Skip to main content

Advertisement

SpringerLink
Log in

Combination of Donepezil and Memantine Attenuated Cognitive Impairment Induced by Mixed Endocrine-Disrupting Chemicals: an In Silico Study

  • Research Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Little is known about the effects of endocrine-disrupting chemicals (EDCs) and the combination of memantine and donepezil on the pathogenesis of cognitive impairment. Here, we aimed to identify in silico the molecular mechanisms of the combination of memantine and donepezil that combat cognitive impairment induced by nine common EDCs using GeneMania, AutoDock Vina, Metascape, SwissADME, MIENTURNET, and miRNAsong. We observed that the mixture of memantine and donepezil had therapeutic effects on mixed EDC-induced cognitive impairment via five genes (TNF, ACHE, BAX, IL1B, and CASP3). With ACHE and TNF, donepezil and memantine both had a high docking score, respectively. The predominant connections among five mutual genes were physical interactions (77.6%). The major pathways associated with memantine and donepezil countering cognitive impairment generated by mixed EDCs were discovered to be “AGE-RAGE signaling pathway in diabetic complications,” “pro-survival signaling of neuroprotectin D1,” and “non-alcoholic fatty liver disease.” The miRNAs and transcription factors implicated in memantine and donepezil protecting against mixed EDCs were hsa-miR-128-3p and hsa-miR-34a-5p, NFKB1, NFKB2, IRF8, and E2F4. The sponges’ tertiary structure predictions for two major miRNAs were provided. The physicochemical and pharmacokinetic properties of memantine and donepezil highlighted the need for a therapeutic combination of these medications to treat cognitive impairment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

The data supporting this study was obtained from the CTD (http://ctdbase.org/).

References

  • Albayrak G, Konac E, Dikmen AU, Bilen CY (2018) Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate cancer cells. Hum Exp Toxicol 37(9):953–958. https://doi.org/10.1177/0960327117747025

    Article  CAS  Google Scholar 

  • Alimoradzadeh R, Mirmiranpour H, Hashemi P, Pezeshki S, Salehi SS (2019) Effect of Memantine on Oxidative and Antioxidant Indexes Among Elderly Patients with Prediabetes and Mild Cognitive Impairment. J Neurol Neurophysiol 10(1):1–5

  • Atack JR, May C, Kaye JA, Kay AD, Rapoport SI (1988) Cerebrospinal fluid cholinesterases in aging and in dementia of the Alzheimer type. Ann Neurol 23(2):161–167. https://doi.org/10.1002/ana.410230209

    Article  CAS  Google Scholar 

  • Ataie A, Ataee R, Shadifar M, Shahabi S, Aghajanpour SM, Hosseinpour Y (2012) Interaction of memantine with homocysteine on the apoptosis in the rat hippocampus cells. Int J Mol Cell Med 1(3):145–152

    Google Scholar 

  • Bartha E, Szelényi J, Szilágyi K, Venter V, Thu Ha NT, Páldi-Haris P, Hollán S (1987) Altered lymphocyte acetylcholinesterase activity in patients with senile dementia. Neurosci Lett 79(1–2):190–194. https://doi.org/10.1016/0304-3940(87)90695-1

    Article  CAS  Google Scholar 

  • Bellanger M, Demeneix B, Grandjean P, Zoeller RT, Trasande L (2015) Neurobehavioral deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab 100(4):1256–1266. https://doi.org/10.1210/jc.2014-4323

    Article  CAS  Google Scholar 

  • Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, Arndt P, Ulzheimer JC, Sonders MS, Baumann C, Waldegger S, Lang F, Koepsell H (1998) Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. J Mole Pharmacol 54(2):342–352. https://doi.org/10.1124/mol.54.2.342

  • Cacabelos R (2007) Donepezil in Alzheimer’s disease: from conventional trials to pharmacogenetics. Neuropsychiatr Dis Treat 3(3):303–333

    CAS  Google Scholar 

  • Castro B, Sánchez P, Torres JM, Ortega E (2015) Bisphenol A, bisphenol F and bisphenol S affect differently 5α-reductase expression and dopamine-serotonin systems in the prefrontal cortex of juvenile female rats. Environ Res 142:281–287. https://doi.org/10.1016/j.envres.2015.07.001

    Article  CAS  Google Scholar 

  • Cosín-Tomás M, Antonell A, Lladó A, Alcolea D, Fortea J, Ezquerra M, Lleó A, Martí MJ, Pallàs M, Sanchez-Valle R, Molinuevo JL, Sanfeliu C, Kaliman P (2017) Plasma miR-34a-5p and miR-545-3p as early biomarkers of Alzheimer’s disease: potential and limitations. Mol Neurobiol 54(7):5550–5562. https://doi.org/10.1007/s12035-016-0088-8

    Article  CAS  Google Scholar 

  • Deng SN, Yan YH, Zhu T L, Ma BK, Fan HR, Liu YM, Li WG, Li F (2019) Long-term NMDAR antagonism correlates weight loss with less eating. 10. https://doi.org/10.3389/fpsyt.2019.00015

  • Duc HN, Oh H, Kim M-S (2021) The effect of mixture of heavy metals on obesity in individuals ≥50 years of age. Biol Trace Elem Res. https://doi.org/10.1007/s12011-021-02972-z

    Article  Google Scholar 

  • Duc Nguyen H, Hee Jo W, Hong Minh Hoang N, Kim MS (2022a) Anti-inflammatory effects of B vitamins protect against tau hyperphosphorylation and cognitive impairment induced by 1,2 diacetyl benzene: an in vitro and in silico study. Int Immunopharmacol 108:108736. https://doi.org/10.1016/j.intimp.2022a.108736

  • Duc Nguyen H, Oh H, Kim MS (2022b) Association between exposure to chemical mixtures in relation to serum total IgE among adults 19–86 years old. Int Immunopharmacol 102:108428. https://doi.org/10.1016/j.intimp.2021.108428

  • Gao X-R, Chen Z, Fang K, Xu J-X, Ge J-F (2021) Protective effect of quercetin against the metabolic dysfunction of glucose and lipids and its associated learning and memory impairments in NAFLD rats. Lipids Health Dis 20(1):164. https://doi.org/10.1186/s12944-021-01590-x

    Article  CAS  Google Scholar 

  • García-Ayllón M-S, Riba-Llena I, Serra-Basante C, Alom J, Boopathy R, Sáez-Valero J (2010) Altered levels of acetylcholinesterase in Alzheimer plasma. PLoS ONE 5(1):e8701. https://doi.org/10.1371/journal.pone.0008701

    Article  CAS  Google Scholar 

  • Getachew B, Hudson T, Heinbockel T, Csoka AB, Tizabi Y (2018) Protective effects of donepezil against alcohol-induced toxicity in cell culture: role of caspase-3. Neurotox Res 34(3):757–762. https://doi.org/10.1007/s12640-018-9913-3

    Article  CAS  Google Scholar 

  • Gomaa AA, Makboul RM, El-Mokhtar MA, Abdel-Rahman EA, Ahmed EA, Nicola MA (2021) Evaluation of the neuroprotective effect of donepezil in type 2 diabetic rats. Fundam Clin Pharmacol 35(1):97–112. https://doi.org/10.1111/fcp.12585

    Article  CAS  Google Scholar 

  • Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, Toppari J, Zoeller RT (2015) EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr Rev 36(6):E1–E150. https://doi.org/10.1210/er.2015-1010%JEndocrineReviews

    Article  CAS  Google Scholar 

  • Homma A, Takeda M, Imai Y, Udaka F, Hasegawa K, Kameyama M, Nishimura T (2000) Clinical efficacy and safety of donepezil on cognitive and global function in patients with Alzheimer's disease. A 24-week, multicenter, double-blind, placebo-controlled study in Japan. E2020 Study Group. Dement Geriatr Cogn Disord 11(6):299–313. https://doi.org/10.1159/000017259

  • Huang FM, Chang YC, Lee SS, Yang ML, Kuan YH (2019) Expression of pro-inflammatory cytokines and mediators induced by Bisphenol A via ERK-NFκB and JAK1/2-STAT3 pathways in macrophages. Environ Toxicol 34(4):486–494. https://doi.org/10.1002/tox.22702

  • Huang XT, Li C, Peng XP, Guo J, Yue SJ, Liu W, Zhao FY, Han JZ, Huang YH, Cheng QM (2017a) An excessive increase in glutamate contributes to glucose-toxicity in β-cells via activation of pancreatic NMDA receptors in rodent diabetes 7(1):1–14

  • Huang YC, Chang WC, Shan, YH, Lin CY, Wang CL, Dai CY, Ho CK, Wu MT, Chuang HY (2017b) Toxic metals increase serum tumor necrosis factor-α levels, modified by essential elements and different types of tumor necrosis factor-α promoter single-nucleotide polymorphisms. Epidemiol 28

  • Jones SV, Kounatidis I (2017) Nuclear factor-kappa B and Alzheimer disease, unifying genetic and environmental risk factors from cell to humans. Front Immunol 8:1805–1805. https://doi.org/10.3389/fimmu.2017.01805

    Article  CAS  Google Scholar 

  • Kabir MT, Uddin MS, Mamun AA, Jeandet P, Aleya L, Mansouri RA, Ashraf GM, Mathew B, Bin-Jumah MN, Abdel-Daim MM (2020) Combination Drug Therapy for the Management of Alzheimer’s Disease 21(9):3272

    CAS  Google Scholar 

  • Keenan AB, Torre D, Lachmann A, Leong AK, Wojciechowicz ML, Utti V, Jagodnik KM, Kropiwnicki E, Wang Z, Ma’ayan A (2019) ChEA3: transcription factor enrichment analysis by orthogonal omics integration. 47(W1):W212-W224

  • Kim H, Lee D, Kim K (2021a) Combined Exposure to Metals in Drinking Water Alters the Dopamine System in Mouse Striatum 18(12):6558

    CAS  Google Scholar 

  • Kim J, Lee HJ, Park SK, Park JH, Jeong HR, Lee S, Lee H, Seol E, Hoe HS (2021b) Donepezil regulates LPS and Aβ-stimulated neuroinflammation through MAPK/NLRP3 inflammasome/STAT3 signaling. Int J Mol Sci 22(19). https://doi.org/10.3390/ijms221910637

  • Kokras N, Stamouli E, Sotiropoulos I, Katirtzoglou EA, Siarkos KT, Dalagiorgou G, Alexandraki KI, Coulocheri S, Piperi C, Politis AM (2018) Acetyl cholinesterase inhibitors and cell-derived peripheral inflammatory cytokines in early stages of Alzheimer's disease. J Clin Psychopharmacol 38(2)

  • Korashy HM, El-Kadi AOS (2006) The role of aryl hydrocarbon receptor and the reactive oxygen species in the modulation of glutathione transferase by heavy metals in murine hepatoma cell lines. Chem Biol Interact 162(3):237–248. https://doi.org/10.1016/j.cbi.2006.07.002

  • Kornhuber J, Kennepohl EM, Bleich S, Wiltfang J, Kraus T, Reulbach U, Meineke I (2007) Memantine pharmacotherapy: a naturalistic study using a population pharmacokinetic approach. Clin Pharmacokinet 46(7):599–612. https://doi.org/10.2165/00003088-200746070-00005

    Article  CAS  Google Scholar 

  • Li Q, Zhang P, Yu X, Zhao Y, Li Q, Zhang Y, Yang Z, Xie Y, Xue P, Sun S, Jia X, Zhou Z, He M, Zhang Y (2017) Lead transiently promotes granulocyte-macrophage progenitor differentiation and subsequently suppresses common myeloid progenitor differentiation. Toxicol Sci 160(2):268–283. https://doi.org/10.1093/toxsci/kfx176%JToxicologicalSciences

    Article  CAS  Google Scholar 

  • Licursi V, Conte F, Fiscon G, Paci P (2019) MIENTURNET: an interactive web tool for microRNA-target enrichment and network-based analysis. BMC Bioinformatics 20(1):545. https://doi.org/10.1186/s12859-019-3105-x

    Article  Google Scholar 

  • Linhartova P, Sampels S (2015) Combined incubation of cadmium, docosahexaenoic and eicosapentaenoic acid results in increased uptake of cadmium and elevated docosapentaenoic acid content in hepatocytes in vitro. Lipids Health Dis 14:156–156. https://doi.org/10.1186/s12944-015-0159-2

    Article  Google Scholar 

  • Lukiw WJ, Cui J-G, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG (2005) A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Investig 115(10):2774–2783. https://doi.org/10.1172/JCI25420

    Article  CAS  Google Scholar 

  • Maćczak A, Duchnowicz P, Sicińska P, Koter-Michalak M, Bukowska B, Michałowicz J (2017) The in vitro comparative study of the effect of BPA, BPS, BPF and BPAF on human erythrocyte membrane; perturbations in membrane fluidity, alterations in conformational state and damage to proteins, changes in ATP level and Na+/K+ ATPase and AChE activities. Food Chem Toxicol 110:351–359. https://doi.org/10.1016/j.fct.2017.10.028

  • Malaisé Y, Le Mentec H, Sparfel L, Guzylack-Piriou L (2020) Differential influences of the BPA, BPS and BPF on in vitro IL-17 secretion by mouse and human T cells. Toxicol In Vitro 69:104993. https://doi.org/10.1016/j.tiv.2020.104993

  • Mao G, Zhou Z, Chen Y, Wang W, Wu X, Feng W, Cobbina SJ, Huang J, Zhang Z, Xu H, Yang L, Wu X (2016) Neurological toxicity of individual and mixtures of low dose arsenic, mono and di (n-butyl) phthalates on sub-chronic exposure to mice. Biol Trace Elem Res 170(1):183–193. https://doi.org/10.1007/s12011-015-0457-6

    Article  CAS  Google Scholar 

  • Matsui K, Mishima M, Nagai Y, Yuzuriha T, Yoshimura T (1999) Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to rat. Drug Metab Dispos 27(12):1406–1414

    CAS  Google Scholar 

  • McGeer EG, McGeer PL (2010) Neuroinflammation in Alzheimer’s disease and mild cognitive impairment: a field in its infancy. J Alzheimers Dis 19(1):355–361. https://doi.org/10.3233/jad-2010-1219

    Article  Google Scholar 

  • Mezeiova E, Spilovska K, Nepovimova E, Gorecki L, Soukup O, Dolezal R, Malinak D, Janockova J, Jun D, Kuca K, Korabecny J (2018) Profiling donepezil template into multipotent hybrids with antioxidant properties. J Enzyme Inhib Med Chem 33(1):583–606. https://doi.org/10.1080/14756366.2018.1443326

    Article  CAS  Google Scholar 

  • Moriguchi S, Ishizuka T, Yabuki Y, Shioda N, Sasaki Y, Tagashira H, Yawo H, Yeh J, Sakagami H, Narahashi TJM (2018) Blockade of the KATP channel Kir6. 2 by memantine represents a novel mechanism relevant to Alzheimer’s disease therapy. 23(2):211–221

  • Muiño E, Maisterra O, Jiménez-Balado J, Cullell N, Carrera C, Torres-Aguila NP, Cárcel-Márquez J, Gallego-Fabrega C, Lledós M, González-Sánchez J, Olmos-Alpiste F, Espejo E, March Á, Pujol R, Rodríguez-Campello A, Romeral G, Krupinski J, Martí-Fàbregas J, Montaner J, Roquer J, Fernández-Cadenas I (2021) Genome-wide transcriptome study in skin biopsies reveals an association of E2F4 with cadasil and cognitive impairment. Sci Rep 11(1):6846–6846. https://doi.org/10.1038/s41598-021-86349-1

    Article  CAS  Google Scholar 

  • Myhrer T (2003) Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res Rev 41(2):268–287. https://doi.org/10.1016/S0165-0173(02)00268-0

  • Nguyen HD, Kim MS (2022) Exposure to a mixture of heavy metals induces cognitive impairment: genes and microRNAs involved. Toxicol 153164. https://doi.org/10.1016/j.tox.2022.153164

  • Nguyen HD, Kim MS (2021) Effects of heavy metal, vitamin, and curry consumption on metabolic syndrome during menopause: a Korean community-based cross-sectional study. J Menopause 28

  • Nguyen HD, Oh H, Hoang NHM, Kim M-S (2021a) Association between heavy metals, high-sensitivity C-reaction protein and 10-year risk of cardiovascular diseases among adult Korean population. Sci Rep 11(1):14664. https://doi.org/10.1038/s41598-021-94158-9

    Article  CAS  Google Scholar 

  • Nguyen HD, Oh H, Jo WH, Hoang NHM, Kim MS (2021b) Mixtures modeling identifies heavy metals and pyrethroid insecticide metabolites associated with obesity. Environ Sci Pollut Res Int. https://doi.org/10.1007/s11356-021-16936-2

    Article  Google Scholar 

  • Nguyen HD, Oh H, Kim M-S (2022) The effects of chemical mixtures on lipid profiles in the Korean adult population: threshold and molecular mechanisms for dyslipidemia involved. Environ Sci Pollut Res. https://doi.org/10.1007/s11356-022-18871-2

    Article  Google Scholar 

  • Nguyen HD, Oh H, Kim MS (2021c) Effects of heavy metals on hypertension during menopause: a Korean community-based cross-sectional study. Menopause. https://doi.org/10.1097/gme.0000000000001865

    Article  Google Scholar 

  • Pais R, Ruano L, Carvalho P, O., Barros, H. (2020) Global cognitive impairment prevalence and incidence in community dwelling older adults—a systematic review. Geriatrics (basel, Switzerland) 5(4):84. https://doi.org/10.3390/geriatrics5040084

    Article  Google Scholar 

  • Qian C, Yang C, Lu M, Bao J, Shen H, Deng B, Li S, Li W, Zhang M, Cao C (2021) Activating AhR alleviates cognitive deficits of Alzheimer’s disease model mice by upregulating endogenous Aβ catabolic enzyme Neprilysin. Theranostics 11(18):8797–8812. https://doi.org/10.7150/thno.61601

    Article  CAS  Google Scholar 

  • Qiu W, Yang M, Liu S, Lei P, Hu L, Chen B, Wu M, Wang KJ (2018) Toxic effects of bisphenol S showing immunomodulation in fish macrophages. Environ Sci Technol 52(2):831–838. https://doi.org/10.1021/acs.est.7b04226

    Article  CAS  Google Scholar 

  • Richetti SK, Rosemberg DB, Ventura-Lima J, Monserrat JM, Bogo MR, Bonan CD (2011) Acetylcholinesterase activity and antioxidant capacity of zebrafish brain is altered by heavy metal exposure. Neurotoxicol 32(1):116–122. https://doi.org/10.1016/j.neuro.2010.11.001

  • Riedel G, Platt B, Micheau J (2003) Glutamate receptor function in learning and memory. Behav Brain Res 140(1–2):1–47. https://doi.org/10.1016/s0166-4328(02)00272-3

    Article  CAS  Google Scholar 

  • Rogers SL, Friedhoff LT (1998) Pharmacokinetic and pharmacodynamic profile of donepezil HCl following single oral doses. Br J Clin Pharmacol 46 Suppl 1(Suppl 1):1–6. https://doi.org/10.1046/j.1365-2125.1998.0460s1001.x

  • Selznick LA, Zheng TS, Flavell RA, Rakic P, Roth KA (2000) Amyloid beta-induced neuronal death is Bax-dependent but caspase-independent. J Neuropathol Exp Neurol 59(4):271–279. https://doi.org/10.1093/jnen/59.4.271%JJournalofNeuropathology&ExperimentalNeurology

    Article  CAS  Google Scholar 

  • Shati AA, El-Kott AF (2021) Resolvin D1 protects against cadmium chloride-induced memory loss and hippocampal damage in rats: a comparison with docosahexaenoic acid. Hum Exp Toxicol 40(12_suppl):S215-S232. https://doi.org/10.1177/09603271211038739

  • Smith RC, Ho BT, Hsu L, Vroulis G, Claghorn J, Schoolar J (1982) Cholinesterase enzymes in the blood of patients with Alzheimer's disease. Life Sci 30(6):543–546. https://doi.org/10.1016/0024-3205(82)90267-3

  • Tavakoli-Ardakani M, Abbaspour H, Farhadi Nasab A, Mazaheri Meibodi A, Kheradmand A (2018) Study of the effect of memantine on negative sign in patients with schizophrenia and schizoaffective disorders. Iran J Pharm Res 17(Suppl):122–129

    CAS  Google Scholar 

  • Tiseo PJ, Foley K, Friedhoff LT (1998a) An evaluation of the pharmacokinetics of donepezil HCl in patients with moderately to severely impaired renal function. Br J Clin Pharmacol 46 Suppl 1(Suppl 1):56–60. https://doi.org/10.1046/j.1365-2125.1998a.0460s1056.x

  • Tiseo PJ, Perdomo CA, Friedhoff LT (1998b) Metabolism and elimination of 14C-donepezil in healthy volunteers: a single-dose study. Br J Clin Pharmacol 46 Suppl 1(Suppl 1):19–24. https://doi.org/10.1046/j.1365-2125.1998b.0460s1019.x

  • Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. 31(2):455–461

  • Wang C, He J, Xu T, Han H, Zhu Z, Meng L, Pang Q, Fan R (2021) Bisphenol A (BPA), BPS and BPB-induced oxidative stress and apoptosis mediated by mitochondria in human neuroblastoma cell lines. Ecotoxicol Environ Saf 207:111299. https://doi.org/10.1016/j.ecoenv.2020.111299

  • Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, Maitland A, Mostafavi S, Montojo J, Shao Q, Wright G, Bader GD, Morris Q (2010) The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 38(suppl_2):W214-W220. https://doi.org/10.1093/nar/gkq537

  • Xu Z, Liu J, Wu X, Huang B, Pan X (2017) Nonmonotonic responses to low doses of xenoestrogens: a review. Environ Res 155:199–207. https://doi.org/10.1016/j.envres.2017.02.018

  • Yick L-W, Tang C-H, Ma OK-F, Kwan JS-C, Chan K-H (2020) Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders. J Neuroinflammation 17(1):236. https://doi.org/10.1186/s12974-020-01913-2

    Article  CAS  Google Scholar 

  • Zeng Q, Man R, Luo Y, Zeng L, Zhong Y, Lu B, Wang X (2017) IRF-8 is involved in amyloid-β1–40 (Aβ1–40)-induced microglial activation: a new implication in Alzheimer’s disease. J Mol Neurosci 63(2):159–164. https://doi.org/10.1007/s12031-017-0966-1

    Article  CAS  Google Scholar 

  • Zhang M, Han W, Xu Y, Li D, Xue Q (2021) Serum miR-128 serves as a potential diagnostic biomarker for Alzheimer’s disease. Neuropsychiatr Dis Treat 17:269–275. https://doi.org/10.2147/NDT.S290925

    Article  Google Scholar 

  • Zhang T, Tian F, Wang J, Zhou S, Dong X, Guo K, Jing J, Zhou Y, Chen Y (2015) Donepezil attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells through SIRT1 activation. Cell Stress Chaperones 20(5):787–792. https://doi.org/10.1007/s12192-015-0601-4

    Article  CAS  Google Scholar 

  • Zubieta JK, Huguelet P, Ohl LE, Koeppe RA, Kilbourn MR, Carr JM, Giordani BJ, Frey KA (2000) High vesicular monoamine transporter binding in asymptomatic bipolar I disorder: sex differences and cognitive correlates. Am J Psychiatry 157(10):1619–1628. https://doi.org/10.1176/appi.ajp.157.10.1619

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon, 57922, Republic of Korea

    Hai Duc Nguyen

Authors
  1. Hai Duc Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HDN: conceptualization, data collection, data analysis and interpretations, methodology, resources, writing—original draft, and critical revision of the manuscript.

Corresponding author

Correspondence to Hai Duc Nguyen.

Ethics declarations

Ethics approval

The manuscript does not involve any animal or human study.

Conflict of interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 249 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nguyen, H.D. Combination of Donepezil and Memantine Attenuated Cognitive Impairment Induced by Mixed Endocrine-Disrupting Chemicals: an In Silico Study. Neurotox Res 40, 2072–2088 (2022). https://doi.org/10.1007/s12640-022-00591-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-022-00591-7

Keywords

Search

Navigation