Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism
The safety of anesthetics on the developing brain has caused concern. Ketamine, an N‑methyl‑D‑aspartate receptor antagonist, is widely used as a general pediatric anesthetic. Recent studies suggested that ketamine alters the plasticity of dendritic spines in the developing brain and may be an import...
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| Veröffentlicht in: | Molecular medicine reports 2018-12, Vol.18 (6), p.5037-5043 |
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| creator | Jiang, Sufang Hao, Zimiao Li, Xuze Bo, Lijun Zhang, Rui Wang, Ying Duan, Xiaofeng Kang, Rongtian Huang, Lining |
| description | The safety of anesthetics on the developing brain has caused concern. Ketamine, an N‑methyl‑D‑aspartate receptor antagonist, is widely used as a general pediatric anesthetic. Recent studies suggested that ketamine alters the plasticity of dendritic spines in the developing brain and may be an important contributing factor to learning and cognitive impairment. However, the underlying molecular mechanism remains poorly understood. Therefore, the aim of the present study was to investigate the effect of ketamine on the plasticity of dendritic spines in cultured hippocampal neurons and the potential underlying mechanisms. After 5 days in vitro, rat hippocampal neurons were exposed to different concentrations (100, 300 and 500 µM) of ketamine for 6 h. Ketamine decreased the number and length of dendritic spines in a dose‑dependent manner. Ketamine at a concentration of 300 µM caused an upregulation of transforming protein RhoA (RhoA) and Rho‑associated kinase (ROCK) protein. These effects were inhibited by the ROCK inhibitor Y27632. These results suggested that ketamine induces loss and shortening of dendritic spines in hippocampal neurons via activation of the RhoA/ROCK signaling pathway. |
| doi_str_mv | 10.3892/mmr.2018.9531 |
| format | Article |
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Ketamine, an N‑methyl‑D‑aspartate receptor antagonist, is widely used as a general pediatric anesthetic. Recent studies suggested that ketamine alters the plasticity of dendritic spines in the developing brain and may be an important contributing factor to learning and cognitive impairment. However, the underlying molecular mechanism remains poorly understood. Therefore, the aim of the present study was to investigate the effect of ketamine on the plasticity of dendritic spines in cultured hippocampal neurons and the potential underlying mechanisms. After 5 days in vitro, rat hippocampal neurons were exposed to different concentrations (100, 300 and 500 µM) of ketamine for 6 h. Ketamine decreased the number and length of dendritic spines in a dose‑dependent manner. Ketamine at a concentration of 300 µM caused an upregulation of transforming protein RhoA (RhoA) and Rho‑associated kinase (ROCK) protein. These effects were inhibited by the ROCK inhibitor Y27632. These results suggested that ketamine induces loss and shortening of dendritic spines in hippocampal neurons via activation of the RhoA/ROCK signaling pathway.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2018.9531</identifier><identifier>PMID: 30280188</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Anesthesia ; Anesthetics ; Animals ; Brain ; Brain research ; Cell Count ; Cellular signal transduction ; Cognitive ability ; Dendritic plasticity ; Dendritic spines ; Dendritic Spines - drug effects ; Dendritic Spines - metabolism ; Dosage and administration ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists ; Glutamic acid receptors ; Hippocampal plasticity ; Hippocampus ; Ketamine ; Ketamine - pharmacology ; Kinases ; Laboratory animals ; Microscopy ; Morphology ; N-Methyl-D-aspartic acid receptors ; Neurons ; Neuroplasticity ; Neurotoxicity ; Pediatrics ; Protein Kinase Inhibitors - pharmacology ; Proteins ; Pyramidal Cells - drug effects ; Pyramidal Cells - metabolism ; Rats ; Rho-associated kinase ; rho-Associated Kinases - antagonists & inhibitors ; rho-Associated Kinases - metabolism ; RhoA protein ; Signal transduction ; Studies</subject><ispartof>Molecular medicine reports, 2018-12, Vol.18 (6), p.5037-5043</ispartof><rights>COPYRIGHT 2018 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2018</rights><rights>Copyright: © Jiang et al. 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-5c49c8d8365045f6d85978c532ff0243e8bfb8056021622e419c276ed7a7c2653</citedby><cites>FETCH-LOGICAL-c482t-5c49c8d8365045f6d85978c532ff0243e8bfb8056021622e419c276ed7a7c2653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30280188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Sufang</creatorcontrib><creatorcontrib>Hao, Zimiao</creatorcontrib><creatorcontrib>Li, Xuze</creatorcontrib><creatorcontrib>Bo, Lijun</creatorcontrib><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Wang, Ying</creatorcontrib><creatorcontrib>Duan, Xiaofeng</creatorcontrib><creatorcontrib>Kang, Rongtian</creatorcontrib><creatorcontrib>Huang, Lining</creatorcontrib><title>Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>The safety of anesthetics on the developing brain has caused concern. Ketamine, an N‑methyl‑D‑aspartate receptor antagonist, is widely used as a general pediatric anesthetic. Recent studies suggested that ketamine alters the plasticity of dendritic spines in the developing brain and may be an important contributing factor to learning and cognitive impairment. However, the underlying molecular mechanism remains poorly understood. Therefore, the aim of the present study was to investigate the effect of ketamine on the plasticity of dendritic spines in cultured hippocampal neurons and the potential underlying mechanisms. After 5 days in vitro, rat hippocampal neurons were exposed to different concentrations (100, 300 and 500 µM) of ketamine for 6 h. Ketamine decreased the number and length of dendritic spines in a dose‑dependent manner. Ketamine at a concentration of 300 µM caused an upregulation of transforming protein RhoA (RhoA) and Rho‑associated kinase (ROCK) protein. These effects were inhibited by the ROCK inhibitor Y27632. These results suggested that ketamine induces loss and shortening of dendritic spines in hippocampal neurons via activation of the RhoA/ROCK signaling pathway.</description><subject>Anesthesia</subject><subject>Anesthetics</subject><subject>Animals</subject><subject>Brain</subject><subject>Brain research</subject><subject>Cell Count</subject><subject>Cellular signal transduction</subject><subject>Cognitive ability</subject><subject>Dendritic plasticity</subject><subject>Dendritic spines</subject><subject>Dendritic Spines - drug effects</subject><subject>Dendritic Spines - metabolism</subject><subject>Dosage and administration</subject><subject>Dose-Response Relationship, Drug</subject><subject>Excitatory Amino Acid Antagonists</subject><subject>Glutamic acid receptors</subject><subject>Hippocampal plasticity</subject><subject>Hippocampus</subject><subject>Ketamine</subject><subject>Ketamine - pharmacology</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Microscopy</subject><subject>Morphology</subject><subject>N-Methyl-D-aspartic acid receptors</subject><subject>Neurons</subject><subject>Neuroplasticity</subject><subject>Neurotoxicity</subject><subject>Pediatrics</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Proteins</subject><subject>Pyramidal Cells - drug effects</subject><subject>Pyramidal Cells - metabolism</subject><subject>Rats</subject><subject>Rho-associated kinase</subject><subject>rho-Associated Kinases - antagonists & inhibitors</subject><subject>rho-Associated Kinases - metabolism</subject><subject>RhoA protein</subject><subject>Signal transduction</subject><subject>Studies</subject><issn>1791-2997</issn><issn>1791-3004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptks2OFCEUhStG44yjS7eGxHW1_BQUbEwmE__iJCZG14SmLl1MCiihuieaWcwr-AY-i4_ik0hn2tFJDAvg8p2TC5ymeUrwiklFX4SQVxQTuVKckXvNMekVaRnG3f3DmirVHzWPSrnAWHDK1cPmiGEqq0YeN1fvYTHBR0ADlMWs_eS_QUGbnC6XESVXy3HIfvEWlbliBflYazuYUt1u0OjnOVkTZjOhCNuc4p74-WPnl5zQzhtk0Mcx_br-PsBcrSAuKIAdTfQlPG4eODMVeHKYT5rPr199Onvbnn948-7s9Ly1naRLy22nrBwkExx33IlBctVLyxl1DtOOgVy7tcRcYEoEpdARZWkvYOhNb6ng7KR5eeM7b9cBBlubyGbSc_bB5K86Ga_vnkQ_6k3aaUGZoJJWg-cHg5y-bOtD6Yu0zbH2rClhjBFB-v4vtTETaB9dqmY2-GL1KReMcamUqtTqP1QdAwRvUwTna_2OoL0R2JxKyeBuGydY7zOgawb0PgN6n4HKP_v3trf0n09nvwE4nrAY</recordid><startdate>20181201</startdate><enddate>20181201</enddate><creator>Jiang, Sufang</creator><creator>Hao, Zimiao</creator><creator>Li, Xuze</creator><creator>Bo, Lijun</creator><creator>Zhang, Rui</creator><creator>Wang, Ying</creator><creator>Duan, Xiaofeng</creator><creator>Kang, Rongtian</creator><creator>Huang, Lining</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. 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drug effects</topic><topic>Dendritic Spines - metabolism</topic><topic>Dosage and administration</topic><topic>Dose-Response Relationship, Drug</topic><topic>Excitatory Amino Acid Antagonists</topic><topic>Glutamic acid receptors</topic><topic>Hippocampal plasticity</topic><topic>Hippocampus</topic><topic>Ketamine</topic><topic>Ketamine - pharmacology</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Microscopy</topic><topic>Morphology</topic><topic>N-Methyl-D-aspartic acid receptors</topic><topic>Neurons</topic><topic>Neuroplasticity</topic><topic>Neurotoxicity</topic><topic>Pediatrics</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Proteins</topic><topic>Pyramidal Cells - drug effects</topic><topic>Pyramidal Cells - metabolism</topic><topic>Rats</topic><topic>Rho-associated kinase</topic><topic>rho-Associated Kinases - antagonists & inhibitors</topic><topic>rho-Associated Kinases - metabolism</topic><topic>RhoA protein</topic><topic>Signal transduction</topic><topic>Studies</topic><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Sufang</creatorcontrib><creatorcontrib>Hao, Zimiao</creatorcontrib><creatorcontrib>Li, Xuze</creatorcontrib><creatorcontrib>Bo, Lijun</creatorcontrib><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Wang, Ying</creatorcontrib><creatorcontrib>Duan, Xiaofeng</creatorcontrib><creatorcontrib>Kang, Rongtian</creatorcontrib><creatorcontrib>Huang, Lining</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular medicine reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Sufang</au><au>Hao, Zimiao</au><au>Li, Xuze</au><au>Bo, Lijun</au><au>Zhang, Rui</au><au>Wang, Ying</au><au>Duan, Xiaofeng</au><au>Kang, Rongtian</au><au>Huang, Lining</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism</atitle><jtitle>Molecular medicine reports</jtitle><addtitle>Mol Med Rep</addtitle><date>2018-12-01</date><risdate>2018</risdate><volume>18</volume><issue>6</issue><spage>5037</spage><epage>5043</epage><pages>5037-5043</pages><issn>1791-2997</issn><eissn>1791-3004</eissn><abstract>The safety of anesthetics on the developing brain has caused concern. Ketamine, an N‑methyl‑D‑aspartate receptor antagonist, is widely used as a general pediatric anesthetic. Recent studies suggested that ketamine alters the plasticity of dendritic spines in the developing brain and may be an important contributing factor to learning and cognitive impairment. However, the underlying molecular mechanism remains poorly understood. Therefore, the aim of the present study was to investigate the effect of ketamine on the plasticity of dendritic spines in cultured hippocampal neurons and the potential underlying mechanisms. After 5 days in vitro, rat hippocampal neurons were exposed to different concentrations (100, 300 and 500 µM) of ketamine for 6 h. Ketamine decreased the number and length of dendritic spines in a dose‑dependent manner. Ketamine at a concentration of 300 µM caused an upregulation of transforming protein RhoA (RhoA) and Rho‑associated kinase (ROCK) protein. These effects were inhibited by the ROCK inhibitor Y27632. These results suggested that ketamine induces loss and shortening of dendritic spines in hippocampal neurons via activation of the RhoA/ROCK signaling pathway.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>30280188</pmid><doi>10.3892/mmr.2018.9531</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | Spandidos Publications Journals; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Anesthesia Anesthetics Animals Brain Brain research Cell Count Cellular signal transduction Cognitive ability Dendritic plasticity Dendritic spines Dendritic Spines - drug effects Dendritic Spines - metabolism Dosage and administration Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists Glutamic acid receptors Hippocampal plasticity Hippocampus Ketamine Ketamine - pharmacology Kinases Laboratory animals Microscopy Morphology N-Methyl-D-aspartic acid receptors Neurons Neuroplasticity Neurotoxicity Pediatrics Protein Kinase Inhibitors - pharmacology Proteins Pyramidal Cells - drug effects Pyramidal Cells - metabolism Rats Rho-associated kinase rho-Associated Kinases - antagonists & inhibitors rho-Associated Kinases - metabolism RhoA protein Signal transduction Studies |
| title | Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism |
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