New therapeutics for the prevention or amelioration of fetal alcohol spectrum disorders: a narrative review of the preclinical literature

References

• Pilatti A, Read JP, Pautassi RM. ELSA 2016 cohort: alcohol, tobacco, and marijuana use and their association with age of drug use onset. Risk Perception, And Social Norms In Argentinean College Freshmen. Frontiers. 2017;8. doi: 10.3389/fpsyg.2017.01452.
   Google Scholar
• Vera BDV, Pilatti A, Pautassi RM. ELSA 2014 cohort: risk factors associated with heavy episodic drinking trajectories in argentinean college students. Front Behav Neurosci. 2020;14:105. doi: 10.3389/fnbeh.2020.00105.
   PubMedGoogle Scholar
• Husky MM, Bharat C, Lépine JP, Kovess-Masfety V. Cohort alcohol use in France and the transition from use to alcohol use disorder and remission. J Psychoactive Drugs. 2019;51:453–62. doi: 10.1080/02791072.2019.1612536.
   PubMed Web of Science ®Google Scholar
• Vera BDV, Pilatti A, Pautassi RM. ELSA cohort 2014: association of age of first drink and progression from first drink to drunkenness on alcohol outcomes in argentinean college freshmen. Am J Drug Alcohol Abuse. 2020;46:58–67. doi: 10.1080/00952990.2019.1608223.
   PubMed Web of Science ®Google Scholar
• Moraes Castro M, Pinto F, Pereiras C, Fischer Castells A, Vogel Agoglia C, Duarte V, Barceló J, Sosa C, González G. Autodeclaración del consumo de marihuana, tabaco, alcohol y derivados de cocaína en embarazadas en 2013 y 2016, Montevideo, Uruguay. Adicciones. 2019;32:173. doi: 10.20882/adicciones.1107.
   Google Scholar
• Lees B, Mewton L, Jacobus J, Valadez EA, Stapinski LA, Teesson M, Tapert SF, Squeglia LM. Association of prenatal alcohol exposure with psychological, behavioral, and neurodevelopmental outcomes in children from the adolescent brain cognitive development study. Am J Psychiatry. 2020;177:1060–72. doi: 10.1176/appi.ajp.2020.20010086.
   PubMed Web of Science ®Google Scholar
• Popova S, Charness ME, Burd L, Crawford A, Hoyme HE, Mukherjee RAS, Riley EP, Elliott EJ. Fetal alcohol spectrum disorders. Nature reviews. Disease Primers. 2023;9:11. doi: 10.1038/s41572-023-00420-x.
   PubMedGoogle Scholar
• Okurame JC, Cannon L, Carter E, Thomas S, Elliott EJ, Rice LJ. Fetal alcohol spectrum disorder resources for health professionals: a scoping review protocol. BMJ Open. 2022;12:e065327. doi: 10.1136/bmjopen-2022-065327.
   PubMedGoogle Scholar
• Chokroborty-Hoque A, Alberry B, Singh SM. Exploring the complexity of intellectual disability in fetal alcohol spectrum disorders. Front Pediatr. 2014;2:90. doi: 10.3389/fped.2014.00090.
   PubMedGoogle Scholar
• Pueta M, Rovasio RA, Abate P, Spear NE, Molina JC. Prenatal and postnatal ethanol experiences modulate consumption of the drug in rat pups, without impairment in the granular cell layer of the main olfactory bulb. Physiol Behav. 2011;102:63–75. doi: 10.1016/j.physbeh.2010.10.009.
   PubMedGoogle Scholar
• Contreras ML, de la Fuente-Ortega E, Vargas-Roberts S, Muñoz DC, Goic CA, Haeger PA. NADPH oxidase isoform 2 (NOX2) is involved in drug addiction vulnerability in progeny developmentally exposed to ethanol. Front Neurosci. 2017;11:338. doi: 10.3389/fnins.2017.00338.
   PubMedGoogle Scholar
• Wille-Bille A, Bellia F, Jimenez Garcia AM, Miranda-Morales RS, D’Addario C, Pautassi RM. Early exposure to environmental enrichment modulates the effects of prenatal ethanol exposure upon opioid gene expression and adolescent ethanol intake. Neuropharmacology. 2020;165:107917. doi: 10.1016/j.neuropharm.2019.107917.
   PubMed Web of Science ®Google Scholar
• Plaza-Briceño W, Estay SF, de la Fuente-Ortega E, Gutiérrez C, Sánchez G, Hidalgo C, Chávez AE, Haeger PA. N-Methyl-d-aspartate receptor modulation by nicotinamide adenine dinucleotide phosphate oxidase type 2 drives synaptic plasticity and spatial memory impairments in rats exposed pre- and postnatally to ethanol. Antioxid Redox Signal. 2020;32:602–17. doi: 10.1089/ars.2019.7787.
   PubMedGoogle Scholar
• Fabio MC, March SM, Molina JC, Nizhnikov ME, Spear NE, Pautassi RM. Prenatal ethanol exposure increases ethanol intake and reduces c-fos expression in infralimbic cortex of adolescent rats. Pharmacol Biochem Behav. 2013;103:842–52. doi: 10.1016/j.pbb.2012.12.009.
   PubMedGoogle Scholar
• Fabio MC, Vivas LM, Pautassi RM. Prenatal ethanol exposure alters ethanol-induced fos immunoreactivity and dopaminergic activity in the mesocorticolimbic pathway of the adolescent brain. Neuroscience. 2015;301:221–34. doi: 10.1016/j.neuroscience.2015.06.003.
   PubMed Web of Science ®Google Scholar
• Walter KR, Ricketts DK, Presswood BH, Smith SM, Mooney SM. Prenatal alcohol exposure causes persistent microglial activation and age- and sex- specific effects on cognition and metabolic outcomes in an Alzheimer’s disease mouse model. Am J Drug Alcohol Abuse. 2023;49:302–20. doi: 10.1080/00952990.2022.2119571.
   PubMed Web of Science ®Google Scholar
• Webster WS, Walsh DA, McEwen SE, Lipson AH. Some teratogenic properties of ethanol and acetaldehyde in C57BL/6J mice: implications for the study of the fetal alcohol syndrome. Teratology. 1983;27:231–43. doi: 10.1002/tera.1420270211.
   PubMedGoogle Scholar
• Risbud RD, Breit KR, Thomas JD. Early developmental alcohol exposure alters behavioral outcomes following adolescent re-exposure in a rat model. Alcohol Clin Exp Res. 2022;46:1993–2009. doi: 10.1111/acer.14950.
   PubMedGoogle Scholar
• Gursky ZH, Klintsova AY. Rat model of late gestational alcohol exposure produces similar life-long changes in thalamic nucleus reuniens following moderate- versus high-dose insult. Alcohol and alcoholism (Oxford, Oxfordshire. Alcohol Alcoholism. 2022;57:413–20. doi: 10.1093/alcalc/agac008.
   PubMedGoogle Scholar
• Schambra UB, Nunley K, Harrison TA, Lewis CN. Consequences of low or moderate prenatal ethanol exposures during gastrulation or neurulation for open field activity and emotionality in mice. Neurotoxicol Teratol. 2016;57:39–53. doi: 10.1016/j.ntt.2016.06.003.
   PubMedGoogle Scholar
• Subbanna S, Basavarajappa BS. Binge-like prenatal ethanol exposure causes impaired cellular differentiation in the embryonic forebrain and synaptic and behavioral defects in adult mice. Brain Sci. 2022;12:793. doi: 10.3390/brainsci12060793.
   PubMedGoogle Scholar
• Rouzer SK, Cole JM, Johnson JM, Varlinskaya EI, Diaz MR. Moderate maternal alcohol exposure on gestational day 12 impacts anxiety-like behavior in offspring. Front Behav Neurosci. 2017;11:183. doi: 10.3389/fnbeh.2017.00183.
   PubMedGoogle Scholar
• Bird CW, Barber MJ, Martin J, Mayfield JJ, Valenzuela CF. The mouse-equivalent of the human BDNF VAL66MET polymorphism increases dorsal hippocampal volume and does not interact with developmental ethanol exposure. Alcohol. 2020;86:17–24. doi: 10.1016/j.alcohol.2020.03.005.
   PubMedGoogle Scholar
• Bariselli S, Mateo Y, Reuveni N, Lovinger DM. Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function. Neuropsychopharmacol. 2023;48:1808–20. doi: 10.1038/s41386-023-01594-4.
   PubMedGoogle Scholar
• Gilpin NW, Richardson HN, Cole M, Koob GF. Vapor inhalation of alcohol in rats. Current Protocols In Neuroscience. 2008;44. doi: 10.1002/0471142301.ns0929s44.
   Google Scholar
• Murawski NJ, Moore EM, Thomas JD, Riley EP. Advances in diagnosis and treatment of fetal alcohol spectrum disorders: from animal models to human studies. Alcohol Res. 2015;37:97–108.
   PubMed Web of Science ®Google Scholar
• O’Connor MJ, Frankel F, Paley B, Schonfeld AM, Carpenter E, Laugeson EA, Marquardt R. A controlled social skills training for children with fetal alcohol spectrum disorders. J Consult Clin Psychol. 2006;74:639–48. doi: 10.1037/0022-006X.74.4.639.
   PubMed Web of Science ®Google Scholar
• Wells AM, Chasnoff IJ, Schmidt CA, Telford E, Schwartz LD. Neurocognitive habilitation therapy for children with fetal alcohol spectrum disorders: an adaptation of the alert program(R). Am J Occup Ther. 2012;66:24–34. doi: 10.5014/ajot.2012.002691.
   PubMed Web of Science ®Google Scholar
• Thomas JD, Fleming S, Riley EP. MK-801 can exacerbate or attenuate behavioral alterations associated with neonatal alcohol exposure in the rat, depending on the timing of administration. Alcohol Clin Exp Res. 2001;25:764–73. doi: 10.1111/j.1530-0277.2001.tb02277.x.
   PubMedGoogle Scholar
• Kusat Ol K, Kanbak G, Oğlakcı Ilhan A, Burukoglu D, Yücel F. The investigation of the prenatal and postnatal alcohol exposure-induced neurodegeneration in rat brain: protection by betaine and/or omega-3. Childs Nerv Syst. 2016;32:467–74. doi: 10.1007/s00381-015-2990-1.
   PubMedGoogle Scholar
• Sogut I, Uysal O, Oglakci A, Yucel F, Kartkaya K, Kanbak G. Prenatal alcohol-induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine. Childs Nerv Syst. 2017;33:407–17. doi: 10.1007/s00381-016-3309-6.
   PubMed Web of Science ®Google Scholar
• Marengo L, Fabio MC, Bernal IS, Salguero A, Molina JC, Moron I, Cendan CM, D’Addario C, Pautassi RM. Folate administration ameliorates neurobehavioral effects of prenatal ethanol exposure. Am J Drug Alcohol Abuse. 2023;49:1–13. doi: 10.1080/00952990.2022.2159425.
   PubMedGoogle Scholar
• Kwan STC, Ricketts DK, Presswood BH, Smith SM, Mooney SM. Prenatal choline supplementation during mouse pregnancy has differential effects in alcohol-exposed fetal organs. Alcohol Clin Exp Res. 2021;45:2471–84. doi: 10.1111/acer.14730.
   PubMedGoogle Scholar
• Wang Y, Feltham BA, Louis XL, Eskin MNA, Suh M. Maternal diets affected ceramides and fatty acids in brain regions of neonatal rats with prenatal ethanol exposure. Nutr Neurosci. 2023;26:60–71. doi: 10.1080/1028415X.2021.2017661.
   PubMedGoogle Scholar
• Hu Y-S, Long N, Pigino G, Brady ST, Lazarov O, Ginsberg SD. Molecular mechanisms of environmental enrichment: impairments in Akt/GSK3β, neurotrophin-3 and CREB signaling. PLOS ONE. 2013;8:e64460. doi: 10.1371/journal.pone.0064460.
   PubMed Web of Science ®Google Scholar
• Helfrich KK, Saini N, Kwan STC, Rivera OC, Hodges R, Smith SM. Gestational iron supplementation improves fetal outcomes in a rat model of prenatal alcohol exposure. Nutrients. 2022;14:1653. doi: 10.3390/nu14081653.
   PubMedGoogle Scholar
• Shili I, Hamdi Y, Marouani A, Ben Lasfar Z, Ghrairi T, Lefranc B, Leprince J, Vaudry D, Olfa MK. Long-term protective effect of PACAP in a fetal alcohol syndrome (FAS) model. Peptides. 2021;146:170630. doi: 10.1016/j.peptides.2021.170630.
   PubMedGoogle Scholar
• Komada M, Hara N, Kawachi S, Kawachi K, Kagawa N, Nagao T, Ikeda Y. Mechanisms underlying neuro-inflammation and neurodevelopmental toxicity in the mouse neocortex following prenatal exposure to ethanol. Sci Rep. 2017;7:4934. doi: 10.1038/s41598-017-04289-1.
   PubMedGoogle Scholar
• Almeida-Toledano L, Andreu-Fernández V, Aras-López R, García-Algar Ó, Martínez L, Gómez-Roig MD. Epigallocatechin gallate ameliorates the effects of prenatal alcohol exposure in a fetal alcohol spectrum disorder-like mouse Model. Int J Mol Sci. 2021;22:715. doi: 10.3390/ijms22020715.
   PubMedGoogle Scholar
• Ieraci A, Herrera DG. Nicotinamide inhibits ethanol-induced caspase-3 and PARP-1 over-activation and subsequent neurodegeneration in the developing mouse cerebellum. Cerebellum. 2018;17:326–35. doi: 10.1007/s12311-017-0916-z.
   PubMedGoogle Scholar
• Thomas JD, La Fiette MH, Quinn VRE, Riley EP. Neonatal choline supplementation ameliorates the effects of prenatal alcohol exposure on a discrimination learning task in rats. Neurotoxicol Teratol. 2000;22:703–11. doi: 10.1016/S0892-0362(00)00097-0.
   PubMed Web of Science ®Google Scholar
• Thomas JD, Garrison M, O’Neill TM. Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats. Neurotoxicol Teratol. 2004;26:35–45. doi: 10.1016/j.ntt.2003.10.002.
   PubMed Web of Science ®Google Scholar
• Thomas JD, O’Neill TM, Dominguez HD. Perinatal choline supplementation does not mitigate motor coordination deficits associated with neonatal alcohol exposure in rats. Neurotoxicol Teratol. 2004;26:223–29. doi: 10.1016/j.ntt.2003.10.005.
   PubMedGoogle Scholar
• Wellmann KA, George F, Brnouti F, Mooney SM. Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure. Behav Brain Res. 2015;286:201–11. doi: 10.1016/j.bbr.2015.02.048.
   PubMed Web of Science ®Google Scholar
• Balaszczuk V, Salguero JA, Villarreal RN, Scaramuzza RG, Mendez S, Abate P. Hyperlocomotion and anxiety- like behavior induced by binge ethanol exposure in rat neonates. Possible ameliorative effects of Omega 3. Behav Brain Res. 2019;372:112022. doi: 10.1016/j.bbr.2019.112022.
   PubMedGoogle Scholar
• Patten AR, Sickmann HM, Dyer RA, Innis SM, Christie BR. Omega-3 fatty acids can reverse the long-term deficits in hippocampal synaptic plasticity caused by prenatal ethanol exposure. Neurosci Lett. 2013;551:7–11. doi: 10.1016/j.neulet.2013.05.051.
   PubMed Web of Science ®Google Scholar
• Marengo L, Barey A, Salguero A, Fabio MC, Cendán CM, Morón-Henche I, D’Addario C, Pautassi RM. Neurobehavioral alterations induced by third-trimester gestation-equivalent ethanol exposure are inhibited by folate administration. Dev Psychobiol. 2023;65:e22426. doi: 10.1002/dev.22426.
   PubMedGoogle Scholar
• Aghaie CI, Hausknecht KA, Wang R, Dezfuli PH, Haj-Dahmane S, Kane CJM, Sigurdson WJ, Shen RY. Prenatal ethanol exposure and postnatal environmental intervention alter dopaminergic neuron and microglia morphology in the ventral tegmental area during adulthood. Alcohol Clin Exp Res. 2020;44:435–44. doi: 10.1111/acer.14275.
   PubMed Web of Science ®Google Scholar
• Wang R, Hausknecht KA, Shen YL, Haj-Dahmane S, Vezina P, Shen RY. Environmental enrichment reverses increased addiction risk caused by prenatal ethanol exposure. Drug Alcohol Depen. 2018;191:343–47. doi: 10.1016/j.drugalcdep.2018.07.013.
   PubMedGoogle Scholar
• Wang R, Martin CD, Lei AL, Hausknecht KA, Turk M, Micov V, Kwarteng F, Ishiwari K, Oubraim S, Wang AL, et al. Prenatal ethanol exposure impairs sensory processing and habituation to visual stimuli, effects normalized by enrichment of postnatal environmental. Alcohol Clin Exp Res. 2022;46:891–906. doi: 10.1111/acer.14818.
   PubMed Web of Science ®Google Scholar
• Thomas JD, Biane JS, O’Bryan KA, O’Neill TM, Dominguez HD. Choline supplementation following third-trimester-equivalent alcohol exposure attenuates behavioral alterations in rats. Behavioral Neuroscience. 2007;121:120–30. doi: 10.1037/0735-7044.121.1.120.
   PubMed Web of Science ®Google Scholar
• Waddell J, Mooney SM. Choline and working memory training improve cognitive deficits caused by prenatal exposure to ethanol. Nutrients. 2017;9:1080. doi: 10.3390/nu9101080.
   PubMedGoogle Scholar
• Waddell J, Hill E, Tang S, Jiang L, Xu S, Mooney SM. Choline plus working memory training improves prenatal alcohol-induced deficits in cognitive flexibility and functional connectivity in adulthood in rats. Nutrients. 2020;12:3513. doi: 10.3390/nu12113513.
   PubMedGoogle Scholar
• Zhang K, Wang H, Xu M, Frank JA, Luo J. Role of MCP-1 and CCR2 in ethanol-induced neuroinflammation and neurodegeneration in the developing brain. J Neuroinflammation. 2018;15:197. doi: 10.1186/s12974-018-1241-2.
   PubMedGoogle Scholar
• Kane CJ, Phelan KD, Han L, Smith RR, Xie J, Douglas JC, Drew PD. Protection of neurons and microglia against ethanol in a mouse model of fetal alcohol spectrum disorders by peroxisome proliferator-activated receptor-γ agonists. Brain Behav Immun. 2011;25:S137–145. doi: 10.1016/j.bbi.2011.02.016.
   PubMed Web of Science ®Google Scholar
• Drew PD, Johnson JW, Douglas JC, Phelan KD, Kane CJ. Pioglitazone blocks ethanol induction of microglial activation and immune responses in the hippocampus, cerebellum, and cerebral cortex in a mouse model of fetal alcohol spectrum disorders. Alcohol Clin Exp Res. 2015;39:445–54. doi: 10.1111/acer.12639.
   PubMed Web of Science ®Google Scholar
• Chastain LG, Franklin T, Gangisetty O, Cabrera MA, Mukherjee S, Shrivastava P, Jabbar S, Sarkar DK. Early life alcohol exposure primes hypothalamic microglia to later-life hypersensitivity to immune stress: possible epigenetic mechanism. Neuropsychopharmacology. 2019;44:1579–88. doi: 10.1038/s41386-019-0326-7.
   PubMed Web of Science ®Google Scholar
• Shrivastava P, Cabrera MA, Chastain LG, Boyadjieva NI, Jabbar S, Franklin T, Sarkar DK. Mu-opioid receptor and delta-opioid receptor differentially regulate microglial inflammatory response to control proopiomelanocortin neuronal apoptosis in the hypothalamus: effects of neonatal alcohol. J Neuroinflammation. 2017;14:83. doi: 10.1186/s12974-017-0844-3.
   PubMedGoogle Scholar
• Wang X, Zhang K, Yang F, Ren Z, Xu M, Frank JA, Ke ZJ, Luo J. Minocycline protects developing brain against ethanol-induced damage. Neuropharmacology. 2018;129:84–99. doi: 10.1016/j.neuropharm.2017.11.019.
   PubMedGoogle Scholar
• Ren Z, Wang X, Xu M, Frank JA, Luo J. Minocycline attenuates ethanol-induced cell death and microglial activation in the developing spinal cord. Alcohol. 2019;79:25–35. doi: 10.1016/j.alcohol.2018.12.002.
   PubMedGoogle Scholar
• Ryan SH, Williams JK, Thomas JD. Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration. Brain Res. 2008;1237:91–100. doi: 10.1016/j.brainres.2008.08.048.
   PubMed Web of Science ®Google Scholar
• Andreu-Fernández V, Serra-Delgado M, Almeida-Toledano L, García-Meseguer À, Vieiros M, Ramos-Triguero A, Muñoz-Lozano C, Navarro-Tapia E, Martínez L, García-Algar Ó, et al. Effect of postnatal epigallocatechin-gallate treatment on cardiac function in mice prenatally exposed to alcohol. Antioxidants (Basel, Switzerland). 2023;12:1067. doi: 10.3390/antiox12051067.
   PubMedGoogle Scholar
• Patten AR, Brocardo PS, Christie BR. Omega-3 supplementation can restore glutathione levels and prevent oxidative damage caused by prenatal ethanol exposure. J Nutr Biochem. 2013;24:760–69. doi: 10.1016/j.jnutbio.2012.04.003.
   PubMed Web of Science ®Google Scholar
• Hannigan JH, Berman RF, Zajac CS. Environmental enrichment and the behavioral effects of prenatal exposure to alcohol in rats. Neurotoxicol Teratol. 1993;15:261–66. doi: 10.1016/0892-0362(93)90007-B.
   PubMed Web of Science ®Google Scholar
• Parks EA, McMechan AP, Hannigan JH, Berman RF. Environmental enrichment alters neurotrophin levels after fetal alcohol exposure in rats. Alcohol Clin Exp Res. 2008;32:1741–51. doi: 10.1111/j.1530-0277.2008.00759.x.
   PubMedGoogle Scholar
• Klintsova AY, Cowell RM, Swain RA, Napper RM, Goodlett CR, Greenough WT. Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats. I. Behavioral results. Brain Res. 1998;800:48–61. doi: 10.1016/S0006-8993(98)00495-8.
   PubMed Web of Science ®Google Scholar
• Klintsova AY, Scamra C, Hoffman M, Napper RMA, Goodlett CR, Greenough WT. Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats: II. A quantitative stereological study of synaptic plasticity in female rat cerebellum. Brain Res. 2002;937:83–93. doi: 10.1016/S0006-8993(02)02492-7.
   PubMed Web of Science ®Google Scholar
• Patten AR, Brocardo PS, Sakiyama C, Wortman RC, Noonan A, Gil-Mohapel J, Christie BR. Impairments in hippocampal synaptic plasticity following prenatal ethanol exposure are dependent on glutathione levels. Hippocampus. 2013;23:1463–75. doi: 10.1002/hipo.22199.
   PubMedGoogle Scholar
• Chen MH, Hong CL, Wang YT, Wang TJ, Chen JR. The effect of astaxanthin treatment on the rat model of fetal alcohol spectrum disorders (FASD). Brain Res Bull. 2022;183:57–72. doi: 10.1016/j.brainresbull.2022.02.017.
   PubMedGoogle Scholar
• Cantacorps L, Montagud-Romero S, Valverde O. Curcumin treatment attenuates alcohol-induced alterations in a mouse model of foetal alcohol spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2020;100:109899. doi: 10.1016/j.pnpbp.2020.109899.
   PubMedGoogle Scholar
• Sharma N, Luhach K, Golani LK, Singh B, Sharma B. Vinpocetine, a PDE1 modulator, regulates markers of cerebral health, inflammation, and oxidative stress in a rat model of prenatal alcohol-induced experimental attention deficit hyperactivity disorder. Alcohol. 2022;105:25–34. doi: 10.1016/j.alcohol.2022.08.005.
   PubMedGoogle Scholar
• Nunes F, Ferreira-Rosa K, Pereira Mdos S, Kubrusly RC, Manhaes AC, Abreu-Villaca Y, Filgueiras CC. Acute administration of vinpocetine, a phosphodiesterase type 1 inhibitor, ameliorates hyperactivity in a mice model of fetal alcohol spectrum disorder. Drug Alcohol Depen. 2011;119:81–87. doi: 10.1016/j.drugalcdep.2011.05.024.
   PubMedGoogle Scholar
• Abreu-Villaca Y, Carvalho-Graca AC, Skinner G, Lotufo BM, Duarte-Pinheiro VHS, Ribeiro-Carvalho A, Manhaes AC, Filgueiras CC. Hyperactivity and memory/learning deficits evoked by developmental exposure to nicotine and/or ethanol are mitigated by cAMP and cGMP signaling cascades activation. Neurotoxicology. 2018;66:150–59. doi: 10.1016/j.neuro.2018.04.003.
   PubMedGoogle Scholar
• Filgueiras CC, Krahe TE, Medina AE. Phosphodiesterase type 1 inhibition improves learning in rats exposed to alcohol during the third trimester equivalent of human gestation. Neurosci Lett. 2010;473:202–07. doi: 10.1016/j.neulet.2010.02.046.
   PubMedGoogle Scholar
• Medina AE, Krahe TE, Ramoa AS. Restoration of neuronal plasticity by a phosphodiesterase type 1 inhibitor in a model of fetal alcohol exposure. J Neurosci. 2006;26:1057–60. doi: 10.1523/JNEUROSCI.4177-05.2006.
   PubMedGoogle Scholar
• Lantz CL, Wang W, Medina AE. Early alcohol exposure disrupts visual cortex plasticity in mice. Int J Dev Neurosci. 2012;30:351–57. doi: 10.1016/j.ijdevneu.2012.05.001.
   PubMedGoogle Scholar
• De La Fuente-Ortega E, Plaza-Briceño W, Vargas-Robert S, Haeger P. Prenatal ethanol exposure misregulates genes involved in iron homeostasis promoting a maladaptation of iron dependent hippocampal synaptic transmission and plasticity. Front Pharmacol. 2019;10:1312. doi: 10.3389/fphar.2019.01312.
   PubMed Web of Science ®Google Scholar
• Li H, Gao L, Ye Z, Du J, Li W, Liang L, Zeng Q, Xi J, Yue W, Li Z. Protective effects of resveratrol on the ethanol-induced disruption of retinogenesis in pluripotent stem cell-derived organoids. FEBS Open Bio. 2023;13:845–66. doi: 10.1002/2211-5463.13601.
   PubMedGoogle Scholar
• Maiese K, Chong ZZ, Hou J, Shang YC. The vitamin nicotinamide: translating nutrition into clinical care. Molecules (Basel, Switzerland). 2009;14:3446–85. doi: 10.3390/molecules14093446.
   PubMed Web of Science ®Google Scholar
• Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6:99–104. doi: 10.1038/sj.cdd.4400476.
   PubMed Web of Science ®Google Scholar
• Goeke CM, Hashimoto JG, Guizzetti M, Vitalone A. Effects of ethanol-and choline-treated astrocytes on hippocampal neuron neurite outgrowth in vitro. Sci Prog. 2021;104:00368504211018943. doi: 10.1177/00368504211018943.
   PubMedGoogle Scholar
• Ceccarini MR, Ceccarelli V, Codini M, Fettucciari K, Calvitti M, Cataldi S, Albi E, Vecchini A, Beccari T. The polyunsaturated fatty acid EPA, but not DHA, enhances neurotrophic factor expression through epigenetic mechanisms and protects against parkinsonian neuronal cell death. Int J Mol Sci. 2022;23:16176. doi: 10.3390/ijms232416176.
   PubMedGoogle Scholar
• Mooney SM, Billings E, McNew M, Munson CA, Shaikh SR, Smith SM. Behavioral changes in FPR2/ALX and Chemr23 receptor knockout mice are exacerbated by prenatal alcohol exposure. Front Neurosci. 2023;17:17. doi: 10.3389/fnins.2023.1187220.
   Google Scholar
• Ojeda L, Nogales F, Murillo L, Carreras O. The role of folic acid and selenium against oxidative damage from ethanol in early life programming: a review. Biochem Cell Biol. 2018;96:178–88. doi: 10.1139/bcb-2017-0069.
   PubMedGoogle Scholar
• Ezquer F, Quintanilla ME, Moya-Flores F, Morales P, Munita JM, Olivares B, Landskron G, Hermoso MA, Ezquer M, Herrera-Marschitz M, et al. Innate gut microbiota predisposes to high alcohol consumption. Addict Biol. 2021;26:e13018. doi: 10.1111/adb.13018.
   PubMedGoogle Scholar
• Fila M, Chojnacki C, Chojnacki J, Blasiak J. Is an “epigenetic diet” for migraines justified? The case of folate and DNA methylation. Nutrients. 2019;11:2763. doi: 10.3390/nu11112763.
   PubMed Web of Science ®Google Scholar
• Medici V, Halsted CH. Folate, alcohol, and liver disease. Mol Nutr Food Res. 2013;57:596–606. doi: 10.1002/mnfr.201200077.
   PubMed Web of Science ®Google Scholar
• Hamid A, Wani NA, Kaur J. New perspectives on folate transport in relation to alcoholism-induced folate malabsorption – association with epigenome stability and cancer development. FEBS J. 2009;276:2175–91. doi: 10.1111/j.1742-4658.2009.06959.x.
   PubMed Web of Science ®Google Scholar
• Murillo-Fuentes ML, Murillo ML, Carreras O. Effects of maternal ethanol consumption during pregnancy or lactation on intestinal absorption of folic acid in suckling rats. Life Sci. 2003;73:2199–209. doi: 10.1016/S0024-3205(03)00570-8.
   PubMedGoogle Scholar
• Simon-O’Brien E, Alaux-Cantin S, Warnault V, Buttolo R, Naassila M, Vilpoux C. The histone deacetylase inhibitor sodium butyrate decreases excessive ethanol intake in dependent animals. Addict Biol. 2015;20:676–89. doi: 10.1111/adb.12161.
   PubMed Web of Science ®Google Scholar
• Jeanblanc J, Lemoine S, Jeanblanc V, Alaux-Cantin S, Naassila M. The class I-Specific HDAC inhibitor MS-275 decreases motivation to consume alcohol and relapse in heavy drinking rats. Int J Neuropsychopharmacol. 2015;18:pyv029. doi: 10.1093/ijnp/pyv029.
   PubMed Web of Science ®Google Scholar
• Wei H, Yu C, Zhang C, Ren Y, Guo L, Wang T, Chen F, Li Y, Zhang X, Wang H, et al. Butyrate ameliorates chronic alcoholic central nervous damage by suppressing microglia-mediated neuroinflammation and modulating the microbiome-gut-brain axis. Biomed Pharmacother. 2023;160:114308. doi: 10.1016/j.biopha.2023.114308.
   PubMedGoogle Scholar
• Dursun I, Jakubowska-Doğru E, Uzbay T. Effects of prenatal exposure to alcohol on activity, anxiety, motor coordination, and memory in young adult wistar rats. Pharmacol Biochem Behav. 2006;85:345–55. doi: 10.1016/j.pbb.2006.09.001.
   PubMed Web of Science ®Google Scholar
• Walter KR, Ricketts DK, Presswood BH, Smith SM, Mooney SM. Prenatal alcohol exposure causes persistent microglial activation and age- and sex- specific effects on cognition and metabolic outcomes in an Alzheimer’s Disease mouse model. Am J Drug Alcohol Abuse. 2022;49:1–19. doi: 10.1080/00952990.2022.2119571.
   Google Scholar
• Ezquer F, Quintanilla ME, Morales P, Santapau D, Munita JM, Moya-Flores F, Ezquer M, Herrera-Marschitz M, Israel Y. A dual treatment blocks alcohol binge-drinking relapse: microbiota as a new player. Drug Alcohol Depen. 2022;236:109466. doi: 10.1016/j.drugalcdep.2022.109466.
   PubMedGoogle Scholar
• Plaza W, Gaschino F, Gutierrez C, Santibañez N, Estay-Olmos C, Sotomayor-Zárate R, De la Fuente-Ortega E, Pautassi RM, Haeger PA. Pre- and postnatal alcohol exposure delays, in female but not in male rats, the extinction of an auditory fear conditioned memory and increases alcohol consumption. Dev Psychobiol. 2020;62:519–31. doi: 10.1002/dev.21925.
   PubMedGoogle Scholar
• Tipyasang R, Kunwittaya S, Mukda S, Kotchabhakdi NJ, Kotchabhakdi N. Enriched environment attenuates changes in water-maze performance and BDNF level caused by prenatal alcohol exposure. Excli J. 2014;13:536–47.
   PubMedGoogle Scholar
• Ratuski AS, Weary DM. Environmental enrichment for rats and mice housed in laboratories: a metareview. Anim. 2022;12:414. doi: 10.3390/ani12040414.
   Google Scholar
• Leger M, Paizanis E, Dzahini K, Quiedeville A, Bouet V, Cassel J-C, Freret T, Schumann-Bard P, Boulouard M. Environmental enrichment duration differentially affects behavior and neuroplasticity in adult mice. Cereb Cortex. 2014;25:4048–61. doi: 10.1093/cercor/bhu119.
   PubMedGoogle Scholar
• Mora-Gallegos A, Rojas-Carvajal M, Salas S, Saborío-Arce A, Fornaguera- Trítrías J, Brenes JC. Age-dependent effects of environmental enrichment on spatial memory and neurochemistry. Neurobiol Learn Mem. 2015;118:96–104. doi: 10.1016/j.nlm.2014.11.012.
   PubMedGoogle Scholar
• Sampedro-Piquero P, Begega A, Arias JL. Increase of glucocorticoid receptor expression after environmental enrichment: relations to spatial memory, exploration and anxiety-related behaviors. Physiol Behav. 2014;129:118–29. doi: 10.1016/j.physbeh.2014.02.048.
   PubMedGoogle Scholar
• Solinas M, Thiriet N, Chauvet C, Jaber M. Prevention and treatment of drug addiction by environmental enrichment. Prog Neurobiol. 2010;92:572–92. doi: 10.1016/j.pneurobio.2010.08.002.
   PubMed Web of Science ®Google Scholar
• Vivinetto AL, Suárez MM, Rivarola MA. Neurobiological effects of neonatal maternal separation and post-weaning environmental enrichment. Behav Brain Res. 2013;240:110–18. doi: 10.1016/j.bbr.2012.11.014.
   PubMed Web of Science ®Google Scholar
• Lam VYY, Raineki C, Ellis L, Yu W, Weinberg J. Interactive effects of prenatal alcohol exposure and chronic stress in adulthood on anxiety-like behavior and central stress-related receptor mRNA expression: Sex- and time-dependent effects. Psychoneuroendocrinology. 2018;97:8–19. doi: 10.1016/j.psyneuen.2018.06.018.
   PubMedGoogle Scholar
• Coles CD, Brown RT, Smith IE, Platzman KA, Erickson S, Falek A. Effects of prenatal alcohol exposure at school age. I. Physical and cognitive development. Neurotoxicol Teratol. 1991;13:357–67. doi: 10.1016/0892-0362(91)90084-A.
   PubMed Web of Science ®Google Scholar
• Taggart TC, Simmons RW, Thomas JD, Riley EP. Children with heavy prenatal alcohol exposure exhibit atypical gait characteristics. Alcohol Clin Exp Res. 2017;41:1648–55. doi: 10.1111/acer.13450.
   PubMedGoogle Scholar
• Dembele K, Yao XH, Chen L, Nyomba BL. Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring. Am J Physiol Regul Integr Comp Physiol. 2006;291:R796–802. doi: 10.1152/ajpregu.00633.2005.
   PubMedGoogle Scholar
• Brocardo PS, Gil-Mohapel J, Wortman R, Noonan A, McGinnis E, Patten AR, Christie BR. The effects of ethanol exposure during distinct periods of brain development on oxidative stress in the adult rat brain. Alcohol Clin Exp Res. 2017;41:26–37. doi: 10.1111/acer.13266.
   PubMedGoogle Scholar
• Zhang Y, Wang H, Li Y, Peng Y. A review of interventions against fetal alcohol spectrum disorder targeting oxidative stress. Int J Dev Neurosci. 2018;71:140–45. doi: 10.1016/j.ijdevneu.2018.09.001.
   PubMedGoogle Scholar
• Brocardo PS, Gil-Mohapel J, Christie BR. The role of oxidative stress in fetal alcohol spectrum disorders. Brain Res Rev. 2011;67:209–25. doi: 10.1016/j.brainresrev.2011.02.001.
   PubMedGoogle Scholar
• Dringen R, Hamprecht B. N-acetylcysteine, but not methionine or 2-oxothiazolidine-4-carboxylate, serves as cysteine donor for the synthesis of glutathione in cultured neurons derived from embryonal rat brain. Neurosci Lett. 1999;259:79–82. doi: 10.1016/S0304-3940(98)00894-5.
   PubMed Web of Science ®Google Scholar
• Bradley R, Lakpa KL, Burd M, Mehta S, Katusic MZ, Greenmyer JR. Fetal alcohol spectrum disorder and iron homeostasis. Nutrients. 2022;14:4223. doi: 10.3390/nu14204223.
   PubMedGoogle Scholar
• Huebner SM, Helfrich KK, Saini N, Blohowiak SE, Cheng AA, Kling PJ, Smith SM. Dietary iron fortification normalizes fetal hematology, hepcidin, and iron distribution in a rat model of prenatal alcohol exposure. Alcohol Clin Exp Res. 2018;42:1022–33. doi: 10.1111/acer.13754.
   PubMedGoogle Scholar
• Carter RC, Senekal M, Duggan CP, Dodge NC, Meintjes EM, Molteno CD, Jacobson JL, Jacobson SW. Gestational weight gain and dietary energy, iron, and choline intake predict severity of fetal alcohol growth restriction in a prospective birth cohort. Am J Clin Nutr. 2022;116:460–69. doi: 10.1093/ajcn/nqac101.
   PubMedGoogle Scholar
• Carter RC, Dodge NC, Molteno CD, Meintjes EM, Jacobson JL, Jacobson SW. Mediating and moderating effects of iron homeostasis alterations on fetal alcohol-related growth and neurobehavioral deficits. Nutrients. 2022;14:4432. doi: 10.3390/nu14204432.
   PubMedGoogle Scholar
• Achur RN, Freeman WM, Vrana KE. Circulating cytokines as biomarkers of alcohol abuse and alcoholism. J Neuroimmune Pharmacol. 2010;5:83–91. doi: 10.1007/s11481-009-9185-z.
   PubMed Web of Science ®Google Scholar
• Drew PD, Kane CJ. Fetal alcohol spectrum disorders and neuroimmune changes. Int Rev Neurobiol. 2014;118:41–80.
   PubMed Web of Science ®Google Scholar
• Kane CJM, Drew PD. Neuroinflammatory contribution of microglia and astrocytes in fetal alcohol spectrum disorders. J Neurosci Res. 2021;99:1973–85. doi: 10.1002/jnr.24735.
   PubMed Web of Science ®Google Scholar
• Merrill JE. Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain development: normal and pathological. Dev Neurosci. 1992;14:1–10. doi: 10.1159/000111642.
   PubMed Web of Science ®Google Scholar
• Bilbo SD, Schwarz JM. The immune system and developmental programming of brain and behavior. Front Neuroendocrinol. 2012;33:267–86. doi: 10.1016/j.yfrne.2012.08.006.
   PubMed Web of Science ®Google Scholar
• Green HF, Nolan YM. Inflammation and the developing brain: consequences for hippocampal neurogenesis and behavior. Neurosci Biobehav Rev. 2014;40:20–34. doi: 10.1016/j.neubiorev.2014.01.004.
   PubMedGoogle Scholar
• Conductier G, Blondeau N, Guyon A, Nahon JL, Rovère C. The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J Neuroimmunol. 2010;224:93–100. doi: 10.1016/j.jneuroim.2010.05.010.
   PubMed Web of Science ®Google Scholar
• Bose S, Cho J. Role of chemokine CCL2 and its receptor CCR2 in neurodegenerative diseases. Arch Pharm Res. 2013;36:1039–50. doi: 10.1007/s12272-013-0161-z.
   PubMed Web of Science ®Google Scholar
• Gao L, Tang H, Nie K, Wang L, Zhao J, Gan R, Huang J, Feng S, Zhu R, Duan Z, et al. MCP-1 and CCR2 gene polymorphisms in Parkinson’s disease in a Han Chinese cohort. Neurol Sci. 2015;36:571–76. doi: 10.1007/s10072-014-1990-3.
   PubMedGoogle Scholar
• Ren Z, Wang X, Yang F, Xu M, Frank JA, Wang H, Wang S, Ke ZJ, Luo J. Ethanol-induced damage to the developing spinal cord: The involvement of CCR2 signaling. Biochimica et biophysica acta. Mol Basis Dis. 2017;1863:2746–61. doi: 10.1016/j.bbadis.2017.07.035.
   PubMedGoogle Scholar
• Christofides A, Konstantinidou E, Jani C, Boussiotis VA. The role of peroxisome proliferator-activated receptors (PPAR) in immune responses. Metabolism. 2021;114:154338. doi: 10.1016/j.metabol.2020.154338.
   PubMed Web of Science ®Google Scholar
• Bernardo A, Levi G, Minghetti L. Role of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its natural ligand 15-deoxy-Delta12, 14-prostaglandin J2 in the regulation of microglial functions. Eur J Neurosci. 2000;12:2215–23. doi: 10.1046/j.1460-9568.2000.00110.x.
   PubMed Web of Science ®Google Scholar
• Drew PD, Xu J, Racke MK. PPAR-gamma: therapeutic potential for multiple sclerosis. PPAR Res. 2008;2008:627463. doi: 10.1155/2008/627463.
   PubMedGoogle Scholar
• Jiang Q, Heneka M, Landreth GE. The role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in Alzheimer’s disease: therapeutic implications. CNS Drugs. 2008;22:1–14. doi: 10.2165/00023210-200822010-00001.
   PubMed Web of Science ®Google Scholar
• Möller T, Bard F, Bhattacharya A, Biber K, Campbell B, Dale E, Eder C, Gan L, Garden GA, Hughes ZA, et al. Critical data-based re-evaluation of minocycline as a putative specific microglia inhibitor. Glia. 2016;64:1788–94. doi: 10.1002/glia.23007.
   PubMedGoogle Scholar
• Carson MD, Warner AJ, Hathaway-Schrader JD, Geiser VL, Kim J, Gerasco JE, Hill WD, Lemasters JJ, Alekseyenko AV, Wu Y, et al. Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice. JCI Insight. 2023;8. doi: 10.1172/jci.insight.160578.
   Google Scholar
• Loughney K, Martins TJ, Harris EA, Sadhu K, Hicks JB, Sonnenburg WK, Beavo JA, Ferguson K. Isolation and characterization of cDnas corresponding to two human calcium, calmodulin-regulated, 3‘,5’-cyclic nucleotide phosphodiesterases. J Biol Chem. 1996;271:796–806. doi: 10.1074/jbc.271.2.796.
   PubMed Web of Science ®Google Scholar
• Medina AE. Therapeutic utility of phosphodiesterase type I inhibitors in neurological conditions. Front Neurosci. 2011;5:21. doi: 10.3389/fnins.2011.00021.
   PubMed Web of Science ®Google Scholar
• Jeon KI, Xu X, Aizawa T, Lim JH, Jono H, Kwon DS, Abe J, Berk BC, Li JD, Yan C. Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proc Natl Acad Sci USA. 2010;107:9795–800. doi: 10.1073/pnas.0914414107.
   PubMed Web of Science ®Google Scholar
• Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Thomas P, Dannenberg AJ. Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes. Am J Physiol Gastrointest Liver Physiol. 2003;284:G321–327. doi: 10.1152/ajpgi.00230.2002.
   PubMed Web of Science ®Google Scholar
• Peng Y, Ao M, Dong B, Jiang Y, Yu L, Chen Z, Hu C, Xu R. Anti-inflammatory effects of curcumin in the inflammatory diseases: status, limitations and countermeasures. Drug Des Devel Ther. 2021;15:4503–25. doi: 10.2147/DDDT.S327378.
   PubMed Web of Science ®Google Scholar
• Yang YM, Cho YE, Hwang S. Crosstalk between oxidative stress and inflammatory liver injury in the pathogenesis of alcoholic liver disease. Int J Mol Sci. 2022;23:774. doi: 10.3390/ijms23020774.
   PubMed Web of Science ®Google Scholar
• Burckhardt M, Herke M, Wustmann T, Watzke S, Langer G, Fink A. Omega-3 fatty acids for the treatment of dementia. Cochrane Db Syst Rev. 2016;4:Cd009002. doi: 10.1002/14651858.CD009002.pub3.
   PubMed Web of Science ®Google Scholar
• Montes S, Yee-Rios Y, Páez-Martínez N. Environmental enrichment restores oxidative balance in animals chronically exposed to toluene: comparison with melatonin. Brain Res Bull. 2019;144:58–67. doi: 10.1016/j.brainresbull.2018.11.007.
   PubMedGoogle Scholar
• Doulames V, Lee S, Shea TB. Environmental enrichment and social interaction improve cognitive function and decrease reactive oxidative species in normal adult mice. Int J Neurosci. 2014;124:369–76. doi: 10.3109/00207454.2013.848441.
   PubMed Web of Science ®Google Scholar
• Suarez A, Fabio MC, Bellia F, Fernandez MS, Pautassi RM. Environmental enrichment during adolescence heightens ethanol intake in female, but not male, adolescent rats that are selectively bred for high and low ethanol intake during adolescence. Am J Drug Alcohol Abuse. 2020;46:553–64. doi: 10.1080/00952990.2020.1770778.
   PubMed Web of Science ®Google Scholar
• Berardo LR, Fabio MC, Pautassi RM. Post-weaning environmental enrichment, but not chronic maternal isolation, enhanced ethanol intake during Periadolescence and early adulthood. Front Behav Neurosci. 2016;10:195. doi: 10.3389/fnbeh.2016.00195.
   PubMed Web of Science ®Google Scholar
• Ratuski A, Weary D. Environmental enrichment for rats and mice housed in laboratories: a metareview. Animals. 2022;12:414. doi: 10.3390/ani12040414.
   Web of Science ®Google Scholar
• Bertrand J. Interventions for children with fetal alcohol spectrum disorders research C. Interventions for children with fetal alcohol spectrum disorders (FASDs): overview of findings for five innovative research projects. Res Dev Disabil. 2009;30:986–1006. doi: 10.1016/j.ridd.2009.02.003.
   PubMed Web of Science ®Google Scholar
• Crofton EJ, Zhang Y, Green TA. Inoculation stress hypothesis of environmental enrichment. Neurosci Biobehav Rev. 2015;49:19–31. doi: 10.1016/j.neubiorev.2014.11.017.
   PubMed Web of Science ®Google Scholar
• Salguero A, Barey A, Virgolini RG, Mujica V, Fabio MC, Miranda-Morales RS, Marengo L, Camarini R, Pautassi RM. Juvenile variable stress modulates, in female but not in male wistar rats, ethanol intake in adulthood. Neurotoxicol Teratol. 2023;100:107306. doi: 10.1016/j.ntt.2023.107306.
   PubMed Web of Science ®Google Scholar
• Wozniak JR, Fink BA, Fuglestad AJ, Eckerle JK, Boys CJ, Sandness KE, Radke JP, Miller NC, Lindgren C, Brearley AM, et al. Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder. J Neurodev Disord. 2020;12:9. doi: 10.1186/s11689-020-09312-7.
   PubMedGoogle Scholar
• Gimbel BA, Anthony ME, Ernst AM, Roediger DJ, de Water E, Eckerle JK, Boys CJ, Radke JP, Mueller BA, Fuglestad AJ, et al. Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes. J Neurodev Disord. 2022;14:59. doi: 10.1186/s11689-022-09470-w.
   PubMedGoogle Scholar
• Jacobson SW, Carter RC, Molteno CD, Stanton ME, Herbert JS, Lindinger NM, Lewis CE, Dodge NC, Hoyme HE, Zeisel SH, et al. Efficacy of maternal choline supplementation during pregnancy in mitigating adverse effects of prenatal alcohol exposure on growth and cognitive function: a randomized, double-blind, placebo-controlled clinical trial. Alcohol Clin Exp Res. 2018;42:1327–41. doi: 10.1111/acer.13769.
   PubMedGoogle Scholar
• Warton FL, Molteno CD, Warton CMR, Wintermark P, Lindinger NM, Dodge NC, Zöllei L, van der Kouwe AJW, Carter RC, Jacobson JL, et al. Maternal choline supplementation mitigates alcohol exposure effects on neonatal brain volumes. Alcohol Clin Exp Res. 2021;45:1762–74. doi: 10.1111/acer.14672.
   PubMedGoogle Scholar
• Pérez-Reytor D, Karahanian E. Alcohol use disorder, neuroinflammation, and intake of dietary fibers: a new approach for treatment. Am J Drug Alcohol Abuse. 2023;49:283–89. doi: 10.1080/00952990.2022.2114005.
   PubMed Web of Science ®Google Scholar
• Cristofori F, Dargenio VN, Dargenio C, Miniello VL, Barone M, Francavilla R. Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body. Front Immunol. 2021;12:578386. doi: 10.3389/fimmu.2021.578386.
   PubMed Web of Science ®Google Scholar
• Wang S, Wu D, Wu F, Sun H, Wang X, Meng H, Lin Q, Jin K, Wang F. Prevotella histicola suppresses ferroptosis to mitigate ethanol-induced gastric mucosal lesions in mice. BMC Complementary Med Ther. 2023;23:118. doi: 10.1186/s12906-023-03946-5.
   PubMedGoogle Scholar
• Johnson S, Knight R, Marmer DJ, Steele RW. Immune deficiency in fetal alcohol syndrome. Pediatr Res. 1981;15:908–11. doi: 10.1203/00006450-198106000-00005.
   PubMed Web of Science ®Google Scholar
• Zhang X, Sliwowska JH, Weinberg J. Prenatal alcohol exposure and fetal programming: effects on neuroendocrine and immune function. Exp Biol Med (Maywood). 2005;230:376–88. doi: 10.1177/15353702-0323006-05.
   PubMed Web of Science ®Google Scholar
• Bermúdez V, Finol F, Parra N, Parra M, Pérez A, Peñaranda L, Vílchez D, Rojas J, Arráiz N, Velasco M. PPAR-gamma agonists and their role in type 2 diabetes mellitus management. Am J Ther. 2010;17:274–83. doi: 10.1097/MJT.0b013e3181c08081.
   PubMed Web of Science ®Google Scholar