Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus.

paper Cited Public

Authors: Gangisetty, Omkaram; Bekdash, Rola; Maglakelidze, George; Sarkar, Dipak K
Year: 2014
Journal: PloS one
PMID: 25409090
DOI: 10.1371/journal.pone.0113228
PMCID: PMC4237387

Figure 1

POMC gene expression and methylation changes in MBH of fetal alcohol exposed rat offspring. A. POMC mRNA levels in MBH of AD, PF and AF rat offspring were measured by quantitative RT-PCR and the amounts were normalized with GAPDH values and expressed as relative mRNA levels. Data are mean ± SEM (n = 6) and were analyzed using one-way ANOVA with Newman-Keuls post-hoc test; *, P<0.05, AF vs AD or PF. B. POMC promoter methylation levels in MBH of AD, PF and AF rat offspring were assayed by real time methylation specific PCR. POMC promoter methylation levels were measured as ratios of methylated verses unmethylated DNA values. Data are mean ± SEM (n = 6) and were analyzed using one-way ANOVA with Newman-Keuls post-hoc test; ***, P<0.001, AF vs AD or PF.

LLM interpretation

This figure consists of two bar charts comparing POMC gene expression and methylation in the MBH of three rat offspring groups: AD, PF, and AF. Panel A shows that relative POMC mRNA levels are significantly lower in the AF group compared to AD and PF groups (*P < 0.05). Panel B shows that the POMC promoter methylation ratio is significantly higher in the AF group compared to the AD and PF groups (***P < 0.001).

Figure 2

Changes in MeCP2 gene and protein levels in MBH of fetal alcohol exposed rat offspring. A. MeCP2 mRNA levels in MBH of AD, PF and AF rat offspring. MeCP2 mRNA levels were measured by quantitative RT-PCR and the amounts were normalized with GAPDH values and expressed as relative mRNA levels. Data are mean ± SEM (n = 6) and were analyzed using one-way ANOVA with Newman-Keuls post-hoc test; *, P<0.05, AF vs. AD or PF. B. A representative western blot gel demonstrating changes in MeCP2 protein levels (top) and actin levels (loading control, bottom) in MBH of AD, PF and AF rat offspring along with quantification measurements were represented as relative protein level (MeCP2/actin). Data are mean ± SEM (n = 6) and were analyzed using one-way ANOVA with Newman-Keuls post-hoc test; **, P<0.01, AF vs. AD or PF. C. MeCP2 protein levels in β-endorphin neurons in the ARC of AD, PF and AF rat offspring were measured by double immunofluorescence methods (MeCP2 proteins are shown in green and β-endorphin shown in red). Representative photographs show double-labeled cells in each group. Histograms show the mean ± SEM (n = 6) values of percent β-EP cells expressing MeCP2 and were analyzed using one-way ANOVA with Newman-Keuls post-hoc test; ***, P<0.001, AF vs. AD or PF.

LLM interpretation

This figure consists of three panels (A-C) comparing MeCP2 levels in the MBH of AD, AF, and PF rat offspring. Panel A shows a bar chart of relative MeCP2 mRNA levels, and Panel B includes a western blot and corresponding bar chart for relative MeCP2 protein levels, both showing a significant increase in the AF group compared to AD and PF (*P<0.05 and **P<0.01, respectively). Panel C displays double immunofluorescence images and a bar chart showing a significantly higher percentage of $\beta$-endorphin (BEP) cells expressing MeCP2 in the AF group (***P<0.001).

Figure 3

Changes in MeCP2 binding onto POMC promoter in ARC and PVN of fetal alcohol exposed rat offspring. A. Schematic representation of POMC promoter with CpG sites and primers flanking MeCP2 binding site. B. The levels of MeCP2 binding on POMC promoter in ARC and PVN of AD, PF and AF rat offspring were measured by ChIP assay. MeCP2 bound DNA pulled by its specific antibody was amplified by real time PCR using primers specific for the POMC promoter. MeCP2 enriched DNA was normalized with GAPDH and expressed as fold enrichment (MeCP2/GAPDH). AD and AF are ARC samples of ad libitum-fed and alcohol-fed rats. ADP and AFP are PVN samples of ad libitum-fed and alcohol-fed rats. Data are mean ± SEM (n = 6) and were analyzed using one-way ANOVA with Newman-Keuls post-hoc test; *, P<0.05, AF vs. AD; a, P<0.001, ADP and AFP versus AD or AF.

LLM interpretation

Figure A is a schematic diagram of the POMC promoter showing CpG sites and the locations of MSP and PCR primers. Figure B is a bar chart showing MeCP2 fold enrichment (normalized to GAPDH) in the ARC and PVN of ad libitum-fed (AD, ADP) and alcohol-fed (AF, AFP) rat offspring. MeCP2 binding is significantly higher in AF compared to AD rats in the ARC (*P<0.05), and overall binding levels are significantly higher in the PVN (ADP and AFP) compared to the ARC (AD and AF) (a, P<0.001).

Figure 4

Effects of lentiviral knockdown of MeCP2 on POMC gene expression levels in fetal alcohol exposed rat offspring. A. A representative western blot gel showing MeCP2 protein levels (top) and actin levels (bottom) in MBH of scr sh (scr) or MeCP2 sh (MeCP) RNA-treated AD, PF and AF rat offspring. Histograms showing MeCP2 and actin ratio values in MBH of AD, PF and AF rats.treated with scr sh or MeCP2 sh RNA. Data are mean ± SEM (n = 6) and were analyzed using one-way ANOVA with Newman-Keuls post-hoc test; *, P<0.05, MeCP2 sh vs. scr-sh; a, P<0.05, AF vs. AD or PF. B. POMC mRNA levels in MBH of scr-sh and MeCP2 sh RNA of AD, PF and AF rat offspring. POMC mRNA amounts were normalized with GAPDH and expressed as relative mRNA level. Data are mean ± SEM (n = 6) and were analyzed using one-way ANOVA with Newman-Keuls post-hoc test; *, P<0.05, AF- vs. AD- or PF-scr-sh-treated groups; a, P<0.05, MeCP2 sh vs. scr-sh (AF group).

LLM interpretation

Figure A consists of a representative western blot and a corresponding bar chart showing that MeCP2 protein levels are significantly reduced in AD, PF, and AF groups treated with MeCP2 shRNA compared to scr-sh controls (*P<0.05), with AF-Scr showing significantly higher levels than AD-Scr or PF-Scr (a, P<0.05). Figure B is a bar chart showing relative POMC mRNA levels, where AF-Scr levels are significantly lower than AD-Scr or PF-Scr (*P<0.05), and MeCP2 knockdown significantly increases POMC mRNA levels specifically in the AF group (a, P<0.05). Both charts display data as mean ± SEM.

Figure 5

Effect of MeCP2 knockdown on stress axis responsiveness in fetal alcohol exposed rat offspring. A. CRH mRNA levels in the MBH of scr sh- or MeCP2 sh RNA-treated AD, PF and AF rat offspring. CRH mRNA amounts were normalized with GAPDH and expressed as relative mRNA level. Data are mean ± SEM (n = 6) and were analyzed using two-way ANOVA with Newman-Keuls post-hoc test; *, P<0.05, AF vs. AD or PF groups; a, P<0.05, MeCP2 sh vs. scr-sh (AF group). B. ACTH levels in plasma of AD, PF or AF rats treated with either scr sh or MeCP2-sh RNA at 0 h and 2 h after LPS treatment. Data are mean ± SEM (n = 6) and were analyzed using two-way ANOVA with Bonferroni post-hoc test; *, P<0.05, AF vs. AD or PF (within Scr sh treatment groups); a, P<0.05, MeCP2 sh vs. scr-sh (AF groups). C. Corticosterone levels in AD, PF or AF rats treated with either scr sh or MeCP2 sh RNA at 0 h and 2 h after LPS treatment. Data are mean ± SEM (n = 6) and were analyzed using two-way ANOVA with Bonferroni post-hoc test; *, P<0.05, AF vs. AD or PF (within Scr sh treatment groups); a, P<0.05, MeCP2 sh vs. scr-sh (AF groups).

LLM interpretation

This figure consists of three bar charts (A, B, and C) comparing the effects of MeCP2 knockdown (Mecp2-sh) versus a control (Scr-sh) across three rat offspring groups: AD, PF, and AF. Panel A shows that CRH mRNA levels in the MBH are significantly elevated in the AF group compared to AD and PF, a trend partially attenuated by MeCP2 knockdown. Panels B and C show that plasma ACTH and corticosterone levels significantly increase 2 hours after LPS treatment specifically in the AF Scr-sh group, with MeCP2 knockdown significantly reducing these responses. Statistical significance is indicated by asterisks (*) for AF vs. AD/PF and the letter 'a' for MeCP2-sh vs. Scr-sh within the AF group.

Figure 6

A Model illustrating the role of promoter methylation and MeCP2 binding in regulation of POMC expression following fetal alcohol exposure.In control rat offspring transcription factor binds to hypomethylated POMC promoter and activates transcription (top). Fetal alcohol exposure promotes hypermethylation of the POMC promoter and recruits MeCP2. MeCP2 binding to CpG methylated POMC promoter prevents the transcription factor's ability to bindto activate gene transcription.

LLM interpretation

This is a schematic diagram illustrating the regulation of POMC expression in control rats versus those with fetal alcohol exposure. In control rats, a transcription factor (TF) binds to a hypomethylated promoter, leading to increased POMC expression. Following fetal alcohol exposure, the promoter becomes hypermethylated and recruits MeCP2, which blocks TF binding and results in decreased POMC expression.

#	Section	Preview
20	Results — Fetal alcohol exposure increases MeCP2 expression and its binding to the POMC promoter in the hypothalamus	Methylated CpG dinucleotides with adjacent A/T-rich sequences are often recognized by MeCP2 [27].…
21	Results — MeCP2 knock down normalizes POMC expression in the hypothalamus of fetal alcohol exposed animals	Because MeCP2 expression and its binding was increased with prenatal ethanol exposure, we…
22	Results — MeCP2 knock down normalizes stress axis hyperresponse in fetal alcohol exposed animals	An endophenotype of the fetal alcohol effect on POMC gene is the hyperresponse of the HPA axis to…
23	Discussion	Fetal alcohol exposure is known to alter HPA axis activity partly via the suppression of POMC…
24	Discussion	MeCP2 is abundantly expressed in the mature brain specifically in the hypothalamus and can either…
25	Discussion	observed in fetal-alcohol exposed rodents and human subjects [2], [34]. MeCP2 regulates chromatin…
26	Discussion	DNA methylation at CpG dinucleotides of gene promoters is a powerful means of gene silencing [35].…
27	Discussion	with methylated CpG sites at the promoter, thereby upregulating the expression of a subset of genes…

Citation	PMID	DOI	Status
ArjonaA, BoyadjievaN, KuhnP, SarkarDK (2006) Fetal ethanol exposure disrupts the daily rhythms of splenic granzyme B, IFN-gamma, and NK cell cytotoxicity in adulthood. Alcohol Clin Exp Res 30: 1039–1044.1673746310.1111/j.1530-0277.2006.00117.x	—	—	—
BakerM, GaukrodgerN, MayosiBM, ImrieH, FarrallM, et al (2005) Association between common polymorphisms of the Proopiomelanocortin gene and body fat distribution: a family study. Diabetes 54: 2492–2496.1604632010.2337/diabetes.54.8.2492	—	—	—
BallestarE, RoperoS, AlaminosM, ArmstrongJ, SetienF, et al (2005) The impact of MECP2 mutations in the expression patterns of Rett syndrome patients. Hum Genet 116: 91–104.1554939410.1007/s00439-004-1200-0	—	—	—
BekdashRA, ZhangC, SarkarDK (2013) Gestational choline supplementation normalized fetal alcohol-induced alterations in histone modifications, DNA methylation, and proopiomelanocortin (POMC) gene expression in β-endorphin-producing POMC neurons of the hypothalamus. Alcohol Clin Exp Res 37: 1133–1142.2341381010.1111/acer.12082PMC3659188	—	—	—
BernalAJ, JirtleRL (2010) Epigenomic disruption: the effects of early developmental exposures. Birth Defects Res A Clin Mol Teratol 88: 938–944.2056827010.1002/bdra.20685PMC2945443	—	—	—
BirdA (1992) The essentials of DNA methylation. Cell 70: 5–8.137798310.1016/0092-8674(92)90526-i	—	—	—
BoyadjievaNI, OrtigüelaM, ArjonaA, ChengX, SarkarDK (2009) Beta-endorphin neuronal cell transplant reduces corticotropin releasing hormone hyperresponse to lipopolysaccharide and eliminates natural killer cell functional deficiencies in fetal alcohol exposed rats. Alcohol Clin Exp Res 33: 931–937.1932062810.1111/j.1530-0277.2009.00911.xPMC2853801	—	—	—
ChahrourM, JungSY, ShawC, ZhouX, WongST, et al (2008) MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320: 1224–1229.1851169110.1126/science.1153252PMC2443785	—	—	—
ChenRZ, AkbarianS, TudorM, JaenischR (2001) Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet 27: 327–331.1124211810.1038/85906	—	—	—
DengJV, RodriguizRM, HutchinsonAN, KimIH, WetselWC, et al (2010) MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants. Nat Neurosci 13: 1128–1136.2071118610.1038/nn.2614PMC2928851	—	—	—
FujitaN, WatanabeS, IchimuraT, TsuruzoeS, ShinkaiY, et al (2003) Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem 278: 24132–24138.1271160310.1074/jbc.M302283200	—	—	—
FuksF, HurdPJ, WolfD, NanX, BirdAP, et al (2003) The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem 278: 4035–4040.1242774010.1074/jbc.M210256200	—	—	—
FyffeSL, NeulJ, SamacoRC, ChaoH, Ben-ShacharS, et al (2008) Deletion of MeCP2 in Sim1-expressing neurons reveals a critical role for MeCP2 in feeding behavior, aggression and the response to stress. Neuron 59: 947–958.1881773310.1016/j.neuron.2008.07.030PMC2597031	—	—	—
GovorkoD, BekdashRA, ZhangC, SarkarDK (2012) Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations. Biol Psychiatry 72: 378–388.2262200010.1016/j.biopsych.2012.04.006PMC3414692	—	—	—
HellemansKG, SliwowskaJH, VermaP, WeinbergJ (2010) Prenatal alcohol exposure: fetal programming and later life vulnerability to stress, depression and anxiety disorders. Neurosci Biobehav Rev 34: 791–807.1954558810.1016/j.neubiorev.2009.06.004PMC5518679	—	—	—
ImH, HollanderJA, BaliP, KennyPJ (2010) MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212. Nature Neuroscience 13: 1120–1128.2071118510.1038/nn.2615PMC2928848	—	—	—
ItohM, IdeS, TakashimaS, KudoS, NomuraY, et al (2007) Methyl CpG-binding protein 2 (a mutation of which causes Rett syndrome) directly regulates insulin-like growth factor binding protein 3 in mouse and human brains. J Neuropathol Exp Neurol 66: 117–123.1727899610.1097/nen.0b013e3180302078	—	—	—
JonesPL, VeenstraGJ, WadePA, VermaakD, KassSU, et al (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19: 187–191.962077910.1038/561	—	—	—
JordanC, LiHH, KwanHC, FranckeU (2007) Cerebellar gene expression profiles of mouse models for Rett syndrome reveal novel MeCP2 targets. BMC Med Genet 20:8: 36.10.1186/1471-2350-8-36PMC193143217584923	—	—	—
KelleyML, BraitmanA, HensonJM, SchroederV, LadageJ, et al (2010) Relationships among depressive mood symptoms and parent and peer relations in collegiate children of alcoholics. Am J Orthopsychiatry 80: 204–212.2055351410.1111/j.1939-0025.2010.01024.x	—	—	—
Latino-MartelP, ChanDS, Druesne-PecolloN, BarrandonE, HercbergS, et al (2010) Maternal alcohol consumption during pregnancy and risk of childhood leukemia: systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 19: 1238–1260.2044791810.1158/1055-9965.EPI-09-1110	—	—	—
LissoniP, BarniS, PaolorossiF, CrispinoS, RovelliF, et al (1987) Evidence for altered opioid activity in patients with cancer. Br J Cancer 56 (6) 834–7.296366210.1038/bjc.1987.300PMC2002387	—	—	—
LiuY, BalaramanY, WangG, NephewKP, ZhouFC (2009) Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation. Epigenetics 4: 500–511.2000956410.4161/epi.4.7.9925PMC2805036	—	—	—
Lopez-SerraL, BallestarE, RoperoS, SetienF, BillardLM, et al (2008) Unmasking of epigenetically silenced candidate tumor suppressor genes by removal of methyl CpG binding domain proteins. Oncogene 27: 3556–3566.1822368710.1038/sj.onc.1211022	—	—	—
LugerTA, ScholzenTE, BrzoskaT, BöhmM (2003) New insights into the functions of alpha-MSH and related peptides in the immune system. Ann N Y Acad Sci 994: 133–140.1285130810.1111/j.1749-6632.2003.tb03172.x	—	—	—
MartinowichK, HattoriD, WuH, FouseS, HeF, et al (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302: 890–893.1459318410.1126/science.1090842	—	—	—
MeehanRR, LewisJD, BirdAP (1992) Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucleic Acids Res 20: 5085–5092.140882510.1093/nar/20.19.5085PMC334288	—	—	—
MillerMW (1992) Circadian rhythm of cell proliferation in the telencephalic ventricular zone: effect of in utero exposure to ethanol. Brain Res 595: 17–24.146795410.1016/0006-8993(92)91447-m	—	—	—
MountjoyKG (2010) Functions for pro-opiomelanocortin-derived peptides in obesity and diabetes. Biochem J 428: 305–324.2050428110.1042/BJ20091957	—	—	—
NanX, MeehanRR, BirdA (1993) Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res 21: 4886–4892.817773510.1093/nar/21.21.4886PMC311401	—	—	—
NanX, NgHH, JohnsonCA, LahertyCD, TurnerBM, et al (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393: 386–389.962080410.1038/30764	—	—	—
Newell-PriceJ (2003) Proopiomelanocortin gene expression and DNA methylation: implications for Cushing's syndrome and beyond. J Endocrinol 177: 365–372.1277311610.1677/joe.0.1770365	—	—	—
Newell-PriceJ, KingP, ClarkAJ (2001) The CpG island promoter of the human proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression. Mol Endocrinol 15: 338–348.1115833810.1210/mend.15.2.0599	—	—	—
PlagemannA, HarderT, RakeA, WaasT, MelchiorK, et al (1999) Observations on the orexigenic hypothalamic neuropeptide Y-system in neonatally overfed weanling rats. J Neuroendocrinol 11: 541–546.1044431110.1046/j.1365-2826.1999.00357.x	—	—	—
PlotskyPM (1991) Pathways to the secretion of adrenocorticotropin: a view from the portal. J Neuroendocrinol 3: 1–9.1921543910.1111/j.1365-2826.1991.tb00231.x	—	—	—
Raffin-SansonML, de KeyzerY, BertagnaX (2003) Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions. Eur J Endocrinol 149: 79–90.1288728310.1530/eje.0.1490079	—	—	—
RizzatoC, SchererD, RudnaiP, GurzauE, KoppovaK, et al (2011) POMC and TP53 genetic variability and risk of basal cell carcinoma of skin: Interaction between host and genetic factors. J Dermatol Sci 63: 47–54.2153641310.1016/j.jdermsci.2011.03.006	—	—	—
SarkarDK, KuhnP, MaranoJ, ChenC, BoyadjievaN (2007) Alcohol exposure during the developmental period induces beta-endorphin neuronal death and causes alteration in the opioid control of stress axis function. Endocrinology 148: 2828–2834.1734730810.1210/en.2006-1606	—	—	—
SchneiderML, MooreCF, KraemerGW, RobertsAD, DeJesusOT (2002) The impact of prenatal stress, fetal alcohol exposure, or both on development: perspectives from a primate model. Psychoneuroendocrinology 27: 285–298.1175078410.1016/s0306-4530(01)00050-6	—	—	—
SmartJL, TolleV, Otero-CorchonV, LowMJ (2007) Central dysregulation of the hypothalamic-pituitary-adrenal axis in neuron-specific proopiomelanocortin-deficient mice. Endocrinology 148: 647–659.1709558810.1210/en.2006-0990	—	—	—
SuttonBS, LangefeldCD, WilliamsAH, NorrisJM, SaadMF, et al (2005) Association of proopiomelanocortin gene polymorphisms with obesity in the IRAS family study. Obes Res 13: 1491–1498.1622204710.1038/oby.2005.180	—	—	—
TaoJ, HuK, ChangQ, WuH, ShermanNE, et al (2009) Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function. Proc Natl Acad Sci U S A 106: 4882–4887.1922511010.1073/pnas.0811648106PMC2660725	—	—	—
WadePA, GegonneA, JonesPL, BallestarE, AubryF, et al (1999) Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat Genet 23 (1) 62–6.1047150010.1038/12664	—	—	—
Wynne O, Sarkar DK (2013) Stress and neuroendocrine-immune interaction: a therapeutic role for β-endorphin. Kusnecov A and Anisman H (eds.) Handbook of Psychoneuroimmunology, Wiley Blackwell, Oxford, UK. pp 198–211.	—	—	—
XueiX, Flury-WetherillL, BierutL, DickD, NurnbergerJJr, et al (2007) The opioid system in alcohol and drug dependence: family-based association study. Am J Med Genet B Neuropsychiatr Genet 144B: 877–884.1750348110.1002/ajmg.b.30531	—	—	—
ZhouZ, HongEJ, CohenS, ZhaoW, HoH, et al (2006) Brain-specific phosphorylation of MeCP2 regualtes activity-dependent BDNF transcription, dendritic growth and spine maturation. Neuron 52: 255–269.1704668910.1016/j.neuron.2006.09.037PMC3962021	—	—	—

In this knowledge base

Title	Year	PMID
Bioinformatic Analysis of DNA Methylation in Neural Progenitor Cell Models of Alcohol Abuse.	2016	27774408

External

Title	Authors	Journal	Year	Link
Synaptic aging and neurodegeneration: the role of synaptic vesicle dynamics and neurotransmitter imbalance.	Wal P et al.	—	2026	→
Developmental pluripotency-associated 4 increases aggressiveness of pituitary neuroendocrine tumors by enhancing cell stemness.	Chaudhary S et al.	—	2025	→
An Epigenetic Manifestation of Alzheimer's Disease: DNA Methylation.	Feng B et al.	—	2024	→
CpG Methylation Levels in HPA Axis Genes Predict Chronic Pain Outcomes Following Trauma Exposure.	Branham EM et al.	—	2023	→
miRNA-383 and miRNA-384 Suppress Proopiomelanocortin Gene Expression in the Hypothalamus: Effects of Early Life Ethanol Exposure.	Gangisetty O et al.	—	2023	→
Neuroimmune Interactions in Fetal Alcohol Spectrum Disorders: Potential Therapeutic Targets and Intervention Strategies.	Mukherjee S et al.	—	2023	→
Prenatal ethanol exposure and changes in fetal neuroendocrine metabolic programming.	Liu L et al.	—	2023	→
The Association of the Hypothalamic-Pituitary-Adrenal Axis with Appetite Regulation in Children with Fetal Alcohol Spectrum Disorders (FASDs).	Podgórski R et al.	—	2023	→
Activation of the anterior cingulate cortex ameliorates anxiety in a preclinical model of fetal alcohol spectrum disorders.	Hwang HM et al.	—	2022	→
Association of prenatal alcohol exposure with offspring DNA methylation in mammals: a systematic review of the evidence.	Bestry M et al.	—	2022	→
Astrocyte ethanol exposure reveals persistent and defined calcium response subtypes and associated gene signatures.	Kim HB et al.	—	2022	→
Transgenerational inheritance of fetal alcohol effects on proopiomelanocortin gene expression and methylation, cortisol response to stress, and anxiety-like behaviors in offspring for three generations in rats: Evidence for male germline transmission.	Gangisetty O et al.	—	2022	→
Epigenetic Impacts of Early Life Stress in Fetal Alcohol Spectrum Disorders Shape the Neurodevelopmental Continuum.	Alberry B et al.	—	2021	→
Maternal choline supplementation in a rat model of periconceptional alcohol exposure: Impacts on the fetus and placenta.	Steane SE et al.	—	2021	→
Sex-Determining Region Y Controls the Effects of Fetal Alcohol Exposure on Proopiomelanocortin Gene Expression.	Gangisetty O et al.	—	2021	→
Alcohol as an early life stressor: Epigenetics, metabolic, neuroendocrine and neurobehavioral implications.	Ciafrè S et al.	—	2020	→
Ethanol has concentration-dependent effects on hypothalamic POMC neuronal excitability.	Leyrer-Jackson JM et al.	—	2020	→
Prenatal alcohol exposure and developmental programming of mental illness.	Burgess DJ et al.	—	2020	→
Prenatal drug exposure and neurodevelopmental programming of glucocorticoid signalling.	Franks AL et al.	—	2020	→
A review on neuroimaging studies of genetic and environmental influences on early brain development.	Gao W et al.	—	2019	→
Clinical presentation, diagnosis, and management of fetal alcohol spectrum disorder.	Wozniak JR et al.	—	2019	→
Early life alcohol exposure primes hypothalamic microglia to later-life hypersensitivity to immune stress: possible epigenetic mechanism.	Chastain LG et al.	—	2019	→
Epigenetic regulation of POMC; implications for nutritional programming, obesity and metabolic disease.	Candler T et al.	—	2019	→
Hypermethylation of Proopiomelanocortin and Period 2 Genes in Blood Are Associated with Greater Subjective and Behavioral Motivation for Alcohol in Humans.	Gangisetty O et al.	—	2019	→
Persistent Changes in Stress-Regulatory Genes in Pregnant Women or Children Exposed Prenatally to Alcohol.	Sarkar DK et al.	—	2019	→
Adult hippocampal MeCP2 preserves the genomic responsiveness to learning required for long-term memory formation.	Gulmez Karaca K et al.	—	2018	→
Atypical fetal development: Fetal alcohol syndrome, nutritional deprivation, teratogens, and risk for neurodevelopmental disorders and psychopathology.	Georgieff MK et al.	—	2018	→
CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice.	Subbanna S et al.	—	2018	→
Alcohol effects on the epigenome in the germline: Role in the inheritance of alcohol-related pathology.	Chastain LG et al.	—	2017	→
Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure.	Gavin DP et al.	—	2017	→
Lack of IL-1R8 in neurons causes hyperactivation of IL-1 receptor pathway and induces MECP2-dependent synaptic defects.	Tomasoni R et al.	—	2017	→
Long-term alterations to DNA methylation as a biomarker of prenatal alcohol exposure: From mouse models to human children with fetal alcohol spectrum disorders.	Laufer BI et al.	—	2017	→
MicroRNA-9 regulates fetal alcohol-induced changes in D2 receptor to promote prolactin production.	Gangisetty O et al.	—	2017	→
Strain-specific programming of prenatal ethanol exposure across generations.	Popoola DO et al.	—	2017	→
The Role of the Melanocortin System in Drug and Alcohol Abuse.	Navarro M	—	2017	→
Turnover of histones and histone variants in postnatal rat brain: effects of alcohol exposure.	Rachdaoui N et al.	—	2017	→
An assessment of molecular pathways of obesity susceptible to nutrient, toxicant and genetically induced epigenetic perturbation.	Xue J et al.	—	2016	→
Bioinformatic Analysis of DNA Methylation in Neural Progenitor Cell Models of Alcohol Abuse.	Oni EN et al.	—	2016	→
Developmental and behavioral consequences of early life maternal separation stress in a mouse model of fetal alcohol spectrum disorder.	Alberry B et al.	—	2016	→
Endogenous opiates and behavior: 2014.	Bodnar RJ	—	2016	→
Preconception Alcohol Increases Offspring Vulnerability to Stress.	Jabbar S et al.	—	2016	→
Sustained Effects of Developmental Exposure to Ethanol on Zebrafish Anxiety-Like Behaviour.	Baiamonte M et al.	—	2016	→
Ethanol deregulates Mecp2/MeCP2 in differentiating neural stem cells via interplay between 5-methylcytosine and 5-hydroxymethylcytosine at the Mecp2 regulatory elements.	Liyanage VR et al.	—	2015	→
Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms.	Gangisetty O et al.	—	2015	→