{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:27:44Z","timestamp":1793312864173,"version":"4.5.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960211"],"award-info":[{"award-number":["81960211"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81460175"],"award-info":[{"award-number":["81460175"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81060093"],"award-info":[{"award-number":["81060093"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["ZCLZ24H0901"],"award-info":[{"award-number":["ZCLZ24H0901"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang medicine and health science and technology project of Zhejiang Provincial Health Commission","award":["2023KY037"],"award-info":[{"award-number":["2023KY037"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Some pregnant women have to experience non-obstetric surgery during pregnancy under general anesthesia. Our previous studies showed that maternal exposure to sevoflurane, isoflurane, propofol, and ketamine causes cognitive deficits in offspring. Histone acetylation has been implicated in synaptic plasticity. Propofol is commonly used in non-obstetric procedures on pregnant women. Previous studies in our laboratory showed that maternal propofol exposure in pregnancy impairs learning and memory in offspring by disturbing histone acetylation. The present study aims to investigate whether HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) could attenuate learning and memory deficits in offspring caused by maternal surgery under propofol anesthesia during mid-pregnancy. Maternal rats were exposed to propofol or underwent abdominal surgery under propofol anesthesia during middle pregnancy. The learning and memory abilities of the offspring rats were assessed using the Morris water maze (MWM) test. The protein levels of histone deacetylase 2 (HDAC2), phosphorylated cAMP response-element binding (p-CREB), brain-derived neurotrophic factor (BDNF), and phosphorylated tyrosine kinase B (p-TrkB) in the hippocampus of the offspring rats were evaluated by immunofluorescence staining and western blot. Hippocampal neuroapoptosis was detected by TUNEL staining. Our results showed that maternal propofol exposure during middle pregnancy impaired the water-maze learning and memory of the offspring rats, increased the protein level of HDAC2 and reduced the protein levels of p-CREB, BDNF and p-TrkB in the hippocampus of the offspring, and such effects were exacerbated by surgery. SAHA alleviated the cognitive dysfunction and rescued the changes in the protein levels of p-CREB, BDNF and p-TrkB induced by maternal propofol exposure alone or maternal propofol exposure plus surgery. Therefore, SAHA could be a potential and promising agent for treating the learning and memory deficits in offspring caused by maternal nonobstetric surgery under propofol anesthesia.<\/jats:p>","DOI":"10.1371\/journal.pone.0295096","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T13:24:14Z","timestamp":1711718654000},"page":"e0295096","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Suberoylanilide hydroxamic acid attenuates cognitive impairment in offspring caused by maternal surgery during mid-pregnancy"],"prefix":"10.1371","volume":"19","author":[{"given":"Yunlin","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0106-0710","authenticated-orcid":true,"given":"Foquan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"issue":"3","key":"pone.0295096.ref001","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1523\/JNEUROSCI.23-03-00876.2003","article-title":"Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits","volume":"23","author":"V. Jevtovic-Todorovic","year":"2003","journal-title":"J Neurosci"},{"issue":"8","key":"pone.0295096.ref002","first-page":"94250","article-title":"Effects of fetal exposure to isoflurane on postnatal memory and learning in rats","volume":"53","author":"Y. Li","year":"2007","journal-title":"Neuropharmacology"},{"issue":"4","key":"pone.0295096.ref003","first-page":"235","article-title":"Anesthesia for non-obstetric surgery in the pregnant patient","volume":"73","author":"M. Van De Velde","year":"2007","journal-title":"Minerva Anestesiol"},{"issue":"2","key":"pone.0295096.ref004","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3390\/brainsci4020356","article-title":"Propofol exposure in pregnant rats induces neurotoxicity and persistent learning deficit in the offspring","volume":"4","author":"M. Xiong","year":"2014","journal-title":"Brain Sci"},{"issue":"3","key":"pone.0295096.ref005","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/ALN.0b013e3182834d5d","article-title":"Sevoflurane anesthesia in pregnant mice induces neurotoxicity in fetal and offspringmice","volume":"118","author":"H. Zheng","year":"2013","journal-title":"Anesthesiology"},{"issue":"Suppl 1","key":"pone.0295096.ref006","doi-asserted-by":"crossref","first-page":"i61","DOI":"10.1093\/bja\/aeq302","article-title":"Early childhood general anaesthesia exposure and neurocognitive development","volume":"105","author":"L. Sun","year":"2010","journal-title":"Br J Anaesth"},{"issue":"2","key":"pone.0295096.ref007","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ajog.2014.09.001","article-title":"Antepartum nonobstetrical surgery at\u226523 weeks\u2019 gestation and risk for preterm delivery.","volume":"212","author":"E.A. Baldwin","year":"2015","journal-title":"Am J Obstet Gynecol"},{"issue":"2","key":"pone.0295096.ref008","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ijoa.2012.01.005","article-title":"Maternal anesthesia and fetal neurodevelopment.","volume":"21","author":"A. Palanisamy","year":"2012","journal-title":"Int J Obstet Anesth"},{"issue":"8","key":"pone.0295096.ref009","doi-asserted-by":"crossref","first-page":"e0160826","DOI":"10.1371\/journal.pone.0160826","article-title":"Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2.","volume":"11","author":"F. Luo","year":"2016","journal-title":"PLoS One"},{"issue":"2","key":"pone.0295096.ref010","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1097\/ALN.0b013e318242b2cd","article-title":"Ketamine-induced neuroapoptosis in the fetal and neonatal rhesus macaque brain","volume":"116","author":"A.M. Brambrink","year":"2012","journal-title":"Anesthesiology"},{"issue":"4","key":"pone.0295096.ref011","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S0092-8674(02)01074-7","article-title":"Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure","volume":"111","author":"Z. Guan","year":"2002","journal-title":"Cell"},{"issue":"6","key":"pone.0295096.ref012","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.neuron.2004.06.002","article-title":"CBP histone acetyltransferase activity is a critical component of memory consolidation","volume":"42","author":"E. Korzus","year":"2004","journal-title":"Neuron"},{"issue":"7","key":"pone.0295096.ref013","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1523\/JNEUROSCI.5819-11.2012","article-title":"Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition","volume":"32","author":"Z. Zhao","year":"2012","journal-title":"J Neurosci"},{"issue":"4","key":"pone.0295096.ref014","doi-asserted-by":"crossref","first-page":"e0125815","DOI":"10.1371\/journal.pone.0125815","article-title":"Neonatal isoflurane exposure induces neurocognitive impairment and abnormal hippocampal histone acetylation in mice.","volume":"10","author":"T. Zhong","year":"2015","journal-title":"PLoS One"},{"key":"pone.0295096.ref015","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.nbd.2016.03.017","article-title":"Role of histone acetylation in long-term neurobehavioral effects of neonatal Exposure to sevoflurane in rats","author":"M. Jia","year":"2016","journal-title":"Neurobiol Dis"},{"issue":"4","key":"pone.0295096.ref016","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1093\/bja\/aeu184","article-title":"Repression of contexual fear memory induced by isoflurane is accompanied by reduction in histone acetylation and rescued by sodium butyrate","volume":"113","author":"T. Zhong","year":"2014","journal-title":"Br J Anaesth"},{"issue":"7141","key":"pone.0295096.ref017","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nature05772","article-title":"Recovery of learning and memory is associated with chromatin remodelling","volume":"447","author":"A. Fischer","year":"2007","journal-title":"Nature"},{"issue":"1","key":"pone.0295096.ref018","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00213-013-3078-9","article-title":"Vorinostat ameliorates impaired fear extinction possibly via the hippocampal NMDA-CaMKII pathway in an animal model of posttraumatic stress disorder","volume":"229","author":"Y. Matsumoto","year":"2013","journal-title":"Psychopharmacology (Berl)"},{"issue":"4","key":"pone.0295096.ref019","doi-asserted-by":"crossref","first-page":"10769","DOI":"10.4238\/2014.December.18.18","article-title":"SAHA attenuates sevoflurane-induced learning and memory impairments in fetal mice","volume":"13","author":"X.F. Lin","year":"2014","journal-title":"Genet Mol Res"},{"issue":"7243","key":"pone.0295096.ref020","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature07925","article-title":"HDAC2 negatively regulates memory formation and synaptic plasticity","volume":"459","author":"J.S. Guan","year":"2009","journal-title":"Nature"},{"issue":"4","key":"pone.0295096.ref021","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s12640-009-9116-z","article-title":"Dysregulation of CREB activation and histone acetylation in 3-nitropropionic acid-treated cortical neurons: prevention by BDNF and NGF.","volume":"17","author":"S. Almeida","year":"2010","journal-title":"Neurotox Res"},{"issue":"6","key":"pone.0295096.ref022","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1097\/00000542-198912000-00003","article-title":"Intravenous propofol during cesarean section: placental transfer, concentrations in breast milk, and neonatal effects. A preliminary study","volume":"71","author":"P. Dailland","year":"1989","journal-title":"Anesthesiology"},{"issue":"1","key":"pone.0295096.ref023","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1046\/j.1365-2710.1998.00124.x","article-title":"Placental transfer and neonatal effects of propofol in caesarean section.","volume":"23","author":"A. S\u00e1nchez-Alcaraz","year":"1998","journal-title":"J Clin Pharm Ther"},{"issue":"Suppl 1","key":"pone.0295096.ref024","doi-asserted-by":"crossref","first-page":"i29","DOI":"10.1093\/bja\/aet173","article-title":"Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain","volume":"110","author":"C. Creeley","year":"2013","journal-title":"Br J Anaesth"},{"key":"pone.0295096.ref025","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neulet.2013.11.061","article-title":"Repeated exposure to propofol impairs spatial learning, inhibits LTP and reduces CaMKII\u03b1 in young rats","volume":"560","author":"J. Gao","year":"2014","journal-title":"Neurosci Lett"},{"issue":"5","key":"pone.0295096.ref026","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1111\/jcmm.13524","article-title":"Propofol exposure during early gestation impairs learning and memory in rat offspring by inhibiting the acetylation of histone","volume":"22","author":"J. Lin","year":"2018","journal-title":"J Cell Mol Med"},{"issue":"10","key":"pone.0295096.ref027","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1111\/jcmm.12884","article-title":"Propofol exposure during late stages of pregnancy impairs learning and memory in rat offspring via the BDNF-TrkB signalling pathway","volume":"20","author":"L. Zhong","year":"2016","journal-title":"J Cell Mol Med"},{"issue":"4","key":"pone.0295096.ref028","first-page":"5428","article-title":"KIF17 mediates the learning and memory impairment in offspring induced by maternal exposure to propofol during middle pregnancy.","volume":"17","author":"L. Wu","year":"2018","journal-title":"Mol Med Rep"},{"issue":"3","key":"pone.0295096.ref029","doi-asserted-by":"crossref","first-page":"251","DOI":"10.4062\/biomolther.2014.120","article-title":"Repeated neonatal propofol administration induces sex-dependent long-term impairments on spatial and recognition memory in rats.","volume":"23","author":"E.L. Gonzales","year":"2015","journal-title":"Biomol Ther (Seoul)"},{"issue":"2","key":"pone.0295096.ref030","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.neuron.2005.08.034","article-title":"NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII","volume":"48","author":"A. Barria","year":"2005","journal-title":"Neuron"},{"issue":"15","key":"pone.0295096.ref031","doi-asserted-by":"crossref","first-page":"6401","DOI":"10.1523\/JNEUROSCI.1001-12.2013","article-title":"Loss of histone deacetylase 2 improves working memory and accelerates extinction learning","volume":"33","author":"M.J. Morris","year":"2013","journal-title":"J Neurosci"},{"issue":"11","key":"pone.0295096.ref032","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1038\/nn.2405","article-title":"CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala","volume":"12","author":"Y. Zhou","year":"2009","journal-title":"Nat Neurosci"},{"issue":"4","key":"pone.0295096.ref033","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1101\/lm.249306","article-title":"CREB antisense oligodeoxynucleotide administration into the dorsal hippocampal CA3 region impairs long- but not short-term spatial memory in mice.","volume":"13","author":"C. Florian","year":"2006","journal-title":"Learn Mem"},{"issue":"7","key":"pone.0295096.ref034","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/cns.12088","article-title":"Rescue of cAMP response element-binding protein signaling reversed spatial memory retention impairments induced by subanesthetic dose of propofol.","volume":"19","author":"H. Zhang","year":"2013","journal-title":"CNS Neurosci Ther"},{"issue":"5594","key":"pone.0295096.ref035","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1126\/science.1075333","article-title":"Postsynaptic signaling and plasticity mechanisms","volume":"298","author":"M. Sheng","year":"2002","journal-title":"Science"},{"key":"pone.0295096.ref036","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.neuroscience.2011.12.015","article-title":"Rapid enrichment of presynaptic protein in boutons undergoing classical conditioning is mediated by brain-derived neurotrophic factor","volume":"203","author":"W. Li","year":"2012","journal-title":"Neuroscience"},{"issue":"6748","key":"pone.0295096.ref037","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/43432","article-title":"Genetic enhancement of learning and memory in mice","volume":"401","author":"Y.P. Tang","year":"1999","journal-title":"Nature"},{"issue":"1","key":"pone.0295096.ref038","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1097\/ANA.0000000000000181","article-title":"Dexmedetomidine Attenuates Neurotoxicity Induced by Prenatal Propofol Exposure","volume":"28","author":"J. Li","year":"2016","journal-title":"J Neurosurg Anesthesiol"},{"issue":"3","key":"pone.0295096.ref039","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/01.anes.0000278892.62305.9c","article-title":"Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits","volume":"107","author":"A. Fredriksson","year":"2007","journal-title":"Anesthesiology"},{"issue":"7","key":"pone.0295096.ref040","first-page":"10696","article-title":"Long-term action of propofol on cognitive function and hippocampal neuroapoptosis in neonatal rats.","volume":"8","author":"D. Han","year":"2015","journal-title":"Int J Clin Exp Med"},{"issue":"4","key":"pone.0295096.ref041","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1213\/ANE.0000000000000380","article-title":"Anesthetic preconditioning inhibits isoflurane-mediated apoptosis in the developing rat brain","volume":"119","author":"J. Peng","year":"2014","journal-title":"Anesth Analg"},{"issue":"3","key":"pone.0295096.ref042","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1097\/ALN.0b013e3182833fae","article-title":"Dual effects of isoflurane on proliferation, differentiation, and survival in human neuroprogenitor cells.","volume":"118","author":"X. Zhao","year":"2013","journal-title":"Anesthesiology"},{"issue":"8","key":"pone.0295096.ref043","first-page":"CD012317","article-title":"Intravenous versus inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non-cardiac surgery","volume":"8","author":"D. Miller","year":"2018","journal-title":"The Cochrane database of systematic reviews"},{"key":"pone.0295096.ref044","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bbi.2017.01.005","article-title":"Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery","volume":"61","author":"B. Zheng","year":"2017","journal-title":"Brain, behavior, and immunity"},{"key":"pone.0295096.ref045","doi-asserted-by":"crossref","first-page":"950093","DOI":"10.3389\/fnbeh.2022.950093","article-title":"Effects of different types of non-cardiac surgical trauma on hippocampus-dependent memory and neuroinflammation","volume":"16","author":"B. Lu","year":"2022","journal-title":"Frontiers in behavioral neuroscience"},{"key":"pone.0295096.ref046","doi-asserted-by":"crossref","first-page":"115582","DOI":"10.1016\/j.biopha.2023.115582","article-title":"Neuroinflammation: The central enabler of postoperative cognitive dysfunction.","volume":"167","author":"Y. Liu","year":"2023","journal-title":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0295096","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T13:24:42Z","timestamp":1711718682000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0295096"}},"subtitle":[],"editor":[{"given":"Uwe","family":"Rudolph","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0295096","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.11.15.567312","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,29]]}}}