Fetal alcohol exposure impairs learning and memory functions and elevates levels of various biochemical markers of Alzheimer's disease in the brain of 12-month-old rats.
Alzheimer's disease-related proteins
acetylcholinesterase
fetal alcohol
memory
Journal
Alcohol, clinical & experimental research
ISSN: 2993-7175
Titre abrégé: Alcohol Clin Exp Res (Hoboken)
Pays: United States
ID NLM: 9918609780906676
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
revised:
15
02
2023
received:
25
08
2022
accepted:
14
03
2023
medline:
21
3
2023
pubmed:
21
3
2023
entrez:
20
3
2023
Statut:
ppublish
Résumé
Alcohol drinking during pregnancy often adversely affects brain development among offspring, inducing persistent central nervous system dysfunction. However, it is unknown whether fetal alcohol exposure (FAE) promotes the biochemical characteristics of Alzheimer's disease in offspring. We used a first- and second-trimester human equivalent rat model of FAE that involves feeding a liquid diet containing 6.7% v/v ethanol from gestational days 7 through 21 in Fischer-344 rats. Control rats were fed an isocaloric liquid diet or rat chow ad libitum. Pups were weaned on postnatal day 21 and housed by sex. They were used for behavioral and biochemical studies at about 12 months of age. Only one male or one female offspring from a litter was included in each experimental group. Fetal alcohol-exposed offspring had poorer learning and memory functions than controls. The experimental animals, both male and female, also had elevated levels of acetylcholinesterase (AChE) activity, hyperphosphorylated-tau protein, β-amyloid (Aβ) and Aβ1-42 proteins, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and Unc-5 netrin receptor C (UNC5C) proteins in the cerebral cortex and hippocampus at 12 months of age. These findings show that FAE increases the expression of some of the biochemical and behavioral phenotypes of Alzheimer's disease.
Sections du résumé
BACKGROUND
BACKGROUND
Alcohol drinking during pregnancy often adversely affects brain development among offspring, inducing persistent central nervous system dysfunction. However, it is unknown whether fetal alcohol exposure (FAE) promotes the biochemical characteristics of Alzheimer's disease in offspring.
METHODS
METHODS
We used a first- and second-trimester human equivalent rat model of FAE that involves feeding a liquid diet containing 6.7% v/v ethanol from gestational days 7 through 21 in Fischer-344 rats. Control rats were fed an isocaloric liquid diet or rat chow ad libitum. Pups were weaned on postnatal day 21 and housed by sex. They were used for behavioral and biochemical studies at about 12 months of age. Only one male or one female offspring from a litter was included in each experimental group.
RESULTS
RESULTS
Fetal alcohol-exposed offspring had poorer learning and memory functions than controls. The experimental animals, both male and female, also had elevated levels of acetylcholinesterase (AChE) activity, hyperphosphorylated-tau protein, β-amyloid (Aβ) and Aβ1-42 proteins, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and Unc-5 netrin receptor C (UNC5C) proteins in the cerebral cortex and hippocampus at 12 months of age.
CONCLUSIONS
CONCLUSIONS
These findings show that FAE increases the expression of some of the biochemical and behavioral phenotypes of Alzheimer's disease.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
882-892Subventions
Organisme : National Institute of Health
ID : R01AA025359
Informations de copyright
© 2023 The Authors. Alcohol: Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.
Références
Alonso, A., Zaidi, T., Novak, M., Grundke-Iqbal, I. & Iqbal, K. (2001) Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proceedings of the National Academy of Sciences of the United States of America, 98, 6923-6928.
Al-Yasari, A., Jabbar, S., Cabrera, M.A., Rousseau, B. & Sarkar, D.K. (2021) Preconception alcohol exposure increases the susceptibility to diabetes in the offspring. Endocrinology, 162, bqaa188.
Arendt, T., Allen, Y., Sinden, J., Schugens, M.M., Marchbanks, R.M., Lantos, P.L. et al. (1988) Cholinergic-rich brain transplants reverse alcohol-induced memory deficits. Nature, 332, 448-450.
Barreda, E.G. & Avila, J. (2011) Is tau a suitable therapeutical target in tauopathies? World Journal of Biological Chemistry, 1, 81-84.
Bartus, R.T., Dean, R.L., 3rd, Beer, B. & Lippa, A.S. (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science, 217(4558), 408-414.
Brady, M.L., Allan, A.M. & Caldwell, K.K. (2012) A limited access mouse model of prenatal alcohol exposure that produces long-lasting deficits in hippocampal-dependent learning and memory. Alcoholism, Clinical and Experimental Research, 36(3), 457-466.
Casamenti, F., Scali, C., Vannucchi, M.G., Bartolini, L. & Pepeu, G. (1993) Long-term ethanol consumption by rats: effect on acetylcholine release in vivo, choline acetyltransferase activity, and behavior. Neuroscience, 56, 465-471.
Chen, L. & Nyomba, B.L. (2003) Effects of prenatal alcohol exposure on glucose tolerance in the rat offspring. Metabolism, 4, 454-462.
Clausen, A., Xiaobo, X., Bi, X. & Baudry, M. (2012) Effects of the superoxide dismutase/catalase mimetic EUK-207 in a mouse model of Alzheimer's disease: protection against and interruption of progression of amyloid and tau pathology and cognitive decline. Journal of Alzheimer's Disease, 30, 183-208.
Cummings, B.J., Pike, C.J., Shankle, R. & Cotman, C.W. (1996) β-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease. Neurobiology of Aging, 17(6), 921-933.
De, A., Boyadjieva, N., Oomizu, S. & Sarkar, D.K. (2002) Ethanol induces hyperprolactinemia by increasing prolactin release and lactotrope growth in female rats. Alcoholism, Clinical and Experimental Research, 26, 1420-1429.
de Oliveira, J.S., Abdalla, F.H., Dornelles, G.L., Adefegha, S.A., Palma, T.V., Signor, C. et al. (2016) Berberine protects against memory impairment and anxiogenic-like behavior in rats submitted to sporadic Alzheimer's-like dementia: involvement of acetylcholinesterase and cell death. Neurotoxicology, 57, 241-250.
Dodge, N.C., Thomas, K.G.F., Meintjes, E.M., Molteno, C.D., Jacobson, J.L. & Jacobson, S.W. (2019) Spatial navigation in children and young disorders. Alcoholism, Clinical and Experimental Research, 43, 2536-2546.
Doehner, W., Praße, L., Wolpers, J., Brückner, M.K., Ueberham, U. & Arendt, T. (2017) Transgenerational transmission of an anticholinergic endophenotype with memory dysfunction. Neurobiology of Aging, 51, 19-30.
Eckardt, M.J., File, S.E., Gessa, G.L., Grant, K.A., Guerri, C., Hoffman, P.L. et al. (1998) Effects of moderate alcohol consumption on the central nervous system. Alcoholism, Clinical and Experimental Research, 22, 998-1040.
Ehlers, C.L., Criado, J.R., Wills, D.N., Liu, W. & Crews, F.T. (2011) Periadolescent ethanol exposure reduces adult forebrain ChAT+IR neurons: correlation with behavioral pathology. Neuroscience, 199, 333-345.
Fernandez, G.M. & Savage, L.M. (2017) Adolescent binge ethanol exposure alters specific forebrain cholinergic cell populations and leads to selective functional deficits in the prefrontal cortex. Neuroscience, 361, 129-143.
Findeis, M.A. (2007) The role of beta-peptide-43 in Alzheimer's disease. Pharmacology & Therapeutics, 116(2), 266-286.
Gangisetty, O., Jabbar, S., Wynne, O. & Sarkar, D.K. (2017) MicroRNA-9 regulates fetal alcohol-induced changes in D2 receptor to promote prolactin production. The Journal of Endocrinology, 235, 1-14.
Gangisetty, O., Mead, E.A. & Sarkar, D.K. (2021) Sex-determining region Y controls the effects of fetal alcohol exposure on proopiomelanocortin gene expression. Frontiers in Neuroscience, 15, 608102.
Gangisetty, O., Palagani, A. & Sarkar, D.K. (2020) Transgenerational inheritance of fetal alcohol exposure adverse effects on immune gene interferon-ϒ. Clinical Epigenetics, 12, 70.
Gangisetty, O., Wynne, O., Jabbar, S., Nasello, C. & Sarkar, D.K. (2015) Fetal alcohol exposure reduces dopamine receptor D2 and increases pituitary weight and prolactin production via epigenetic mechanisms. PLoS One, 10, e0140699.
Gavin, C.E., Kates, B., Gerken, L.A. & Rodier, P.M. (1994) Patterns of growth deficiency in rats exposed in utero to undernutrition, ethanol, or the neuroteratogen mythylazoxymethanol (NAM). Teratology, 49(2), 113-121.
Giri, M., Zhang, M. & Lü, Y. (2016) Genes associated with Alzheimer's disease: an overview and current status. Clinical Interventions in Aging, 11, 665-681.
Gocmez, S.S., Şahin, T.D., Yazir, Y., Duruksu, G., Eraldemir, F.C., Polat, S. et al. (2019) Resveratrol prevents cognitive deficits by attenuating oxidative damage and inflammation in a rat model of streptozotocin diabetes-induced vascular dementia. Physiology & Behavior, 15, 198-207.
Goedert, M., Klug, A. & Crowther, R.A. (2006) Tau protein, the paired helical filament and Alzheimer's disease. Journal of Alzheimer's Disease, 9(3 Suppl), 195-207.
Govorko, D., Bekdash, R.A., Zhang, C. & Sarkar, D.K. (2012) Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations. Biological Psychiatry, 72, 378-388.
Heymann, D., Stern, Y., Cosentino, S., Tatarina-Nulman, O., Dorrejo, J.N. & Gu, Y. (2016) The association between alcohol use and the progression of Alzheimer's disease. Current Alzheimer Research, 13, 1356-1362.
Hoffman, J.L., Faccidomo, S., Kim, M., Taylor, S.M., Agoglia, A.E., May, A.M. et al. (2019) Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer's disease. International Review of Neurobiology, 148, 169-230.
Huang, D., Cai, Z. & Xiao, M. (2014) Alzheimer's disease and prenatal maternal stress. Aging Neurodegener, 2, 1-5.
Huang, D., Yu, M., Yang, S., Lou, D., Zhou, W., Zheng, L. et al. (2018) Ethanol alters APP processing and aggravates Alzheimer-associated phenotypes. Molecular Neurobiology, 55, 5006-5018.
Jabbar, S., Reuhl, K. & Sarkar, D.K. (2018) Prenatal alcohol exposure increases the susceptibility to develop aggressive prolactinomas in the pituitary gland. Scientific Reports, 8, 7720.
Jacob, A. & Wang, P. (2020) Alcohol intoxication and cognition: implications on mechanisms and therapeutic strategies. Frontiers in Neuroscience, 14, 102.
Kar, S., Slowikowski, S.P., Westaway, D. & Mount, H.T. (2004) Interactions between beta-amyloid and central cholinergic neurons: implications for Alzheimer's disease. Journal of Psychiatry & Neuroscience, 29, 427-441.
Kukull, W.A., Higdon, R., Bowen, J.D., McCormick, W.C., Teri, L., Schellenberg, G.D. et al. (2002) Dementia and Alzheimer disease incidence: a prospective cohort study. Archives of Neurology, 59, 1737-1746.
Lagarde, J., Sarazin, M., Chauviré, V., Stankoff, B., Kas, A., Lacomblez, L. et al. (2017) Cholinergic changes in aging and Alzheimer disease: an [18F]-F-A-85380 exploratory PET study. Alzheimer Disease and Associated Disorders, 31, 8-12.
Lahiri, D.K., Farlow, M.R., Sambamurti, K., Greig, N.H., Giacobini, E. & Schneider, L.S. (2003) A critical analysis of new molecular targets and strategies for drug developments in Alzheimer's disease. Current Drug Targets, 4, 97-112.
Lane, C.A., Hardy, J. & Schott, J.M. (2018) Alzheimer's disease. European Journal of Neurology, 25, 59-70.
Laurent, C., Buée, L. & Blum, D. (2018) Tau and neuroinflammation: what impact for Alzheimer's disease and tauopathies? Biometrical Journal, 41, 21-33.
Li, Q., Wang, B., Sun, F.R., Li, J.Q., Cao, X.P. & Tan, L. (2018) The role of UNC5C in Alzheimer's disease. Annals of Translational Medicine, 6, 178.
Lloret, A., Fuchsberger, T., Giraldo, E. & Viña, J. (2015) Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer׳s disease. Free Radical Biology & Medicine, 83, 186-191.
Logan, R.W., Wynne, O., Maglakelidze, G., Zhang, C., O'Connell, S., Boyadjieva, N.I. et al. (2015) β-Endorphin neuronal transplantation into the hypothalamus alters anxiety-like behaviors in prenatal alcohol-exposed rats and alcohol-non-preferring and alcohol-preferring rats. Alcoholism, Clinical and Experimental Research, 39, 146-157.
Miller, M.W. (1992) Circadian rhythm of cell proliferation in the telencephalic ventricular zone: effect of in utero exposure to ethanol. Brain Research, 595, 17-24.
Moreland, N., La Grange, L. & Montoya, R. (2002) Impact of in utero exposure to EtOH on corpus callosum development and paw preference in rats: protective effects of silymarin. BMC Complementary and Alternative Medicine, 2, 10.
Muralidar, S., Ambi, S.V., Sekaran, S., Thirumalai, D. & Palaniappan, B. (2020) Role of tau protein in Alzheimer's disease: The prime pathological player. International Journal of Biological Macromolecules, 163, 1599-1617.
Neil, C.D., Kevin, G.F.T., Ernesta, M.M., Christopher, D.M., Joseph, L.J. & Sandra, W.J. (2020) Reduced hippocampal volumes partially mediate effects of prenatal alcohol exposure on spatial navigation on a virtual water maze task in children. Alcoholism, Clinical and Experimental Research, 44, 844-855.
Neumann, U., Rueeger, H., Machauer, R., Veenstra, S.J., Lueoend, R.M., Tintelnot-Blomley, M. et al. (2015) A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice. Molecular Neurodegeneration, 10, 44.
O'Brien, R.J. & Wong, P.C. (2011) Amyloid precursor protein processing and Alzheimer's disease. Annual Review of Neuroscience, 34, 185-204.
Pierzynowska, K., Podlacha, M., Gaffke, L., Majkutewicz, I., Mantej, J., Węgrzyn, A. et al. (2019) Autophagy-dependent mechanism of genistein-mediated elimination of behavioral and biochemical defects in the rat model of sporadic Alzheimer's disease. Neuropharmacology, 148, 332-346.
Powell-Doherty, R.D., Abbott, A.R.N., Nelson, L.A. & Bertke, A.S. (2020) Amyloid-β and p-tau anti-threat response to herpes simplex virus 1 infection in primary adult murine hippocampal neurons. Journal of Virology, 16, e01874-19.
Ravi, R.P. & Reddy, H. (2017) Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer's disease neurons. Journal of Alzheimer's Disease, 57, 975-999.
Rehm, J., Hasan, O.S.M., Black, S.E., Shield, K.D. & Schwarzinger, M. (2019) Alcohol use and dementia: a systematic scoping review. Alzheimer's Research & Therapy, 11, 1.
Reitz, C., Brayne, C. & Mayeux, R. (2011) Epidemiology of Alzheimer disease. Nature Reviews. Neurology, 7, 137-152.
Rodrigue, K.M., Kennedy, K.M. & Park, D.C. (2009) Beta-amyloid deposition and the aging brain. Neuropsychology Review, 19, 436-450.
Samaneh, S., Nesa, A., Reihaneh, M., Reza, G., Maryam, K.A., Siamak, S. et al. (2021) Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats. Behavioral and Brain Functions, 17, 9. Available from: https://doi.org/10.1186/s12993-021-00184-y
Samant, N.P. & Gupta, G.L. (2022) Avicularin attenuates memory impairment in rats with amyloid Beta-induced Alzheimer's disease. Neurotoxicity Research, 40, 140-153.
Sanchez, L.M., Goss, J., Wagner, J., Davies, S., Savage, D.D., Hamilton, D.A. et al. (2019) Moderate prenatal alcohol exposure impairs performance by adult male rats in an object-place paired-associate task. Behavioural Brain Research, 360, 228-234.
Sepulcre, J., Sabuncu, M.R., Becker, A., Sperling, R. & Johnson, K.A. (2013) In vivo characterization of the early states of the amyloid-beta network. Brain, 136, 2239-2252.
Slone Wilcoxon, J. & Redei, E.E. (2004) Prenatal programming of adult thyroid function by alcohol and thyroid hormonesm. Journal of Physiology-Endocrinology and Metabolism, 287, E318-E326.
Subbanna, S. & Basavarajappa, B.S. (2022) Binge-like prenatal ethanol exposure causes impaired cellular differentiation in the embryonic forebrain and synaptic and behavioral defects in adult mice. Brain Sciences, 12, 793.
Sun, J.H., Wang, H.F., Zhu, X.C., Yu, W.J., Tan, C.C., Jiang, T. et al. (2016) The impact of UNC5C genetic variations on neuroimaging in Alzheimer's disease. Molecular Neurobiology, 53, 6759-6767.
Swanson, D.J., King, M.A., Walker, D.W. & Heaton, M.B. (1995) Chronic prenatal ethanol exposure alters the normal ontogeny of choline acetyltransferase activity in the rat septohippocampal system. Alcoholism, Clinical and Experimental Research, 19, 1252-1260.
Talesa, V.N. (2001) Acetylcholinesterase in Alzheimer's disease. Mechanisms of Ageing and Development, 122, 1961-1969.
Thomas, J.D., La-Fiette, M.H., Quinn, V.R. & Riley, E.P. (2000) Neonatal choline supplementation ameliorates the effects of prenatal alcohol exposure on a discrimination learning task in rats. Neurotoxicology and Teratology, 22, 703-711.
Toso, L., Roberson, R., Woodard, J., Abebe, D. & Spong, C.Y. (2006) Prenatal alcohol exposure alters GABA(a)alpha5 expression: a mechanism of alcohol-induced learning dysfunction. American Journal of Obstetrics and Gynecology, 195, 522-527.
Uban, K.A., Sliwowska, J.H., Lieblich, S., Ellis, L.A., Yu, W.K., Weinberg, J. et al. (2010) Prenatal alcohol exposure reduces the proportion of newly produced neurons and glia in the dentate gyrus of the hippocampus in female rats. Hormones and Behavior, 58, 835-843.
Vassar, R., Kovacs, D.M., Yan, R. & Wong, P.C. (2009) The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential. The Journal of Neuroscience, 29, 12787-12794.
Vetreno, R.P. & Crews, F.T. (2018) Adolescent binge ethanol-induced loss of basal forebrain cholinergic neurons and neuroimmune activation are prevented by exercise and indomethacin. PLoS One, 13, e0204500.
Willoughby, K.A., Sheard, E.D., Nash, K. & Rovet, J. (2008) Effects of prenatal alcohol exposure on hippocampal volume, verbal learning, and verbal and spatial recall in late childhood. Journal of the International Neuropsychological Society, 14, 1022-1023.
Xiong, H., Callaghan, D., Wodzinska, J., Xu, J., Premyslova, M. & Liu, Q.Y. (2011) Biochemical and behavioral characterization of the double transgenic mouse model (APPswe/PS1dE9) of Alzheimer's disease. Neuroscience Bulletin, 27, 221-232.
Yidi, W., Bradley, A.F., Michael, N.A.E. & Miyoung, S. (2021) Differential effects of maternal diets on birth outcomes and metabolic parameters in rats after ethanol consumption during pregnancy. The British Journal of Nutrition, 126, 1130-1139.