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Repetitive Pain in Neonatal Male Rats Impairs Hippocampus-Dependent Fear Memory Later in Life
Preterm infants in neonatal intensive care units are inevitably subjected to numerous painful procedures. However, little is known about the consequences of early pain experience on fear memory formation later in life. We hypothesized that exposure to repetitive pain in early life triggered hippocam...
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Published in: | Frontiers in neuroscience 2020-07, Vol.14, p.722-722 |
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description | Preterm infants in neonatal intensive care units are inevitably subjected to numerous painful procedures. However, little is known about the consequences of early pain experience on fear memory formation later in life. We hypothesized that exposure to repetitive pain in early life triggered hippocampal synaptic plasticity and resulted in memory deficiency in prepubertal and adult rats. From the day of birth (P0) to postnatal day 7 (P7), neonatal male rat pups were randomly assigned to either needle pricks or tactile touches repetitively every 6 hours. Trace fear conditioning was performed on rats on P24-P26 and P87-P89. On P24 and P87, rats were sacrificed for molecular and electrophysiological studies. On P24-26 and P87-89, rats that experienced neonatal needle treatment showed a significant reduction in freezing time in the contextual fear conditioning (P |
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However, little is known about the consequences of early pain experience on fear memory formation later in life. We hypothesized that exposure to repetitive pain in early life triggered hippocampal synaptic plasticity and resulted in memory deficiency in prepubertal and adult rats. From the day of birth (P0) to postnatal day 7 (P7), neonatal male rat pups were randomly assigned to either needle pricks or tactile touches repetitively every 6 hours. Trace fear conditioning was performed on rats on P24-P26 and P87-P89. On P24 and P87, rats were sacrificed for molecular and electrophysiological studies. On P24-26 and P87-89, rats that experienced neonatal needle treatment showed a significant reduction in freezing time in the contextual fear conditioning (P<0.05) and trace fear conditioning tests (P<0.05). Moreover, repetitive neonatal procedural pain caused a significant decrease in the magnitude of hippocampal long-term potentiation induced by high-frequency stimulation. Furthermore, rats that experienced neonatal needle treatment demonstrated sustained downregulation of NR1, NR2A, NR2B, and GluR1 expression in the hippocampus. Therefore, neonatal pain is related to deficits in hippocampus-related fear memory later in life and might be caused by impairments in hippocampal synaptic plasticity.</description><identifier>ISSN: 1662-453X</identifier><identifier>ISSN: 1662-4548</identifier><identifier>EISSN: 1662-453X</identifier><identifier>DOI: 10.3389/fnins.2020.00722</identifier><identifier>PMID: 32733201</identifier><language>eng</language><publisher>Lausanne: Frontiers Research Foundation</publisher><subject>Behavior ; Early experience ; Fear conditioning ; fear memory ; Gene expression ; glutamate ; Glutamate receptors ; Glutamic acid receptors (ionotropic) ; Hippocampal plasticity ; Hippocampus ; Infants ; Intensive care units ; Laboratory animals ; Long-term potentiation ; Medical research ; Memory ; Neonates ; Neuroscience ; Pain ; procedural pain ; Rodents ; Studies ; Synaptic plasticity ; Tonic immobility</subject><ispartof>Frontiers in neuroscience, 2020-07, Vol.14, p.722-722</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright © 2020 Xia, Min, Chen, Ling, Chen and Li. 2020 Xia, Min, Chen, Ling, Chen and Li</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-baed230fbc5299f2d3bcc878179b3b0698d48377e442b6d0b650cbd5009e17783</citedby><cites>FETCH-LOGICAL-c467t-baed230fbc5299f2d3bcc878179b3b0698d48377e442b6d0b650cbd5009e17783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2421241293/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2421241293?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25751,27922,27923,37010,37011,44588,53789,53791,74896</link.rule.ids></links><search><creatorcontrib>Xia, Dongqing</creatorcontrib><creatorcontrib>Min, Cuiting</creatorcontrib><creatorcontrib>Chen, Yinhua</creatorcontrib><creatorcontrib>Ling, Ru</creatorcontrib><creatorcontrib>Chen, Mengying</creatorcontrib><creatorcontrib>Li, Xiaonan</creatorcontrib><title>Repetitive Pain in Neonatal Male Rats Impairs Hippocampus-Dependent Fear Memory Later in Life</title><title>Frontiers in neuroscience</title><description>Preterm infants in neonatal intensive care units are inevitably subjected to numerous painful procedures. However, little is known about the consequences of early pain experience on fear memory formation later in life. We hypothesized that exposure to repetitive pain in early life triggered hippocampal synaptic plasticity and resulted in memory deficiency in prepubertal and adult rats. From the day of birth (P0) to postnatal day 7 (P7), neonatal male rat pups were randomly assigned to either needle pricks or tactile touches repetitively every 6 hours. Trace fear conditioning was performed on rats on P24-P26 and P87-P89. On P24 and P87, rats were sacrificed for molecular and electrophysiological studies. On P24-26 and P87-89, rats that experienced neonatal needle treatment showed a significant reduction in freezing time in the contextual fear conditioning (P<0.05) and trace fear conditioning tests (P<0.05). Moreover, repetitive neonatal procedural pain caused a significant decrease in the magnitude of hippocampal long-term potentiation induced by high-frequency stimulation. Furthermore, rats that experienced neonatal needle treatment demonstrated sustained downregulation of NR1, NR2A, NR2B, and GluR1 expression in the hippocampus. Therefore, neonatal pain is related to deficits in hippocampus-related fear memory later in life and might be caused by impairments in hippocampal synaptic plasticity.</description><subject>Behavior</subject><subject>Early experience</subject><subject>Fear conditioning</subject><subject>fear memory</subject><subject>Gene expression</subject><subject>glutamate</subject><subject>Glutamate receptors</subject><subject>Glutamic acid receptors (ionotropic)</subject><subject>Hippocampal plasticity</subject><subject>Hippocampus</subject><subject>Infants</subject><subject>Intensive care units</subject><subject>Laboratory animals</subject><subject>Long-term potentiation</subject><subject>Medical research</subject><subject>Memory</subject><subject>Neonates</subject><subject>Neuroscience</subject><subject>Pain</subject><subject>procedural pain</subject><subject>Rodents</subject><subject>Studies</subject><subject>Synaptic plasticity</subject><subject>Tonic immobility</subject><issn>1662-453X</issn><issn>1662-4548</issn><issn>1662-453X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdksFrFDEUhwdRbK3ePQ548TJr8jKbZC6CVGsXtipFwYuEl-RNzTIzmSazhf73zuwWsUJIQvK9j5fwK4rXnK2E0M27dghDXgEDtmJMATwpTrmUUNVr8fPpP_uT4kXOO8Yk6BqeFycClBDA-Gnx65pGmsIU7qj8hmEo5_GF4oATduUVdlRe45TLTT9iSLm8DOMYHfbjPlcf58rB0zCVF4SpvKI-pvtyixOlxbINLb0snrXYZXr1sJ4VPy4-fT-_rLZfP2_OP2wrV0s1VRbJg2CtdWtomha8sM5ppblqrLBMNtrXWihFdQ1Wemblmjnr14w1xJXS4qzYHL0-4s6MKfSY7k3EYA4HMd0YTFNwHRlNVoDXYDnw2mmP3s6zFNBa9Eyy2fX-6Br3tifv5gcm7B5JH98M4be5iXdGCTm3ugjePghSvN1TnkwfsqOuw4HiPhuooVFKat3M6Jv_0F3cp2H-qoXiUHNoxEyxI-VSzDlR-7cZzsySA3PIgVlyYA45EH8Aa6ilsg</recordid><startdate>20200708</startdate><enddate>20200708</enddate><creator>Xia, Dongqing</creator><creator>Min, Cuiting</creator><creator>Chen, Yinhua</creator><creator>Ling, Ru</creator><creator>Chen, Mengying</creator><creator>Li, Xiaonan</creator><general>Frontiers Research Foundation</general><general>Frontiers Media S.A</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20200708</creationdate><title>Repetitive Pain in Neonatal Male Rats Impairs Hippocampus-Dependent Fear Memory Later in Life</title><author>Xia, Dongqing ; Min, Cuiting ; Chen, Yinhua ; Ling, Ru ; Chen, Mengying ; Li, Xiaonan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-baed230fbc5299f2d3bcc878179b3b0698d48377e442b6d0b650cbd5009e17783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Behavior</topic><topic>Early experience</topic><topic>Fear conditioning</topic><topic>fear memory</topic><topic>Gene expression</topic><topic>glutamate</topic><topic>Glutamate receptors</topic><topic>Glutamic acid receptors (ionotropic)</topic><topic>Hippocampal plasticity</topic><topic>Hippocampus</topic><topic>Infants</topic><topic>Intensive care units</topic><topic>Laboratory animals</topic><topic>Long-term potentiation</topic><topic>Medical research</topic><topic>Memory</topic><topic>Neonates</topic><topic>Neuroscience</topic><topic>Pain</topic><topic>procedural pain</topic><topic>Rodents</topic><topic>Studies</topic><topic>Synaptic plasticity</topic><topic>Tonic immobility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xia, Dongqing</creatorcontrib><creatorcontrib>Min, Cuiting</creatorcontrib><creatorcontrib>Chen, Yinhua</creatorcontrib><creatorcontrib>Ling, Ru</creatorcontrib><creatorcontrib>Chen, Mengying</creatorcontrib><creatorcontrib>Li, Xiaonan</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>Biological Sciences</collection><collection>ProQuest Science Journals</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Frontiers in neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xia, Dongqing</au><au>Min, Cuiting</au><au>Chen, Yinhua</au><au>Ling, Ru</au><au>Chen, Mengying</au><au>Li, Xiaonan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Repetitive Pain in Neonatal Male Rats Impairs Hippocampus-Dependent Fear Memory Later in Life</atitle><jtitle>Frontiers in neuroscience</jtitle><date>2020-07-08</date><risdate>2020</risdate><volume>14</volume><spage>722</spage><epage>722</epage><pages>722-722</pages><issn>1662-453X</issn><issn>1662-4548</issn><eissn>1662-453X</eissn><abstract>Preterm infants in neonatal intensive care units are inevitably subjected to numerous painful procedures. However, little is known about the consequences of early pain experience on fear memory formation later in life. We hypothesized that exposure to repetitive pain in early life triggered hippocampal synaptic plasticity and resulted in memory deficiency in prepubertal and adult rats. From the day of birth (P0) to postnatal day 7 (P7), neonatal male rat pups were randomly assigned to either needle pricks or tactile touches repetitively every 6 hours. Trace fear conditioning was performed on rats on P24-P26 and P87-P89. On P24 and P87, rats were sacrificed for molecular and electrophysiological studies. On P24-26 and P87-89, rats that experienced neonatal needle treatment showed a significant reduction in freezing time in the contextual fear conditioning (P<0.05) and trace fear conditioning tests (P<0.05). Moreover, repetitive neonatal procedural pain caused a significant decrease in the magnitude of hippocampal long-term potentiation induced by high-frequency stimulation. Furthermore, rats that experienced neonatal needle treatment demonstrated sustained downregulation of NR1, NR2A, NR2B, and GluR1 expression in the hippocampus. Therefore, neonatal pain is related to deficits in hippocampus-related fear memory later in life and might be caused by impairments in hippocampal synaptic plasticity.</abstract><cop>Lausanne</cop><pub>Frontiers Research Foundation</pub><pmid>32733201</pmid><doi>10.3389/fnins.2020.00722</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Behavior Early experience Fear conditioning fear memory Gene expression glutamate Glutamate receptors Glutamic acid receptors (ionotropic) Hippocampal plasticity Hippocampus Infants Intensive care units Laboratory animals Long-term potentiation Medical research Memory Neonates Neuroscience Pain procedural pain Rodents Studies Synaptic plasticity Tonic immobility |
title | Repetitive Pain in Neonatal Male Rats Impairs Hippocampus-Dependent Fear Memory Later in Life |
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