Ketamine exerts neurotoxic effects on the offspring of pregnant rats via the Wnt/β-catenin pathway
Ketamine is an anesthetic and analgesic drug widely used in clinical anesthesia. To ensure the safety of anesthesia, it is necessary to study its side effects. Pregnancy is a key period for the development and growth of offspring. During this period, the proliferation and differentiation of brain ce...
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| Veröffentlicht in: | Environmental science and pollution research international 2020-01, Vol.27 (1), p.305-314 |
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| description | Ketamine is an anesthetic and analgesic drug widely used in clinical anesthesia. To ensure the safety of anesthesia, it is necessary to study its side effects. Pregnancy is a key period for the development and growth of offspring. During this period, the proliferation and differentiation of brain cells and the synaptic formation are easily affected by external stimuli. Therefore, the aim of this study was to evaluate the effect of ketamine. Ketamine anesthesia was administered to rats in the second trimester of pregnancy, and two behavioral tests were performed, including contextual and cued fear conditioning test (CFC) and Morris water maze (MWM). At the end of the behavioral test, Nissl and Golgi staining were used to detect the dendrite density of hippocampal neurons to reveal the effect of maternal ketamine anesthesia on the hippocampus of offspring. Key proteins and their downstream transcription factors in Wnt/β-catenin signaling pathway from the embryonic development to the adulthood were studied. Our results showed that rats receiving maternal ketamine suffered from nerve injury. The density of hippocampal nerves and dendritic spine changed. Some genes related to Wnt/β-catenin pathway and Tcf/Lef were downregulated. In conclusion, maternal anesthesia with ketamine in the second trimester of pregnancy can lead to cognitive memory impairment and neurotoxicity in the hippocampus of offspring through Wnt/ β-catenin signaling pathway. |
| doi_str_mv | 10.1007/s11356-019-06753-z |
| format | Article |
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To ensure the safety of anesthesia, it is necessary to study its side effects. Pregnancy is a key period for the development and growth of offspring. During this period, the proliferation and differentiation of brain cells and the synaptic formation are easily affected by external stimuli. Therefore, the aim of this study was to evaluate the effect of ketamine. Ketamine anesthesia was administered to rats in the second trimester of pregnancy, and two behavioral tests were performed, including contextual and cued fear conditioning test (CFC) and Morris water maze (MWM). At the end of the behavioral test, Nissl and Golgi staining were used to detect the dendrite density of hippocampal neurons to reveal the effect of maternal ketamine anesthesia on the hippocampus of offspring. Key proteins and their downstream transcription factors in Wnt/β-catenin signaling pathway from the embryonic development to the adulthood were studied. Our results showed that rats receiving maternal ketamine suffered from nerve injury. The density of hippocampal nerves and dendritic spine changed. Some genes related to Wnt/β-catenin pathway and Tcf/Lef were downregulated. In conclusion, maternal anesthesia with ketamine in the second trimester of pregnancy can lead to cognitive memory impairment and neurotoxicity in the hippocampus of offspring through Wnt/ β-catenin signaling pathway.</description><identifier>ISSN: 0944-1344</identifier><identifier>EISSN: 1614-7499</identifier><identifier>DOI: 10.1007/s11356-019-06753-z</identifier><identifier>PMID: 31786764</identifier><language>eng</language><publisher>Germany: Springer Nature B.V</publisher><subject>Analgesics ; Analgesics - toxicity ; Anesthesia ; Animals ; beta Catenin - metabolism ; Cell differentiation ; Cell proliferation ; Cognitive ability ; Cognitive Dysfunction - metabolism ; Dendritic spines ; Dendritic structure ; Density ; Down-Regulation ; Embryogenesis ; Embryonic growth stage ; Environmental science ; External stimuli ; Fear conditioning ; Female ; Hippocampus ; Hippocampus - drug effects ; Ketamine ; Ketamine - toxicity ; LEF protein ; Male ; Memory - drug effects ; Memory Disorders - chemically induced ; Nerves ; Nervous System - drug effects ; Neurons - metabolism ; Neurotoxicity ; Neurotoxicity Syndromes - metabolism ; Offspring ; Pregnancy ; Rats ; Rodents ; Side effects ; Signal transduction ; Signaling ; Spine ; Transcription factors ; Wnt protein ; Wnt Signaling Pathway - drug effects ; β-Catenin</subject><ispartof>Environmental science and pollution research international, 2020-01, Vol.27 (1), p.305-314</ispartof><rights>Environmental Science and Pollution Research is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31786764$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xintong</creatorcontrib><creatorcontrib>Zhao, Jinghua</creatorcontrib><creatorcontrib>Chang, Tian</creatorcontrib><creatorcontrib>Wang, Qi</creatorcontrib><creatorcontrib>Liu, Wenhan</creatorcontrib><creatorcontrib>Gao, Li</creatorcontrib><title>Ketamine exerts neurotoxic effects on the offspring of pregnant rats via the Wnt/β-catenin pathway</title><title>Environmental science and pollution research international</title><addtitle>Environ Sci Pollut Res Int</addtitle><description>Ketamine is an anesthetic and analgesic drug widely used in clinical anesthesia. To ensure the safety of anesthesia, it is necessary to study its side effects. Pregnancy is a key period for the development and growth of offspring. During this period, the proliferation and differentiation of brain cells and the synaptic formation are easily affected by external stimuli. Therefore, the aim of this study was to evaluate the effect of ketamine. Ketamine anesthesia was administered to rats in the second trimester of pregnancy, and two behavioral tests were performed, including contextual and cued fear conditioning test (CFC) and Morris water maze (MWM). At the end of the behavioral test, Nissl and Golgi staining were used to detect the dendrite density of hippocampal neurons to reveal the effect of maternal ketamine anesthesia on the hippocampus of offspring. Key proteins and their downstream transcription factors in Wnt/β-catenin signaling pathway from the embryonic development to the adulthood were studied. Our results showed that rats receiving maternal ketamine suffered from nerve injury. The density of hippocampal nerves and dendritic spine changed. Some genes related to Wnt/β-catenin pathway and Tcf/Lef were downregulated. In conclusion, maternal anesthesia with ketamine in the second trimester of pregnancy can lead to cognitive memory impairment and neurotoxicity in the hippocampus of offspring through Wnt/ β-catenin signaling pathway.</description><subject>Analgesics</subject><subject>Analgesics - toxicity</subject><subject>Anesthesia</subject><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>Cell differentiation</subject><subject>Cell proliferation</subject><subject>Cognitive ability</subject><subject>Cognitive Dysfunction - metabolism</subject><subject>Dendritic spines</subject><subject>Dendritic structure</subject><subject>Density</subject><subject>Down-Regulation</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Environmental science</subject><subject>External stimuli</subject><subject>Fear conditioning</subject><subject>Female</subject><subject>Hippocampus</subject><subject>Hippocampus - drug effects</subject><subject>Ketamine</subject><subject>Ketamine - toxicity</subject><subject>LEF protein</subject><subject>Male</subject><subject>Memory - drug effects</subject><subject>Memory Disorders - chemically induced</subject><subject>Nerves</subject><subject>Nervous System - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurotoxicity</subject><subject>Neurotoxicity Syndromes - metabolism</subject><subject>Offspring</subject><subject>Pregnancy</subject><subject>Rats</subject><subject>Rodents</subject><subject>Side effects</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Spine</subject><subject>Transcription factors</subject><subject>Wnt protein</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>β-Catenin</subject><issn>0944-1344</issn><issn>1614-7499</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNo1kM1OwzAQhC0EoqXwAhyQJc6mduzY8RFV_AkkLiCO0dpdt6moExIHWh6LB-GZiKCcZjT6NKsdQk4FvxCcm2knhMw148Iyrk0u2eceGQstFDPK2n0y5lYpJqRSI3LUdSvOM24zc0hGUphCG63GxN9jgnUVkeIG29TRiH1bp3pTeYohoB-iOtK0RFqH0DVtFReDo02Liwgx0RYG4r2CX-Qlpun3F_OQMFaRNpCWH7A9JgcBXjs82emEPF9fPc1u2cPjzd3s8oE1mbSJgebeu-A0iLkpZAGADgsfwGovi9yZLCAUIoMQ7Jwrp31QuQMlXW5QF0pOyPlfb9PWbz12qVzVfRuHk2UmlcyU5VIM1NmO6t0a5-Xw0hrabfm_ifwB7N5nBA</recordid><startdate>202001</startdate><enddate>202001</enddate><creator>Zhang, Xintong</creator><creator>Zhao, Jinghua</creator><creator>Chang, Tian</creator><creator>Wang, Qi</creator><creator>Liu, Wenhan</creator><creator>Gao, Li</creator><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QL</scope><scope>7SN</scope><scope>7T7</scope><scope>7TV</scope><scope>7U7</scope><scope>7WY</scope><scope>7WZ</scope><scope>7X7</scope><scope>7XB</scope><scope>87Z</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8FL</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BEZIV</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FRNLG</scope><scope>FYUFA</scope><scope>F~G</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K60</scope><scope>K6~</scope><scope>K9.</scope><scope>L.-</scope><scope>M0C</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>P64</scope><scope>PATMY</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQBIZ</scope><scope>PQBZA</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope></search><sort><creationdate>202001</creationdate><title>Ketamine exerts neurotoxic effects on the offspring of pregnant rats via the Wnt/β-catenin pathway</title><author>Zhang, Xintong ; Zhao, Jinghua ; Chang, Tian ; Wang, Qi ; Liu, Wenhan ; Gao, Li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p239t-a60ccbfb6a1d7838aaebe8cfa96c385b72fea812aff9d04b6cf45ba43b57e6843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analgesics</topic><topic>Analgesics - 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drug effects</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Xintong</creatorcontrib><creatorcontrib>Zhao, Jinghua</creatorcontrib><creatorcontrib>Chang, Tian</creatorcontrib><creatorcontrib>Wang, Qi</creatorcontrib><creatorcontrib>Liu, Wenhan</creatorcontrib><creatorcontrib>Gao, Li</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Ecology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Pollution Abstracts</collection><collection>Toxicology Abstracts</collection><collection>ABI/INFORM Collection</collection><collection>ABI/INFORM Global (PDF only)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ABI/INFORM Global (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ABI/INFORM Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Business Premium Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Business Premium Collection (Alumni)</collection><collection>Health Research Premium Collection</collection><collection>ABI/INFORM Global (Corporate)</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Business Collection (Alumni Edition)</collection><collection>ProQuest Business Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ABI/INFORM Professional Advanced</collection><collection>ABI/INFORM Global</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Business</collection><collection>ProQuest One Business (Alumni)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><jtitle>Environmental science and pollution research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xintong</au><au>Zhao, Jinghua</au><au>Chang, Tian</au><au>Wang, Qi</au><au>Liu, Wenhan</au><au>Gao, Li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ketamine exerts neurotoxic effects on the offspring of pregnant rats via the Wnt/β-catenin pathway</atitle><jtitle>Environmental science and pollution research international</jtitle><addtitle>Environ Sci Pollut Res Int</addtitle><date>2020-01</date><risdate>2020</risdate><volume>27</volume><issue>1</issue><spage>305</spage><epage>314</epage><pages>305-314</pages><issn>0944-1344</issn><eissn>1614-7499</eissn><abstract>Ketamine is an anesthetic and analgesic drug widely used in clinical anesthesia. To ensure the safety of anesthesia, it is necessary to study its side effects. Pregnancy is a key period for the development and growth of offspring. During this period, the proliferation and differentiation of brain cells and the synaptic formation are easily affected by external stimuli. Therefore, the aim of this study was to evaluate the effect of ketamine. Ketamine anesthesia was administered to rats in the second trimester of pregnancy, and two behavioral tests were performed, including contextual and cued fear conditioning test (CFC) and Morris water maze (MWM). At the end of the behavioral test, Nissl and Golgi staining were used to detect the dendrite density of hippocampal neurons to reveal the effect of maternal ketamine anesthesia on the hippocampus of offspring. Key proteins and their downstream transcription factors in Wnt/β-catenin signaling pathway from the embryonic development to the adulthood were studied. Our results showed that rats receiving maternal ketamine suffered from nerve injury. The density of hippocampal nerves and dendritic spine changed. Some genes related to Wnt/β-catenin pathway and Tcf/Lef were downregulated. In conclusion, maternal anesthesia with ketamine in the second trimester of pregnancy can lead to cognitive memory impairment and neurotoxicity in the hippocampus of offspring through Wnt/ β-catenin signaling pathway.</abstract><cop>Germany</cop><pub>Springer Nature B.V</pub><pmid>31786764</pmid><doi>10.1007/s11356-019-06753-z</doi><tpages>10</tpages></addata></record> |
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| subjects | Analgesics Analgesics - toxicity Anesthesia Animals beta Catenin - metabolism Cell differentiation Cell proliferation Cognitive ability Cognitive Dysfunction - metabolism Dendritic spines Dendritic structure Density Down-Regulation Embryogenesis Embryonic growth stage Environmental science External stimuli Fear conditioning Female Hippocampus Hippocampus - drug effects Ketamine Ketamine - toxicity LEF protein Male Memory - drug effects Memory Disorders - chemically induced Nerves Nervous System - drug effects Neurons - metabolism Neurotoxicity Neurotoxicity Syndromes - metabolism Offspring Pregnancy Rats Rodents Side effects Signal transduction Signaling Spine Transcription factors Wnt protein Wnt Signaling Pathway - drug effects β-Catenin |
| title | Ketamine exerts neurotoxic effects on the offspring of pregnant rats via the Wnt/β-catenin pathway |
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