{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:52:56Z","timestamp":1784811176798,"version":"3.55.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T00:00:00Z","timestamp":1360108800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0055559","type":"journal-article","created":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T21:57:52Z","timestamp":1360187872000},"page":"e55559","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["De Novo Synthesized Estradiol Protects against Methylmercury-Induced Neurotoxicity in Cultured Rat Hippocampal Slices"],"prefix":"10.1371","volume":"8","author":[{"given":"Takeshi","family":"Yamazaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Ishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Komatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Munetsuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Onizaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiko","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suguru","family":"Kawato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Mukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,2,6]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1210\/rp.57.1.357","article-title":"Estrogen actions throughout the brain","volume":"57","author":"B McEwen","year":"2002","journal-title":"Recent Prog Horm Res"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.yfrne.2009.04.014","article-title":"Neuroprotective actions of sex steroids in Parkinson&apos;s disease","volume":"30","author":"M Bourque","year":"2009","journal-title":"Front Neuroendocrinol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.yfrne.2009.04.015","article-title":"Protective actions of sex steroid hormones in Alzheimer&apos;s disease","volume":"30","author":"CJ Pike","year":"2009","journal-title":"Front Neuroendocrinol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.yfrne.2009.04.007","article-title":"Neuroprotective effects of estrogens following ischemic stroke","volume":"30","author":"S Suzuki","year":"2009","journal-title":"Front Neuroendocrinol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nrn846","article-title":"Oestrogen as a neuroprotective hormone","volume":"3","author":"C Behl","year":"2002","journal-title":"Nat Rev Neurosci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/S0306-4522(03)00167-2","article-title":"17 Beta-oestradiol attenuates dexamethasone-induced lethal and sublethal neuronal damage in the striatum and hippocampus","volume":"120","author":"LE Haynes","year":"2003","journal-title":"Neuroscience"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/toxsci\/kfp081","article-title":"Estrogen and tamoxifen protect against Mn-induced toxicity in rat cortical primary cultures of neurons and astrocytes","volume":"110","author":"ES Lee","year":"2009","journal-title":"Toxicol Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1177\/153537020623100505","article-title":"Novel mechanisms for estrogen-induced neuroprotection","volume":"231","author":"M Singh","year":"2006","journal-title":"Exp Biol Med (Maywood)"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/j.1471-4159.2008.05805.x","article-title":"Mechanism of okadaic acid-induced neuronal death and the effect of estrogens","volume":"108","author":"KD Yi","year":"2009","journal-title":"J Neurochem"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1080\/10408440802233259","article-title":"The endocrine effects of mercury in humans and wildlife","volume":"39","author":"SW Tan","year":"2009","journal-title":"Crit Rev Toxicol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/1097-4547(20001115)62:4<557::AID-JNR10>3.0.CO;2-9","article-title":"Antioxidants J811 and 17beta-estradiol protect cerebellar granule cells from methylmercury-induced apoptotic cell death","volume":"62","author":"E Dare","year":"2000","journal-title":"J Neurosci Res"},{"key":"ref12","first-page":"1","article-title":"Neurosteroids: of the nervous system, by the nervous system, for the nervous system","volume":"52","author":"EE Baulieu","year":"1997","journal-title":"Recent Prog Horm Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1210\/en.2010-0607","article-title":"Developmental time course of estradiol, testosterone, and dihydrotestosterone levels in discrete regions of male and female rat brain","volume":"152","author":"AT Konkle","year":"2011","journal-title":"Endocrinology"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"5913","DOI":"10.1523\/JNEUROSCI.5186-03.2004","article-title":"Hippocampal synapses depend on hippocampal estrogen synthesis","volume":"24","author":"O Kretz","year":"2004","journal-title":"J Neurosci"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"4260","DOI":"10.1210\/en.2008-1644","article-title":"Retinoic acid stimulates 17beta-estradiol and testosterone synthesis in rat hippocampal slice cultures","volume":"150","author":"E Munetsuna","year":"2009","journal-title":"Endocrinology"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00441-011-1221-7","article-title":"Estrogen synthesis in the hippocampus","volume":"345","author":"L Fester","year":"2011","journal-title":"Cell Tissue Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1073\/pnas.2630225100","article-title":"Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons","volume":"101","author":"Y Hojo","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1097\/01.ftd.0000160275.85450.32","article-title":"Methylmercury: recent advances in the understanding of its neurotoxicity","volume":"27","author":"M Aschner","year":"2005","journal-title":"Ther Drug Monit"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3109\/10408369708998098","article-title":"The toxicology of mercury","volume":"34","author":"TW Clarkson","year":"1997","journal-title":"Crit Rev Clin Lab Sci"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1126\/science.181.4096.230","article-title":"Methylmercury poisoning in Iraq","volume":"181","author":"F Bakir","year":"1973","journal-title":"Science"},{"key":"ref21","article-title":"Minamata disease","volume":"20","author":"K Eto","year":"2000","journal-title":"Neuropathology"},{"key":"ref22","first-page":"73","article-title":"Pathology of Minamata disease. With special reference to its pathogenesis","volume":"32","author":"T Takeuchi","year":"1982","journal-title":"Acta Pathol Jpn"},{"key":"ref23","first-page":"607","article-title":"Distribution and fate of mercury in tissue of human organs in Minamata disease","volume":"1","author":"M Okabe","year":"1980","journal-title":"Neurotoxicology"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1177\/019262339702500612","article-title":"Pathology of Minamata disease","volume":"25","author":"K Eto","year":"1997","journal-title":"Toxicol Pathol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.etap.2008.11.005","article-title":"17beta-estradiol decreases methylmercury-induced neurotoxicity in male mice","volume":"27","author":"KS Malagutti","year":"2009","journal-title":"Environ Toxicol Pharmacol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.brainres.2004.02.066","article-title":"Estrogen receptor subtypes alpha and beta contribute to neuroprotection and increased Bcl-2 expression in primary hippocampal neurons","volume":"1010","author":"L Zhao","year":"2004","journal-title":"Brain Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.neuint.2012.03.004","article-title":"Tributyltin induces oxidative stress and neuronal injury by inhibiting glutathione S-transferase in rat organotypic hippocampal slice cultures","volume":"60","author":"Y Ishihara","year":"2012","journal-title":"Neurochem Int"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1254\/jphs.SC0070119","article-title":"A low-cost method for brain slice cultures","volume":"104","author":"R Koyama","year":"2007","journal-title":"J Pharmacol Sci"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0165-0270(90)90007-3","article-title":"Progressive incorporation of propidium iodide in cultured mouse neurons correlates with declining electrophysiological status: a fluorescence scale of membrane integrity","volume":"31","author":"JD Macklis","year":"1990","journal-title":"J Neurosci Methods"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/BF00269095","article-title":"Differential kinetics of propidium iodide uptake in apoptotic and necrotic thymocytes","volume":"100","author":"M Vitale","year":"1993","journal-title":"Histochemistry"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"5106","DOI":"10.1210\/en.2009-0305","article-title":"Comparison between hippocampus-synthesized and circulation-derived sex steroids in the hippocampus","volume":"150","author":"Y Hojo","year":"2009","journal-title":"Endocrinology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s007260070029","article-title":"Excitatory amino acid neurotoxicity and modulation of glutamate receptor expression in organotypic brain slice cultures","volume":"19","author":"J Zimmer","year":"2000","journal-title":"Amino Acids"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1111\/j.1471-4159.2007.04882.x","article-title":"Developmental mercury exposure elicits acute hippocampal cell death, reductions in neurogenesis, and severe learning deficits during puberty","volume":"103","author":"A Falluel-Morel","year":"2007","journal-title":"J Neurochem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.yfrne.2009.04.016","article-title":"Neuroprotective actions of brain aromatase","volume":"30","author":"CJ Saldanha","year":"2009","journal-title":"Front Neuroendocrinol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.brainresrev.2004.12.018","article-title":"Glia-neuron crosstalk in the neuroprotective mechanisms of sex steroid hormones","volume":"48","author":"D Garcia-Ovejero","year":"2005","journal-title":"Brain Res Brain Res Rev"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s11064-005-9004-8","article-title":"Synaptic plasticity in the hippocampus: effects of estrogen from the gonads or hippocampus?","volume":"31","author":"GM Rune","year":"2006","journal-title":"Neurochem Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1124\/pr.58.4.8","article-title":"International Union of Pharmacology. LXIV. Estrogen receptors","volume":"58","author":"K Dahlman-Wright","year":"2006","journal-title":"Pharmacol Rev"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1177\/019262339702500613","article-title":"A review of experimental methylmercury toxicity in rats: neuropathology and evidence for apoptosis","volume":"25","author":"K Nagashima","year":"1997","journal-title":"Toxicol Pathol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1165\/ajrcmb.20.6.3424","article-title":"Oxidative stress produced by marijuana smoke. An adverse effect enhanced by cannabinoids","volume":"20","author":"TA Sarafian","year":"1999","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ref40","first-page":"17","article-title":"Oxidative stress in neurotoxic effects of methylmercury poisoning","volume":"17","author":"S Yee","year":"1996","journal-title":"Neurotoxicology"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.cbi.2010.04.007","article-title":"Methylmercury-induced neurotoxicity and apoptosis","volume":"188","author":"S Ceccatelli","year":"2010","journal-title":"Chem Biol Interact"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.pneurobio.2003.09.005","article-title":"Aromatase: a neuroprotective enzyme","volume":"71","author":"LM Garcia-Segura","year":"2003","journal-title":"Prog Neurobiol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1172\/JCI109433","article-title":"Transport of steroid hormones through the rat blood-brain barrier. Primary role of albumin-bound hormone","volume":"64","author":"WM Pardridge","year":"1979","journal-title":"J Clin Invest"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0006-8993(95)01208-7","article-title":"Variability of brain lesions in rats administered methylmercury at various postnatal development phases","volume":"705","author":"K Wakabayashi","year":"1995","journal-title":"Brain Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.neuro.2009.08.001","article-title":"Methylmercury induces neuropathological changes with tau hyperphosphorylation mainly through the activation of the c-jun-N-terminal kinase pathway in the cerebral cortex, but not in the hippocampus of the mouse brain","volume":"30","author":"M Fujimura","year":"2009","journal-title":"Neurotoxicology"},{"key":"ref46","first-page":"651","article-title":"Mercury level and histochemical distribution in a human brain with Minamata disease following a long-term clinical course of twenty-six years","volume":"10","author":"T Takeuchi","year":"1989","journal-title":"Neurotoxicology"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1046\/j.1365-2265.1998.00390.x","article-title":"Aromatase in the human central nervous system","volume":"48","author":"H Sasano","year":"1998","journal-title":"Clin Endocrinol (Oxf)"}],"updated-by":[{"DOI":"10.1371\/annotation\/52376e1c-1a2d-44af-a129-849345da78a0","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2013,4,22]],"date-time":"2013-04-22T00:00:00Z","timestamp":1366588800000}}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0055559","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T10:36:05Z","timestamp":1562668565000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0055559"}},"subtitle":[],"editor":[{"given":"Allan","family":"Siegel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,2,6]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2013,2,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0055559","relation":{"correction":[{"id-type":"doi","id":"10.1371\/annotation\/52376e1c-1a2d-44af-a129-849345da78a0","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,6]]}}}