{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:34:20Z","timestamp":1786980860297,"version":"build-2736575974"},"reference-count":87,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["Edital Universal (Proc. 401507\/2016)"],"award-info":[{"award-number":["Edital Universal (Proc. 401507\/2016)"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["INCT (EN 465671\/2014-4)"],"award-info":[{"award-number":["INCT (EN 465671\/2014-4)"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"publisher","award":["PRONEX (16\/2551-0000465-0)"],"award-info":[{"award-number":["PRONEX (16\/2551-0000465-0)"]}],"id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Mol Neurobiol"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1007\/s10571-021-01132-0","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T06:03:40Z","timestamp":1627538620000},"page":"2697-2714","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mild Hyperhomocysteinemia Causes Anxiety-like Behavior and Brain Hyperactivity in Rodents: Are ATPase and Excitotoxicity by NMDA Receptor Overstimulation Involved in this Effect?"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7328-6092","authenticated-orcid":false,"given":"Tiago Marcon","family":"dos Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3002-472X","authenticated-orcid":false,"given":"Cassiana","family":"Siebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8318-4818","authenticated-orcid":false,"given":"Larissa Daniele","family":"Bobermin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8611-4890","authenticated-orcid":false,"given":"Andr\u00e9","family":"Quincozes-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8769-1147","authenticated-orcid":false,"given":"Angela T. S.","family":"Wyse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"1132_CR2","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.bbr.2010.02.015","volume":"210","author":"NS Arteni","year":"2010","unstructured":"Arteni NS, Pereira LO, Rodrigues AL et al (2010) Lateralized and sex-dependent behavioral and morphological effects of unilateral neonatal cerebral hypoxia-ischemia in the rat. Behav Brain Res 210:92\u201398. https:\/\/doi.org\/10.1016\/j.bbr.2010.02.015","journal-title":"Behav Brain Res"},{"key":"1132_CR3","unstructured":"Bailey KR, Crawley JN (2009) Anxiety-Related Behaviors in Mice. In: Buccafusco JJ (ed) Methods of Behavior Analysis in Neuroscience., 2nd edition. Boca Raton (FL): CRC Press\/Taylor & Francis, Boca Raton (FL)"},{"key":"1132_CR4","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s00204-011-0674-5","volume":"85","author":"L Baird","year":"2011","unstructured":"Baird L, Dinkova-Kostova AT (2011) The cytoprotective role of the Keap1-Nrf2 pathway. Arch Toxicol 85:241\u2013272. https:\/\/doi.org\/10.1007\/s00204-011-0674-5","journal-title":"Arch Toxicol"},{"key":"1132_CR5","doi-asserted-by":"publisher","first-page":"327","DOI":"10.31887\/DCNS.2015.17.3\/bbandelow","volume":"17","author":"B Bandelow","year":"2015","unstructured":"Bandelow B, Michaelis S (2015) Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci 17:327\u2013335","journal-title":"Dialogues Clin Neurosci"},{"key":"1132_CR6","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1093\/scan\/nsy073","volume":"13","author":"EL Belleau","year":"2018","unstructured":"Belleau EL, Pedersen WS, Miskovich TA et al (2018) Cortico-limbic connectivity changes following fear extinction and relationships with trait anxiety. Soc Cogn Affect Neurosci 13:1037\u20131046. https:\/\/doi.org\/10.1093\/scan\/nsy073","journal-title":"Soc Cogn Affect Neurosci"},{"key":"1132_CR7","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/fcp.12145","volume":"29","author":"P Bhatia","year":"2015","unstructured":"Bhatia P, Singh N (2015) Homocysteine excess: Delineating the possible mechanism of neurotoxicity and depression. Fundam Clin Pharmacol 29:522\u2013528. https:\/\/doi.org\/10.1111\/fcp.12145","journal-title":"Fundam Clin Pharmacol"},{"key":"1132_CR8","first-page":"1","volume-title":"Biology of the NMDA Receptor","author":"ML Blanke","year":"2009","unstructured":"Blanke ML, Vandongen AMJ (2009) Activation Mecanisms of the NMDA Receptor. In: Van Dongen A (ed) Biology of the NMDA Receptor. CRC Press\/Taylor & Francis, Boca Raton (FL), pp 1\u201324"},{"key":"1132_CR9","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s10517-005-0404-1","volume":"140","author":"AA Boldyrev","year":"2005","unstructured":"Boldyrev AA (2005) Homocysteinic acid causes oxidative stress in lymphocytes by potentiating toxic effect of NMDA. Bull Exp Biol Med 140:33\u201337. https:\/\/doi.org\/10.1007\/s10517-005-0404-1","journal-title":"Bull Exp Biol Med"},{"key":"1132_CR10","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","volume":"72","author":"M Bradford","year":"1976","unstructured":"Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248\u2013254","journal-title":"Anal Biochem"},{"key":"1132_CR11","first-page":"347","volume":"108","author":"RW Browne","year":"1998","unstructured":"Browne RW, Armstrong D (1998) Reduced glutathione and glutathione disulfide. Methods Mol Biol 108:347\u2013352","journal-title":"Methods Mol Biol"},{"key":"1132_CR12","doi-asserted-by":"publisher","first-page":"687","DOI":"10.2147\/NDT.S3272","volume":"4","author":"H Carageorgiou","year":"2008","unstructured":"Carageorgiou H, Sideris AC, Messari I et al (2008) The effects of rivastigmine plus selegiline on brain acetylcholinesterase, (Na+, K+)-, Mg2+- ATPase activities, antioxidant status, and learning performance of aged rats. Neuropsychiatr Dis Treat 4:687\u2013699","journal-title":"Neuropsychiatr Dis Treat"},{"key":"1132_CR13","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/0003-2697(86)90640-8","volume":"157","author":"K Chan","year":"1986","unstructured":"Chan K, Delfert D, Junger K (1986) A direct colorimetric assay for Ca2+-stimulated ATPase activity. Anal Biochem 157:375\u2013380","journal-title":"Anal Biochem"},{"key":"1132_CR14","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.mehy.2015.03.027","volume":"85","author":"S Choudhury","year":"2015","unstructured":"Choudhury S, Borah A (2015) Activation of NMDA receptor by elevated homocysteine in chronic liver disease contributes to encephalopathy. Med Hypotheses 85:64\u201367. https:\/\/doi.org\/10.1016\/j.mehy.2015.03.027","journal-title":"Med Hypotheses"},{"key":"1132_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08568-9","author":"K Chung","year":"2017","unstructured":"Chung K, Chiou H, Chen Y (2017) Associations between serum homocysteine levels and anxiety and depression among children and adolescents in Taiwan. Sci Rep. https:\/\/doi.org\/10.1038\/s41598-017-08568-9","journal-title":"Sci Rep"},{"key":"1132_CR16","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1373\/clinchem.2011.164855","volume":"57","author":"R Clarke","year":"2011","unstructured":"Clarke R (2011) Homocysteine, B vitamins, and the risk of cardiovascular disease. Clin Chem 57:1201\u20131202. https:\/\/doi.org\/10.1373\/clinchem.2011.164855","journal-title":"Clin Chem"},{"key":"1132_CR17","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1007\/s11064-010-0245-9","volume":"35","author":"L Crema","year":"2010","unstructured":"Crema L, Schlabitz M, Tagliari B et al (2010) Na+, K+-ATPase activity is reduced in Amygdala of rats with chronic stress-induced anxiety-like behavior. Neurochem Res 35:1787\u20131795. https:\/\/doi.org\/10.1007\/s11064-010-0245-9","journal-title":"Neurochem Res"},{"key":"1132_CR18","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1089\/neu.2015.4068","volume":"33","author":"FF da Silva","year":"2016","unstructured":"da Silva FF, de Ferreira AP, O, Ribeiro LR, et al (2016) The impact of previous physical training on redox signaling after traumatic brain injury in rats: A behavioral and neurochemical approach. J Neurotrauma 33:1317\u20131330. https:\/\/doi.org\/10.1089\/neu.2015.4068","journal-title":"J Neurotrauma"},{"key":"1132_CR1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.59566\/IJBS.2014.10085","volume":"10","author":"GR de Arnaiz","year":"2014","unstructured":"de Arnaiz GR, L, Ordieres MGL, (2014) Brain Na+, K+-ATPase activity in aging and disease. Int J Biomed Sci 10:85\u2013102","journal-title":"Int J Biomed Sci"},{"key":"1132_CR85","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1023\/A:1007504525301","volume":"25","author":"AT de Wyse","year":"2000","unstructured":"de Wyse AT, S, Streck EL, Worm P, et al (2000) Preconditioning prevents the inhibition of NA+, K+-ATPase activity after brain ischemia. Neurochem Res 25:971\u2013975. https:\/\/doi.org\/10.1023\/A:1007504525301","journal-title":"Neurochem Res"},{"key":"1132_CR19","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s11064-013-1230-x","volume":"39","author":"LA Diehl","year":"2014","unstructured":"Diehl LA, Pereira NDSC, Laureano DP et al (2014) Contextual fear conditioning in maternal separated rats: The amygdala as a site for alterations. Neurochem Res 39:384\u2013393. https:\/\/doi.org\/10.1007\/s11064-013-1230-x","journal-title":"Neurochem Res"},{"key":"1132_CR20","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.abb.2006.06.025","volume":"453","author":"AQ dos Santos","year":"2006","unstructured":"dos Santos AQ, Nardin P, Funchal C et al (2006) Resveratrol increases glutamate uptake and glutamine synthetase activity in C6 glioma cells. Arch Biochem Biophys 453:161\u2013167. https:\/\/doi.org\/10.1016\/j.abb.2006.06.025","journal-title":"Arch Biochem Biophys"},{"key":"1132_CR21","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-019-00674-8","author":"TM dos Santos","year":"2019","unstructured":"dos Santos TM, Siebert C, Federizzi M et al (2019) Chronic mild Hyperhomocysteinemia impairs energy metabolism, promotes DNA damage and induces a Nrf2 response to oxidative stress in rats brain. Cell Mol Neurobiol. https:\/\/doi.org\/10.1007\/s10571-019-00674-8","journal-title":"Cell Mol Neurobiol"},{"key":"1132_CR22","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ijdevneu.2016.12.003","volume":"56","author":"TM dos Santos","year":"2017","unstructured":"dos Santos TM, Kolling J, Siebert C et al (2017) Effects of previous physical exercise to chronic stress on long-term aversive memory and oxidative stress in amygdala and hippocampus of rats. Int J Dev Neurosci 56:58\u201367. https:\/\/doi.org\/10.1016\/j.ijdevneu.2016.12.003","journal-title":"Int J Dev Neurosci"},{"key":"1132_CR23","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.psychres.2017.04.032","volume":"254","author":"E Esnafoglu","year":"2017","unstructured":"Esnafoglu E, Yaman E (2017) Vitamin B12, folic acid, homocysteine and vitamin D levels in children and adolescents with obsessive compulsive disorder. Psychiatry Res 254:232\u2013237. https:\/\/doi.org\/10.1016\/j.psychres.2017.04.032","journal-title":"Psychiatry Res"},{"key":"1132_CR24","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1515\/CCLM.2007.341","volume":"45","author":"JD Finkelstein","year":"2007","unstructured":"Finkelstein JD (2007) Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine. Clin Chem Lab Med 45:1694\u20131699. https:\/\/doi.org\/10.1515\/CCLM.2007.341","journal-title":"Clin Chem Lab Med"},{"key":"1132_CR25","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.neuint.2012.06.003","volume":"61","author":"K Foo","year":"2012","unstructured":"Foo K, Blumenthal L, Man HY (2012) Regulation of neuronal bioenergy homeostasis by glutamate. Neurochem Int 61:389\u2013396. https:\/\/doi.org\/10.1016\/j.neuint.2012.06.003","journal-title":"Neurochem Int"},{"key":"1132_CR26","doi-asserted-by":"publisher","first-page":"5515","DOI":"10.1167\/iovs.10-6870","volume":"52","author":"PS Ganapathy","year":"2011","unstructured":"Ganapathy PS, White RE, Ha Y et al (2011) The role of N-methyl-D-aspartate receptor activation in homocysteine-induced death of retinal ganglion cells. Investig Ophthalmol vis Sci 52:5515\u20135524. https:\/\/doi.org\/10.1167\/iovs.10-6870","journal-title":"Investig Ophthalmol vis Sci"},{"key":"1132_CR27","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/0003-2697(82)90118-X","volume":"126","author":"LC Green","year":"1982","unstructured":"Green LC, Wagner DA, Glogowski J et al (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131\u2013138. https:\/\/doi.org\/10.1016\/0003-2697(82)90118-X","journal-title":"Anal Biochem"},{"key":"1132_CR28","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1007\/s11055-016-0386-7","volume":"47","author":"Grigor\u2019yan GA, Gulyaeva N V,","year":"2017","unstructured":"Grigor\u2019yan GA, Gulyaeva N V, (2017) Modeling depression in animals\u202f: Behavior as the basis for the methodology, assessment criteria, and classification. Neurosci Behav Physiol 47:204\u2013216. https:\/\/doi.org\/10.1007\/s11055-016-0386-7","journal-title":"Neurosci Behav Physiol"},{"key":"1132_CR29","doi-asserted-by":"publisher","first-page":"4667","DOI":"10.1523\/JNEUROSCI.23-11-04667.2003","volume":"23","author":"K Ikeda","year":"2003","unstructured":"Ikeda K, Onaka T, Yamakado M et al (2003) Degeneration of the amygdala\/piriform cortex and enhanced fear\/anxiety behaviors in sodium pump alpha2 subunit (Atp1a2)-deficient mice. J Neurosci 23:4667\u20134676","journal-title":"J Neurosci"},{"key":"1132_CR30","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1152\/physrev.00018.2015","volume":"96","author":"I Izquierdo","year":"2016","unstructured":"Izquierdo I, Furini CRG, Myskiw JC (2016) Fear memory. Physiol Rev 96:695\u2013750. https:\/\/doi.org\/10.1152\/physrev.00018.2015","journal-title":"Physiol Rev"},{"issue":"33","key":"1132_CR31","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.pnpbp.2008.11.002","volume":"33","author":"T Jendricko","year":"2009","unstructured":"Jendricko T, Andelko V, Grubisic-llic M et al (2009) Progress in Neuro-Psychopharmacology & Biological Psychiatry Homocysteine and serum lipids concentration in male war veterans with posttraumatic stress disorder. Prog Neuro-Psychopharmacology Biol Psychiatry 33(33):134\u2013140. https:\/\/doi.org\/10.1016\/j.pnpbp.2008.11.002","journal-title":"Prog Neuro-Psychopharmacology Biol Psychiatry"},{"key":"1132_CR32","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1038\/npp.2015.16","volume":"40","author":"CS John","year":"2015","unstructured":"John CS, Sypek EI, Carlezon WA et al (2015) Blockade of the GLT-1 transporter in the central nucleus of the amygdala induces both anxiety and depressive-like symptoms. Neuropsychopharmacol 40:1700\u20131708. https:\/\/doi.org\/10.1038\/npp.2015.16","journal-title":"Neuropsychopharmacol"},{"key":"1132_CR33","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.pnpbp.2016.01.008","volume":"67","author":"HK Kim","year":"2016","unstructured":"Kim HK, Nunes PV, Oliveira KC et al (2016) Neuropathological relationship between major depression and dementia: A hypothetical model and review. Prog Neuro-Psychopharmacology Biol Psychiatry 67:51\u201357. https:\/\/doi.org\/10.1016\/j.pnpbp.2016.01.008","journal-title":"Prog Neuro-Psychopharmacology Biol Psychiatry"},{"key":"1132_CR34","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.bbr.2011.04.025","volume":"223","author":"MJ Kim","year":"2011","unstructured":"Kim MJ, Loucks R, a, Palmer AL, et al (2011) The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety. Behav Brain Res 223:403\u2013410. https:\/\/doi.org\/10.1016\/j.bbr.2011.04.025","journal-title":"Behav Brain Res"},{"key":"1132_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphys.2016.00195","volume":"7","author":"PF Kinoshita","year":"2016","unstructured":"Kinoshita PF, Leite JA, Orellana AMM et al (2016) The influence of Na+, K+-ATPase on glutamate signaling in neurodegenerative diseases and senescence. Front Physiol 7:1\u201319. https:\/\/doi.org\/10.3389\/fphys.2016.00195","journal-title":"Front Physiol"},{"key":"1132_CR36","doi-asserted-by":"publisher","DOI":"10.1002\/syn.22067","volume":"73","author":"A Kumagai","year":"2019","unstructured":"Kumagai A, Sasaki T, Matsuoka K et al (2019) Monitoring of glutamate-induced excitotoxicity by mitochondrial oxygen consumption. Synapse 73:e22067. https:\/\/doi.org\/10.1002\/syn.22067","journal-title":"Synapse"},{"key":"1132_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12986-017-0233-z","volume":"14","author":"A Kumar","year":"2017","unstructured":"Kumar A, Palfrey HA, Pathak R et al (2017) The metabolism and significance of homocysteine in nutrition and health. Nutr Metab 14:1\u201312. https:\/\/doi.org\/10.1186\/s12986-017-0233-z","journal-title":"Nutr Metab"},{"key":"1132_CR39","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/s0166-4328(02)00326-1","volume":"141","author":"D Lavinsky","year":"2003","unstructured":"Lavinsky D, Arteni NS, Netto CA (2003) Agmatine induces anxiolysis in the elevated plus maze task in adult rats. Behav Brain Res 141:19\u201324. https:\/\/doi.org\/10.1016\/s0166-4328(02)00326-1","journal-title":"Behav Brain Res"},{"key":"1132_CR40","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1021\/tx00026a012","volume":"5","author":"CP Lebel","year":"1992","unstructured":"Lebel CP, Ischiropoulos H (1992) Bondys SC (1992) Evaluation of the probe 2\u2018,7\u2018-dichiorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227\u2013231","journal-title":"Chem Res Toxicol"},{"key":"1132_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnins.2015.00469","volume":"9","author":"J Lewerenz","year":"2015","unstructured":"Lewerenz J, Maher P, Maher P (2015) Chronic glutamate toxicity in neurodegenerative diseases \u2014 what is the evidence? Front Neurosci 9:1\u201320. https:\/\/doi.org\/10.3389\/fnins.2015.00469","journal-title":"Front Neurosci"},{"key":"1132_CR42","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1002\/jnr.24042","volume":"95","author":"PA Li","year":"2017","unstructured":"Li PA, Hou X, Hao S (2017) Mitochondrial biogenesis in neurodegeneration. J Neurosci Res 95:2025\u20132029. https:\/\/doi.org\/10.1002\/jnr.24042","journal-title":"J Neurosci Res"},{"key":"1132_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0176725","volume":"12","author":"YY Liu","year":"2017","unstructured":"Liu YY, Zhou XY, Yang LN et al (2017) Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats. PLoS ONE 12:1\u201316. https:\/\/doi.org\/10.1371\/journal.pone.0176725","journal-title":"PLoS ONE"},{"key":"1132_CR44","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1007\/s12035-017-0463-0","volume":"55","author":"A Longoni","year":"2017","unstructured":"Longoni A, Bellaver B, Bobermin LD et al (2017) Homocysteine induces glial reactivity in adult rat astrocyte cultures. Mol Neurobiol 55:1966\u20131976. https:\/\/doi.org\/10.1007\/s12035-017-0463-0","journal-title":"Mol Neurobiol"},{"key":"1132_CR45","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/0304-3894(92)87011-4","volume":"193","author":"O Lowry","year":"1951","unstructured":"Lowry O, Rosebrough N, Farr A, Randall R (1951) Protein measurement with the Folin phenol reagent. Readings 193:265\u2013275. https:\/\/doi.org\/10.1016\/0304-3894(92)87011-4","journal-title":"Readings"},{"key":"1132_CR46","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1111\/j.1749-6632.1988.tb22338.x","volume":"551","author":"ME Maguire","year":"1988","unstructured":"Maguire ME (1988) Magnesium and Cell Proliferation. Ann New York Acad Sci 551:201\u2013217","journal-title":"Ann New York Acad Sci"},{"key":"1132_CR47","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.ymgme.2014.10.006","volume":"113","author":"PR Mandaviya","year":"2014","unstructured":"Mandaviya PR, Stolk L, Heil SG (2014) Homocysteine and DNA methylation\u202f: A review of animal and human literature. Mol Genet Metab 113:243\u2013252. https:\/\/doi.org\/10.1016\/j.ymgme.2014.10.006","journal-title":"Mol Genet Metab"},{"key":"1132_CR48","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.1113\/jphysiol.2012.248575","volume":"591","author":"R Marek","year":"2013","unstructured":"Marek R, Strobel C, Bredy TW, Sah P (2013) The amygdala and medial prefrontal cortex: Partners in the fear circuit. J Physiol 591:2381\u20132391. https:\/\/doi.org\/10.1113\/jphysiol.2012.248575","journal-title":"J Physiol"},{"key":"1132_CR49","volume-title":"Handbook of methods for oxygen radical research","author":"S Marklund","year":"1985","unstructured":"Marklund S (1985) Pyrogallol autoxidation. In: Greenwald RA (ed) Handbook of methods for oxygen radical research, 4th edn. CRC Press, Boca Raton","edition":"4"},{"key":"1132_CR50","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.mehy.2011.06.021","volume":"77","author":"WN Marsden","year":"2011","unstructured":"Marsden WN (2011) Stressor-induced NMDAR dysfunction as a unifying hypothesis for the aetiology, pathogenesis and comorbidity of clinical depression. Med Hypotheses 77:508\u2013528. https:\/\/doi.org\/10.1016\/j.mehy.2011.06.021","journal-title":"Med Hypotheses"},{"key":"1132_CR51","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.ijdevneu.2009.11.004","volume":"28","author":"C Matt\u00e9","year":"2010","unstructured":"Matt\u00e9 C, Mussulini BHMBHM, dos Santos TMTM et al (2010) Hyperhomocysteinemia reduces glutamate uptake in parietal cortex of rats. Int J Dev Neurosci 28:183\u2013187. https:\/\/doi.org\/10.1016\/j.ijdevneu.2009.11.004","journal-title":"Int J Dev Neurosci"},{"key":"1132_CR52","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/cphy.c150021","volume":"6","author":"KS McCully","year":"2015","unstructured":"McCully KS (2015) Homocysteine metabolism, atherosclerosis, and diseases of aging. Compr Physiol 6:471\u2013505. https:\/\/doi.org\/10.1002\/cphy.c150021","journal-title":"Compr Physiol"},{"key":"1132_CR53","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.neuropharm.2011.07.014","volume":"62","author":"BS McEwen","year":"2012","unstructured":"McEwen BS, Eiland L, Hunter RG, Miller MM (2012) Stress and anxiety: Structural plasticity and epigenetic regulation as a consequence of stress. Neuropharmacology 62:3\u201312. https:\/\/doi.org\/10.1016\/j.neuropharm.2011.07.014","journal-title":"Neuropharmacology"},{"key":"1132_CR54","doi-asserted-by":"publisher","first-page":"38382","DOI":"10.1074\/jbc.M110.146258","volume":"285","author":"H Minagawa","year":"2010","unstructured":"Minagawa H, Watanabe A, Akatsu H et al (2010) Homocysteine, another risk factor for alzheimer disease, impairs apolipoprotein E3 function. J Biol Chem 285:38382\u201338388. https:\/\/doi.org\/10.1074\/jbc.M110.146258","journal-title":"J Biol Chem"},{"key":"1132_CR55","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1523\/JNEUROSCI.4464-06.2007","volume":"27","author":"AE Moseley","year":"2007","unstructured":"Moseley AE, Williams MT, Schaefer TL et al (2007) Deficiency in Na+, K+-ATPase alpha isoform genes alters spatial learning, motor activity, and anxiety in mice. J Neurosci 27:616\u2013626. https:\/\/doi.org\/10.1523\/JNEUROSCI.4464-06.2007","journal-title":"J Neurosci"},{"key":"1132_CR56","first-page":"55","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann T (1983) Rapid Colorimetric Assay for Cellular Growth and Survival\u202f: Application to Proliferation and Cytotoxicity Assays 65:55\u201363","journal-title":"Rapid Colorimetric Assay for Cellular Growth and Survival : Application to Proliferation and Cytotoxicity Assays"},{"key":"1132_CR57","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/9781118840634.ch7","volume-title":"Diet and exercise in cognitive function and neurological diseases","author":"A Moustafa","year":"2015","unstructured":"Moustafa A, Hewedi D, Eissa A et al (2015) Homocysteine levels in neurologicaL disorders. In: Farooqui T, Farooqui AA (eds) Diet and exercise in cognitive function and neurological diseases. John Wiley & Sons Inc, First Edit, pp 73\u201381"},{"key":"1132_CR58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnbeh.2014.00343","volume":"8","author":"AA Moustafa","year":"2014","unstructured":"Moustafa AA, Hewedi DH, Eissa AM et al (2014) Homocysteine levels in schizophrenia and affective disorders \u2014 focus on cognition. Front Behav Neurosci 8:1\u201310. https:\/\/doi.org\/10.3389\/fnbeh.2014.00343","journal-title":"Front Behav Neurosci"},{"key":"1132_CR59","first-page":"21","volume":"107","author":"CK Nielsen","year":"2000","unstructured":"Nielsen CK, Arnt J, Sa C (2000) Intracranial Self-Stimulation and Sucrose Intake Differ as Hedonic Measures following Chronic Mild Stress\u202f: Interstrain and Interindividual Differences 107:21\u201333","journal-title":"Intracranial Self-Stimulation and Sucrose Intake Differ as Hedonic Measures following Chronic Mild Stress : Interstrain and Interindividual Differences"},{"key":"1132_CR60","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.neulet.2010.06.072","volume":"481","author":"K Park","year":"2010","unstructured":"Park K, Oh JH, Yoo H et al (2010) Neuroscience Letters ( \u2212 ) -Epigallocatechin-3- O -gallate ( EGCG ) reverses caffeine-induced anxiogenic-like effects. Neurosci Lett 481:131\u2013134. https:\/\/doi.org\/10.1016\/j.neulet.2010.06.072","journal-title":"Neurosci Lett"},{"key":"1132_CR61","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.physbeh.2014.04.011","volume":"130","author":"G Patki","year":"2014","unstructured":"Patki G, Solanki N, Atrooz F et al (2014) Novel mechanistic insights into treadmill exercise based rescue of social defeat-induced anxiety-like behavior and memory impairment in rats. Physiol Behav 130:135\u2013144. https:\/\/doi.org\/10.1016\/j.physbeh.2014.04.011","journal-title":"Physiol Behav"},{"key":"1132_CR62","volume-title":"The Rat Brain in Stereotaxic Coordinates, 6th Editio","author":"G Paxinos","year":"2007","unstructured":"Paxinos G, Watson C (2007) The Rat Brain in Stereotaxic Coordinates, 6th Editio. Academic Press, San Diego, CA"},{"key":"1132_CR63","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/0165-0270(85)90031-7","volume":"14","author":"S Pellow","year":"1985","unstructured":"Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149\u2013167. https:\/\/doi.org\/10.1016\/0165-0270(85)90031-7","journal-title":"J Neurosci Methods"},{"key":"1132_CR64","doi-asserted-by":"publisher","DOI":"10.1002\/9780470475973.ch18","author":"RE Petrea","year":"2008","unstructured":"Petrea RE, Seshadri S (2008) Homocysteine and neurological disorders. Glutathione Sulfur Amin Acids Hum Heal Dis. https:\/\/doi.org\/10.1002\/9780470475973.ch18","journal-title":"Glutathione Sulfur Amin Acids Hum Heal Dis"},{"key":"1132_CR65","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/266730a0","volume":"266","author":"RD Porsolt","year":"1977","unstructured":"Porsolt RD, Le PM, Jalfre M (1977) Depression\u202f: a new animal model sensitive to antidepressant treatments. Nature 266:730\u2013732","journal-title":"Nature"},{"key":"1132_CR66","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1017\/S1368980018003610","volume":"22","author":"J Roig\u00e9-Castellv\u00ed","year":"2019","unstructured":"Roig\u00e9-Castellv\u00ed J, Murphy M, Fern\u00e1ndez-Ballart J, Canals J (2019) Moderately elevated preconception fasting plasma total homocysteine is a risk factor for psychological problems in childhood. Public Health Nutr 22:1615\u20131623. https:\/\/doi.org\/10.1017\/S1368980018003610","journal-title":"Public Health Nutr"},{"key":"1132_CR67","doi-asserted-by":"publisher","unstructured":"Rubin H (2005) Central Roles of Mg2+ and MgATP2- in the Regulation of Protein Synthesis and Cell Proliferation\u202f: Significance for Neoplastic Transformation. Adv Cancer Res 1\u201358. Doi: https:\/\/doi.org\/10.1016\/S0065-230X(05)93001-7","DOI":"10.1016\/S0065-230X(05)93001-7"},{"key":"1132_CR68","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/0014-4827(82)90314-7","volume":"139","author":"H Sanui","year":"1982","unstructured":"Sanui H, Rubin H (1982) Changes of intracellular and externally bound cations accompanying serum stimulation of mouse BALB\/c 3T3 cells. Exp Cell Res 139:15\u201325","journal-title":"Exp Cell Res"},{"key":"1132_CR69","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.ijdevneu.2011.06.004","volume":"29","author":"EBS Scherer","year":"2011","unstructured":"Scherer EBS, da Cunha AA, Kolling J et al (2011) Development of an animal model for chronic mild hyperhomocysteinemia and its response to oxidative damage. Int J Dev Neurosci 29:693\u2013699. https:\/\/doi.org\/10.1016\/j.ijdevneu.2011.06.004","journal-title":"Int J Dev Neurosci"},{"key":"1132_CR70","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s11010-013-1598-6","volume":"378","author":"EBS Scherer","year":"2013","unstructured":"Scherer EBS, Loureiro SO, Vuaden FC et al (2013) Mild hyperhomocysteinemia reduces the activity and immunocontent, but does not alter the gene expression, of catalytic \u03b1 subunits of cerebral Na +, K+-ATPase. Mol Cell Biochem 378:91\u201397. https:\/\/doi.org\/10.1007\/s11010-013-1598-6","journal-title":"Mol Cell Biochem"},{"key":"1132_CR71","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/145370a0","volume":"8","author":"J Schulkin","year":"2006","unstructured":"Schulkin J (2006) Angst and the amygdala. Dialogues Clin Neurosci 8:407\u2013416. https:\/\/doi.org\/10.1038\/145370a0","journal-title":"Dialogues Clin Neurosci"},{"key":"1132_CR72","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1111\/bcpt.12424","volume":"117","author":"M Sharma","year":"2015","unstructured":"Sharma M, Tiwari M, Tiwari RK (2015) Hyperhomocysteinemia: Impact on neurodegenerative diseases. Basic Clin Pharmacol Toxicol 117:287\u2013296. https:\/\/doi.org\/10.1111\/bcpt.12424","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"1132_CR73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms17101733","volume":"17","author":"H Skovierov\u00e1","year":"2016","unstructured":"Skovierov\u00e1 H, Vidomanov\u00e1 E, Mahmood S et al (2016) The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int J Mol Sci 17:1\u201318. https:\/\/doi.org\/10.3390\/ijms17101733","journal-title":"Int J Mol Sci"},{"key":"1132_CR74","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/515180a","volume":"15","author":"K Smith","year":"2014","unstructured":"Smith K (2014) Mental health: a world of depression. Nature 15:180\u2013181","journal-title":"Nature"},{"key":"1132_CR75","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s11010-014-2296-8","volume":"401","author":"I Srejovic","year":"2014","unstructured":"Srejovic I, Jakovljevic V, Zivkovic V et al (2014) The effects of the modulation of NMDA receptors by homocysteine thiolactone and dizocilpine on cardiodynamics and oxidative stress in isolated rat heart. Mol Cell Biochem 401:97\u2013105. https:\/\/doi.org\/10.1007\/s11010-014-2296-8","journal-title":"Mol Cell Biochem"},{"key":"1132_CR76","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1586\/ern.09.75","volume":"9","author":"O Stanger","year":"2009","unstructured":"Stanger O, Fowler B, Pietrzik K et al (2009) Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: Review and treatment recommendations. Expert Rev Neurother 9:1393\u20131412. https:\/\/doi.org\/10.1586\/ern.09.75","journal-title":"Expert Rev Neurother"},{"key":"1132_CR77","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s11010-013-1919-9","volume":"388","author":"N Stefanello","year":"2014","unstructured":"Stefanello N, Schmatz R, Belmonte L et al (2014) Effects of chlorogenic acid, caffeine, and coffee on behavioral and biochemical parameters of diabetic rats. Mol Cell Biochem 388:277\u2013286. https:\/\/doi.org\/10.1007\/s11010-013-1919-9","journal-title":"Mol Cell Biochem"},{"key":"1132_CR78","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1097\/ALN.0b013e318212ba87","volume":"4","author":"T Steimer","year":"2002","unstructured":"Steimer T (2002) The biology of fear- and anxiety-related behaviors. Dialogues Clin Neurosci 4:231\u2013249. https:\/\/doi.org\/10.1097\/ALN.0b013e318212ba87","journal-title":"Dialogues Clin Neurosci"},{"key":"1132_CR79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4021\/jocmr2010.02.263w","volume":"2","author":"M Suhail","year":"2010","unstructured":"Suhail M (2010) Na, K-ATPase: Ubiquitous multifunctional transmembrane protein and its relevance to various pathophysiological conditions. J Clin Med Res 2:1\u201317. https:\/\/doi.org\/10.4021\/jocmr2010.02.263w","journal-title":"J Clin Med Res"},{"key":"1132_CR80","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0445-0","author":"B Tagliari","year":"2010","unstructured":"Tagliari B, Dos Santos TM, Cunha AA et al (2010) Chronic variable stress induces oxidative stress and decreases butyrylcholinesterase activity in blood of rats. J Neural Transm. https:\/\/doi.org\/10.1007\/s00702-010-0445-0","journal-title":"J Neural Transm"},{"key":"1132_CR81","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/s11064-010-0367-0","volume":"36","author":"B Tagliari","year":"2011","unstructured":"Tagliari B, Tagliari AP, Schmitz F et al (2011) Chronic variable stress alters inflammatory and cholinergic parameters in hippocampus of rats. Neurochem Res a 36:487\u2013493. https:\/\/doi.org\/10.1007\/s11064-010-0367-0","journal-title":"Neurochem Res a"},{"key":"1132_CR82","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.44","author":"AA Walf","year":"2007","unstructured":"Walf AA, Frye CA (2007). The Use of the Elevated plus Maze as an Assay of Anxiety-Related Behavior in Rodents. https:\/\/doi.org\/10.1038\/nprot.2007.44","journal-title":"The Use of the Elevated plus Maze as an Assay of Anxiety-Related Behavior in Rodents"},{"key":"1132_CR83","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S0076-6879(81)77046-0","volume":"77","author":"A Wendel","year":"1981","unstructured":"Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325\u2013333","journal-title":"Methods Enzymol"},{"key":"1132_CR84","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/biof.71","volume":"36","author":"KT Williams","year":"2010","unstructured":"Williams KT, Schalinske KL (2010) Homocysteine metabolism and its relation to health and disease. BioFactors 36:19\u201324. https:\/\/doi.org\/10.1002\/biof.71","journal-title":"BioFactors"},{"key":"1132_CR86","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.physbeh.2003.10.002","volume":"80","author":"ATS Wyse","year":"2004","unstructured":"Wyse ATS, Bavaresco CS, Reis EA et al (2004) Training in inhibitory avoidance causes a reduction of Na+, K+-ATPase activity in rat hippocampus. Physiol Behav 80:475\u2013479. https:\/\/doi.org\/10.1016\/j.physbeh.2003.10.002","journal-title":"Physiol Behav"},{"key":"1132_CR87","doi-asserted-by":"publisher","DOI":"10.1016\/J.BRAINRES.2019.146592","volume":"1728","author":"ATS Wyse","year":"2020","unstructured":"Wyse ATS, Sanches EF, Dos Santos TM et al (2020) Chronic mild hyperhomocysteinemia induces anxiety-like symptoms, aversive memory deficits and hippocampus atrophy in adult rats: New insights into physiopathological mechanisms. Brain Res 1728:146592. https:\/\/doi.org\/10.1016\/J.BRAINRES.2019.146592","journal-title":"Brain Res"},{"key":"1132_CR88","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1007\/s00702-014-1180-8","volume":"121","author":"Y Zhou","year":"2014","unstructured":"Zhou Y, Danbolt NC (2014) Glutamate as a neurotransmitter in the healthy brain. J Neural Transm 121:799\u2013817. https:\/\/doi.org\/10.1007\/s00702-014-1180-8","journal-title":"J Neural Transm"}],"container-title":["Cellular and Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-021-01132-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10571-021-01132-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-021-01132-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T11:41:59Z","timestamp":1699270919000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10571-021-01132-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":87,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["1132"],"URL":"https:\/\/doi.org\/10.1007\/s10571-021-01132-0","relation":{},"ISSN":["0272-4340","1573-6830"],"issn-type":[{"value":"0272-4340","type":"print"},{"value":"1573-6830","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,29]]},"assertion":[{"value":"7 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest. All authors have approved the final article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Wistar male rats (thirty days old, 70\u201380\u00a0g) were obtained from the Central Animal House of Biochemistry Department, Institute of Basic Health Sciences at the Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. Animals were maintained with lights on 7:00 a.m. at 7:00\u00a0p.m. (12:12\u00a0h light\/dark cycle) in a colony room constant temperature (22\u2009\u00b1\u20091\u00a0\u00b0C), with ad libitum 20% protein commercial chow (w\/w) and water (3\u20134 animals per home cage). The rats were randomized into two groups: control and HCY. Every effort was made to minimize the number of animals and the distress caused throughout the experiment. Official government guidelines for animal care by the Brazilian Federal Law No. 11,794 of October 08, 2008, the NIH Guide to the Care and Use of Laboratory Animals (NIH Publication No. 80\u201323, 1996), and the ARRIVE guidelines were followed to work development. The experimental protocol was approved by UFRGS Ethics Committee for Animals Use (#33301\/2017). The reagents and part of the inputs used in the assays were purchased from Sigma-Aldrich (San Luis, Missouri, EUA) or Merck Millipore (Burlington, Massachusetts, EUA).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}