{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:35:51Z","timestamp":1793093751452,"version":"4.5.0"},"reference-count":142,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan","id":[{"id":"https:\/\/ror.org\/03w2j5y17","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Trace Elem Res"],"DOI":"10.1007\/s12011-026-05296-y","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:11:36Z","timestamp":1786630296000},"page":"8731-8757","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effects of Metformin and Memantine Against Arsenic-Induced Neurotoxicity: Insights from In-Silico and In-Vivo Studies"],"prefix":"10.1007","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0872-8251","authenticated-orcid":false,"given":"Noor Ul Huda","family":"Khola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8269-707X","authenticated-orcid":false,"given":"Mahnoor","family":"Hayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imtisal","family":"Muzaffar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-8169","authenticated-orcid":false,"given":"Touqeer","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"5296_CR1","doi-asserted-by":"publisher","first-page":"100052","DOI":"10.1016\/j.hazadv.2022.100052","volume":"5","author":"JO Fatoki","year":"2022","unstructured":"Fatoki JO, Badmus JA (2022) Arsenic as an environmental and human health antagonist: A review of its toxicity and disease initiation. J Hazard Mater Adv 5:100052. https:\/\/doi.org\/10.1016\/j.hazadv.2022.100052","journal-title":"J Hazard Mater Adv"},{"key":"5296_CR2","doi-asserted-by":"publisher","unstructured":"Mochizuki H (2019) Arsenic neurotoxicity in humans. Int J Mol Sci 20. https:\/\/doi.org\/10.3390\/IJMS20143418","DOI":"10.3390\/IJMS20143418"},{"key":"5296_CR3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1146\/annurev-pharmtox-030220-013418","volume":"61","author":"QY Chen","year":"2021","unstructured":"Chen QY, Costa M (2021) Arsenic: a global environmental challenge. Annu Rev Pharmacol Toxicol 61:47\u201363","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"5296_CR4","doi-asserted-by":"publisher","first-page":"101079","DOI":"10.1016\/j.gsf.2020.08.015","volume":"12","author":"E Shaji","year":"2021","unstructured":"Shaji E, Santosh M, Sarath KV et al (2021) Arsenic contamination of groundwater: A global synopsis with focus on the Indian Peninsula. Geosci Front 12:101079","journal-title":"Geosci Front"},{"key":"5296_CR5","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3961\/jpmph.14.036","volume":"47","author":"J-Y Chung","year":"2014","unstructured":"Chung J-Y, Yu S-D, Hong Y-S (2014) Environmental source of arsenic exposure. J Prev Med public Heal 47:253","journal-title":"J Prev Med public Heal"},{"key":"5296_CR6","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/jox15020047","volume":"15","author":"G Ahmed","year":"2025","unstructured":"Ahmed G, Rahaman MS, Perez E, Khan KM (2025) Associations of Environmental Exposure to Arsenic, Manganese, Lead, and Cadmium with Alzheimer\u2019s Disease: A Review of Recent Evidence from Mechanistic Studies. J Xenobiotics 15:47","journal-title":"J Xenobiotics"},{"key":"5296_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.parkreldis.2021.05.029","volume":"88","author":"C-P Lee","year":"2021","unstructured":"Lee C-P, Zhu C-H, Su C-C (2021) Increased prevalence of Parkinson\u2019s disease in soils with high arsenic levels. Parkinsonism Relat Disord 88:19\u201323","journal-title":"Parkinsonism Relat Disord"},{"key":"5296_CR8","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1007\/S40011-021-01272-9\/FIGURES\/6","volume":"91","author":"N Singh","year":"2021","unstructured":"Singh N, Sharma B (2021) On the Mechanisms of Heavy Metal-Induced Neurotoxicity: Amelioration by Plant Products. Proc Natl Acad Sci India Sect B - Biol Sci 91:743\u2013751. https:\/\/doi.org\/10.1007\/S40011-021-01272-9\/FIGURES\/6","journal-title":"Proc Natl Acad Sci India Sect B - Biol Sci"},{"key":"5296_CR9","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1289\/ehp.1002086","volume":"119","author":"S Ahmed","year":"2011","unstructured":"Ahmed S, Khoda SM, Rekha RS et al (2011) Arsenic-associated oxidative stress, inflammation, and immune disruption in human placenta and cord blood. Environ Health Perspect 119:258\u2013264","journal-title":"Environ Health Perspect"},{"key":"5296_CR10","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1093\/toxsci\/kfm162","volume":"99","author":"W He","year":"2007","unstructured":"He W, Greenwell RJ, Brooks DM et al (2007) Arsenic exposure in pregnant mice disrupts placental vasculogenesis and causes spontaneous abortion. Toxicol Sci 99:244\u2013253","journal-title":"Toxicol Sci"},{"key":"5296_CR11","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1146\/annurev-nutr-080508-141102","volume":"29","author":"M Vahter","year":"2009","unstructured":"Vahter M (2009) Effects of arsenic on maternal and fetal health. Annu Rev Nutr 29:381\u2013399","journal-title":"Annu Rev Nutr"},{"key":"5296_CR12","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.scitotenv.2013.03.047","volume":"454","author":"M Rodr\u00edguez-Barranco","year":"2013","unstructured":"Rodr\u00edguez-Barranco M, Lacasa\u00f1a M, Aguilar-Gardu\u00f1o C et al (2013) Association of arsenic, cadmium and manganese exposure with neurodevelopment and behavioural disorders in children: a systematic review and meta-analysis. Sci Total Environ 454:562\u2013577","journal-title":"Sci Total Environ"},{"key":"5296_CR13","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s40572-014-0012-1","volume":"1","author":"CR Tyler","year":"2014","unstructured":"Tyler CR, Allan AM (2014) The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in Human and Rodent Studies: A Review. Curr Environ Heal Rep 1:132\u2013147","journal-title":"Curr Environ Heal Rep"},{"key":"5296_CR14","doi-asserted-by":"publisher","unstructured":"Thakur M, Rachamalla M, Niyogi S et al (2021) Molecular mechanism of arsenic-induced neurotoxicity including neuronal dysfunctions. Int J Mol Sci 22. https:\/\/doi.org\/10.3390\/ijms221810077","DOI":"10.3390\/ijms221810077"},{"key":"5296_CR15","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.envres.2010.01.007","volume":"110","author":"LC S\u00e1nchez-Pe\u00f1a","year":"2010","unstructured":"S\u00e1nchez-Pe\u00f1a LC, Petrosyan P, Morales M et al (2010) Arsenic species, AS3MT amount, and AS3MT gen expression in different brain regions of mouse exposed to arsenite. Environ Res 110:428\u2013434","journal-title":"Environ Res"},{"key":"5296_CR16","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.envpol.2017.11.083","volume":"234","author":"X Du","year":"2018","unstructured":"Du X, Tian M, Wang X et al (2018) Cortex and hippocampus DNA epigenetic response to a long-term arsenic exposure via drinking water. Environ Pollut 234:590\u2013600. https:\/\/doi.org\/10.1016\/j.envpol.2017.11.083","journal-title":"Environ Pollut"},{"key":"5296_CR17","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/S12011-020-02044-8","volume":"198","author":"N Medda","year":"2020","unstructured":"Medda N, Patra R, Ghosh TK, Maiti S (2020) Neurotoxic Mechanism of Arsenic: Synergistic Effect of Mitochondrial Instability, Oxidative Stress, and Hormonal-Neurotransmitter Impairment. Biol Trace Elem Res 198:8\u201315. https:\/\/doi.org\/10.1007\/S12011-020-02044-8","journal-title":"Biol Trace Elem Res"},{"key":"5296_CR18","doi-asserted-by":"publisher","first-page":"103804","DOI":"10.1016\/j.fbio.2024.103804","volume":"59","author":"Z Huang","year":"2024","unstructured":"Huang Z, Guo L, Huang J et al (2024) Neurotoxicity and brain metabolic dysfunction induced by long-term food-derived arsenic exposure. Food Biosci 59:103804. https:\/\/doi.org\/10.1016\/j.fbio.2024.103804","journal-title":"Food Biosci"},{"key":"5296_CR19","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1007\/S00775-019-01740-8","volume":"248 24","author":"C Garza-Lomb\u00f3","year":"2019","unstructured":"Garza-Lomb\u00f3 C, Pappa A, Panayiotidis MI et al (2019) Arsenic-induced neurotoxicity: a mechanistic appraisal. JBIC J Biol Inorg Chem 2019 248 24:1305\u20131316. https:\/\/doi.org\/10.1007\/S00775-019-01740-8","journal-title":"JBIC J Biol Inorg Chem 2019"},{"key":"5296_CR20","doi-asserted-by":"publisher","DOI":"10.2174\/0109298673315956240829094938","author":"A Choudhary","year":"2024","unstructured":"Choudhary A, Pandey R, Padhy D et al (2024) Changes in Energy Dynamics in Arsenic Exposure Based Neurotoxicity: A Comprehensive Review. Curr Med Chem. https:\/\/doi.org\/10.2174\/0109298673315956240829094938","journal-title":"Curr Med Chem"},{"key":"5296_CR21","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1007\/s12035-014-8753-2","volume":"51","author":"T Huo","year":"2015","unstructured":"Huo T, Li W, Zhang Y et al (2015) Excitotoxicity induced by realgar in the rat hippocampus: the involvement of learning memory injury, dysfunction of glutamate metabolism and NMDA receptors. Mol Neurobiol 51:980\u2013994","journal-title":"Mol Neurobiol"},{"key":"5296_CR22","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3389\/fncel.2015.00021","volume":"9","author":"LA Ramos-Ch\u00e1vez","year":"2015","unstructured":"Ramos-Ch\u00e1vez LA, Rend\u00f3n-L\u00f3pez CRR, Zepeda A et al (2015) Neurological effects of inorganic arsenic exposure: altered cysteine\/glutamate transport, NMDA expression and spatial memory impairment. Front Cell Neurosci 9:21","journal-title":"Front Cell Neurosci"},{"key":"5296_CR23","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1007\/s00204-017-2111-x","volume":"92","author":"J Nelson-Mora","year":"2018","unstructured":"Nelson-Mora J, Escobar ML, Rodr\u00edguez-Dur\u00e1n L et al (2018) Gestational exposure to inorganic arsenic (iAs3+) alters glutamate disposition in the mouse hippocampus and ionotropic glutamate receptor expression leading to memory impairment. Arch Toxicol 92:1037\u20131048","journal-title":"Arch Toxicol"},{"key":"5296_CR24","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.etap.2015.09.016","volume":"40","author":"KSM Abdul","year":"2015","unstructured":"Abdul KSM, Jayasinghe SS, Chandana EPS et al (2015) Arsenic and human health effects: A review. Environ Toxicol Pharmacol 40:828\u2013846","journal-title":"Environ Toxicol Pharmacol"},{"key":"5296_CR25","doi-asserted-by":"publisher","first-page":"3787","DOI":"10.1007\/S00204-017-2100-0","volume":"91","author":"G Bj\u00f8rklund","year":"2017","unstructured":"Bj\u00f8rklund G, Mutter J, Aaseth J (2017) Metal chelators and neurotoxicity: lead, mercury, and arsenic. Arch Toxicol 91:3787\u20133797. https:\/\/doi.org\/10.1007\/S00204-017-2100-0","journal-title":"Arch Toxicol"},{"key":"5296_CR26","doi-asserted-by":"publisher","first-page":"113691","DOI":"10.1016\/J.FCT.2023.113691","volume":"175","author":"M Shayan","year":"2023","unstructured":"Shayan M, Barangi S, Hosseinzadeh H, Mehri S (2023) The protective effect of natural or chemical compounds against arsenic-induced neurotoxicity: Cellular and molecular mechanisms. Food Chem Toxicol 175:113691. https:\/\/doi.org\/10.1016\/J.FCT.2023.113691","journal-title":"Food Chem Toxicol"},{"key":"5296_CR27","doi-asserted-by":"crossref","unstructured":"Nosengo N (2016) Can you teach old drugs new tricks?","DOI":"10.1038\/534314a"},{"key":"5296_CR28","doi-asserted-by":"publisher","first-page":"66","DOI":"10.18231\/j.jpbs.2023.011","volume":"11","author":"S Khan","year":"2023","unstructured":"Khan S, Agnihotri J, Patil S, Khan N (2023) Drug repurposing: A futuristic approach in drug discovery. J Pharm Biol Sci 11:66\u201369","journal-title":"J Pharm Biol Sci"},{"key":"5296_CR29","doi-asserted-by":"publisher","first-page":"838173","DOI":"10.3389\/fnagi.2022.838173","volume":"14","author":"M-R Du","year":"2022","unstructured":"Du M-R, Gao Q-Y, Liu C-L et al (2022) Exploring the pharmacological potential of metformin for neurodegenerative diseases. Front Aging Neurosci 14:838173","journal-title":"Front Aging Neurosci"},{"key":"5296_CR30","doi-asserted-by":"publisher","unstructured":"Taheri M, Roghani M, Sedaghat R (2024) Metformin mitigates trimethyltin-induced cognition impairment and hippocampal neurodegeneration. Cell Mol Neurobiol 44. https:\/\/doi.org\/10.1007\/S10571-024-01502-4","DOI":"10.1007\/S10571-024-01502-4"},{"key":"5296_CR31","doi-asserted-by":"publisher","first-page":"e17873","DOI":"10.1016\/j.heliyon.2023.e17873","volume":"9","author":"S Rabieipoor","year":"2023","unstructured":"Rabieipoor S, Zare M, Ettcheto M et al (2023) Metformin restores cognitive dysfunction and histopathological deficits in an animal model of sporadic Alzheimer\u2019s disease. Heliyon 9:e17873. https:\/\/doi.org\/10.1016\/j.heliyon.2023.e17873","journal-title":"Heliyon"},{"key":"5296_CR32","doi-asserted-by":"publisher","unstructured":"Campbell JM, Stephenson MD, de Courten B, et al (2018) Metformin use associated with reduced risk of dementia in patients with diabetes: A systematic review and meta-analysis. J Alzheimers Dis 65 (4):1225\u20131236. https:\/\/doi.org\/10.3233\/JAD-180263","DOI":"10.3233\/JAD-180263"},{"key":"5296_CR33","doi-asserted-by":"crossref","unstructured":"Hashemi M, Roohi-Azizi M, Hashemi F (2022) Anti-apoptotic effect of memantine in a rat hippocampal cell model of Alzheimer\u2019s disease. morphology and cellular mechanism","DOI":"10.21203\/rs.3.rs-1693554\/v1"},{"key":"5296_CR34","doi-asserted-by":"publisher","first-page":"465","DOI":"10.2165\/00002512-200320060-00005","volume":"20","author":"B Jarvis","year":"2003","unstructured":"Jarvis B, Figgitt DP (2003) Memantine Drugs Aging 20:465\u2013476","journal-title":"Memantine Drugs Aging"},{"key":"5296_CR35","doi-asserted-by":"publisher","first-page":"55","DOI":"10.2174\/157015908783769671","volume":"6","author":"CG Parsons","year":"2008","unstructured":"Parsons CG, Rammes G, Danysz W (2008) Pharmacodynamics of Memantine: An Update. Curr Neuropharmacol 6:55\u201378. https:\/\/doi.org\/10.2174\/157015908783769671","journal-title":"Curr Neuropharmacol"},{"key":"5296_CR36","doi-asserted-by":"publisher","first-page":"5034","DOI":"10.1007\/s12035-016-0020-2","volume":"54","author":"W Liu","year":"2017","unstructured":"Liu W, Xu Z, Yang T et al (2017) Memantine, a Low-Affinity NMDA Receptor Antagonist, Protects against Methylmercury-Induced Cytotoxicity of Rat Primary Cultured Cortical Neurons, Involvement of Ca(2+) Dyshomeostasis Antagonism, and Indirect Antioxidation Effects. Mol Neurobiol 54:5034\u20135050. https:\/\/doi.org\/10.1007\/s12035-016-0020-2","journal-title":"Mol Neurobiol"},{"key":"5296_CR37","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/j.1527-3458.2003.tb00254.x","volume":"9","author":"MA Rogawski","year":"2003","unstructured":"Rogawski MA, Wenk GL (2003) The neuropharmacological basis for the use of memantine in the treatment of Alzheimer\u2019s disease. CNS Drug Rev 9:275\u2013308","journal-title":"CNS Drug Rev"},{"key":"5296_CR38","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.2165\/00003495-200666110-00015","volume":"66","author":"DM Robinson","year":"2006","unstructured":"Robinson DM, Keating GM (2006) Memantine: a review of its use in Alzheimer\u2019s disease. Drugs 66:1515\u20131534","journal-title":"Drugs"},{"key":"5296_CR39","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1002\/ibra.12098","volume":"9","author":"B Tang","year":"2023","unstructured":"Tang B, Wang Y, Ren J (2023) Basic information about memantine and its treatment of Alzheimer\u2019s disease and other clinical applications. Ibrain 9:340\u2013348","journal-title":"Ibrain"},{"key":"5296_CR40","doi-asserted-by":"publisher","first-page":"6688","DOI":"10.1080\/21655979.2022.2026553","volume":"13","author":"Y Wang","year":"2022","unstructured":"Wang Y, Jiang B, Luo W (2022) Memantine ameliorates oxaliplatin-induced neurotoxicity via mitochondrial protection. Bioengineered 13:6688\u20136697","journal-title":"Bioengineered"},{"key":"5296_CR41","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s12974-024-03072-0","volume":"21","author":"M Wang","year":"2024","unstructured":"Wang M, Tian T, Zhou H et al (2024) Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson\u2019s disease through Mfn2-cGAS signaling. J Neuroinflammation 21:81. https:\/\/doi.org\/10.1186\/s12974-024-03072-0","journal-title":"J Neuroinflammation"},{"key":"5296_CR42","unstructured":"Nih O, Oer O (2011) Guide laboratory animals for the care and use of Eighth Edition Committee for the Update of the Guide for the Care and Use of Laboratory Animals Institute for Laboratory Animal Research Division on Earth and Life Studies"},{"key":"5296_CR43","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1093\/ilar.43.4.244","volume":"43","author":"MFW Festing","year":"2002","unstructured":"Festing MFW, Altman DG (2002) Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR J 43:244\u2013258. https:\/\/doi.org\/10.1093\/ilar.43.4.244","journal-title":"ILAR J"},{"key":"5296_CR44","doi-asserted-by":"publisher","unstructured":"OECD (2025) Test 407: Repeated dose 28-day oral toxicity study in rodents. OECD Guidel Test Chem Sect 4. https:\/\/doi.org\/10.1787\/9789264070684-EN","DOI":"10.1787\/9789264070684-EN"},{"key":"5296_CR45","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1111\/j.1476-5381.2010.00873.x","volume":"160","author":"JC McGrath","year":"2010","unstructured":"McGrath JC, Drummond GB, McLachlan EM et al (2010) Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160:1573\u20131576","journal-title":"Br J Pharmacol"},{"key":"5296_CR46","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.neuro.2019.02.004","volume":"72","author":"S Keshavarzi","year":"2019","unstructured":"Keshavarzi S, Kermanshahi S, Karami L et al (2019) Protective role of metformin against methamphetamine induced anxiety, depression, cognition impairment and neurodegeneration in rat: The role of CREB\/BDNF and Akt\/GSK3 signaling pathways. Neurotoxicology 72:74\u201384. https:\/\/doi.org\/10.1016\/j.neuro.2019.02.004","journal-title":"Neurotoxicology"},{"key":"5296_CR47","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.bbr.2011.06.031","volume":"225","author":"RA Abdel-Aal","year":"2011","unstructured":"Abdel-Aal RA, Assi A-AA, Kostandy BB (2011) Memantine prevents aluminum-induced cognitive deficit in rats. Behav Brain Res 225:31\u201338","journal-title":"Behav Brain Res"},{"key":"5296_CR48","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.taap.2009.07.017","volume":"240","author":"RS Yadav","year":"2009","unstructured":"Yadav RS, Sankhwar ML, Shukla RK et al (2009) Attenuation of arsenic neurotoxicity by curcumin in rats. Toxicol Appl Pharmacol 240:367\u2013376. https:\/\/doi.org\/10.1016\/j.taap.2009.07.017","journal-title":"Toxicol Appl Pharmacol"},{"key":"5296_CR49","doi-asserted-by":"publisher","first-page":"125","DOI":"10.2174\/1871527321666220225112241","volume":"22","author":"MK Arora","year":"2022","unstructured":"Arora MK, Singh D, Tomar R, Jangra A (2022) Neuroprotective Efficacy of Edaravone against Arsenic-Induced Behavioral and Neurochemical Deficits in Rats: Amelioration of Cholinergic and Mitochondrial Functions. CNS Neurol Disord - Drug Targets 22:125\u2013136. https:\/\/doi.org\/10.2174\/1871527321666220225112241","journal-title":"CNS Neurol Disord - Drug Targets"},{"key":"5296_CR50","unstructured":"Agency for Toxic Substances and Disease Registry - ATSDR (EUA) (2016) Addendum to the toxicological profile for arsenic. Division of toxicology and human health sciences. Agency Toxic Subst Dis Regist 7"},{"key":"5296_CR51","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.neuro.2011.07.004","volume":"32","author":"RS Yadav","year":"2011","unstructured":"Yadav RS, Chandravanshi LP, Shukla RK et al (2011) Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats. Neurotoxicology 32:760\u2013768. https:\/\/doi.org\/10.1016\/j.neuro.2011.07.004","journal-title":"Neurotoxicology"},{"key":"5296_CR52","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.neuro.2010.05.001","volume":"31","author":"RS Yadav","year":"2010","unstructured":"Yadav RS, Shukla RK, Sankhwar ML et al (2010) Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats. Neurotoxicology 31:533\u2013539","journal-title":"Neurotoxicology"},{"key":"5296_CR53","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/s0361-9230(01)00477-4","volume":"55","author":"VM Rodr\u00edguez","year":"2001","unstructured":"Rodr\u00edguez VM, Carrizales L, Jim\u00e9nez-Capdeville ME et al (2001) The effects of sodium arsenite exposure on behavioral parameters in the rat. Brain Res Bull 55:301\u2013308. https:\/\/doi.org\/10.1016\/s0361-9230(01)00477-4","journal-title":"Brain Res Bull"},{"key":"5296_CR54","doi-asserted-by":"publisher","first-page":"e2312810","DOI":"10.1001\/jamanetworkopen.2023.12810","volume":"6","author":"N Vaidya","year":"2023","unstructured":"Vaidya N, Holla B, Heron J et al (2023) Neurocognitive analysis of low-level arsenic exposure and executive function mediated by brain anomalies among children, adolescents, and young adults in India. JAMA Netw Open 6:e2312810\u2013e2312810","journal-title":"JAMA Netw Open"},{"key":"5296_CR55","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1289\/ehp.6964","volume":"112","author":"GA Wasserman","year":"2004","unstructured":"Wasserman GA, Liu X, Parvez F et al (2004) Water arsenic exposure and children\u2019s intellectual function in Araihazar, Bangladesh. Environ Health Perspect 112:1329\u20131333. https:\/\/doi.org\/10.1289\/ehp.6964","journal-title":"Environ Health Perspect"},{"key":"5296_CR56","doi-asserted-by":"publisher","unstructured":"Pilipenko V, Narbute K, Pupure J et al (2020) Neuroprotective potential of antihyperglycemic drug metformin in streptozocin-induced rat model of sporadic Alzheimer\u2019s disease. Eur J Pharmacol 881. https:\/\/doi.org\/10.1016\/j.ejphar.2020.173290","DOI":"10.1016\/j.ejphar.2020.173290"},{"key":"5296_CR57","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s12640-025-00771-1","volume":"43","author":"AFK Vizuete","year":"2025","unstructured":"Vizuete AFK, Moreira AP, Zin LEF et al (2025) Neuroprotective Roles of Metformin in a Streptozotocin-Induced Dementia Model in Rats. Neurotox Res 43:48","journal-title":"Neurotox Res"},{"key":"5296_CR58","doi-asserted-by":"publisher","first-page":"946879","DOI":"10.3389\/fnins.2022.946879","volume":"16","author":"L-Y Zhou","year":"2022","unstructured":"Zhou L-Y, Chen X-Q, Yu B-B et al (2022) The effect of metformin on ameliorating neurological function deficits and tissue damage in rats following spinal cord injury: A systematic review and network meta-analysis. Front Neurosci 16:946879. https:\/\/doi.org\/10.3389\/fnins.2022.946879","journal-title":"Front Neurosci"},{"key":"5296_CR59","first-page":"245","volume":"37","author":"EE Abrahamson","year":"2019","unstructured":"Abrahamson EE, Poloyac SM, Dixon CE et al (2019) Acute and chronic effects of single dose memantine after controlled cortical impact injury in adult rats. Restor Neurol Neurosci 37:245\u2013263","journal-title":"Restor Neurol Neurosci"},{"key":"5296_CR60","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/0014-2999(90)90206-l","volume":"185","author":"M Seif el Nasr","year":"1990","unstructured":"Seif el Nasr M, Peruche B, Rossberg C et al (1990) Neuroprotective effect of memantine demonstrated in vivo and in vitro. Eur J Pharmacol 185:19\u201324. https:\/\/doi.org\/10.1016\/0014-2999(90)90206-l","journal-title":"Eur J Pharmacol"},{"key":"5296_CR61","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3389\/FNBEH.2014.00140\/ABSTRACT","volume":"8","author":"A Pu\u015bcian","year":"2014","unstructured":"Pu\u015bcian A, \u0141eski S, G\u00f3rkiewicz T et al (2014) A novel automated behavioral test battery assessing cognitive rigidity in two genetic mouse models of autism. Front Behav Neurosci 8:140. https:\/\/doi.org\/10.3389\/FNBEH.2014.00140\/ABSTRACT","journal-title":"Front Behav Neurosci"},{"key":"5296_CR62","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/978-1-4939-8994-2_10","volume":"1916","author":"AK Kraeuter","year":"2019","unstructured":"Kraeuter AK, Guest PC, Sarnyai Z (2019) The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods Mol Biol 1916:105\u2013111. https:\/\/doi.org\/10.1007\/978-1-4939-8994-2_10","journal-title":"Methods Mol Biol"},{"key":"5296_CR63","doi-asserted-by":"publisher","first-page":"725","DOI":"10.2174\/1874467215666220928110557","volume":"16","author":"S Ishaq","year":"2023","unstructured":"Ishaq S, Siyar S, Basri R et al (2023) Neuroprotective Effects of Shogaol in Metals (Al, As and Pb) and High-fat diet-induced Neuroinflammation and Behavior in Mice. Curr Mol Pharmacol 16:725\u2013750. https:\/\/doi.org\/10.2174\/1874467215666220928110557","journal-title":"Curr Mol Pharmacol"},{"key":"5296_CR64","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.brainresbull.2019.02.013","volume":"147","author":"G Iqbal","year":"2019","unstructured":"Iqbal G, Ahmed T (2019) Co-exposure of metals and high fat diet causes aging like neuropathological changes in non-aged mice brain. Brain Res Bull 147:148\u2013158","journal-title":"Brain Res Bull"},{"key":"5296_CR65","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/0003-2697(72)90132-7","volume":"47","author":"AK Sinha","year":"1972","unstructured":"Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389\u2013394. https:\/\/doi.org\/10.1016\/0003-2697(72)90132-7","journal-title":"Anal Biochem"},{"key":"5296_CR66","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1007\/s10534-023-00570-1","volume":"37","author":"H Asghar","year":"2024","unstructured":"Asghar H, Siddiqui A, Batool L et al (2024) Post-exposure self-recovery reverses oxidative stress, ameliorates pathology and neurotransmitters imbalance and rescues spatial memory after time-dependent aluminum exposure in rat brain. Biometals 37:819\u2013838","journal-title":"Biometals"},{"key":"5296_CR67","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.lfs.2015.01.016","volume":"124","author":"S Haider","year":"2015","unstructured":"Haider S, Liaquat L, Shahzad S et al (2015) A high dose of short term exogenous d-galactose administration in young male rats produces symptoms simulating the natural aging process. Life Sci 124:110\u2013119. https:\/\/doi.org\/10.1016\/j.lfs.2015.01.016","journal-title":"Life Sci"},{"key":"5296_CR68","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.lfs.2018.12.009","volume":"217","author":"L Liaquat","year":"2019","unstructured":"Liaquat L, Sadir S, Batool Z et al (2019) Acute aluminum chloride toxicity revisited: Study on DNA damage and histopathological, biochemical and neurochemical alterations in rat brain. Life Sci 217:202\u2013211. https:\/\/doi.org\/10.1016\/j.lfs.2018.12.009","journal-title":"Life Sci"},{"key":"5296_CR69","doi-asserted-by":"publisher","DOI":"10.3791\/3564","author":"GJ Gage","year":"2012","unstructured":"Gage GJ, Kipke DR, Shain W (2012) Whole animal perfusion fixation for rodents. J Vis Exp. https:\/\/doi.org\/10.3791\/3564","journal-title":"J Vis Exp"},{"key":"5296_CR70","doi-asserted-by":"publisher","unstructured":"Feldman AT, Wolfe D (2014) Tissue processing and hematoxylin and eosin staining. Methods Mol Biol. 1180:31\u201343. https:\/\/doi.org\/10.1007\/978-1-4939-1050-2_3","DOI":"10.1007\/978-1-4939-1050-2_3"},{"key":"5296_CR71","doi-asserted-by":"publisher","first-page":"e3465","DOI":"10.21769\/BioProtoc.3465","volume":"9","author":"AR Crowe","year":"2019","unstructured":"Crowe AR, Yue W (2019) Semi-quantitative determination of protein expression using immunohistochemistry staining and analysis: an integrated protocol. Bio-protocol 9:e3465\u2013e3465","journal-title":"Bio-protocol"},{"key":"5296_CR72","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s11064-022-03723-9","volume":"48","author":"AE Essawy","year":"2023","unstructured":"Essawy AE, Mohamed AI, Ali RG et al (2023) Analysis of melatonin-modulating effects against tartrazine-induced neurotoxicity in male rats: biochemical, pathological and immunohistochemical markers. Neurochem Res 48:131\u2013141","journal-title":"Neurochem Res"},{"key":"5296_CR73","doi-asserted-by":"publisher","unstructured":"Oviosun A, Oviosun EC, Nto NJ et al (2025) Zingerone attenuates cadmium-induced neuroinflammation, oxidative stress and cognitive deficit on the prefrontal cortex of adult Wistar rats. J Exp Pharmacol 17:323 \u2013341. https:\/\/doi.org\/10.2147\/JEP.S519571","DOI":"10.2147\/JEP.S519571"},{"key":"5296_CR74","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1093\/toxsci\/kfaa144","volume":"178","author":"MM Hossain","year":"2020","unstructured":"Hossain MM, Belkadi A, Al-Haddad S, Richardson JR (2020) Deltamethrin exposure inhibits adult hippocampal neurogenesis and causes deficits in learning and memory in mice. Toxicol Sci 178:347\u2013357","journal-title":"Toxicol Sci"},{"key":"5296_CR75","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.brainres.2006.09.005","volume":"1122","author":"H Aslan","year":"2006","unstructured":"Aslan H, Songur A, Tunc AT et al (2006) Effects of formaldehyde exposure on granule cell number and volume of dentate gyrus: a histopathological and stereological study. Brain Res 1122:191\u2013200","journal-title":"Brain Res"},{"key":"5296_CR76","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1101\/lm.688207","volume":"14","author":"RP Kesner","year":"2007","unstructured":"Kesner RP (2007) Behavioral functions of the CA3 subregion of the hippocampus. Learn Mem 14:771\u2013781","journal-title":"Learn Mem"},{"key":"5296_CR77","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0079-6123(07)63001-5","volume":"163","author":"DG Amaral","year":"2007","unstructured":"Amaral DG, Scharfman HE, Lavenex P (2007) The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). Prog Brain Res 163:3\u2013790","journal-title":"Prog Brain Res"},{"key":"5296_CR78","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.ntt.2008.05.001","volume":"30","author":"AM Smith","year":"2008","unstructured":"Smith AM, Pappalardo D, Chen W-JA (2008) Estimation of neuronal numbers in rat hippocampus following neonatal amphetamine exposure: a stereology study. Neurotoxicol Teratol 30:495\u2013502","journal-title":"Neurotoxicol Teratol"},{"key":"5296_CR79","doi-asserted-by":"publisher","unstructured":"Chauhan P, Jethwa K, Rathawa A et al (2021) The anatomy of the hippocampus. In: Pluta R (ed) Cerebral ischemia. Chapter 2. Exon Publications, Brisbane (AU), 17\u201330. https:\/\/doi.org\/10.36255\/exonpublications.cerebralischemia.2021.hippocampus","DOI":"10.36255\/exonpublications.cerebralischemia.2021.hippocampus"},{"key":"5296_CR80","doi-asserted-by":"publisher","unstructured":"Jia A, Xu L, Wang Y (2021) Venn diagrams in bioinformatics. Brief Bioinform 22. https:\/\/doi.org\/10.1093\/BIB\/BBAB108","DOI":"10.1093\/BIB\/BBAB108"},{"key":"5296_CR81","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1021\/acs.jproteome.8b00702","volume":"18","author":"NT Doncheva","year":"2019","unstructured":"Doncheva NT, Morris JH, Gorodkin J, Jensen LJ (2019) Cytoscape StringApp: Network Analysis and Visualization of Proteomics Data. J Proteome Res 18:623\u2013632. https:\/\/doi.org\/10.1021\/acs.jproteome.8b00702","journal-title":"J Proteome Res"},{"key":"5296_CR82","doi-asserted-by":"publisher","unstructured":"Tang D, Chen M, Huang X et al (2023) SRplot: a free online platform for data visualization and graphing. PLoS ONE 18. https:\/\/doi.org\/10.1371\/journal.pone.0294236","DOI":"10.1371\/journal.pone.0294236"},{"key":"5296_CR83","doi-asserted-by":"publisher","first-page":"57605","DOI":"10.18632\/oncotarget.17745","volume":"8","author":"CV Rao","year":"2017","unstructured":"Rao CV, Pal S, Mohammed A et al (2017) Biological effects and epidemiological consequences of arsenic exposure, and reagents that can ameliorate arsenic damage in vivo. Oncotarget 8:57605\u201357621. https:\/\/doi.org\/10.18632\/oncotarget.17745","journal-title":"Oncotarget"},{"key":"5296_CR84","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/S00204-024-03903-2","volume":"2024","author":"K Jomova","year":"2024","unstructured":"Jomova K, Alomar SY, Nepovimova E et al (2024) Heavy metals: toxicity and human health effects. Arch Toxicol 2024:1\u201357. https:\/\/doi.org\/10.1007\/S00204-024-03903-2","journal-title":"Arch Toxicol"},{"key":"5296_CR85","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1080\/17460441.2025.2474661","volume":"20","author":"E Carroll","year":"2025","unstructured":"Carroll E, Scaber J, Huber KVM et al (2025) Drug repurposing in amyotrophic lateral sclerosis (ALS). Expert Opin Drug Discov 20:447\u2013464","journal-title":"Expert Opin Drug Discov"},{"key":"5296_CR86","doi-asserted-by":"publisher","unstructured":"Volbracht C, Van Beek J, Zhu C, et al (2006) Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity. Eur J Neurosci 23: (10) 2611\u20132622. https:\/\/doi.org\/10.1111\/j.1460-9568.2006.04787.x","DOI":"10.1111\/j.1460-9568.2006.04787.x"},{"key":"5296_CR87","doi-asserted-by":"publisher","first-page":"5681","DOI":"10.1002\/alz.13349","volume":"19","author":"B Zheng","year":"2023","unstructured":"Zheng B, Su B, Ahmadi-Abhari S et al (2023) Dementia risk in patients with type 2 diabetes: Comparing metformin with no pharmacological treatment. Alzheimer\u2019s Dement 19:5681\u20135689","journal-title":"Alzheimer\u2019s Dement"},{"key":"5296_CR88","doi-asserted-by":"publisher","first-page":"1415740","DOI":"10.3389\/fphar.2024.1415740","volume":"15","author":"W Cui","year":"2024","unstructured":"Cui W, Lv C, Geng P et al (2024) Novel targets and therapies of metformin in dementia: old drug, new insights. Front Pharmacol 15:1415740","journal-title":"Front Pharmacol"},{"key":"5296_CR89","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.neuropharm.2007.07.013","volume":"53","author":"CG Parsons","year":"2007","unstructured":"Parsons CG, St\u00f6ffler A, Danysz W (2007) Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system-too little activation is bad, too much is even worse. Neuropharmacology 53:699\u2013723","journal-title":"Neuropharmacology"},{"key":"5296_CR90","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.neuroscience.2014.05.011","volume":"273","author":"MY Liu","year":"2014","unstructured":"Liu MY, Wang S, Yao WF et al (2014) Memantine improves spatial learning and memory impairments by regulating NGF signaling in APP\/PS1 transgenic mice. Neuroscience 273:141\u2013151","journal-title":"Neuroscience"},{"key":"5296_CR91","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/J.BBR.2010.03.036","volume":"221","author":"J Lockrow","year":"2010","unstructured":"Lockrow J, Boger H, Bimonte-Nelson H, Granholm AC, EFFECTS OF LONG-TERM MEMANTINE ON MEMORY AND NEUROPATHOLOGY IN TS65DN MICE, A MODEL FOR DOWN SYNDROME (2010) Behav Brain Res 221:610. https:\/\/doi.org\/10.1016\/J.BBR.2010.03.036","journal-title":"Behav Brain Res"},{"key":"5296_CR92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4236\/aad.2020.91001","volume":"9","author":"A Shata","year":"2020","unstructured":"Shata A, Elkashef W, Hamouda MA, Eissa H (2020) Effect of artesunate vs memantine in aluminum chloride induced model of neurotoxicity in rats. Adv Alzheimer\u2019s Dis 9:1\u201319","journal-title":"Adv Alzheimer\u2019s Dis"},{"key":"5296_CR93","doi-asserted-by":"crossref","unstructured":"Hayat M, Khola NUH, Ahmed T (2025) A systematic review of preclinical studies investigating the effects of pharmacological agents on learning and memory in prolonged aluminum-exposure-induced neurotoxicity. Brain Sci","DOI":"10.3390\/brainsci15080849"},{"key":"5296_CR94","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1016\/j.neuroscience.2007.03.018","volume":"146","author":"CP Dias","year":"2007","unstructured":"Dias CP, De Lima MNM, Presti-Torres J et al (2007) Memantine reduces oxidative damage and enhances long-term recognition memory in aged rats. Neuroscience 146:1719\u20131725","journal-title":"Neuroscience"},{"key":"5296_CR95","doi-asserted-by":"crossref","unstructured":"Dutta S, Shah RB, Singhal S et al (2023) Metformin: a review of potential mechanism and therapeutic utility beyond diabetes. Drug Des Devel Ther 1907\u20131932","DOI":"10.2147\/DDDT.S409373"},{"key":"5296_CR96","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","volume":"20","author":"M Foretz","year":"2014","unstructured":"Foretz M, Guigas B, Bertrand L et al (2014) Metformin: from mechanisms of action to therapies. Cell Metab 20:953\u2013966","journal-title":"Cell Metab"},{"key":"5296_CR97","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s11011-014-9632-2","volume":"30","author":"G Ashabi","year":"2015","unstructured":"Ashabi G, Khalaj L, Khodagholi F et al (2015) Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia. Metab Brain Dis 30:747\u2013754","journal-title":"Metab Brain Dis"},{"key":"5296_CR98","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.coph.2005.09.007","volume":"6","author":"JW Johnson","year":"2006","unstructured":"Johnson JW, Kotermanski SE (2006) Mechanism of action of memantine. Curr Opin Pharmacol 6:61\u201367","journal-title":"Curr Opin Pharmacol"},{"key":"5296_CR99","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/nrd1958","volume":"5","author":"SA Lipton","year":"2006","unstructured":"Lipton SA (2006) Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov 5:160\u2013170","journal-title":"Nat Rev Drug Discov"},{"key":"5296_CR100","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1007\/s12640-013-9386-3","volume":"24","author":"W Liu","year":"2013","unstructured":"Liu W, Xu Z, Deng Y et al (2013) Protective effects of memantine against methylmercury-induced glutamate dyshomeostasis and oxidative stress in rat cerebral cortex. Neurotox Res 24:320\u2013337","journal-title":"Neurotox Res"},{"key":"5296_CR101","unstructured":"Sankhla MS, Sharma K, Kumar R (2017) Heavy metal causing neurotoxicity in human health. Int J Innov Res Sci Eng Technol 6 (5):7721\u20137726"},{"key":"5296_CR102","doi-asserted-by":"publisher","first-page":"117016","DOI":"10.1016\/j.ecoenv.2024.117016","volume":"285","author":"L Cheng","year":"2024","unstructured":"Cheng L, Zhang Y, Lv M et al (2024) Impaired learning and memory in male mice induced by sodium arsenite was associated with MMP-2\/MMP-9-mediated blood-brain barrier disruption and neuronal apoptosis. Ecotoxicol Environ Saf 285:117016. https:\/\/doi.org\/10.1016\/j.ecoenv.2024.117016","journal-title":"Ecotoxicol Environ Saf"},{"key":"5296_CR103","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/S00580-020-03097-W","volume":"29","author":"A Hosseinzadeh","year":"2020","unstructured":"Hosseinzadeh A, Houshmand G, Kalantar M et al (2020) Neuroprotective effects of gallic acid against neurotoxicity induced by sodium arsenite in rats. Comp Clin Path 29:621\u2013629. https:\/\/doi.org\/10.1007\/S00580-020-03097-W","journal-title":"Comp Clin Path"},{"key":"5296_CR104","doi-asserted-by":"publisher","unstructured":"Maiti S, Acharyya N, Ghosh TK et al (2017) Green tea (Camellia sinensis) protects against arsenic neurotoxicity via antioxidative mechanism and activation of superoxide dismutase activity. Cent Nerv Syst Agents Med Chem 17. https:\/\/doi.org\/10.2174\/1871524917666170201145102","DOI":"10.2174\/1871524917666170201145102"},{"key":"5296_CR105","doi-asserted-by":"publisher","unstructured":"Chu F, Yang W, Li Y et al (2023) Subchronic arsenic exposure induces behavioral impairments and hippocampal damage in rats. Toxics 11:970 11:970. https:\/\/doi.org\/10.3390\/TOXICS11120970","DOI":"10.3390\/TOXICS11120970"},{"key":"5296_CR106","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s12017-015-8343-0","volume":"17","author":"SN Amin","year":"2015","unstructured":"Amin SN, El-Aidi AA, Ali MM et al (2015) Modification of hippocampal markers of synaptic plasticity by memantine in animal models of acute and repeated restraint stress: implications for memory and behavior. Neuromolecular Med 17:121\u2013136","journal-title":"Neuromolecular Med"},{"key":"5296_CR107","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/S10571-024-01502-4\/FIGURES\/6","volume":"44","author":"M Taheri","year":"2024","unstructured":"Taheri M, Roghani M, Sedaghat R (2024) Metformin Mitigates Trimethyltin-Induced Cognition Impairment and Hippocampal Neurodegeneration. Cell Mol Neurobiol 44:1\u201313. https:\/\/doi.org\/10.1007\/S10571-024-01502-4\/FIGURES\/6","journal-title":"Cell Mol Neurobiol"},{"key":"5296_CR108","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.neulet.2016.07.061","volume":"630","author":"K Kakefuda","year":"2016","unstructured":"Kakefuda K, Ishisaka M, Tsuruma K et al (2016) Memantine, an NMDA receptor antagonist, improves working memory deficits in DGK\u03b2 knockout mice. Neurosci Lett 630:228\u2013232. https:\/\/doi.org\/10.1016\/j.neulet.2016.07.061","journal-title":"Neurosci Lett"},{"key":"5296_CR109","doi-asserted-by":"publisher","first-page":"4360","DOI":"10.1002\/FSN3.3028","volume":"10","author":"Z Islam","year":"2022","unstructured":"Islam Z, Islam J, Tony SR et al (2022) Mulberry leaves juice attenuates arsenic-induced neurobehavioral and hepatic disorders in mice. Food Sci Nutr 10:4360\u20134370. https:\/\/doi.org\/10.1002\/FSN3.3028","journal-title":"Food Sci Nutr"},{"key":"5296_CR110","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1007\/s11011-023-01170-1","volume":"38","author":"M Khaleghi-Mehr","year":"2023","unstructured":"Khaleghi-Mehr M, Delshad A-A, Shafie-Damavandi S, Roghani M (2023) Metformin mitigates amyloid \u03b21-40-induced cognitive decline via attenuation of oxidative\/nitrosative stress and neuroinflammation. Metab Brain Dis 38:1127\u20131142. https:\/\/doi.org\/10.1007\/s11011-023-01170-1","journal-title":"Metab Brain Dis"},{"key":"5296_CR111","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s12031-017-0915-z","volume":"62","author":"S Ahmed","year":"2017","unstructured":"Ahmed S, Mahmood Z, Javed A et al (2017) Effect of metformin on adult hippocampal neurogenesis: comparison with donepezil and links to cognition. J Mol Neurosci 62:88\u201398","journal-title":"J Mol Neurosci"},{"key":"5296_CR112","doi-asserted-by":"publisher","first-page":"114978","DOI":"10.1016\/j.bbr.2024.114978","volume":"466","author":"E Aksoz","year":"2024","unstructured":"Aksoz E, Akyol BA, Korkut O (2024) The role of the cholinergic system in the memory-protecting effects of metformin in a model of scopolamine-induced memory impairment in aged rats. Behav Brain Res 466:114978. https:\/\/doi.org\/10.1016\/j.bbr.2024.114978","journal-title":"Behav Brain Res"},{"key":"5296_CR113","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1002\/hipo.22270","volume":"24","author":"R Ishikawa","year":"2014","unstructured":"Ishikawa R, Kim R, Namba T et al (2014) Time-dependent enhancement of hippocampus\u2010dependent memory after treatment with memantine: Implications for enhanced hippocampal adult neurogenesis. Hippocampus 24:784\u2013793","journal-title":"Hippocampus"},{"key":"5296_CR114","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s12010-018-2723-5","volume":"186","author":"M Soni","year":"2018","unstructured":"Soni M, Prakash C, Dabur R, Kumar V (2018) Protective Effect of Hydroxytyrosol Against Oxidative Stress Mediated by Arsenic-Induced Neurotoxicity in Rats. Appl Biochem Biotechnol 186:27\u201339. https:\/\/doi.org\/10.1007\/s12010-018-2723-5","journal-title":"Appl Biochem Biotechnol"},{"key":"5296_CR115","doi-asserted-by":"publisher","first-page":"8281","DOI":"10.3390\/ijms23158281","volume":"23","author":"N Li","year":"2022","unstructured":"Li N, Zhou T, Fei E (2022) Actions of metformin in the brain: a new perspective of metformin treatments in related neurological disorders. Int J Mol Sci 23:8281","journal-title":"Int J Mol Sci"},{"key":"5296_CR116","doi-asserted-by":"publisher","first-page":"112280","DOI":"10.1016\/j.biopha.2021.112280","volume":"144","author":"N Sritawan","year":"2021","unstructured":"Sritawan N, Suwannakot K, Naewla S et al (2021) Effect of metformin treatment on memory and hippocampal neurogenesis decline correlated with oxidative stress induced by methotrexate in rats. Biomed Pharmacother 144:112280. https:\/\/doi.org\/10.1016\/j.biopha.2021.112280","journal-title":"Biomed Pharmacother"},{"key":"5296_CR117","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3390\/molecules28010417","volume":"28","author":"R Jadhav","year":"2023","unstructured":"Jadhav R, Kulkarni YA (2023) Neuroprotective effect of quercetin and memantine against AlCl3-induced neurotoxicity in albino wistar rats. Molecules 28:417","journal-title":"Molecules"},{"key":"5296_CR118","doi-asserted-by":"publisher","first-page":"100050","DOI":"10.1016\/j.dscb.2022.100050","volume":"7","author":"RN Ugbaja","year":"2022","unstructured":"Ugbaja RN, Akinhanmi TF, Onunkwor BO et al (2022) Flavonoid-rich fractions of C. volubile and V. amygdalina alleviates arsenic-induced neurotoxicity by improving neurosignaling and antioxidant capacity in rats\u2019 brain. Brain Disord 7:100050","journal-title":"Brain Disord"},{"key":"5296_CR119","doi-asserted-by":"publisher","unstructured":"Chu F, Yang W, Li Y et al (2023) Subchronic arsenic exposure induces behavioral impairments and hippocampal damage in rats. Toxics 11. https:\/\/doi.org\/10.3390\/toxics11120970","DOI":"10.3390\/toxics11120970"},{"key":"5296_CR120","doi-asserted-by":"publisher","unstructured":"Sritawan N, Prajit R, Chaisawang P et al (2020) Metformin alleviates memory and hippocampal neurogenesis decline induced by methotrexate chemotherapy in a rat model. Biomed Pharmacother 131. https:\/\/doi.org\/10.1016\/j.biopha.2020.110651","DOI":"10.1016\/j.biopha.2020.110651"},{"key":"5296_CR121","doi-asserted-by":"publisher","first-page":"100365","DOI":"10.1016\/j.tria.2024.100365","volume":"38","author":"V Blossom","year":"2025","unstructured":"Blossom V, Ullal SD, Rai R et al (2025) Effect of metformin on the neuronal morphology of frontal cortex and hippocampal regions in lipopolysaccharide induced neuroinflammation in male Wistar rats. Transl Res Anat 38:100365. https:\/\/doi.org\/10.1016\/j.tria.2024.100365","journal-title":"Transl Res Anat"},{"key":"5296_CR122","doi-asserted-by":"publisher","unstructured":"Al Za\u2019abi M, Ali BH, Al Suleimani Y et al (2021) The effect of metformin in diabetic and non-diabetic rats with experimentally-induced chronic kidney disease. Biomolecules 11. https:\/\/doi.org\/10.3390\/biom11060814","DOI":"10.3390\/biom11060814"},{"key":"5296_CR123","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.1016\/s0024-3205(01)01359-5","volume":"69","author":"VB Kumar","year":"2001","unstructured":"Kumar VB, Bernardo AE, Vyas K et al (2001) Effect of metformin on nitric oxide synthase in genetically obese (ob\/ob) mice. Life Sci 69:2789\u20132799. https:\/\/doi.org\/10.1016\/s0024-3205(01)01359-5","journal-title":"Life Sci"},{"key":"5296_CR124","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/S12011-018-1286-1","volume":"186","author":"LP Chandravanshi","year":"2018","unstructured":"Chandravanshi LP, Gupta R, Shukla RK (2018) Developmental Neurotoxicity of Arsenic: Involvement of Oxidative Stress and Mitochondrial Functions. Biol Trace Elem Res 186:185\u2013198. https:\/\/doi.org\/10.1007\/S12011-018-1286-1","journal-title":"Biol Trace Elem Res"},{"key":"5296_CR125","doi-asserted-by":"publisher","first-page":"105029","DOI":"10.1016\/j.envint.2019.105029","volume":"131","author":"Y Karim","year":"2019","unstructured":"Karim Y, Siddique AE, Hossen F et al (2019) Dose-dependent relationships between chronic arsenic exposure and cognitive impairment and serum brain-derived neurotrophic factor. Environ Int 131:105029. https:\/\/doi.org\/10.1016\/j.envint.2019.105029","journal-title":"Environ Int"},{"key":"5296_CR126","doi-asserted-by":"publisher","first-page":"113686","DOI":"10.1016\/J.BIOPHA.2022.113686","volume":"156","author":"G Cao","year":"2022","unstructured":"Cao G, Gong T, Du Y et al (2022) Mechanism of metformin regulation in central nervous system: Progression and future perspectives. Biomed Pharmacother 156:113686. https:\/\/doi.org\/10.1016\/J.BIOPHA.2022.113686","journal-title":"Biomed Pharmacother"},{"key":"5296_CR127","doi-asserted-by":"publisher","first-page":"486","DOI":"10.3390\/ph18040486","volume":"18","author":"W Kruczkowska","year":"2025","unstructured":"Kruczkowska W, Ga\u0142\u0119ziewska J, Buczek P et al (2025) Overview of Metformin and Neurodegeneration: A Comprehensive Review. Pharmaceuticals 18:486","journal-title":"Pharmaceuticals"},{"key":"5296_CR128","unstructured":"Wu H-M, Lu R-B, Hong J-S, Chen S-L (2009) Memantine protects inflammation-related degeneration of dopamine neurons through inhibition of over-activated microglia and release of neurotrophic factors from astroglia"},{"key":"5296_CR129","doi-asserted-by":"publisher","first-page":"40934","DOI":"10.1021\/acsomega.3c06250","volume":"8","author":"X Zheng","year":"2023","unstructured":"Zheng X, Li W, Xiang Q et al (2023) Memantine Attenuates Cognitive and Emotional Dysfunction in Mice with Sepsis-Associated Encephalopathy. ACS omega 8:40934\u201340943. https:\/\/doi.org\/10.1021\/acsomega.3c06250","journal-title":"ACS omega"},{"key":"5296_CR130","doi-asserted-by":"publisher","unstructured":"Ameen O, Samaka RM, Abo-Elsoud RAA (2022) Metformin alleviates neurocognitive impairment in aging via activation of AMPK\/BDNF\/PI3K pathway. Sci Rep 12:17084. https:\/\/doi.org\/10.1038\/s41598-022-20945-7","DOI":"10.1038\/s41598-022-20945-7"},{"key":"5296_CR131","doi-asserted-by":"publisher","first-page":"137","DOI":"10.3389\/fnins.2016.00137","volume":"10","author":"KH Aung","year":"2016","unstructured":"Aung KH, Kyi-Tha-Thu C, Sano K et al (2016) Prenatal exposure to arsenic impairs behavioral flexibility and cortical structure in mice. Front Neurosci 10:137","journal-title":"Front Neurosci"},{"key":"5296_CR132","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1093\/toxsci\/kfu208","volume":"143","author":"A Ashok","year":"2015","unstructured":"Ashok A, Rai NK, Tripathi S, Bandyopadhyay S (2015) Exposure to As-, Cd-, and Pb-mixture induces A\u03b2, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats. Toxicol Sci 143:64\u201380. https:\/\/doi.org\/10.1093\/toxsci\/kfu208","journal-title":"Toxicol Sci"},{"key":"5296_CR133","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s43188-024-00255-y","volume":"40","author":"K Fatema","year":"2024","unstructured":"Fatema K, Haidar Z, Tanim MTH et al (2024) Unveiling the link between arsenic toxicity and diabetes: an in silico exploration into the role of transcription factors. Toxicol Res 40:653\u2013672. https:\/\/doi.org\/10.1007\/s43188-024-00255-y","journal-title":"Toxicol Res"},{"key":"5296_CR134","first-page":"196","volume":"15","author":"Y Saisho","year":"2015","unstructured":"Saisho Y (2015) Metformin and inflammation: its potential beyond glucose-lowering effect. Endocrine, Metab Immune Disord Targets (Formerly Curr Drug Targets-Immune. Endocr Metab Disord 15:196\u2013205","journal-title":"Endocr Metab Disord"},{"key":"5296_CR135","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1016\/j.biopha.2017.04.054","volume":"91","author":"J Zhao","year":"2017","unstructured":"Zhao J, Yu Y, Wu Z et al (2017) Memantine inhibits degradation of the articular cartilage extracellular matrix induced by advanced glycation end products (AGEs). Biomed Pharmacother 91:1193\u20131198. https:\/\/doi.org\/10.1016\/j.biopha.2017.04.054","journal-title":"Biomed Pharmacother"},{"key":"5296_CR136","doi-asserted-by":"publisher","first-page":"125997","DOI":"10.1016\/j.jhazmat.2021.125997","volume":"417","author":"X Liu","year":"2021","unstructured":"Liu X, Chen Y, Wang H et al (2021) Microglia-derived IL-1\u03b2 promoted neuronal apoptosis through ER stress-mediated signaling pathway PERK\/eIF2\u03b1\/ATF4\/CHOP upon arsenic exposure. J Hazard Mater 417:125997","journal-title":"J Hazard Mater"},{"key":"5296_CR137","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.toxlet.2013.10.013","volume":"224","author":"T-H Lu","year":"2014","unstructured":"Lu T-H, Tseng T-J, Su C-C et al (2014) Arsenic induces reactive oxygen species-caused neuronal cell apoptosis through JNK\/ERK-mediated mitochondria-dependent and GRP 78\/CHOP-regulated pathways. Toxicol Lett 224:130\u2013140","journal-title":"Toxicol Lett"},{"key":"5296_CR138","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1007\/S00213-021-05871-2","volume":"238","author":"K Mehta","year":"2021","unstructured":"Mehta K, Pandey KK, Kaur B et al (2021) Resveratrol attenuates arsenic-induced cognitive deficits via modulation of Estrogen-NMDAR-BDNF signalling pathway in female mouse hippocampus. Psychopharmacology 238:2485\u20132502. https:\/\/doi.org\/10.1007\/S00213-021-05871-2","journal-title":"Psychopharmacology"},{"key":"5296_CR139","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1097\/WNR.0000000000001577","volume":"32","author":"X Chen","year":"2021","unstructured":"Chen X, Xiang X, Xie T et al (2021) Memantine protects blood-brain barrier integrity and attenuates neurological deficits through inhibiting nitric oxide synthase ser1412 phosphorylation in intracerebral hemorrhage rats: involvement of peroxynitrite-related matrix metalloproteinase-9\/NLRP3. NeuroReport 32:228\u2013237. https:\/\/doi.org\/10.1097\/WNR.0000000000001577","journal-title":"NeuroReport"},{"key":"5296_CR140","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1038\/sj.jcbfm.9600213","volume":"26","author":"S-T Lee","year":"2006","unstructured":"Lee S-T, Chu K, Jung K-H et al (2006) Memantine reduces hematoma expansion in experimental intracerebral hemorrhage, resulting in functional improvement. J Cereb blood flow Metab Off J Int Soc Cereb Blood Flow Metab 26:536\u2013544. https:\/\/doi.org\/10.1038\/sj.jcbfm.9600213","journal-title":"J Cereb blood flow Metab Off J Int Soc Cereb Blood Flow Metab"},{"key":"5296_CR141","doi-asserted-by":"publisher","first-page":"3889300","DOI":"10.1155\/2022\/3889300","volume":"2022","author":"S-K Sims","year":"2022","unstructured":"Sims S-K, Wilken-Resman B, Smith CJ et al (2022) Brain-Derived Neurotrophic Factor and Nerve Growth Factor Therapeutics for Brain Injury: The Current Translational Challenges in Preclinical and Clinical Research. Neural Plast 2022:3889300. https:\/\/doi.org\/10.1155\/2022\/3889300","journal-title":"Neural Plast"},{"key":"5296_CR142","doi-asserted-by":"publisher","first-page":"121390","DOI":"10.1016\/j.lfs.2023.121390","volume":"316","author":"AA Alzokaky","year":"2023","unstructured":"Alzokaky AA, Al-Karmalawy AA, Saleh MA et al (2023) Metformin ameliorates doxorubicin-induced cardiotoxicity targeting HMGB1\/TLR4\/NLRP3 signaling pathway in mice. Life Sci 316:121390. https:\/\/doi.org\/10.1016\/j.lfs.2023.121390","journal-title":"Life Sci"}],"updated-by":[{"DOI":"10.1007\/s12011-026-05353-6","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000}}],"container-title":["Biological Trace Element Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12011-026-05296-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12011-026-05296-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12011-026-05296-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:02:38Z","timestamp":1793091758000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12011-026-05296-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":142,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,11]]}},"alternative-id":["5296"],"URL":"https:\/\/doi.org\/10.1007\/s12011-026-05296-y","relation":{},"ISSN":["1559-0720"],"issn-type":[{"value":"1559-0720","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]},"assertion":[{"value":"12 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s12011-026-05353-6","URL":"https:\/\/doi.org\/10.1007\/s12011-026-05353-6","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was conducted in compliance with the guidelines of the Institute of Laboratory Animal Research (ILAR). The animal study protocol was approved by the Internal Review Board ASAB, NUST (approval number: IRB no. 07- 2023-ASAB-02\/02).","order":1,"name":"Ethics","label":"Institutional Review Board Statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Informed Consent Statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing Interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}