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

References

• Gosdin LK, Deputy NP, Kim SY, Dang EP, Denny CH. Alcohol consumption and binge drinking during pregnancy among adults aged 18-49 years - United States, 2018-2020. MMWR Morb Mortal Wkly Rep [Internet]. 2022 Jan 7;71:10–13. doi:10.15585/mmwr.mm7101a2.
   PubMed Web of Science ®Google Scholar
• May PA, Chambers CD, Kalberg WO, Zellner J, Feldman H, Buckley D, Kopald D, Hasken JM, Xu R, Honerkamp-Smith G, et al. Prevalence Of fetal alcohol spectrum disorders in 4 US communities. JAMA [Internet]. 2018 Feb 6;319:474–82. doi:10.1001/jama.2017.21896.
   PubMed Web of Science ®Google Scholar
• Hellemans KGC, Verma P, Yoon E, Yu W, Weinberg J. Prenatal alcohol exposure increases vulnerability to stress and anxiety-like disorders in adulthood. Ann N Y Acad Sci [Internet]. 2008 Nov;1144:154–75. doi:10.1196/annals.1418.016.
   PubMed Web of Science ®Google Scholar
• Kodituwakku P, Kodituwakku E. Cognitive and behavioral profiles of children with fetal alcohol spectrum disorders. Curr Dev Disord Reports [Internet]. 2014;1:149–60. doi:10.1007/s40474-014-0022-6.
   Google Scholar
• O’Connor MJ, Shah B, Whaley S, Cronin P, Gunderson B, Graham J. Psychiatric illness in a clinical sample of children with prenatal alcohol exposure. Am J Drug Alcohol Abuse. 2002 Nov;28:743–54. doi:10.1081/ADA-120015880.
   PubMed Web of Science ®Google Scholar
• Himmelreich M, Lutke CJ, Hargrove E. The lay of the land: fetal alcohol spectrum disorder (FASD) as a whole-body diagnosis. In: Begun AL M Murray, editors. The Routledge handbook of social work and addictive behaviors [Internet]. 1st ed. London (England): Routledge; 2020. https://www.routledgehandbooks.com/doi/10.4324/9780429203121-14.
   Google Scholar
• Kable JA, Mehta PK, Coles CD. Alterations in insulin levels in adults with prenatal alcohol exposure. Alcohol Clin Exp Res [Internet]. 2021 Mar [accessed 2021 Feb 24];45:500–06. https://pubmed.ncbi.nlm.nih.gov/33486796.
   PubMed Web of Science ®Google Scholar
• Lunde ER, Washburn SE, Golding MC, Bake S, Miranda RC, Ramadoss J. Alcohol-Induced developmental origins of adult-onset diseases. Alcohol Clin Exp Res [Internet]. 2016 July [accessed 2016 June 2];40:1403–14. https://www.ncbi.nlm.nih.gov/pubmed/27254466.
   PubMed Web of Science ®Google Scholar
• Vaiserman AM. Early-life exposure to substance abuse and risk of type 2 diabetes in adulthood. Curr Diab Rep [Internet]. 2015;15:48. doi:10.1007/s11892-015-0624-3.
   PubMed Web of Science ®Google Scholar
• Weeks O, Bossé GD, Oderberg IM, Akle S, Houvras Y, Wrighton PJ, LaBella K, Iversen I, Tavakoli S, Adatto I, et al. Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood. J Clin Invest [Internet]. 2020 May 1;1302252–69. https://pubmed.ncbi.nlm.nih.gov/32202514.
   PubMed Web of Science ®Google Scholar
• Fuglestad AJ, Boys CJ, Chang P-N, Miller BS, Eckerle JK, Deling L, Fink BA, Hoecker HL, Hickey MK, Jimenez-Vega JM, et al. Overweight and obesity among children and adolescents with fetal alcohol spectrum disorders. Alcohol Clin Exp Res. 2014 Sept;38:2502–08. doi:10.1111/acer.12516.
   PubMed Web of Science ®Google Scholar
• Werts RL, Van Calcar SC, Wargowski DS, Smith SM. Inappropriate feeding behaviors and dietary intakes in children with fetal alcohol spectrum disorder or probable prenatal alcohol exposure. Alcohol Clin Exp Res [Internet]. 2014 Mar [accessed 2013 Oct 24];38:871–78. https://pubmed.ncbi.nlm.nih.gov/24164456.
   PubMed Web of Science ®Google Scholar
• Amos-Kroohs RM, Fink BA, Smith CJ, Chin L, Van Calcar SC, Wozniak JR, Smith SM. Abnormal eating behaviors are common in children with fetal alcohol spectrum disorder. J Pediatr [Internet]. 2016;169:194–200.e1. https://www.sciencedirect.com/science/article/pii/S0022347615012834.
   PubMed Web of Science ®Google Scholar
• Akison LK, Reid N, Wyllie M, Moritz KM. Adverse health outcomes in offspring associated with fetal alcohol exposure: a systematic review of clinical and preclinical studies with a focus on metabolic and body composition outcomes. Alcohol Clin Exp Res. 2019 July;43:1324–43. doi:10.1111/acer.14078.
   PubMed Web of Science ®Google Scholar
• Dobson CC, Mongillo DL, Brien DC, Stepita R, Poklewska-Koziell M, Winterborn A, Holloway AC, Brien JF, Reynolds JN. Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring. Nutr Diabetes [Internet]. 2012 Dec 17;2e57. https://pubmed.ncbi.nlm.nih.gov/23247731.
   PubMed Web of Science ®Google Scholar
• Gårdebjer EM, Anderson ST, Pantaleon M, Wlodek ME, Moritz KM. Maternal alcohol intake around the time of conception causes glucose intolerance and insulin insensitivity in rat offspring, which is exacerbated by a postnatal high‐fat diet. Faseb J. 2015;29:2690–701. doi:10.1096/fj.14-268979.
   PubMed Web of Science ®Google Scholar
• Gårdebjer EM, Cuffe JSM, Ward LC, Steane S, Anderson ST, Dorey ES, Kalisch-Smith JI, Pantaleon M, Chong S, Yamada L, et al. Effects of periconceptional maternal alcohol intake and a postnatal high-fat diet on obesity and liver disease in male and female rat offspring. Am J Physiol Endocrinol Metab. 2018 Oct;315:E694–704. doi:10.1152/ajpendo.00251.2017.
   PubMed Web of Science ®Google Scholar
• Probyn ME, Parsonson KR, Gårdebjer EM, Ward LC, Wlodek ME, Anderson ST, Moritz KM. Impact of low dose prenatal ethanol exposure on glucose homeostasis in Sprague-Dawley rats aged up to eight months. PLoS One [Internet]. 2013 Mar 22;8:e59718. doi:10.1371/journal.pone.0059718.
   PubMed Web of Science ®Google Scholar
• Smith SM, Pjetri E, Friday WB, Presswood BH, Ricketts DK, Walter KR, Mooney SM. Aging-related behavioral, adiposity, and glucose impairments and their association following prenatal alcohol exposure in the C57BL/6J mouse. Nutrients. 2022;14:1438. doi:10.3390/nu14071438.
   PubMed Web of Science ®Google Scholar
• Noor S, Milligan ED. Lifelong impacts of moderate prenatal alcohol exposure on neuroimmune function. Front Immunol [Internet]. 2018 May 22;9:1107. doi:10.3389/fimmu.2018.01107.
   PubMed Web of Science ®Google Scholar
• Reid N, Moritz KM, Akison LK. Adverse health outcomes associated with fetal alcohol exposure: a systematic review focused on immune-related outcomes. Pediatr Allergy Immunol [Internet]. 2019 June 19;30:698–707. doi:10.1111/pai.13099.
   PubMed Web of Science ®Google Scholar
• Kane CJM, Phelan KD, Drew PD. Neuroimmune mechanisms in fetal alcohol spectrum disorder. Dev Neurobiol [Internet]. 2012 Oct [accessed 2012 Sept 1];72:1302–16. https://pubmed.ncbi.nlm.nih.gov/22623427.
   PubMed Web of Science ®Google Scholar
• Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–67. doi:10.1038/nature05485.
   PubMed Web of Science ®Google Scholar
• Bodnar TS, Hill LA, Weinberg J. Evidence for an immune signature of prenatal alcohol exposure in female rats. Brain Behav Immun [Internet]. 2016 Nov [accessed 2016 June 2];58:130–41. https://www.ncbi.nlm.nih.gov/pubmed/27263429.
   PubMed Web of Science ®Google Scholar
• Raineki C, Bodnar TS, Holman PJ, Baglot SL, Lan N, Weinberg J. Effects of early-life adversity on immune function are mediated by prenatal environment: role of prenatal alcohol exposure. Brain Behav Immun [Internet]. 2017 Nov [accessed 2017 July 8];66:210–20. https://www.ncbi.nlm.nih.gov/pubmed/28698116.
   PubMed Web of Science ®Google Scholar
• Cantacorps L, Alfonso-Loeches S, Moscoso-Castro M, Cuitavi J, Gracia-Rubio I, López-Arnau R, Escubedo E, Guerri C, Valverde O. Maternal alcohol binge drinking induces persistent neuroinflammation associated with myelin damage and behavioural dysfunctions in offspring mice. Neuropharmacology [Internet]. 2017;123:368–84. doi:10.1016/j.neuropharm.2017.05.034.
   PubMed Web of Science ®Google Scholar
• Pascual M, Montesinos J, Montagud-Romero S, Forteza J, Rodríguez-Arias M, Miñarro J, Guerri C. TLR4 response mediates ethanol-induced neurodevelopment alterations in a model of fetal alcohol spectrum disorders. J Neuroinflammation [Internet]. 2017;14:145. doi:10.1186/s12974-017-0918-2.
   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 [Internet]. 2019;44:1579–88. doi:10.1038/s41386-019-0326-7.
   PubMed Web of Science ®Google Scholar
• Tremblay M-È, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. The role of microglia in the healthy brain. J Neurosci [Internet]. 2011 Nov 9;31:16064–69. doi:10.1523/JNEUROSCI.4158-11.2011.
   PubMed Web of Science ®Google Scholar
• Drew PD, Kane CJM. Fetal alcohol spectrum disorders and neuroimmune changes. Int Rev Neurobiol [Internet]. 2014;118:41–80. https://www.ncbi.nlm.nih.gov/pubmed/25175861.
   PubMed Web of Science ®Google Scholar
• Kane CJM, Drew PD. Neuroinflammatory contribution of microglia and astrocytes in fetal alcohol spectrum disorders. J Neurosci Res [Internet]. 2021 Aug [accessed 2020 Sept 22];99:1973–85. https://pubmed.ncbi.nlm.nih.gov/32959429.
   PubMed Web of Science ®Google Scholar
• Kane CJM, Drew PD. Inflammatory responses to alcohol in the CNS: nuclear receptors as potential therapeutics for alcohol-induced neuropathologies. J Leukoc Biol [Internet]. 2016 Nov [accessed 2016 July 26];100:951–59. https://www.ncbi.nlm.nih.gov/pubmed/27462100.
   PubMed Web of Science ®Google Scholar
• Wang P, Liu B-Y, Wu M-M, Wei X-Y, Sheng S, You S-W, Shang L-X, Kuang F. Moderate prenatal alcohol exposure suppresses the TLR4-mediated innate immune response in the hippocampus of young rats. Neurosci Lett [Internet]. 2019 Apr 23 [accessed 2019 Nov 6];699:77–83. http://www.sciencedirect.com/science/article/pii/S0304394019300679.
   PubMed Web of Science ®Google Scholar
• Alzheimer’s Association. Alzheimer’s disease facts and figures [Internet]. 2022. https://www.alz.org/alzheimers-dementia/facts-figures.
   Google Scholar
• Ferretti L, McCurry SM, Logsdon R, Gibbons L, Teri L. Anxiety and Alzheimer’s disease. J Geriatr Psychiatry Neurol [Internet]. 2001 Mar 1;14:52–58. doi:10.1177/089198870101400111.
   PubMed Web of Science ®Google Scholar
• Skaper SD, Facci L, Zusso M, Giusti P. An inflammation-centric view of neurological disease: beyond the neuron. Front Cell Neurosci [Internet]. 2018 Mar 21;12:72. doi:10.3389/fncel.2018.00072.
   PubMed Web of Science ®Google Scholar
• DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener [Internet]. 2019;14:32. doi:10.1186/s13024-019-0333-5.
   PubMed Web of Science ®Google Scholar
• Meraz Rios MA, Toral-Rios D, Franco-Bocanegra D, Villeda-Hernández J, Campos-Peña V. Inflammatory process in Alzheimer’s disease [Internet]. Front Integr Neurosci. 2013;7:59. https://www.frontiersin.org/article/10.3389/fnint.2013.00059.
   PubMedGoogle Scholar
• Yang J-Y, Xue X, Tian H, Wang X-X, Dong Y-X, Wang F, Zhao Y-N, Yao X-C, Cui W, Wu C-F, et al. Role of microglia in ethanol-induced neurodegenerative disease: pathological and behavioral dysfunction at different developmental stages. Pharmacol Ther [Internet]. 2014;144321–37. doi:10.1016/j.pharmthera.2014.07.002.
   PubMed Web of Science ®Google Scholar
• Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, et al. National institute on aging–Alzheimer’s association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimer’s Dement. 2012 Jan;8:1–13. doi:10.1016/j.jalz.2011.10.007.
   PubMed Web of Science ®Google Scholar
• Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, et al. National institute on aging–Alzheimer’s association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol. 2012 Jan;123:1–11. doi:10.1007/s00401-011-0910-3.
   PubMed Web of Science ®Google Scholar
• Bertram L, Tanzi RE. Alzheimer's disease risk genes: 29 and counting. Nat Rev Neurol. 2019 Apr;15:191–92. doi:10.1038/s41582-019-0158-4.
   PubMed Web of Science ®Google Scholar
• Downer B, Zanjani F, Fardo DW. The relationship between midlife and late life alcohol consumption, APOE e4 and the decline in learning and memory among older adults. Alcohol Alcohol [Internet]. 2014 [accessed 2013 Sept 18];49:17–22. https://www.ncbi.nlm.nih.gov/pubmed/24049153.
   PubMed Web of Science ®Google Scholar
• Pugazhenthi S, Qin L, Reddy PH. Common neurodegenerative pathways in obesity, diabetes, and Alzheimer’s disease. Biochim Biophys Acta Mol Basis Dis. 2017 May;1863:1037–45. doi:10.1016/j.bbadis.2016.04.017.
   PubMed Web of Science ®Google Scholar
• Rehm J, Hasan OSM, Black SE, Shield KD, Schwarzinger M. Alcohol use and dementia: a systematic scoping review. Alzheimers Res Ther [Internet]. 2019 Jan 5;11:1. doi:10.1186/s13195-018-0453-0.
   PubMed Web of Science ®Google Scholar
• Xu W, Tan L, Wang H-F, Jiang T, Tan M-S, Tan L, Zhao Q-F, Li J-Q. Meta-Analysis of modifiable risk factors for Alzheimer’s disease. J Neurol Neurosurg Psychiatry [Internet]. 2015 Dec 1;861299 LP–306. http://jnnp.bmj.com/content/86/12/1299.abstract.
   Web of Science ®Google Scholar
• Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM, et al. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron [Internet]. 2003;39409–21. doi:10.1016/S0896-6273(03)00434-3.
   PubMed Web of Science ®Google Scholar
• Billings LM, Oddo S, Green KN, McGaugh JL, LaFerla FM. Intraneuronal Aβ causes the onset of early alzheimer’s disease-related cognitive deficits in transgenic mice. Neuron. 2005 Mar;45:675–88. doi:10.1016/j.neuron.2005.01.040.
   PubMed Web of Science ®Google Scholar
• Caruso D, Barron AM, Brown MA, Abbiati F, Carrero P, Pike CJ, Garcia-Segura LM, Melcangi RC. Age-related changes in neuroactive steroid levels in 3xTg-AD mice. Neurobiol Aging [Internet]. 2013;341080–89. doi:10.1016/j.neurobiolaging.2012.10.007.
   PubMed Web of Science ®Google Scholar
• Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ. Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet [Internet]. 2014 Apr 23;5:88. doi:10.3389/fgene.2014.00088.
   PubMed Web of Science ®Google Scholar
• Fagan SG, Bechet S, Dev KK. Fingolimod rescues memory and improves pathological hallmarks in the 3xTg-AD model of Alzheimer’s disease. Mol Neurobiol [Internet]. 2022;59:1882–95. doi:10.1007/s12035-021-02613-5.
   PubMed Web of Science ®Google Scholar
• Belfiore R, Rodin A, Ferreira E, Velazquez R, Branca C, Caccamo A, Oddo S. Temporal and regional progression of Alzheimer’s disease-like pathology in 3xTg-AD mice. Aging Cell [Internet]. 2019 Feb [accessed 2018 Nov 28];18:e12873. https://pubmed.ncbi.nlm.nih.gov/30488653.
   PubMed Web of Science ®Google Scholar
• Robison LS, Gannon OJ, Thomas MA, Salinero AE, Abi-Ghanem C, Poitelon Y, Belin S, Zuloaga KL. Role of sex and high-fat diet in metabolic and hypothalamic disturbances in the 3xTg-AD mouse model of Alzheimer’s disease. J Neuroinflammation [Internet]. 2020 Sept 29;17:285. doi:10.1186/s12974-020-01956-5.
   PubMed Web of Science ®Google Scholar
• Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, et al. Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement. Circulation. 2005;112:2735–52. doi:10.1161/CIRCULATIONAHA.105.169404.
   PubMed Web of Science ®Google Scholar
• Bangen KJ, Armstrong NM, Au R, Gross AL. Metabolic syndrome and cognitive trajectories in the Framingham offspring study. Brandt J, editor. J Alzheimer’s Dis. 2019 Aug;71:931–43.
   PubMed Web of Science ®Google Scholar
• Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies. Diabetologia. 2005;48:2460–69. doi:10.1007/s00125-005-0023-4.
   PubMed Web of Science ®Google Scholar
• Frisardi V, Solfrizzi V, Seripa D, Capurso C, Santamato A, Sancarlo D, Vendemiale G, Pilotto A, Panza F. Metabolic-cognitive syndrome: a cross-talk between metabolic syndrome and Alzheimer’s disease. Ageing Res Rev. 2010 Oct;9:399–417. doi:10.1016/j.arr.2010.04.007.
   PubMed Web of Science ®Google Scholar
• Panza F, Frisardi V, Capurso C, Imbimbo BP, Vendemiale G, Santamato A, D’Onofrio G, Seripa D, Sancarlo D, Pilotto A, et al. Metabolic syndrome and cognitive impairment: current epidemiology and possible underlying mechanisms. J Alzheimers Dis. 2010;21:691–724. doi:10.3233/JAD-2010-091669.
   PubMed Web of Science ®Google Scholar
• Strachan MWJ, Deary IJ, Ewing FME, Frier BM. Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies. Diabetes Care American Diabetes Association Inc. 1997;20:438–45. doi:10.2337/diacare.20.3.438.
   PubMed Web of Science ®Google Scholar
• Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A, Fuino RL, Kawaguchi KR, Samoyedny AJ, Wilson RS, et al. Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest. 2012 Apr;122:1316–38. doi:10.1172/JCI59903.
   PubMed Web of Science ®Google Scholar
• Thomas KR, Bangen KJ, Weigand AJ, Edmonds EC, Sundermann E, Wong CG, Eppig J, Werhane ML, Delano-Wood L, Bondi MW, et al. Type II diabetes interacts with Alzheimer's disease risk factors to predict functional decline. Alzheimer Dis Assoc Disord. 2019;34:10–17. doi:10.1097/WAD.0000000000000332.
   Web of Science ®Google Scholar
• Watts AS, Loskutova N, Burns JM, Johnson DK. Metabolic syndrome and cognitive decline in early Alzheimer’s disease and healthy older adults. J Alzheimer’s Dis. 2013 Apr;35:253–65. doi:10.3233/JAD-121168.
   PubMed Web of Science ®Google Scholar
• Amos-Kroohs RM, Nelson DW, Hacker TA, Yen C-L, Smith SM. Does prenatal alcohol exposure cause a metabolic syndrome? (Non-)evidence from a mouse model of fetal alcohol spectrum disorder. PLoS One [Internet]. 2018 June 28;13:e0199213. doi:10.1371/journal.pone.0199213.
   PubMed Web of Science ®Google Scholar
• Yao X-H, Chen L, Nyomba BLG. Adult rats prenatally exposed to ethanol have increased gluconeogenesis and impaired insulin response of hepatic gluconeogenic genes. J Appl Physiol. 2006 Feb;100:642–48. doi:10.1152/japplphysiol.01115.2005.
   PubMed Web of Science ®Google Scholar
• Yao X-H, Nyomba BLG. Hepatic insulin resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring. Am J Physiol Regul Integr Comp Physiol. 2008 June;294:R1797–806. doi:10.1152/ajpregu.00804.2007.
   PubMed Web of Science ®Google Scholar
• Cook JC, Lynch ME, Coles CD. Association analysis: fetal alcohol spectrum disorder and hypertension status in children and adolescents. Alcohol Clin Exp Res. 2019 Aug;43:1727–33. doi:10.1111/acer.14121.
   PubMed Web of Science ®Google Scholar
• Spohr HL, Willms J, Steinhausen HC. Prenatal alcohol exposure and long-term developmental consequences. Lancet. 1993 Apr;341:907–10. doi:10.1016/0140-6736(93)91207-3.
   PubMed Web of Science ®Google Scholar
• Baeta-Corral R, Johansson B, Giménez-Llort L. Long-term treatment with low-dose caffeine worsens BPSD-like profile in 3xTg-AD mice model of Alzheimer’s disease and affects mice with normal aging. Front Pharmacol [Internet]. 2018 Feb 15;9:79. doi:10.3389/fphar.2018.00079.
   PubMed Web of Science ®Google Scholar
• Reeves PG, Nielsen FH, Fahey GCJ. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr U S. 1993;123:1939–51.
   PubMed Web of Science ®Google Scholar
• Mooney SM, Pjetri E, Friday WB, Smith SM. Growth and behavioral differences in a C57BL/6J mouse model of prenatal alcohol exposure. Alcohol [Internet]. 2021;97:51–57. doi:10.1016/j.alcohol.2021.09.031.
   PubMed Web of Science ®Google Scholar
• Virdee MS, Saini N, Kay CD, Neilson AP, Ting S, Kwan C, Helfrich KK, Mooney SM, Smith SM. An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder. Sci Reports [Internet]. 2021;11:248. doi:10.1038/s41598-020-80093-8.
   PubMed Web of Science ®Google Scholar
• Saini N, Virdee MS, Helfrich KK, Kwan ST, Mooney SM, Smith SM. Untargeted metabolome analysis reveals reductions in maternal hepatic glucose and amino acid content that correlate with fetal organ weights in a mouse model of fetal alcohol spectrum disorders. Nutrients. 2022;14:1096.
   PubMed Web of Science ®Google Scholar
• Wehner JM, Radcliffe RA. Cued and contextual fear conditioning in mice. Curr Protoc Neurosci [Internet]. 2004 Apr 1;27:8.5C.1–8.5C.14. doi:10.1002/0471142301.ns0805cs27.
   Google Scholar
• Bartholomae E, Johnson Z, Moore J, Ward K, Kressler J. Reducing glycemic indicators with moderate intensity stepping of varied, short durations in people with pre-diabetes. J Sports Sci Med. 2018 Dec;17:680–85.
   PubMed Web of Science ®Google Scholar
• Choi J-H, Kim S-H, Lee E-B, Kim J-S, Jung J-E, Jeong U-Y, Kim J-H, Jang H-H, Park S-Y, Kim G-C, et al. Anti-diabetic effects of allium hookeri extracts prepared by different methods in type 2 C57BL/J-db/db mice. Pharmaceuticals (Basel). 2022 Apr;15:486. doi:10.3390/ph15040486.
   PubMedGoogle Scholar
• Mooney SM, Miller MW. Role of neurotrophins on postnatal neurogenesis in the thalamus: prenatal exposure to ethanol. Neuroscience [Internet]. 2011 Apr 14 [accessed 2011 Jan 26];179:256–66. https://pubmed.ncbi.nlm.nih.gov/21277941.
   PubMed Web of Science ®Google Scholar
• Drew PD, Johnson JW, Douglas JC, Phelan KD, Kane CJM. 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 [Internet]. 2015 Mar [accessed 2015 Feb 19];39:445–54. https://www.ncbi.nlm.nih.gov/pubmed/25703036.
   PubMed Web of Science ®Google Scholar
• Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B [Internet]. 1995 Jan 1;57:289–300. doi:10.1111/j.2517-6161.1995.tb02031.x.
   Web of Science ®Google Scholar
• de la Monte SM, Tong M. Brain metabolic dysfunction at the core of Alzheimer’s disease. Biochem Pharmacol [Internet]. 2014 Apr 15 [accessed 2013 Dec 28];88:548–59. https://pubmed.ncbi.nlm.nih.gov/24380887.
   PubMed Web of Science ®Google Scholar
• España J, Giménez-Llort L, Valero J, Miñano A, Rábano A, Rodriguez-Alvarez J, LaFerla FM, Saura CA. Intraneuronal β-amyloid accumulation in the amygdala enhances fear and anxiety in Alzheimer’s disease transgenic mice. Biol Psychiatry [Internet]. 2010;67:513–21. doi:10.1016/j.biopsych.2009.06.015.
   PubMed Web of Science ®Google Scholar
• Stover KR, Campbell MA, Van Winssen CM, Brown RE. Early detection of cognitive deficits in the 3xTg-AD mouse model of Alzheimer’s disease. Behav Brain Res [Internet]. 2015;289:29–38. doi:10.1016/j.bbr.2015.04.012.
   PubMed Web of Science ®Google Scholar
• Filali M, Lalonde R, Theriault P, Julien C, Calon F, Planel E. Cognitive and non-cognitive behaviors in the triple transgenic mouse model of Alzheimer’s disease expressing mutated APP, PS1, and Mapt (3xTg-AD). Behav Brain Res [Internet]. 2012;234334–42. doi:10.1016/j.bbr.2012.07.004.
   PubMed Web of Science ®Google Scholar
• Hoffman JL, Faccidomo S, Kim M, Taylor SM, Agoglia AE, May AM, Smith EN, Wong LC, Hodge CW. Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer’s disease. Int Rev Neurobiol [Internet]. 2019 [accessed 2019 Oct 23];148:169–230. https://pubmed.ncbi.nlm.nih.gov/31733664.
   PubMed Web of Science ®Google Scholar
• Billings LM, Green KN, McGaugh JL, LaFerla FM. Learning decreases a beta*56 and tau pathology and ameliorates behavioral decline in 3xTg-AD mice. J Neurosci [Internet]. 2007 Jan 24;27:751–61. doi:10.1523/JNEUROSCI.4800-06.2007.
   PubMed Web of Science ®Google Scholar
• Janson J, Laedtke T, Parisi JE, O’Brien P, Petersen RC, Butler PC. Increased risk of type 2 diabetes in Alzheimer disease. Diabetes. 2004 Feb;53:474–81. doi:10.2337/diabetes.53.2.474.
   PubMed Web of Science ®Google Scholar
• Christensen A, Liu J, Pike CJ. Aging reduces estradiol protection against neural but not metabolic effects of obesity in female 3xTg-AD mice. Front Aging Neurosci [Internet]. 2020 May 5;12:113. doi:10.3389/fnagi.2020.00113.
   PubMed Web of Science ®Google Scholar
• Tabassum S, Misrani A, Yang L. Exploiting common aspects of obesity and Alzheimer’s disease. Front Hum Neurosci. 2020;14:602360. doi:10.3389/fnhum.2020.602360.
   PubMed Web of Science ®Google Scholar
• Julien C, Tremblay C, Phivilay A, Berthiaume L, Emond V, Julien P, Calon F. High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model. Neurobiol Aging. 2010 Sept;31:1516–31. doi:10.1016/j.neurobiolaging.2008.08.022.
   PubMed Web of Science ®Google Scholar
• Ho L, Qin W, Pompl PN, Xiang Z, Wang J, Zhao Z, Peng Y, Cambareri G, Rocher A, Mobbs CV, et al. Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease. FASEB J off Publ Fed Am Soc Exp Biol. 2004 May;18:902–04.
   PubMed Web of Science ®Google Scholar
• Vandal M, White PJ, Chevrier G, Tremblay C, St-Amour I, Planel E, Marette A, Calon F. Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer’s disease. FASEB J off Publ Fed Am Soc Exp Biol. 2015 Oct;29:4273–84.
   PubMed Web of Science ®Google Scholar
• Spinelli R, Parrillo L, Longo M, Florese P, Desiderio A, Zatterale F, Miele C, Raciti GA, Beguinot F. Molecular basis of ageing in chronic metabolic diseases. J Endocrinol Invest [Internet]. 2020;43:1373–89. doi:10.1007/s40618-020-01255-z.
   PubMed Web of Science ®Google Scholar
• Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, Haneuse S, Craft S, Montine TJ, Kahn SE, et al. Glucose levels and risk of dementia. N Engl J Med [Internet]. 2013 Aug 8;369540–48. doi:10.1056/NEJMoa1215740.
   PubMed Web of Science ®Google Scholar
• Xu WL, Atti AR, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Midlife overweight and obesity increase late-life dementia risk: a population-based twin study. Neurology [Internet]. 2011 May 3;76:1568–74. doi:10.1212/WNL.0b013e3182190d09.
   PubMed Web of Science ®Google Scholar
• Whitmer RA, Gustafson DR, Barrett-Connor E, Haan MN, Gunderson EP, Yaffe K. Central obesity and increased risk of dementia more than three decades later. Neurology. 2008 Sept;71:1057–64. doi:10.1212/01.wnl.0000306313.89165.ef.
   PubMed Web of Science ®Google Scholar
• Alfaro FJ, Gavrieli A, Saade-Lemus P, Lioutas V-A, Upadhyay J, Novak V. White matter microstructure and cognitive decline in metabolic syndrome: a review of diffusion tensor imaging. Metabolism [Internet]. 2018;78:52–68. doi:10.1016/j.metabol.2017.08.009.
   PubMed Web of Science ®Google Scholar
• Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell [Internet]. 2010 Mar 19;140:918–34. doi:10.1016/j.cell.2010.02.016.
   PubMed Web of Science ®Google Scholar
• Raghunathan R, Liu C-H, Kouka A, Singh M, Miranda RC, Larin KV. Dose-response analysis of microvasculature changes in the murine fetal brain and the maternal extremities due to prenatal ethanol exposure. J Biomed Opt [Internet]. 2020 Nov;25:126001. doi:10.1117/1.JBO.25.12.126001.
   PubMed Web of Science ®Google Scholar
• Tan C, Liu Y, Zhang H, Di C, Xu D, Liang C, Zhang N, Han B, Lang W. Neuroprotective effects of probiotic-supplemented diet on cognitive behavior of 3xTg-AD mice. J Healthc Eng [Internet]. 2022 Jan 5;2022:4602428. https://pubmed.ncbi.nlm.nih.gov/35035837.
   PubMed Web of Science ®Google Scholar
• Aghaie CI, Hausknecht KA, Wang R, Dezfuli PH, Haj-Dahmane S, Kane CJM, Sigurdson WJ, Shen R-Y. Prenatal ethanol exposure and postnatal environmental intervention alter dopaminergic neuron and microglia morphology in the ventral tegmental area during adulthood. Alcohol Clin Exp Res [Internet]. 2020 Feb [accessed 2020 Jan 25];44:435–44. https://pubmed.ncbi.nlm.nih.gov/31872887.
   PubMed Web of Science ®Google Scholar
• Rajesh Y, Kanneganti T-D. Innate immune cell death in neuroinflammation and Alzheimer’s disease. Cells. 2022 June;11:1885. doi:10.3390/cells11121885.
   PubMed Web of Science ®Google Scholar