W. J., and West, J. R. (2001). Developmental alcohol and circadian clock function. Alcohol. Res. Health 25, 136-140.
19. Eisenstat, D. D., Liu, J. K., Mione, M., Zhong, W., Yu, G., Anderson, S. A., et al. (1999). DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation. J. Comp. Neurol . 414, 217-237. doi: 10.1002/(SICI)1096-9861(19991115)414:2%3C217::AID-CNE6%3E3.0.CO;2-I
20. Ellis, B. J., Essex, M. J., and Boyce, W. T. (2005). Biological sensitivity to context: II. Empirical explorations of an evolutionary-developmental theory. Dev. Psychopathol . 17, 303-328. doi: 10.1017/S0954579405050157
21. Fast, D. K., and Conry, J. (2004). The challenge of fetal alcohol syndrome in the criminal legal system. Addict. Biol . 9, 161-166. discussion: 167-168. doi: 10.1080/13556210410001717042
22. Fowler, A. K., Hewetson, A., Agrawal, R. G., Dagda, M., Dagda, R., Moaddel, R., et al. (2012). Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base excision repair in adult brain. J. Biol. Chem . 287, 43533-43542. doi: 10.1074/jbc.M112.401497
23. Franklin, T. B., Russig, H., Weiss, I. C., Graff, J., Linder, N., Michalon, A., et al. (2010). Epigenetic transmission of the impact of early stress across generations. Biol. Psychiatry 68, 408-415. doi: 10.1016/j.biopsych.2010.05.036
24. Fryer, S. L., Schweinsburg, B. C., Bjorkquist, O. A., Frank, L. R., Mattson, S. N., Spadoni, A. D., et al. (2009). Characterization of white matter microstructure in fetal alcohol spectrum disorders. Alcohol. Clin. Exp. Res . 33, 514-521. doi: 10.1111/j.1530-0277.2008.00864.x
25. Garro, A. J., McBeth, D. L., Lima, V., and Lieber, C. S. (1991). Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol. Clin. Exp. Res . 15, 395-398. doi: 10.1111/j.1530-0277.1991.tb00536.x
26. Geisen, M. J., Di Meglio, T., Pasqualetti, M., Ducret, S., Brunet, J. F., Chedotal, A., et al. (2008). Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signaling. PLoS Biol . 6:e142. doi: 10.1371/journal.pbio.0060142
27. Ghanem, N., Andrusiak, M. G., Svoboda, D., Al Lafi, S. M., Julian, L. M., McClellan, K. A., et al. (2012). The Rb/E2F pathway modulates neurogenesis through direct regulation of the Dlx1/Dlx2 bigene cluster. J. Neurosci . 32, 8219-8230. doi: 10.1523/JNEUROSCI.1344-12.2012
28. Gilliam, D. M., Kotch, L. E., Dudek, B. C., and Riley, E. P. (1989). Ethanol teratogenesis in selectivity bred long-sleep and short-sleep mice: a comparison to inbred C57BL/6J mice. Alcohol. Clin. Exp. Res . 13, 667-672. doi: 10.1111/j.1530-0277.1989.tb00402.x
29. Girotti, M., Weinberg, M. S., and Spencer, R. L. (2007). Differential responses of hypothalamus-pituitary-adrenal axis immediate early genes to corticosterone and circadian drive. Endocrinology 148, 2542-2552. doi: 10.1210/en.2006-1304
30. Govorko, D., Bekdash, R. A., Zhang, C., and Sarkar, D. K. (2012). Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations. Biol. Psychiatry 72, 378-388. doi: 10.1016/j.biopsych.2012.04.006
31. Green, M. L., Singh, A. V., Zhang, Y., Nemeth, K. A., Sulik, K. K., and Knudsen, T. B. (2007). Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome. Dev. Dynam . 236, 613-631. doi: 10.1002/dvdy.21048
32. Groenendyk, J., and Michalak, M. (2014). Disrupted WNT signaling in mouse embryonic stem cells in the absence of calreticulin. Stem Cell Rev . 10, 191-206. doi: 10.1007/s12015-013-9488-6
33. Guo, W., Crossey, E. L., Zhang, L., Zucca, S., George, O. L., Valenzuela, C. F., et al. (2011). Alcohol exposure decreases CREB binding protein expression and histone acetylation in the developing cerebellum. PLoS ONE 6:e19351. doi: 10.1371/journal.pone.0019351
34. Halsted, C. H., Villanueva, J. A., Devlin, A. M., Niemela, O., Parkkila, S., Garrow, T. A., et al. (2002). Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig. Proc. Natl. Acad. Sci. U.S.A . 99, 10072-10077. doi: 10.1073/pnas.112336399
35. Hannigan, J. H., O'Leary-Moore, S. K., and Berman, R. F. (2007). Postnatal environmental or experiential amelioration of neurobehavioral effects of perinatal alcohol exposure in rats. Neurosci. Biobehav. Rev . 31, 202-211. doi: 10.1016/j.neubiorev.2006.06.019
36. Hard, M. L., Abdolell, M., Robinson, B. H., and Koren, G. (2005). Gene-expression analysis after alcohol exposure in the developing mouse. J. Lab. Clin. Med . 145, 47-54. doi: 10.1016/j.lab.2004.11.011
37. Harlap, S., and Shiono, P. H. (1980). Alcohol, smoking, and incidence of spontaneous abortions in the first and second trimester. Lancet 2, 173-176. doi: 10.1016/S0140-6736(80)90061-6
38. Haycock, P. C. (2009). Fetal alcohol spectrum disorders: the epigenetic perspective. Biol. Reprod . 81, 607-617. doi: 10.1095/biolreprod.108.074690
39. Haycock, P. C., and Ramsay, M. (2009). Exposure of mouse embryos to ethanol during preimplantation development: effect on DNA methylation in the h19 imprinting control region. Biol. Reprod . 81, 618-627. doi: 10.1095/biolreprod.108.074682
40. Hellemans, K. G., Verma, P., Yoon, E., Yu, W., and Weinberg, J. (2008). Prenatal alcohol exposure increases vulnerability to stress and anxiety-like disorders in adulthood. Ann. N.Y. Acad. Sci . 1144, 154-175. doi: 10.1196/annals.1418.016
41. Hu, Z., Yu, D., Gu, Q. H., Yang, Y., Tu, K., Zhu, J., et al. (2014). miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression. Nat. Commun . 5, 3263. doi: 10.1038/ncomms4263
42. Ikonomidou, C., Bittigau, P., Ishimaru, M. J., Wozniak, D. F., Koch, C., Genz, K., et al. (2000). Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287, 1056-1060. doi: 10.1126/science.287.5455.1056
43. Kaminen-Ahola, N., Ahola, A., Maga, M., Mallitt, K. A., Fahey, P., Cox, T. C., et al. (2010). Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model. PLoS Genet . 6:e1000811. doi: 10.1371/journal.pgen.1000811
44. Kim, J. S., and Shukla, S. D. (2006). Acute in vivo effect of ethanol (binge drinking) on histone H3 modifications in rat tissues. Alcohol Alcohol . 41, 126-132. doi: 10.1093/alcalc/agh248
45. Kirpich, I., Ghare, S., Zhang, J., Gobejishvili, L., Kharebava, G., Barve, S. J., et al. (2012). Binge alcohol-induced microvesicular liver steatosis and injury are associated with down-regulation of hepatic Hdac 1, 7, 9, 10, 11 and up-regulation of Hdac 3. Alcohol. Clin. Exp. Res . 36, 1578-1586. doi: 10.1111/j.1530-0277.2012.01751.x
46. Kirpich, I., Zhang, J., Gobejishvili, L., Kharebava, G., Barker, D., Ghare, S., et al. (2013). Binge ethanol-induced HDAC3 down-regulates Cpt1alpha expression leading to hepatic steatosis and injury. Alcohol. Clin. Exp. Res . 37, 1920-1929. doi: 10.1111/acer.12172
47. Kleiber, M. L., Laufer, B. I., Wright, E., Diehl, E. J., and Singh, S. M. (2012). Long-term alterations to the brain transcriptome in a maternal voluntary consumption model of fetal alcohol spectrum disorders. Brain Res . 1458, 18-33. doi: 10.1016/j.brainres.2012.04.016
48. Kleiber, M. L., Mantha, K., Stringer, R. L., and Singh, S. M. (2013). Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure. J. Neurodev. Disord . 5:6. doi: 10.1186/1866-1955-5-6
49. Kleiber, M. L., Wright, E., and Singh, S. M. (2011). Maternal voluntary drinking in C57BL/6J mice: advancing a model for fetal alcohol spectrum disorders. Behav. Brain Res . 223, 376-387. doi: 10.1016/j.bbr.2011.05.005
50. Kodituwakku, P. W. (2010). A neurodevelopmental framework for the development of interventions for children with fetal alcohol spectrum disorders. Alcohol 44, 717-728. doi: 10.1016/j.alcohol.2009.10.009
51. Korosi, A., and Baram, T. Z. (2009). The pathways from mother's love to baby's future. Front. Behav. Neurosci . 3:27. doi: 10.3389/neuro.08.027.2009
52. Laufer, B. I., Mantha, K., Kleiber, M. L., Diehl, E. J., Addison, S. M., and Singh, S. M. (2013). Long-lasting alterations to DNA methylation and ncRNAs could underlie the effects of fetal alcohol exposure in mice. Dis. Model. Mech . 6, 977-992. doi: 10.1242/dmm.010975
53. Lebel, C., Rasmussen, C., Wyper, K., Walker, L., Andrew, G., Yager, J., et al. (2008). Brain diffusion abnormalities in children with fetal alcohol spectrum disorder. Alcohol. Clin. Exp. Res . 32, 1732-1740. doi: 10.1111/j.1530-0277.2008.00750.x
54. Light, K. E., Belcher, S. M., and Pierce, D. R. (2002). Time course and manner of Purkinje neuron death following a single ethanol exposure on postnatal day 4 in the developing rat. Neuroscience 114, 327-337. doi: 10.1016/S0306-4522(02)00344-5
55. Liu, Y., Balaraman, Y., Wang, G., Nephew, K. P., and Zhou, F. C. (2009). Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation. Epigenetics 4, 500-511. doi: 10.4161/epi.4.7.9925
56. Mameli, M., Zamudio, P. A., Carta, M., and Valenzuela, C. F. (2005). Developmentally regulated actions of alcohol on hippocampal glutamatergic transmission. J. Neurosci . 25, 8027-8036. doi: 10.1523/JNEUROSCI.2434-05.2005
57. Mantha, K., Kleiber, M. L., and Singh, S. M. (2013). Neurodevelopmental timing of ethanol exposure may contribute to observed heterogeneity of behavioural deficits in a mouse model of Fetal Alcohol Spectrum Disorder (FASD). J. Behav. Brain Sci . 3, 85-99. doi: 10.4236/jbbs.2013.31009
58. Mantha, K., Laufer, B. I., and Singh, S. M. (2014). Molecular changes during neurodevelopment following second-trimester binge ethanol exposure in a mouse model of fetal alcohol spectrum disorders: from immediate effects to long-term adaptation. Dev. Neurosci . 36, 29-43. doi: 10.1159/000357496
59. Mejia, L. A., Litterman, N., Ikeuchi, Y., de la Torre-Ubieta, L., Bennett, E. J., Zhang, C., et al. (2013). A Novel Hap1-Tsc1 interaction regulates neuronal mTORC1 signaling and morphogenesis in the brain. J. Neurosci . 33, 18015-18021. doi: 10.1523/JNEUROSCI.2290-13.2013
60. Miller, M. W., and Nowakowski, R. S. (1991). Effect of prenatal exposure to ethanol on the cell cycle kinetics and growth fraction in the proliferative zones of fetal rat cerebral cortex. Alcohol. Clin. Exp. Res . 15, 229-232. doi: 10.1111/j.1530-0277.1991.tb01861.x
61. Morison, I. M., Ramsay, J. P., and Spencer, H. G. (2005). A census of mammalian imprinting. Trends Genet . 21, 457-465. doi: 10.1016/j.tig.2005.06.008
62. Noctor, S. C., Martinez-Cerdeno, V., Ivic, L., and Kriegstein, A. R. (2004). Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat. Neurosci . 7, 136-144. doi: 10.1038/nn1172
63. Norman, A. L., Crocker, N., Mattson, S. N., and Riley, E. P. (2009). Neuroimaging and fetal alcohol spectrum disorders. Dev. Disabil. Res. Rev . 15, 209-217. doi: 10.1002/ddrr.72
64. Nowak, J. S., and Michlewski, G. (2013). miRNAs in development and pathogenesis of the nervous system. Biochem. Soc. Trans . 41, 815-820. doi: 10.1042/BST20130044
65. Nowoslawski, L., Klocke, B. J., and Roth, K. A. (2005). Molecular regulation of acute ethanol-induced neuron apoptosis. J. Neuropathol. Exp. Neurol . 64, 490-497.
66. Olney, J. W., Ishimaru, M. J., Bittigau, P., and Ikonomidou, C. (2000). Ethanol-induced apoptotic neurodegeneration in the developing brain. Apoptosis 5, 515-521. doi: 10.1023/A:1009685428847
67. Olney, J. W., Tenkova, T., Dikranian, K., Qin, Y. Q., Labruyere, J., and Ikonomidou, C. (2002). Ethanol-induced apoptotic neurodegeneration in the developing C57BL/6 mouse brain. Brain Res. Dev. Brain Res . 133, 115-126. doi: 10.1016/S0165-3806(02)00279-1
68. Orlova, K. A., and Crino, P. B. (2010). The tuberous sclerosis complex. Ann. N.Y. Acad. Sci . 1184, 87-105. doi: 10.1111/j.1749-6632.2009.05117.x
69. 3 at Lys-4 and Lys-9 correlate with up- & down-regulation of genes by ethanol in hepatocytes. Life Sci . 81, 979-987. doi: 10.1016/j.lfs.2007.07.030
70. Peadon, E., Rhys-Jones, B., Bower, C., and Elliott, E. J. (2009). Systematic review of interventions for children with Fetal Alcohol Spectrum Disorders. BMC Pediatr . 9:35. doi: 10.1186/1471-2431-9-35
71. Prock, T. L., and Miranda, R. C. (2007). Embryonic cerebral cortical progenitors are resistant to apoptosis, but increase expression of suicide receptor DISC-complex genes and suppress autophagy following ethanol exposure. Alcohol. Clin. Exp. Res . 31, 694-703. doi: 10.1111/j.1530-0277.2007.00354.x
72. Puglia, M. P., and Valenzuela, C. F. (2010). Ethanol acutely inhibits ionotropic glutamate receptor-mediated responses and long-term potentiation in the developing CA1 hippocampus. Alcohol. Clin. Exp. Res . 34, 594-606. doi: 10.1111/j.1530-0277.2009.01128.x
73. Reik, W., Dean, W., and Walter, J. (2001). Epigenetic reprogramming in mammalian development. Science 293, 1089-1093. doi: 10.1126/science.1063443
74. Resendiz, M., Chen, Y., Ozturk, N. C., and Zhou, F. C. (2013). Epigenetic medicine and fetal alcohol spectrum disorders. Epigenomics 5, 73-86. doi: 10.2217/epi.12.80
75. Romeo, R. D., Mueller, A., Sisti, H. M., Ogawa, S., McEwen, B. S., and Brake, W. G. (2003). Anxiety and fear behaviors in adult male and female C57BL/6 mice are modulated by maternal separation. Horm. Behav . 43, 561-567. doi: 10.1016/S0018-506X(03)00063-1
76. Sakata-Haga, H., Dominguez, H. D., Sei, H., Fukui, Y., Riley, E. P., and Thomas, J. D. (2006). Alterations in circadian rhythm phase shifting ability in rats following ethanol exposure during the third trimester brain growth spurt. Alcohol. Clin. Exp. Res . 30, 899-907. doi: 10.1111/j.1530-0277.2006.00105.x
77. Sampson, P. D., Streissguth, A. P., Bookstein, F. L., Little, R. E., Clarren, S. K., Dehaene, P., et al. (1997). Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology 56, 317-326. doi: 10.1002/(SICI)1096-9926(199711)56:5<317::AID-TERA5>3.0.CO;2-U
78. Sathyan, P., Golden, H. B., and Miranda, R. C. (2007). Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. J. Neurosci . 27, 8546-8557. doi: 10.1523/JNEUROSCI.1269-07.2007
79. Sato, F., Tsuchiya, S., Meltzer, S. J., and Shimizu, K. (2011). MicroRNAs and epigenetics. FEBS J . 278, 1598-1609. doi: 10.1111/j.1742-4658.2011.08089.x
80. Shonkoff, J. P., Boyce, W. T., and McEwen, B. S. (2009). Neuroscience, molecular biology, and the childhood roots of health disparities: building a new framework for health promotion and disease prevention. JAMA 301, 2252-2259. doi: 10.1001/jama.2009.754
81. Shukla, S. D., Velazquez, J., French, S. W., Lu, S. C., Ticku, M. K., and Zakhari, S. (2008). Emerging role of epigenetics in the actions of alcohol. Alcohol. Clin. Exp. Res . 32, 1525-1534. doi: 10.1111/j.1530-0277.2008.00729.x
82. Sowell, E. R., Johnson, A., Kan, E., Lu, L. H., van Horn, J. D., Toga, A. W., et al. (2008a). Mapping white matter integrity and neurobehavioral correlates in children with fetal alcohol spectrum disorders. J. Neurosci . 28, 1313-1319. doi: 10.1523/JNEUROSCI.5067-07.2008
83. Sowell, E. R., Mattson, S. N., Kan, E., Thompson, P. M., Riley, E. P., and Toga, A. W. (2008b). Abnormal cortical thickness and brain-behavior correlation patterns in individuals with heavy prenatal alcohol exposure. Cereb. Cortex 18, 136-144. doi: 10.1093/cercor/bhm039
84. Stade, B., Ali, A., Bennett, D., Campbell, D., Johnston, M., Lens, C., et al. (2009). The burden of prenatal exposure to alcohol: revised measurement of cost. Can. J. Clin. Pharmacol . 16, e91-e102.
85. Streissguth, A. P., Barr, H. M., Sampson, P. D., and Bookstein, F. L. (1994). Prenatal alcohol and offspring development: the first fourteen years. Drug Alcohol Depend . 36, 89-99. doi: 10.1016/0376-8716(94)90090-6
86. Streissguth, A. P., and O'Malley, K. (2000). Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders. Semin. Clin. Neuropsychiatry 5, 177-190. doi: 10.1053/scnp.2000.6729
87. Subbanna, S., Shivakumar, M., Psychoyos, D., Xie, S., and Basavarajappa, B. S. (2013a). Anandamide-CB1 receptor signaling contributes to postnatal ethanol-induced neonatal neurodegeneration, adult synaptic, and memory deficits. J. Neurosci . 33, 6350-6366. doi: 10.1523/JNEUROSCI.3786-12.2013
88. Subbanna, S., Shivakumar, M., Umapathy, N. S., Saito, M., Mohan, P. S., Kumar, A., et al. (2013b). G9a-mediated histone methylation regulates ethanol-induced neurodegeneration in the neonatal mouse brain. Neurobiol. Dis . 54, 475-485. doi: 10.1016/j.nbd.2013.01.022
89. Sulik, K. K. (2005). Genesis of alcohol-induced craniofacial dysmorphism. Exp. Biol. Med . 230, 366-375.
90. Toso, L., Poggi, S. H., Roberson, R., Woodard, J., Park, J., Abebe, D., et al. (2006). Prevention of alcohol-induced learning deficits in fetal alcohol syndrome mediated through NMDA and GABA receptors. Am. J. Obstet. Gynecol . 194, 681-686. doi: 10.1016/j.ajog.2006.01.003
91. Ungerer, M., Knezovich, J., and Ramsay, M. (2013). In utero alcohol exposure, epigenetic changes, and their consequences. Alcohol Res 35, 37-46.
92. Veazey, K. J., Carnahan, M. N., Muller, D., Miranda, R. C., and Golding, M. C. (2013). Alcohol-induced epigenetic alterations to developmentally crucial genes regulating neural stemness and differentiation. Alcohol. Clin. Exp. Res . 37, 1111-1122. doi: 10.1111/acer.12080
93. Wang, L. L., Zhang, Z., Li, Q., Yang, R., Pei, X., Xu, Y., et al. (2009). Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation. Hum. Reprod . 24, 562-579. doi: 10.1093/humrep/den439
94. Weinberg, J., Sliwowska, J. H., Lan, N., and Hellemans, K. G. (2008). Prenatal alcohol exposure: foetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome. J. Neuroendocrinol . 20, 470-488. doi: 10.1111/j.1365-2826.2008.01669.x
95. Weinstock, M. (2010). Intrauterine factors as determinants of depressive disorder. Isr. J. Psychiatry Relat. Sci . 47, 36-45.
96. Xu, J., Yeon, J. E., Chang, H., Tison, G., Chen, G. J., Wands, J., et al. (2003). Ethanol impairs insulin-stimulated neuronal survival in the developing brain: role of PTEN phosphatase. J. Biol. Chem . 278, 26929-26937. doi: 10.1074/jbc.M300401200
97. Yoshimura, T., Arimura, N., and Kaibuchi, K. (2006). Molecular mechanisms of axon specification and neuronal disorders. Ann. N.Y. Acad. Sci . 1086, 116-125. doi: 10.1196/annals.1377.013
98. Young, C., and Olney, J. W. (2006). Neuroapoptosis in the infant mouse brain triggered by a transient small increase in blood alcohol concentration. Neurobiol. Dis . 22, 548-554. doi: 10.1016/j.nbd.2005.12.015
99. Young, C., Roth, K. A., Klocke, B. J., West, T., Holtzman, D. M., Labruyere, J., et al. (2005). Role of caspase-3 in ethanol-induced developmental neurodegeneration. Neurobiol. Dis . 20, 608-614. doi: 10.1016/j.nbd.2005.04.014
100. Zhou, F. C., Zhao, Q., Liu, Y., Goodlett, C. R., Liang, T., McClintick, J. N., et al. (2011). Alteration of gene expression by alcohol exposure at early neurulation. BMC Genomics 12:124. doi: 10.1186/1471-2164-12-124