Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Neurodevelopmental Disorders
Published in: Journal of Neurodevelopmental Disorders 1/2013

Open Access 01-12-2013 | Research

Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure

Authors: Morgan L Kleiber, Katarzyna Mantha, Randa L Stringer, Shiva M Singh

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2013

Login to get access

Abstract

Background

Maternal alcohol consumption is known to adversely affect fetal neurodevelopment. While it is known that alcohol dose and timing play a role in the cognitive and behavioral changes associated with prenatal alcohol exposure, it is unclear what developmental processes are disrupted that may lead to these phenotypes.

Methods

Mice (n=6 per treatment per developmental time) were exposed to two acute doses of alcohol (5 g/kg) at neurodevelopmental times representing the human first, second, or third trimester equivalent. Mice were reared to adulthood and changes to their adult brain transcriptome were assessed using expression arrays. These were then categorized based on Gene Ontology annotations, canonical pathway associations, and relationships to interacting molecules.

Results

The results suggest that ethanol disrupts biological processes that are actively occurring at the time of exposure. These include cell proliferation during trimester one, cell migration and differentiation during trimester two, and cellular communication and neurotransmission during trimester three. Further, although ethanol altered a distinct set of genes depending on developmental timing, many of these show interrelatedness and can be associated with one another via ‘hub’ molecules and pathways such as those related to huntingtin and brain-derived neurotrophic factor.

Conclusions

These changes to brain gene expression represent a ‘molecular footprint’ of neurodevelopmental alcohol exposure that is long-lasting and correlates with active processes disrupted at the time of exposure. This study provides further support that there is no neurodevelopmental time when alcohol cannot adversely affect the developing brain.
Appendix
Available only for authorised users
Literature
1.
Chudley AE, Conry J, Cook JL, Loock C, Rosales T, LeBlanc N: Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. CMAJ. 2005, 172: S1-S21.PubMedCentralPubMedCrossRef
2.
Rasmussen C: Executive functioning and working memory in fetal alcohol spectrum disorder. Alcohol Clin Exp Res. 2005, 29: 1359-1367.PubMedCrossRef
3.
Streissguth AP, O’Malley K: Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders. Semin Clin Neuropsychiatry. 2000, 5: 177-190.PubMedCrossRef
4.
Marchetta CM, Denny CH, Floyd RL, Cheal NE, Sniezek JE: Alcohol use and binge drinking among women of childbearing age-United States, 2006-2010. MMWR Morb Mortal Wkly Rep. 2012, 61: 534-538.
5.
Bertrand J, Floyd LL, Weber MK: Guidelines for identifying and referring persons with fetal alcohol syndrome. MMWR Recomm Rep. 2005, 54: 1-14.PubMed
6.
Lupton C, Burd L, Harwood R: Cost of fetal alcohol spectrum disorders. Am J Med Genet C Semin Med Genet. 2004, 127C: 42-50.PubMedCrossRef
7.
Stade B, Ali A, Bennett D, Campbell D, Johnston M, Lens C, Tran S, Koren G: The burden of prenatal exposure to alcohol: revised measurement of cost. Can J Clin Pharmacol. 2009, 16: e91-102.PubMed
8.
Fast DK, Conry J: The challenge of fetal alcohol syndrome in the criminal legal system. Addict Biol. 2004, 9: 161-166. discussion 167-8PubMedCrossRef
9.
Famy C, Streissguth AP, Unis AS: Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects. Am J Psychiatry. 1998, 155: 552-554.PubMedCrossRef
10.
Nash K, Sheard E, Rovet J, Koren G: Understanding fetal alcohol spectrum disorders (FASDs): toward identification of a behavioral phenotype. ScientificWorldJournal. 2008, 8: 873-882.PubMedCrossRef
11.
Green ML, Singh AV, Zhang Y, Nemeth KA, Sulik KK, Knudsen TB: Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome. Dev Dyn. 2007, 236: 613-631.PubMedCrossRef
12.
Hard ML, Abdolell M, Robinson BH, Koren G: Gene-expression analysis after alcohol exposure in the developing mouse. J Lab Clin Med. 2005, 145: 47-54.PubMedCrossRef
13.
Zhou FC, Zhao Q, Liu Y, Goodlett CR, Liang T, McClintick JN, Edenberg HJ, Li L: Alteration of gene expression by alcohol exposure at early neurulation. BMC Genomics. 2011, 12: 124-PubMedCentralPubMedCrossRef
14.
Chen CP, Kuhn P, Advis JP, Sarkar DK: Prenatal ethanol exposure alters the expression of period genes governing the circadian function of beta-endorphin neurons in the hypothalamus. J Neurochem. 2006, 97: 1026-1033.PubMedCrossRef
15.
Kleiber ML, Laufer BI, Wright E, Diehl EJ, Singh SM: Long-term alterations to the brain transcriptome in a maternal voluntary consumption model of fetal alcohol spectrum disorders. Brain Res. 2012, 1458: 18-33.PubMedCrossRef
16.
Toso L, Poggi SH, Abebe D, Roberson R, Dunlap V, Park J, Spong CY: N-methyl-D-aspartate subunit expression during mouse development altered by in utero alcohol exposure. Am J Obstet Gynecol. 2005, 193: 1534-1539.PubMedCrossRef
17.
Toso L, Roberson R, Woodard J, Abebe D, Spong CY: Prenatal alcohol exposure alters GABA(A)alpha5 expression: a mechanism of alcohol-induced learning dysfunction. Am J Obstet Gynecol. 2006, 195: 522-527.PubMedCrossRef
18.
Clancy B, Darlington RB, Finlay BL: Translating developmental time across mammalian species. Neuroscience. 2001, 105: 7-17.PubMedCrossRef
19.
20.
21.
Mantha K, Kleiber ML, Singh SM: 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. 2013, 3: 85-99.CrossRef
22.
Hunt PS, Jacobson SE, Torok EJ: Deficits in trace fear conditioning in a rat model of fetal alcohol exposure: dose-response and timing effects. Alcohol. 2009, 43: 465-474.PubMedCentralPubMedCrossRef
23.
Lipinski RJ, Hammond P, O’Leary-Moore SK, Ament JJ, Pecevich SJ, Jiang Y, Budin F, Parnell SE, Suttie M, Godin EA, Everson JL, Dehart DB, Oguz I, Holloway HT, Styner MA, Johnson GA, Sulik KK: Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent. PLoS One. 2012, 7: e43067-PubMedCentralPubMedCrossRef
24.
Barr HM, Bookstein FL, O’Malley KD, Connor PD, Huggins JE, Streissguth AP: Binge drinking during pregnancy as a predictor of psychiatric disorders on the Structured Clinical Interview for DSM-IV in young adult offspring. Am J Psychiatry. 2006, 163: 1061-1065.PubMedCrossRef
25.
Schlessinger AR, Cowan WM, Gottlieb DI: An autoradiographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat. J Comp Neurol. 1975, 159: 149-175.PubMedCrossRef
26.
Wozniak DF, Hartman RE, Boyle MP, Vogt SK, Brooks AR, Tenkova T, Young C, Olney JW, Muglia LJ: Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning/memory deficits in juveniles followed by progressive functional recovery in adults. Neurobiol Dis. 2004, 17: 403-414.PubMedCrossRef
27.
Ikonomidou C, Bittigau P, Ishimaru MJ, Wozniak DF, Koch C, Genz K, Price MT, Stefovska V, Horster F, Tenkova T, Dikranian K, Olney JW: Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science. 2000, 287: 1056-1060.PubMedCrossRef
28.
29.
Dennis G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA: DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003, 4: P3-PubMedCrossRef
30.
da Huang W, Sherman BT, Lempicki RA: Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009, 37: 1-13.PubMedCrossRef
31.
Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008, 3: 1101-1108.PubMedCrossRef
32.
Olney JW, Tenkova T, Dikranian K, Qin YQ, Labruyere J, Ikonomidou C: Ethanol-induced apoptotic neurodegeneration in the developing C57BL/6 mouse brain. Brain Res Dev Brain Res. 2002, 133: 115-126.PubMedCrossRef
33.
Young C, Olney JW: Neuroapoptosis in the infant mouse brain triggered by a transient small increase in blood alcohol concentration. Neurobiol Dis. 2006, 22: 548-554.PubMedCrossRef
34.
Fagerlund A, Heikkinen S, Autti-Ramo I, Korkman M, Timonen M, Kuusi T, Riley EP, Lundbom N: Brain metabolic alterations in adolescents and young adults with fetal alcohol spectrum disorders. Alcohol Clin Exp Res. 2006, 30: 2097-2104.PubMedCrossRef
35.
Jirikowic T, Olson HC, Kartin D: Sensory processing, school performance, and adaptive behavior of young school-age children with fetal alcohol spectrum disorders. Phys Occup Ther Pediatr. 2008, 28: 117-136.PubMedCrossRef
36.
Stade B, Beyene J, Buller K, Ross S, Patterson K, Stevens B, Sgro M, Ungar W, Watson W, Koren G: Feeling different: the experience of living with fetal alcohol spectrum disorder. J Popul Ther Clin Pharmacol. 2011, 18: e475-485.PubMed
37.
Dobbing J: The later growth of the brain and its vulnerability. Pediatrics. 1974, 53: 2-6.PubMed
38.
Blakley PM, Scott WJ: Determination of the proximate teratogen of the mouse fetal alcohol syndrome. 2. Pharmacokinetics of the placental transfer of ethanol and acetaldehyde. Toxicol Appl Pharmacol. 1984, 72: 364-371.PubMedCrossRef
39.
Rice D, Barone S: Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect . 2000, Suppl 3: 511-533.CrossRef
40.
Allan AM, Chynoweth J, Tyler LA, Caldwell KK: A mouse model of prenatal ethanol exposure using a voluntary drinking paradigm. Alcohol Clin Exp Res. 2003, 27: 2009-2016.PubMedCrossRef
41.
Kleiber ML, Wright E, Singh SM: Maternal voluntary drinking in C57BL/6J mice: Advancing a model for fetal alcohol spectrum disorders. Behav Brain Res. 2011, 223: 376-387.PubMedCrossRef
42.
McMurray MS, Williams SK, Jarrett TM, Cox ET, Fay EE, Overstreet DH, Walker CH, Johns JM: Gestational ethanol and nicotine exposure: effects on maternal behavior, oxytocin, and offspring ethanol intake in the rat. Neurotoxicol Teratol. 2008, 30: 475-486.PubMedCentralPubMedCrossRef
43.
Chang GQ, Karatayev O, Liang SC, Barson JR, Leibowitz SF: Prenatal ethanol exposure stimulates neurogenesis in hypothalamic and limbic peptide systems: possible mechanism for offspring ethanol overconsumption. Neuroscience. 2012, 222: 417-428.PubMedCentralPubMedCrossRef
44.
Dubois C, Naassila M, Daoust M, Pierrefiche O: Early chronic ethanol exposure in rats disturbs respiratory network activity and increases sensitivity to ethanol. J Physiol. 2006, 576: 297-307.PubMedCentralPubMedCrossRef
45.
Alati R, Al Mamun A, Williams GM, O’Callaghan M, Najman JM, Bor W: In utero alcohol exposure and prediction of alcohol disorders in early adulthood: a birth cohort study. Arch Gen Psychiatry. 2006, 63: 1009-1016.PubMedCrossRef
46.
47.
Kirstein M, Farinas I: Sensing life: regulation of sensory neuron survival by neurotrophins. Cell Mol Life Sci. 2002, 59: 1787-1802.PubMedCrossRef
48.
49.
Je HS, Zhou J, Yang F, Lu B: Distinct mechanisms for neurotrophin-3-induced acute and long-term synaptic potentiation. J Neurosci. 2005, 25: 11719-11729.PubMedCrossRef
50.
Chao MV: Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci. 2003, 4: 299-309.PubMedCrossRef
51.
Lykissas MG, Batistatou AK, Charalabopoulos KA, Beris AE: The role of neurotrophins in axonal growth, guidance, and regeneration. Curr Neurovasc Res. 2007, 4: 143-151.PubMedCrossRef
52.
Uys JD, Marais L, Faure J, Prevoo D, Swart P, Mohammed AH, Stein DJ, Daniels WM: Developmental trauma is associated with behavioral hyperarousal, altered HPA axis activity, and decreased hippocampal neurotrophin expression in the adult rat. Ann N Y Acad Sci. 2006, 1071: 542-546.PubMedCrossRef
53.
Reus GZ, Stringari RB, Ribeiro KF, Cipriano AL, Panizzutti BS, Stertz L, Lersch C, Kapczinski F, Quevedo J: Maternal deprivation induces depressive-like behaviour and alters neurotrophin levels in the rat brain. Neurochem Res. 2011, 36: 460-466.PubMedCrossRef
54.
Shimazu K, Zhao M, Sakata K, Akbarian S, Bates B, Jaenisch R, Lu B: NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis. Learn Mem. 2006, 13: 307-315.PubMedCentralPubMedCrossRef
55.
Zhao L, Rosales C, Seburn K, Ron D, Ackerman SL: Alteration of the unfolded protein response modifies neurodegeneration in a mouse model of Marinesco-Sjogren syndrome. Hum Mol Genet. 2010, 19: 25-35.PubMedCentralPubMedCrossRef
56.
Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG: Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK. Proc Natl Acad Sci U S A. 2002, 99: 15920-15925.PubMedCentralPubMedCrossRef
57.
Singer HS, Chiu AY, Meiri KF, Morell P, Nelson PG, Tennekoon G: Advances in understanding the development of the nervous system. Curr Opin Neurol. 1994, 7: 153-159.PubMedCrossRef
58.
Camarillo C, Miranda RC: 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. 2008, 14: 159-171.PubMedCentralPubMed
59.
Hansen DV, Lui JH, Parker PR, Kriegstein AR: Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature. 2010, 464: 554-561.PubMedCrossRef
60.
Stevenson JR, Schroeder JP, Nixon K, Besheer J, Crews FT, Hodge CW: Abstinence following alcohol drinking produces depression-like behavior and reduced hippocampal neurogenesis in mice. Neuropsychopharmacology. 2009, 34: 1209-1222.PubMedCentralPubMedCrossRef
61.
He J, Nixon K, Shetty AK, Crews FT: Chronic alcohol exposure reduces hippocampal neurogenesis and dendritic growth of newborn neurons. Eur J Neurosci. 2005, 21: 2711-2720.PubMedCrossRef
62.
Hansson AC, Nixon K, Rimondini R, Damadzic R, Sommer WH, Eskay R, Crews FT, Heilig M: Long-term suppression of forebrain neurogenesis and loss of neuronal progenitor cells following prolonged alcohol dependence in rats. Int J Neuropsychopharmacol. 2010, 13: 583-593.PubMedCrossRef
63.
Eisenstat DD, Liu JK, Mione M, Zhong W, Yu G, Anderson SA, Ghattas I, Puelles L, Rubenstein JL: DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation. J Comp Neurol. 1999, 414: 217-237.PubMedCrossRef
64.
Liu JK, Ghattas I, Liu S, Chen S, Rubenstein JL: Dlx genes encode DNA-binding proteins that are expressed in an overlapping and sequential pattern during basal ganglia differentiation. Dev Dyn. 1997, 210: 498-512.PubMedCrossRef
65.
Ghanem N, Andrusiak MG, Svoboda D, Al Lafi SM, Julian LM, McClellan KA, De Repentigny Y, Kothary R, Ekker M, Blais A, Park DS, Slack RS: The Rb/E2F pathway modulates neurogenesis through direct regulation of the Dlx1/Dlx2 bigene cluster. J Neurosci. 2012, 32: 8219-8230.PubMedCrossRef
66.
Jones DL, Howard MA, Stanco A, Rubenstein JL, Baraban SC: Deletion of Dlx1 results in reduced glutamatergic input to hippocampal interneurons. J Neurophysiol. 2011, 105: 1984-1991.PubMedCentralPubMedCrossRef
67.
Letinic K, Zoncu R, Rakic P: Origin of GABAergic neurons in the human neocortex. Nature. 2002, 417: 645-649.PubMedCrossRef
68.
Tajuddin NF, Druse MJ: In utero ethanol exposure decreased the density of serotonin neurons. Maternal ipsapirone treatment exerted a protective effect. Brain Res Dev Brain Res. 1999, 117: 191-197.CrossRef
69.
Schneider ML, Moore CF, Barr CS, Larson JA, Kraemer GW: Moderate prenatal alcohol exposure and serotonin genotype interact to alter CNS serotonin function in rhesus monkey offspring. Alcohol Clin Exp Res. 2011, 35: 912-920.PubMedCentralPubMedCrossRef
70.
Sari Y, Zhou FC: Prenatal alcohol exposure causes long-term serotonin neuron deficit in mice. Alcohol Clin Exp Res. 2004, 28: 941-948.PubMedCrossRef
71.
Hofmann CE, Ellis L, Yu WK, Weinberg J: Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol. Alcohol Clin Exp Res. 2007, 31: 345-355.PubMedCrossRef
72.
Grailhe R, Waeber C, Dulawa SC, Hornung JP, Zhuang X, Brunner D, Geyer MA, Hen R: Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor. Neuron. 1999, 22: 581-591.PubMedCrossRef
73.
Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003, 301: 386-389.PubMedCrossRef
74.
Higley JD, Linnoila M: Low central nervous system serotonergic activity is traitlike and correlates with impulsive behavior. A nonhuman primate model investigating genetic and environmental influences on neurotransmission. Ann N Y Acad Sci. 1997, 836: 39-56.PubMedCrossRef
75.
Mehlman PT, Higley JD, Faucher I, Lilly AA, Taub DM, Vickers J, Suomi SJ, Linnoila M: Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. Am J Psychiatry. 1994, 151: 1485-1491.PubMedCrossRef
76.
Olney JW, Wozniak DF, Farber NB, Jevtovic-Todorovic V, Bittigau P, Ikonomidou C: The enigma of fetal alcohol neurotoxicity. Ann Med. 2002, 34: 109-119.PubMedCrossRef
77.
Mameli M, Zamudio PA, Carta M, Valenzuela CF: Developmentally regulated actions of alcohol on hippocampal glutamatergic transmission. J Neurosci. 2005, 25: 8027-8036.PubMedCrossRef
78.
Puglia MP, Valenzuela CF: Ethanol acutely inhibits ionotropic glutamate receptor-mediated responses and long-term potentiation in the developing CA1 hippocampus. Alcohol Clin Exp Res. 2010, 34: 594-606.PubMedCentralPubMedCrossRef
79.
Servais L, Hourez R, Bearzatto B, Gall D, Schiffmann SN, Cheron G: Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome. Proc Natl Acad Sci U S A. 2007, 104: 9858-9863.PubMedCentralPubMedCrossRef
80.
Kim MH, Choi J, Yang J, Chung W, Kim JH, Paik SK, Kim K, Han S, Won H, Bae YS, Cho SH, Seo J, Bae YC, Choi SY, Kim E: Enhanced NMDA receptor-mediated synaptic transmission, enhanced long-term potentiation, and impaired learning and memory in mice lacking IRSp53. J Neurosci. 2009, 29: 1586-1595.PubMedCrossRef
81.
Cotman CW, Monaghan DT, Ganong AH: Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity. Annu Rev Neurosci. 1988, 11: 61-80.PubMedCrossRef
82.
Rabacchi S, Bailly Y, Delhaye-Bouchaud N, Mariani J: Involvement of the N-methyl D-aspartate (NMDA) receptor in synapse elimination during cerebellar development. Science. 1992, 256: 1823-1825.PubMedCrossRef
83.
Luthi A, Schwyzer L, Mateos JM, Gahwiler BH, McKinney RA: NMDA receptor activation limits the number of synaptic connections during hippocampal development. Nat Neurosci. 2001, 4: 1102-1107.PubMedCrossRef
84.
Gambrill AC, Barria A: NMDA receptor subunit composition controls synaptogenesis and synapse stabilization. Proc Natl Acad Sci U S A. 2011, 108: 5855-5860.PubMedCentralPubMedCrossRef
85.
Liu L, Wong TP, Pozza MF, Lingenhoehl K, Wang Y, Sheng M, Auberson YP, Wang YT: Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science. 2004, 304: 1021-1024.PubMedCrossRef
86.
Kullander K, Klein R: Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol. 2002, 3: 475-486.PubMedCrossRef
87.
Dalva MB, Takasu MA, Lin MZ, Shamah SM, Hu L, Gale NW, Greenberg ME: EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell. 2000, 103: 945-956.PubMedCrossRef
88.
Henkemeyer M, Itkis OS, Ngo M, Hickmott PW, Ethell IM: Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus. J Cell Biol. 2003, 163: 1313-1326.PubMedCentralPubMedCrossRef
89.
Henderson JT, Georgiou J, Jia Z, Robertson J, Elowe S, Roder JC, Pawson T: The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function. Neuron. 2001, 32: 1041-1056.PubMedCrossRef
90.
Grootendorst J, Kempes MM, Lucassen PJ, Dalm S, de Kloet ER, Oitzl MS: Differential effect of corticosterone on spatial learning abilities in apolipoprotein E knockout and C57BL/6J mice. Brain Res. 2002, 953: 281-285.PubMedCrossRef
91.
Masliah E, Mallory M, Ge N, Alford M, Veinbergs I, Roses AD: Neurodegeneration in the central nervous system of apoE-deficient mice. Exp Neurol. 1995, 136: 107-122.PubMedCrossRef
92.
Raber J, Akana SF, Bhatnagar S, Dallman MF, Wong D, Mucke L: Hypothalamic-pituitary-adrenal dysfunction in Apoe(-/-) mice: possible role in behavioral and metabolic alterations. J Neurosci. 2000, 20: 2064-2071.PubMed
93.
Karpac J, Ostwald D, Bui S, Hunnewell P, Shankar M, Hochgeschwender U: Development, maintenance, and function of the adrenal gland in early postnatal proopiomelanocortin-null mutant mice. Endocrinology. 2005, 146: 2555-2562.PubMedCrossRef
94.
Kane MA, Folias AE, Wang C, Napoli JL: Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity. FASEB J. 2010, 24: 823-832.PubMedCentralPubMedCrossRef
95.
Kumar A, Singh CK, DiPette DD, Singh US: Ethanol impairs activation of retinoic acid receptors in cerebellar granule cells in a rodent model of fetal alcohol spectrum disorders. Alcohol Clin Exp Res. 2010, 34: 928-937.PubMedCentralPubMedCrossRef
96.
Grummer MA, Zachman RD: Prenatal ethanol consumption alters the expression of cellular retinol binding protein and retinoic acid receptor mRNA in fetal rat embryo and brain. Alcohol Clin Exp Res. 1995, 19: 1376-1381.PubMedCrossRef
97.
Xu Y, Tang Y, Li Y: Effect of folic acid on prenatal alcohol-induced modification of brain proteome in mice. Br J Nutr. 2008, 99: 455-461.PubMedCrossRef
98.
Wang LL, Zhang Z, Li Q, Yang R, Pei X, Xu Y, Wang J, Zhou SF, Li Y: Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation. Hum Reprod. 2009, 24: 562-579.PubMedCrossRef
99.
Sakata-Haga H, Dominguez HD, Sei H, Fukui Y, Riley EP, Thomas JD: Alterations in circadian rhythm phase shifting ability in rats following ethanol exposure during the third trimester brain growth spurt. Alcohol Clin Exp Res. 2006, 30: 899-907.PubMedCrossRef
100.
Earnest DJ, Chen WJ, West JR: Developmental alcohol and circadian clock function. Alcohol Res Health. 2001, 25: 136-140.PubMed
101.
Nasir J, Floresco SB, O’Kusky JR, Diewert VM, Richman JM, Zeisler J, Borowski A, Marth JD, Phillips AG, Hayden MR: Targeted disruption of the Huntington’s disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell. 1995, 81: 811-823.PubMedCrossRef
102.
Tong Y, Ha TJ, Liu L, Nishimoto A, Reiner A, Goldowitz D: Spatial and temporal requirements for huntingtin (Htt) in neuronal migration and survival during brain development. J Neurosci. 2011, 31: 14794-14799.PubMedCentralPubMedCrossRef
103.
Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, Timmusk T, Sipione S, Cattaneo E: Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science. 2001, 293: 493-498.PubMedCrossRef
104.
Guerri C: Neuroanatomical and neurophysiological mechanisms involved in central nervous system dysfunctions induced by prenatal alcohol exposure. Alcohol Clin Exp Res. 1998, 22: 304-312.PubMedCrossRef
105.
Demjaha A, Maccabe JH, Murray RM: How genes and environmental factors determine the different neurodevelopmental trajectories of schizophrenia and bipolar disorder. Schizophr Bull. 2011, 38: 209-214.PubMedCentralPubMedCrossRef
106.
Dufour-Rainfray D, Vourc’h P, Tourlet S, Guilloteau D, Chalon S, Andres CR: Fetal exposure to teratogens: evidence of genes involved in autism. Neurosci Biobehav Rev. 2011, 35: 1254-1265.PubMedCrossRef
107.
Kaminen-Ahola N, Ahola A, Maga M, Mallitt KA, Fahey P, Cox TC, Whitelaw E, Chong S: Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model. PLoS Genet. 2010, 6: e1000811-PubMedCentralPubMedCrossRef
108.
Liu Y, Balaraman Y, Wang G, Nephew KP, Zhou FC: Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation. Epigenetics. 2009, 4: 500-511.PubMedCentralPubMedCrossRef
109.
Sathyan P, Golden HB, Miranda RC: 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. 2007, 27: 8546-8557.PubMedCentralPubMedCrossRef
110.
Miranda RC: MicroRNAs and fetal brain development: implications for ethanol teratology during the second trimester period of neurogenesis. Front Genet. 2011, 3: 77-
111.
Wang G, Wang X, Wang Y, Yang JY, Li L, Nephew KP, Edenberg HJ, Zhou FC, Liu Y: Identification of transcription factor and microRNA binding sites in responsible to fetal alcohol syndrome. BMC Genomics. 2008, Suppl 1: S19-CrossRef
Metadata
Title
Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure
Authors
Morgan L Kleiber
Katarzyna Mantha
Randa L Stringer
Shiva M Singh
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Neurodevelopmental Disorders / Issue 1/2013
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI
https://doi.org/10.1186/1866-1955-5-6

Other articles of this Issue 1/2013

Journal of Neurodevelopmental Disorders 1/2013 Go to the issue

Research

Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome

Review

Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins

Review

Sensory and motor secondary symptoms as indicators of brain vulnerability

Research

Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study

Research

Spontaneous and cued gaze-following in autism and Williams syndrome

Review

Eye tracking in early autism research