{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:22:11Z","timestamp":1765545731280,"version":"3.37.3"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,14]],"date-time":"2012-04-14T00:00:00Z","timestamp":1334361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Homocysteine is a neurotoxic amino acid that accumulates in several disorders including homocystinuria, neurodegenerative and neuroinflammatory diseases. In the present study we evaluated the effect of acute and chronic hyperhomocysteinemia on Akt, NF\u2010\u03baB\/p65, GSK\u20103\u03b2, as well as<jats:italic>Tau<\/jats:italic>protein in hippocampus of rats. For acute treatment, rats received a single injection of homocysteine (0.6 \u03bcmol\/g body weight) or saline (control). For chronic treatment, rats received daily subcutaneous injections of homocysteine (0.3\u20130.6 \u03bcmol\/g body weight) or saline (control) from the 6th to the 28th days\u2010of\u2010age. One or 12 h after the last injection, rats were euthanized, the hippocampus was removed and samples were submitted to electrophoresis followed by Western blotting. Results showed that acute hyperhomocysteinemia increases Akt phosphorylation, cytosolic and nuclear immunocontent of NF\u2010\u03baB\/p65 subunit and<jats:italic>Tau<\/jats:italic>protein phosphorylation, but reduces GSK\u20103\u03b2 phosphorylation at 1 h after homocysteine injection. However, 12 h after acute hyperhomocysteinemia there is no effect on Akt and GSK\u20103\u03b2 phosphorylation. Furthermore, chronic hyperhomocysteinemia did not alter Akt and GSK\u20103\u03b2 phosphorylation at 1 h and 12 h after the last administration of this amino acid. Our data showed that Akt, NF\u2010\u03baB\/p65, GSK\u20103\u03b2 and<jats:italic>Tau<\/jats:italic>protein are activated in hippocampus of rats subjected to acute hyperhomocysteinemia, suggesting that these signaling pathways may be, at least in part, important contributors to the neuroinflammation and\/or brain dysfunction observed in some hyperhomocystinuric patients.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2012.04.001","type":"journal-article","created":{"date-parts":[[2012,4,14]],"date-time":"2012-04-14T05:56:15Z","timestamp":1334382975000},"page":"369-374","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evidence that AKT and GSK\u20103\u03b2 pathway are involved in acute hyperhomocysteinemia"],"prefix":"10.1002","volume":"30","author":[{"given":"Aline A.","family":"da Cunha","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula","family":"Horn","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia Instituto de Ci\u00eancias Biol\u00f3gicas Universidade Federal de Rio Grande Rio Grande RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana B.","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia B.","family":"Grudzinski","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samanta O.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9a G.K.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maira J.","family":"da Cunha","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christianne G.","family":"Salbego","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela T.S.","family":"Wyse","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,4,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000108264.67601.2C"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2005.06.021"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.01.008"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2007.01.014"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3350001"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.22.2905"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-010-9188-8"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.10.1422"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(98)80149-X"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.02.016"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000209545.29671.31"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10686"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000115161.10646.67"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/82.2.335"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.26.2.4640"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(01)00011-9"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306976200"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.10.026"},{"key":"e_1_2_6_21_1","first-page":"515","article-title":"Review of the role of hyperhomocysteinemia and B\u2010vitamin deficiency in neurological and psychiatric disorders\u2013current evidence and preliminary recommendations","volume":"75","author":"Herrmann W.","year":"2007","journal-title":"Fortschritte der Neurologie\u2010Psychiatrie"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10416"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03033381"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409816200"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2003.12.004"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-006-9128-5"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(96)13011-1"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.24.9356-9363.2000"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri910"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21868"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00433-0"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1221"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2008.08.011"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.07.023"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1385\/NMM:3:2:65"},{"issue":"2","key":"e_1_2_6_36_1","doi-asserted-by":"crossref","first-page":"E536","DOI":"10.1371\/journal.pone.0000536","article-title":"Mitochondrial oxidative stress causes hyperphosphorylation of tau","volume":"20","author":"Melov S.","year":"2007","journal-title":"PLoS One"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2008.11.029"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2002.02976.x"},{"key":"e_1_2_6_39_1","series-title":"The Metabolic and Molecular Basis of Inherited Disease","first-page":"1279","volume-title":"Disorders of transsulfuration","author":"Mudd S.H.","year":"2001"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.04.088"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2007.356"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4956-07.2008"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)02323-1"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01640"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.3.1355"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2565"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1516-44462004000100013"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3423"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021670607647"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023815119931"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi035627j"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2008.10.014"},{"key":"e_1_2_6_53_1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1042\/bj3520817","article-title":"Homocysteine stimulates nuclear factor kappaB activity and monocyte chemoattractant protein\u20101 expression in vascular smooth\u2010muscle cells: a possible role for protein kinase C","volume":"3","author":"Wang G.","year":"2000","journal-title":"The Biochemical Journal"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2003.223"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199804093381507"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.12.010"},{"key":"e_1_2_6_57_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.55782\/ane-2006-1619","article-title":"Excitotoxic neuronal injury in chronic homocysteine neurotoxicity studied in vitro: the role of NMDA and group I metabotropic glutamate receptors","volume":"66","author":"Zieminska E.","year":"2006","journal-title":"Acta Neurobiologiae Experimentalis"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.274.6.R1704"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2006.03.007"}],"container-title":["International Journal of Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0736574812003802?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0736574812003802?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.ijdevneu.2012.04.001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.ijdevneu.2012.04.001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.ijdevneu.2012.04.001","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.ijdevneu.2012.04.001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T06:27:38Z","timestamp":1713853658000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1016\/j.ijdevneu.2012.04.001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,14]]},"references-count":58,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,8]]}},"alternative-id":["10.1016\/j.ijdevneu.2012.04.001"],"URL":"https:\/\/doi.org\/10.1016\/j.ijdevneu.2012.04.001","archive":["Portico"],"relation":{},"ISSN":["0736-5748","1873-474X"],"issn-type":[{"type":"print","value":"0736-5748"},{"type":"electronic","value":"1873-474X"}],"subject":[],"published":{"date-parts":[[2012,4,14]]},"assertion":[{"value":"2012-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-04-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-04-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}