{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:11:41Z","timestamp":1792789901474,"version":"4.5.0"},"reference-count":98,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health","doi-asserted-by":"publisher","award":["AA-011431"],"award-info":[{"award-number":["AA-011431"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health","doi-asserted-by":"publisher","award":["AA028408"],"award-info":[{"award-number":["AA028408"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health","doi-asserted-by":"publisher","award":["AA032106"],"award-info":[{"award-number":["AA032106"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health","doi-asserted-by":"publisher","award":["CAS-1264908"],"award-info":[{"award-number":["CAS-1264908"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["AA-011431"],"award-info":[{"award-number":["AA-011431"]}]},{"name":"National Cancer Institute","award":["AA028408"],"award-info":[{"award-number":["AA028408"]}]},{"name":"National Cancer Institute","award":["AA032106"],"award-info":[{"award-number":["AA032106"]}]},{"name":"National Cancer Institute","award":["CAS-1264908"],"award-info":[{"award-number":["CAS-1264908"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Prenatal alcohol exposure (PAE) models can cause neurodevelopmental abnormalities like those observed in fetal alcohol spectrum disorder (FASD). Previous studies link experimental PAE effects in the brain to impaired signaling through insulin\/IGF and Notch pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Importantly, concurrent administration of peroxisome proliferator-activated receptor agonists or dietary soy prevented many aspects of FASD due to their insulin-sensitizing, anti-inflammatory, and antioxidant properties. Objective: To determine if dietary soy interventions during pregnancy would be sufficient to normalize central nervous system structure and function, we examined the effects of maternal gestation-limited dietary soy on cerebellar postnatal development, motor function, and critical signaling pathways. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source. The ethanol and soy feedings were discontinued upon delivery. The offspring were subjected to rotarod motor function tests, and on postnatal day 35, they were sacrificed to harvest cerebella for histological and molecular studies. Results: Despite the postnatal cessation of alcohol exposure, chronic gestational exposure reduced brain weight, caused cerebellar hypoplasia, and impaired motor performance. Gestational dietary soy prevented the ethanol-associated reduction in brain weight and largely restored the histological integrity of the cerebellum but failed to normalize motor performance. Ethanol withdrawal abolished the impairments in insulin\/IGF signaling that were previously associated with ongoing ethanol exposures, but ethanol\u2019s inhibitory effects on Notch and Wnt signaling persisted. Soy significantly increased cerebellar expression of the insulin and IGF-1 receptors and abrogated several ethanol-associated impairments in Notch and Wnt signaling. Conclusions: Although gestation-restricted dietary soy has significant positive effects on neurodevelopment, optimum prevention of FASD\u2019s long-term effects will likely require dietary soy intervention during the critical periods of postnatal development, even after alcohol exposures have ceased.<\/jats:p>","DOI":"10.3390\/nu17050812","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T08:04:44Z","timestamp":1740643484000},"page":"812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Prenatal Dietary Soy on Cerebellar Neurodevelopment and Function in Experimental Fetal Alcohol Spectrum Disorder"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5886-2306","authenticated-orcid":false,"given":"Suzanne M.","family":"de la Monte","sequence":"first","affiliation":[{"name":"Departments of Pathology and Laboratory Medicine, Neurosurgery, and Neurology, Rhode Island Hospital, Providence, RI 02903, USA"},{"name":"Women & Infants Hospital, Brown University Health, Providence, RI 02905, USA"},{"name":"Alpert Medical School of Brown University, Providence, RI 02903, USA"},{"name":"Department of Medicine, Rhode Island Hospital, Brown University Health, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5927-5832","authenticated-orcid":false,"given":"Ming","family":"Tong","sequence":"additional","affiliation":[{"name":"Alpert Medical School of Brown University, Providence, RI 02903, USA"},{"name":"Department of Medicine, Rhode Island Hospital, Brown University Health, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Ziplow","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience and Biology, Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Princess","family":"Mark","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rhode Island Hospital, Brown University Health, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9029-6170","authenticated-orcid":false,"given":"Stephanie","family":"Van","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience and Biology, Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van Ahn","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience and Biology, Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"ref_1","first-page":"977","article-title":"Fetal alcohol spectrum disorder","volume":"45","author":"Nayak","year":"2008","journal-title":"Indian Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/ptj\/73.9.599","article-title":"Fetal alcohol syndrome: Review of the literature with implications for physical therapists","volume":"73","author":"Osborn","year":"1993","journal-title":"Phys. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Moore, E.M., and Xia, Y. (2021). Neurodevelopmental Trajectories Following Prenatal Alcohol Exposure. Front. Hum. Neurosci., 15.","DOI":"10.3389\/fnhum.2021.695855"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11065-011-9166-x","article-title":"Fetal alcohol spectrum disorders: An overview","volume":"21","author":"Riley","year":"2011","journal-title":"Neuropsychol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/15353702-0323006-03","article-title":"Fetal alcohol spectrum disorders: An overview with emphasis on changes in brain and behavior","volume":"230","author":"Riley","year":"2005","journal-title":"Exp. Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4729","DOI":"10.1093\/cercor\/bhaa020","article-title":"Graded Cerebellar Lobular Volume Deficits in Adolescents and Young Adults with Fetal Alcohol Spectrum Disorders (FASD)","volume":"30","author":"Sullivan","year":"2020","journal-title":"Cereb. Cortex"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/sj.npp.1301219","article-title":"Brain morphometry and cognitive performance in detoxified alcohol-dependents with preserved psychosocial functioning","volume":"32","author":"Chanraud","year":"2007","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/ar.b.20114","article-title":"Damage to the human cerebellum from prenatal alcohol exposure: The anatomy of a simple biometrical explanation","volume":"289","author":"Bookstein","year":"2006","journal-title":"Anat. Rec. B New Anat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/ddrr.72","article-title":"Neuroimaging and fetal alcohol spectrum disorders","volume":"15","author":"Norman","year":"2009","journal-title":"Dev. Disabil. Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00787-014-0571-6","article-title":"Fetal alcohol spectrum disorders","volume":"23","author":"Dorrie","year":"2014","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ntt.2012.11.001","article-title":"Different patterns of regional Purkinje cell loss in the cerebellar vermis as a function of the timing of prenatal ethanol exposure in an ovine model","volume":"35","author":"Sawant","year":"2013","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cealie, M.Y., Douglas, J.C., Swan, H.K., Vonkaenel, E.D., McCall, M.N., Drew, P.D., and Majewska, A.K. (2024). Developmental Ethanol Exposure Impacts Purkinje Cells but Not Microglia in the Young Adult Cerebellum. Cells, 13.","DOI":"10.3390\/cells13050386"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ijdevneu.2004.11.002","article-title":"Cerebellar granule cell and Bergmann glial cell maturation in the rat is disrupted by pre- and post-natal exposure to moderate levels of ethanol","volume":"23","year":"2005","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.alcohol.2008.09.009","article-title":"Ethanol inhibition of aspartyl-asparaginyl-beta-hydroxylase in fetal alcohol spectrum disorder: Potential link to the impairments in central nervous system neuronal migration","volume":"43","author":"Tong","year":"2009","journal-title":"Alcohol"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.alcohol.2021.07.003","article-title":"Ethanol effects on cerebellar myelination in a postnatal mouse model of fetal alcohol spectrum disorders","volume":"96","author":"Douglas","year":"2021","journal-title":"Alcohol"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/BF02935589","article-title":"Insulin and insulin-like growth factor receptors in the nervous system","volume":"3","author":"Adamo","year":"1989","journal-title":"Mol. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/jnr.490390202","article-title":"The insulin-like growth factor I system in the rat cerebellum: Developmental regulation and role in neuronal survival and differentiation","volume":"39","author":"Pons","year":"1994","journal-title":"J. Neurosci. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1756-6606-4-13","article-title":"si-RNA inhibition of brain insulin or insulin-like growth factor receptors causes developmental cerebellar abnormalities: Relevance to fetal alcohol spectrum disorder","volume":"4","author":"Tong","year":"2011","journal-title":"Mol. Brain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.alcohol.2023.01.006","article-title":"Dietary soy prevents fetal demise, intrauterine growth restriction, craniofacial dysmorphic features, and impairments in placentation linked to gestational alcohol exposure: Pivotal role of insulin and insulin-like growth factor signaling networks","volume":"110","author":"Qi","year":"2023","journal-title":"Alcohol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"347","DOI":"10.4161\/oxim.3.5.13296","article-title":"Aspartyl-(asparaginyl) beta-hydroxylase, hypoxia-inducible factor-alpha and Notch cross-talk in regulating neuronal motility","volume":"3","author":"Lawton","year":"2010","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.humpath.2006.06.005","article-title":"Role of aspartyl-(asparaginyl) beta-hydroxylase in placental implantation: Relevance to early pregnancy loss","volume":"38","author":"Gundogan","year":"2007","journal-title":"Hum. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/hep.21272","article-title":"Aspartyl-asparagyl beta hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms","volume":"44","author":"Cantarini","year":"2006","journal-title":"Hepatology"},{"key":"ref_23","unstructured":"Tong, M., Gao, J.S., Borgas, D., and de la Monte, S.M. (2013). Phosphorylation Modulates Aspartyl-(Asparaginyl)-beta Hydroxylase Protein Expression, Catalytic Activity and Migration in Human Immature Neuronal Cerebellar Cells. Cell Biol., 6."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s00018-022-04285-3","article-title":"WNT and NOTCH signaling in human trophoblast development and differentiation","volume":"79","author":"Dietrich","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mehta, S., Hingole, S., and Chaudhary, V. (2021). The Emerging Mechanisms of Wnt Secretion and Signaling in Development. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.714746"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wong, S.K., Mohamad, N.V., Jayusman, P.A., and Ibrahim, N. (2023). A Review on the Crosstalk between Insulin and Wnt\/beta-Catenin Signalling for Bone Health. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512441"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12016","DOI":"10.1074\/jbc.M111.337048","article-title":"Cross-talk between insulin and Wnt signaling in preadipocytes: Role of Wnt co-receptor low density lipoprotein receptor-related protein-5 (LRP5)","volume":"287","author":"Palsgaard","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1007\/s00018-014-1644-x","article-title":"Wnt-Notch signalling crosstalk in development and disease","volume":"71","author":"Collu","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Acar, A., Hidalgo-Sastre, A., Leverentz, M.K., Mills, C.G., Woodcock, S., Baron, M., Collu, G.M., and Brennan, K. (2021). Inhibition of Wnt signalling by Notch via two distinct mechanisms. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-88618-5"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1001\/jamapediatrics.2017.1919","article-title":"Global Prevalence of Fetal Alcohol Spectrum Disorder Among Children and Youth: A Systematic Review and Meta-analysis","volume":"171","author":"Lange","year":"2017","journal-title":"JAMA Pediatr."},{"key":"ref_31","first-page":"238","article-title":"Targeting Alzheimer\u2019s Disease Neuro-Metabolic Dysfunction with a Small Molecule Nuclear Receptor Agonist (T3D-959) Reverses Disease Pathologies","volume":"6","author":"Tong","year":"2016","journal-title":"J. Alzheimers Dis. Park."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s13340-021-00519-0","article-title":"The forgotten type 2 diabetes mellitus medicine: Rosiglitazone","volume":"13","author":"Xu","year":"2022","journal-title":"Diabetol. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/cbdd.12806","article-title":"Multitargeted bioactive ligands for PPARs discovered in the last decade","volume":"88","author":"Zhang","year":"2016","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"El-Shemy, H.A. (2013). Soybean, Nutrition and Health. Soybean-Bio-Active Compounds, IntechOpen.","DOI":"10.5772\/45866"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tong, M., Ziplow, J.L., Mark, P., and de la Monte, S.M. (2022). Dietary Soy Prevents Alcohol-Mediated Neurocognitive Dysfunction and Associated Impairments in Brain Insulin Pathway Signaling in an Adolescent Rat Model. Biomolecules, 12.","DOI":"10.3390\/biom12050676"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Westerhuis, J.A.W., Dudink, J., Wijnands, B., De Zeeuw, C.I., and Canto, C.B. (2024). Impact of Intrauterine Insults on Fetal and Postnatal Cerebellar Development in Humans and Rodents. Cells, 13.","DOI":"10.20944\/preprints202411.0405.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.36922\/gpd.3113","article-title":"Association between dietary soy prevention of fetal alcohol spectrum disorder and normalization of placental insulin and insulin-like growth factor signaling networks and downstream effector molecule expression","volume":"3","author":"Gundogan","year":"2024","journal-title":"Gene Protein Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.placenta.2007.10.002","article-title":"Impaired placentation in fetal alcohol syndrome","volume":"29","author":"Gundogan","year":"2008","journal-title":"Placenta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11130-007-0041-0","article-title":"Commercial soy protein ingredients as isoflavone sources for functional foods","volume":"62","author":"Genovese","year":"2007","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/jn\/133.1.9","article-title":"A proteomic investigation of isolated soy proteins with variable effects in experimental and clinical studies","volume":"133","author":"Gianazza","year":"2003","journal-title":"J. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s11689-020-09353-y","article-title":"Controlling litter effects to enhance rigor and reproducibility with rodent models of neurodevelopmental disorders","volume":"13","author":"Jimenez","year":"2021","journal-title":"J. Neurodev. Disord."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lazic, S.E., and Essioux, L. (2013). Improving basic and translational science by accounting for litter-to-litter variation in animal models. BMC Neurosci., 14.","DOI":"10.1186\/1471-2202-14-37"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4172\/2161-0681.1000106","article-title":"Sustained Impairments in Brain Insulin\/IGF Signaling in Adolescent Rats Subjected to Binge Alcohol Exposures during Development","volume":"2","author":"Ewenczyk","year":"2012","journal-title":"J. Clin. Exp. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e2401716121","DOI":"10.1073\/pnas.2401716121","article-title":"The serine phosphorylations in the IRS-1 PIR domain abrogate IRS-1 and IR interaction","volume":"121","author":"Woo","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","first-page":"238","article-title":"Motor Function Deficits Following Chronic Prenatal Ethanol Exposure are Linked to Impairments in Insulin\/IGF, Notch and Wnt Signaling in the Cerebellum","volume":"4","author":"Tong","year":"2013","journal-title":"J. Diabetes Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.placenta.2015.02.010","article-title":"Dose effect of gestational ethanol exposure on placentation and fetal growth","volume":"36","author":"Gundogan","year":"2015","journal-title":"Placenta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"A37","DOI":"10.1016\/j.placenta.2013.06.110","article-title":"Effects of dietary soy on ethanol-impaired placentation and fetal growth","volume":"34","author":"Gundogan","year":"2013","journal-title":"Placenta"},{"key":"ref_48","first-page":"1","article-title":"Altered Oligodendroglial and Neuroglial Gene Expression in Adult Rat Cerebral White Matter Following Short- and Long-Term Ethanol Exposures and Brief Abstinence","volume":"7","author":"Yalcin","year":"2018","journal-title":"J. Drug Alc. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/alcalc\/agn079","article-title":"Mechanisms of neurodegeneration and regeneration in alcoholism","volume":"44","author":"Crews","year":"2009","journal-title":"Alcohol Alcohol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1080\/13556219971399","article-title":"Cortical metabolite alterations in abstinent cocaine and cocaine\/alcohol-dependent subjects: Proton magnetic resonance spectroscopic imaging","volume":"4","author":"Meyerhoff","year":"1999","journal-title":"Addict. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/j.1369-1600.2012.00441.x","article-title":"White matter volume in alcohol use disorders: A meta-analysis","volume":"18","author":"Monnig","year":"2013","journal-title":"Addict. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.neurobiolaging.2005.05.007","article-title":"Dysmorphology and microstructural degradation of the corpus callosum: Interaction of age and alcoholism","volume":"27","author":"Pfefferbaum","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Yadav, D., Ostrea, E.M., Cheng, C.T., Kisseih, E., Maddipati, K.R., and Thomas, R.L. (2024). Effect of docosahexaenoic acid and olive oil supplementation on pup weight in alcohol-exposed pregnant rats. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1334285"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.ntt.2005.07.006","article-title":"Chronic prenatal ethanol exposure increases apoptosis in the hippocampus of the term fetal guinea pig","volume":"27","author":"Green","year":"2005","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1210\/er.2005-0011","article-title":"Endocrine regulation of human fetal growth: The role of the mother, placenta, and fetus","volume":"27","author":"Murphy","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/JOE-10-0174","article-title":"Maternal growth factor regulation of human placental development and fetal growth","volume":"207","author":"Forbes","year":"2010","journal-title":"J. Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11154-007-9044-2","article-title":"The insulin-like growth factor system and the fetal brain: Effects of poor maternal nutrition","volume":"8","author":"McDonald","year":"2007","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1093\/jn\/132.9.2605","article-title":"Soy protein supplementation increases serum insulin-like growth factor-I in young and old men but does not affect markers of bone metabolism","volume":"132","author":"Khalil","year":"2002","journal-title":"J. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ejphar.2011.12.032","article-title":"IGF-I receptor signaling pathway is involved in the neuroprotective effect of genistein in the neuroblastoma SK-N-SH cells","volume":"677","author":"Gao","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0169-328X(93)90065-W","article-title":"Differential expression of brain-derived neurotrophic factor, neurotrophin-3, and low-affinity nerve growth factor receptor during the postnatal development of the rat cerebellar system","volume":"17","author":"Rocamora","year":"1993","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_61","first-page":"233","article-title":"Sequence of cellular events in cerebellar ontogeny relevant to expression of neuronal abnormalities in ataxia-telangiectasia","volume":"19","author":"Vinters","year":"1985","journal-title":"Kroc Found. Ser."},{"key":"ref_62","first-page":"1051","article-title":"Alcohol-mediated Purkinje cell loss in the absence of hypoxemia during the third trimester in an ovine model system","volume":"25","author":"West","year":"2001","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_63","unstructured":"de La Monte, S.M., and Sutherland, G.T. Dual Stages of Alcohol-Related Cerebral White Matter Degeneration Reviewed: Early-Stage Stress\/Neuroinflammation Versus Late-Stage Impaired Insulin\/IGF Signaling Through Akt-mTOR\u2014Review, ASN Neuro, in press."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Kim, M., Jun, S., Park, H., Tanaka-Yamamoto, K., and Yamamoto, Y. (2023). Regulation of cerebellar network development by granule cells and their molecules. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1236015"},{"key":"ref_65","first-page":"e477","article-title":"Insulin resistance in experimental alcohol-induced liver disease","volume":"23","author":"Yeon","year":"2008","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"104R","DOI":"10.1203\/01.PDR.0000159632.70510.3D","article-title":"Notch signaling, brain development, and human disease","volume":"57","author":"Lasky","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrn3024","article-title":"Not(ch) just development: Notch signalling in the adult brain","volume":"12","author":"Ables","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"39543","DOI":"10.1074\/jbc.M006753200","article-title":"Aspartyl beta -hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin","volume":"275","author":"Dinchuk","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_69","first-page":"1261","article-title":"Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation","volume":"60","author":"Ince","year":"2000","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"14322","DOI":"10.1016\/S0021-9258(19)49715-9","article-title":"cDNA cloning and expression of bovine aspartyl (asparaginyl) beta-hydroxylase","volume":"267","author":"Jia","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1021\/bi951520n","article-title":"Site-directed mutagenesis of residues in a conserved region of bovine aspartyl (asparaginyl) beta-hydroxylase: Evidence that histidine 675 has a role in binding Fe2+","volume":"35","author":"McGinnis","year":"1996","journal-title":"Biochemistry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.nbd.2013.10.009","article-title":"Evidence that collaboration between HIF-1alpha and Notch-1 promotes neuronal cell death in ischemic stroke","volume":"62","author":"Cheng","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.neuroscience.2018.10.037","article-title":"HIF-1alpha is Critical for the Activation of Notch Signaling in Neurogenesis During Acute Epilepsy","volume":"394","author":"Li","year":"2018","journal-title":"Neuroscience"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1073\/pnas.0711591105","article-title":"Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways","volume":"105","author":"Zheng","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"24027","DOI":"10.1074\/jbc.M704102200","article-title":"Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor","volume":"282","author":"Coleman","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/cdd.2008.12","article-title":"Biology of HIF-1alpha","volume":"15","author":"Weidemann","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.prp.2011.06.001","article-title":"siRNA inhibition of aspartyl-asparaginyl beta-hydroxylase expression impairs cell motility, Notch signaling, and fetal growth","volume":"207","author":"Gundogan","year":"2011","journal-title":"Pathol. Res. Pr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1002\/hep.27275","article-title":"A cell-surface beta-hydroxylase is a biomarker and therapeutic target for hepatocellular carcinoma","volume":"60","author":"Aihara","year":"2014","journal-title":"Hepatology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1744-9081-6-68","article-title":"Role of aspartyl-(asparaginyl)-beta-hydroxylase mediated notch signaling in cerebellar development and function","volume":"6","author":"Silbermann","year":"2010","journal-title":"Behav. Brain Funct."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/scrt190","article-title":"Oxidative stress-induced Notch1 signaling promotes cardiogenic gene expression in mesenchymal stem cells","volume":"4","author":"Boopathy","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Clark, J.L., Taylor, C.G., and Zahradka, P. (2018). Rebelling against the (Insulin) Resistance: A Review of the Proposed Insulin-Sensitizing Actions of Soybeans, Chickpeas, and Their Bioactive Compounds. Nutrients, 10.","DOI":"10.3390\/nu10040434"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1194\/jlr.M500067-JLR200","article-title":"Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa\/fa rats","volume":"46","author":"Tovar","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1016\/j.metabol.2008.04.001","article-title":"Effects of soy protein and isoflavones on insulin resistance and adiponectin in male monkeys","volume":"57","author":"Wagner","year":"2008","journal-title":"Metabolism"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6818","DOI":"10.1523\/JNEUROSCI.19-16-06818.1999","article-title":"Hypoxia-Inducible Factor-1\u03b1 Mediates Hypoxia-Induced Delayed Neuronal Death That Involves p53","volume":"19","author":"Halterman","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Tang, Y.Y., Wang, D.C., Wang, Y.Q., Huang, A.F., and Xu, W.D. (2022). Emerging role of hypoxia-inducible factor-1alpha in inflammatory autoimmune diseases: A comprehensive review. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1073971"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.freeradbiomed.2024.04.239","article-title":"Interplay between hypoxia inducible Factor-1 and mitochondria in cardiac diseases","volume":"221","author":"Belaidi","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/glia.21081","article-title":"WNT signaling in activated microglia is proinflammatory","volume":"59","author":"Halleskog","year":"2011","journal-title":"Glia"},{"key":"ref_88","first-page":"E619","article-title":"Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice","volume":"114","author":"Chen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Subashini, C., Dhanesh, S.B., Chen, C.M., Riya, P.A., Meera, V., Divya, T.S., Kuruvilla, R., Buttler, K., and James, J. (2017). Wnt5a is a crucial regulator of neurogenesis during cerebellum development. Sci. Rep., 7.","DOI":"10.1038\/srep42523"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Suthon, S., Perkins, R.S., Bryja, V., Miranda-Carboni, G.A., and Krum, S.A. (2021). WNT5B in Physiology and Disease. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.667581"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Pascual-Vargas, P., and Salinas, P.C. (2021). A Role for Frizzled and Their Post-Translational Modifications in the Mammalian Central Nervous System. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.692888"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e364","DOI":"10.1038\/oncsis.2017.69","article-title":"Non-canonical WNT\/PCP signalling in cancer: Fzd6 takes centre stage","volume":"6","author":"Corda","year":"2017","journal-title":"Oncogenesis"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"803","DOI":"10.2119\/molmed.2015.00192","article-title":"Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury","volume":"21","author":"Ott","year":"2015","journal-title":"Mol. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1093\/cvr\/cvab197","article-title":"The EP300\/TP53 pathway, a suppressor of the Hippo and canonical WNT pathways, is activated in human hearts with arrhythmogenic cardiomyopathy in the absence of overt heart failure","volume":"118","author":"Rouhi","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neuron.2010.06.002","article-title":"Dixdc1 is a critical regulator of DISC1 and embryonic cortical development","volume":"67","author":"Singh","year":"2010","journal-title":"Neuron"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/nn.2855","article-title":"Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination","volume":"14","author":"Fancy","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/bdra.20713","article-title":"Prenatal choline supplementation mitigates behavioral alterations associated with prenatal alcohol exposure in rats","volume":"88","author":"Thomas","year":"2010","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s11689-020-09312-7","article-title":"Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder","volume":"12","author":"Wozniak","year":"2020","journal-title":"J. Neurodev. Disord."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/5\/812\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:43:31Z","timestamp":1760028211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/5\/812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,26]]},"references-count":98,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["nu17050812"],"URL":"https:\/\/doi.org\/10.3390\/nu17050812","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,26]]}}}