Oxidative stress and Na,K-ATPase activity differential regulation in brainstem and forebrain of Wistar Audiogenic rats may lead to increased seizure susceptibility
•Wistar Audiogenic Rats present increased oxidative stress markers in brainstem.•Wistar Audiogenic Rats present increased Na,K-ATPase activity in forebrain.•Increased Na,K-ATPase activity may maintain Wistar Audiogenic Rats’ brain function.•Oxidative stress may lead to hyperexcitation in Wistar Audi...
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| Veröffentlicht in: | Brain research 2018-01, Vol.1679, p.171-178 |
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| creator | Parreira, Gabriela Machado Resende, Maria Daniela Aparecida Garcia, Israel José Pereira Sartori, Daniela Bueno Umeoka, Eduardo Henrique de Lima Godoy, Lívea Dornela Garcia-Cairasco, Norberto Barbosa, Leandro Augusto Santos, Hérica de Lima Tilelli, Cristiane Queixa |
| description | •Wistar Audiogenic Rats present increased oxidative stress markers in brainstem.•Wistar Audiogenic Rats present increased Na,K-ATPase activity in forebrain.•Increased Na,K-ATPase activity may maintain Wistar Audiogenic Rats’ brain function.•Oxidative stress may lead to hyperexcitation in Wistar Audiogenic Rats’ brainstem.
The Wistar Audiogenic Rat (WAR) is a well-characterized seizure-prone, inbred rodent strain that, when acutely stimulated with high-intensity sounds, develops brainstem-dependent tonic-clonic seizures that can evolve to limbic-like, myoclonic (forebrain) seizures when the acoustic stimuli are presented chronically (audiogenic kindling). In order to investigate possible mechanisms underlying WAR susceptibility to seizures, we evaluated Na,K-ATPase activity, Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and oxidative stress markers in whole forebrain and whole brainstem samples of naïve WAR, as compared to samples from control Wistar rats. We also evaluated the expression levels of α1 and α3 isoforms of Na,K-ATPase in forebrain samples. We observed increased Na,K-ATPase activity in forebrain samples and increased oxidative stress markers (lipid peroxidation, glutathione peroxidase and superoxide dismutase) in brainstem samples of WAR. The Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and expression levels of α1 and α3 isoforms of Na,K-ATPase were unaltered. In view of previous data showing that the membrane potentials from naïve WAR’s neurons are less negative than that from neurons from Wistar rats, we suggest that Na,K-ATPase increased activity might be involved in a compensatory mechanism necessary to maintain WAR’s brains normal activity. Additionally, ongoing oxidative stress in the brainstem could bring Na,K-ATPase activity back to normal levels, which may explain why WAR’s present increased susceptibility to seizures triggered by high-intensity sound stimulation. |
| doi_str_mv | 10.1016/j.brainres.2017.12.001 |
| format | Article |
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The Wistar Audiogenic Rat (WAR) is a well-characterized seizure-prone, inbred rodent strain that, when acutely stimulated with high-intensity sounds, develops brainstem-dependent tonic-clonic seizures that can evolve to limbic-like, myoclonic (forebrain) seizures when the acoustic stimuli are presented chronically (audiogenic kindling). In order to investigate possible mechanisms underlying WAR susceptibility to seizures, we evaluated Na,K-ATPase activity, Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and oxidative stress markers in whole forebrain and whole brainstem samples of naïve WAR, as compared to samples from control Wistar rats. We also evaluated the expression levels of α1 and α3 isoforms of Na,K-ATPase in forebrain samples. We observed increased Na,K-ATPase activity in forebrain samples and increased oxidative stress markers (lipid peroxidation, glutathione peroxidase and superoxide dismutase) in brainstem samples of WAR. The Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and expression levels of α1 and α3 isoforms of Na,K-ATPase were unaltered. In view of previous data showing that the membrane potentials from naïve WAR’s neurons are less negative than that from neurons from Wistar rats, we suggest that Na,K-ATPase increased activity might be involved in a compensatory mechanism necessary to maintain WAR’s brains normal activity. Additionally, ongoing oxidative stress in the brainstem could bring Na,K-ATPase activity back to normal levels, which may explain why WAR’s present increased susceptibility to seizures triggered by high-intensity sound stimulation.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2017.12.001</identifier><identifier>PMID: 29225049</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Acoustic Stimulation - adverse effects ; Adenosine Triphosphatases - metabolism ; Animals ; Audiogenic seizures ; Brain Stem - enzymology ; Brain Stem - pathology ; Disease Models, Animal ; Glutathione Peroxidase - metabolism ; K-ATPase ; Kindling, Neurologic - physiology ; Lipid composition ; Lipid Peroxidation ; Neurons - enzymology ; Oxidative stress ; Oxidative Stress - physiology ; Prosencephalon - enzymology ; Prosencephalon - pathology ; Protein Isoforms - metabolism ; Rats ; Rats, Wistar ; Seizures - etiology ; Seizures - metabolism ; Seizures - pathology ; Sodium-Potassium-Exchanging ATPase - metabolism ; Wistar audiogenic rats</subject><ispartof>Brain research, 2018-01, Vol.1679, p.171-178</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-2cd2b1e1071b5eb8d3a94c455cc54851dcbceded222db3d4ec67f91e05be66a13</citedby><cites>FETCH-LOGICAL-c368t-2cd2b1e1071b5eb8d3a94c455cc54851dcbceded222db3d4ec67f91e05be66a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006899317305358$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29225049$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Parreira, Gabriela Machado</creatorcontrib><creatorcontrib>Resende, Maria Daniela Aparecida</creatorcontrib><creatorcontrib>Garcia, Israel José Pereira</creatorcontrib><creatorcontrib>Sartori, Daniela Bueno</creatorcontrib><creatorcontrib>Umeoka, Eduardo Henrique de Lima</creatorcontrib><creatorcontrib>Godoy, Lívea Dornela</creatorcontrib><creatorcontrib>Garcia-Cairasco, Norberto</creatorcontrib><creatorcontrib>Barbosa, Leandro Augusto</creatorcontrib><creatorcontrib>Santos, Hérica de Lima</creatorcontrib><creatorcontrib>Tilelli, Cristiane Queixa</creatorcontrib><title>Oxidative stress and Na,K-ATPase activity differential regulation in brainstem and forebrain of Wistar Audiogenic rats may lead to increased seizure susceptibility</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>•Wistar Audiogenic Rats present increased oxidative stress markers in brainstem.•Wistar Audiogenic Rats present increased Na,K-ATPase activity in forebrain.•Increased Na,K-ATPase activity may maintain Wistar Audiogenic Rats’ brain function.•Oxidative stress may lead to hyperexcitation in Wistar Audiogenic Rats’ brainstem.
The Wistar Audiogenic Rat (WAR) is a well-characterized seizure-prone, inbred rodent strain that, when acutely stimulated with high-intensity sounds, develops brainstem-dependent tonic-clonic seizures that can evolve to limbic-like, myoclonic (forebrain) seizures when the acoustic stimuli are presented chronically (audiogenic kindling). In order to investigate possible mechanisms underlying WAR susceptibility to seizures, we evaluated Na,K-ATPase activity, Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and oxidative stress markers in whole forebrain and whole brainstem samples of naïve WAR, as compared to samples from control Wistar rats. We also evaluated the expression levels of α1 and α3 isoforms of Na,K-ATPase in forebrain samples. We observed increased Na,K-ATPase activity in forebrain samples and increased oxidative stress markers (lipid peroxidation, glutathione peroxidase and superoxide dismutase) in brainstem samples of WAR. The Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and expression levels of α1 and α3 isoforms of Na,K-ATPase were unaltered. In view of previous data showing that the membrane potentials from naïve WAR’s neurons are less negative than that from neurons from Wistar rats, we suggest that Na,K-ATPase increased activity might be involved in a compensatory mechanism necessary to maintain WAR’s brains normal activity. Additionally, ongoing oxidative stress in the brainstem could bring Na,K-ATPase activity back to normal levels, which may explain why WAR’s present increased susceptibility to seizures triggered by high-intensity sound stimulation.</description><subject>Acoustic Stimulation - adverse effects</subject><subject>Adenosine Triphosphatases - metabolism</subject><subject>Animals</subject><subject>Audiogenic seizures</subject><subject>Brain Stem - enzymology</subject><subject>Brain Stem - pathology</subject><subject>Disease Models, Animal</subject><subject>Glutathione Peroxidase - metabolism</subject><subject>K-ATPase</subject><subject>Kindling, Neurologic - physiology</subject><subject>Lipid composition</subject><subject>Lipid Peroxidation</subject><subject>Neurons - enzymology</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - physiology</subject><subject>Prosencephalon - enzymology</subject><subject>Prosencephalon - pathology</subject><subject>Protein Isoforms - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Seizures - etiology</subject><subject>Seizures - metabolism</subject><subject>Seizures - pathology</subject><subject>Sodium-Potassium-Exchanging ATPase - metabolism</subject><subject>Wistar audiogenic rats</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUctu1DAUtRCIDoVfqLxkQYLtxEm8Y1TxEhVlUcTS8uOmuqMkHmynYvgdfhR3pmXL6sr3npd1CLngrOaMd293tY0GlwipFoz3NRc1Y_wJ2fChF1UnWvaUbBhjXTUo1ZyRFyntyrNpFHtOzoQSQrJWbcif61_oTcY7oCkXtUTN4ulX8-ZLtb35ZhJQ48oV84F6HEeIsGQ0E41wu06FFxaKCz1mSRnmI3sMEY4bGkb6A1M2kW5Xj-EWFnQ0mpzobA50AuNpDkXARShWnibA32ssUdbkYJ_R4lScX5Jno5kSvHqY5-T7h_c3l5-qq-uPny-3V5VruiFXwnlhOXDWcyvBDr4xqnWtlM7JdpDcO-vAgxdCeNv4FlzXj4oDkxa6zvDmnLw-6e5j-LlCynrGkmOazAJhTZqrXkrVtP1QoN0J6mJIKcKo9xFnEw-aM31fkN7px4L0fUGaC10KKsSLB4_VzuD_0R4bKYB3JwCUn94hRJ0cwlKSYwSXtQ_4P4-_PVyqIw</recordid><startdate>20180115</startdate><enddate>20180115</enddate><creator>Parreira, Gabriela Machado</creator><creator>Resende, Maria Daniela Aparecida</creator><creator>Garcia, Israel José Pereira</creator><creator>Sartori, Daniela Bueno</creator><creator>Umeoka, Eduardo Henrique de Lima</creator><creator>Godoy, Lívea Dornela</creator><creator>Garcia-Cairasco, Norberto</creator><creator>Barbosa, Leandro Augusto</creator><creator>Santos, Hérica de Lima</creator><creator>Tilelli, Cristiane Queixa</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20180115</creationdate><title>Oxidative stress and Na,K-ATPase activity differential regulation in brainstem and forebrain of Wistar Audiogenic rats may lead to increased seizure susceptibility</title><author>Parreira, Gabriela Machado ; Resende, Maria Daniela Aparecida ; Garcia, Israel José Pereira ; Sartori, Daniela Bueno ; Umeoka, Eduardo Henrique de Lima ; Godoy, Lívea Dornela ; Garcia-Cairasco, Norberto ; Barbosa, Leandro Augusto ; Santos, Hérica de Lima ; Tilelli, Cristiane Queixa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-2cd2b1e1071b5eb8d3a94c455cc54851dcbceded222db3d4ec67f91e05be66a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Acoustic Stimulation - adverse effects</topic><topic>Adenosine Triphosphatases - metabolism</topic><topic>Animals</topic><topic>Audiogenic seizures</topic><topic>Brain Stem - enzymology</topic><topic>Brain Stem - pathology</topic><topic>Disease Models, Animal</topic><topic>Glutathione Peroxidase - metabolism</topic><topic>K-ATPase</topic><topic>Kindling, Neurologic - physiology</topic><topic>Lipid composition</topic><topic>Lipid Peroxidation</topic><topic>Neurons - enzymology</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - physiology</topic><topic>Prosencephalon - enzymology</topic><topic>Prosencephalon - pathology</topic><topic>Protein Isoforms - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Seizures - etiology</topic><topic>Seizures - metabolism</topic><topic>Seizures - pathology</topic><topic>Sodium-Potassium-Exchanging ATPase - metabolism</topic><topic>Wistar audiogenic rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Parreira, Gabriela Machado</creatorcontrib><creatorcontrib>Resende, Maria Daniela Aparecida</creatorcontrib><creatorcontrib>Garcia, Israel José Pereira</creatorcontrib><creatorcontrib>Sartori, Daniela Bueno</creatorcontrib><creatorcontrib>Umeoka, Eduardo Henrique de Lima</creatorcontrib><creatorcontrib>Godoy, Lívea Dornela</creatorcontrib><creatorcontrib>Garcia-Cairasco, Norberto</creatorcontrib><creatorcontrib>Barbosa, Leandro Augusto</creatorcontrib><creatorcontrib>Santos, Hérica de Lima</creatorcontrib><creatorcontrib>Tilelli, Cristiane Queixa</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Parreira, Gabriela Machado</au><au>Resende, Maria Daniela Aparecida</au><au>Garcia, Israel José Pereira</au><au>Sartori, Daniela Bueno</au><au>Umeoka, Eduardo Henrique de Lima</au><au>Godoy, Lívea Dornela</au><au>Garcia-Cairasco, Norberto</au><au>Barbosa, Leandro Augusto</au><au>Santos, Hérica de Lima</au><au>Tilelli, Cristiane Queixa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oxidative stress and Na,K-ATPase activity differential regulation in brainstem and forebrain of Wistar Audiogenic rats may lead to increased seizure susceptibility</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2018-01-15</date><risdate>2018</risdate><volume>1679</volume><spage>171</spage><epage>178</epage><pages>171-178</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><abstract>•Wistar Audiogenic Rats present increased oxidative stress markers in brainstem.•Wistar Audiogenic Rats present increased Na,K-ATPase activity in forebrain.•Increased Na,K-ATPase activity may maintain Wistar Audiogenic Rats’ brain function.•Oxidative stress may lead to hyperexcitation in Wistar Audiogenic Rats’ brainstem.
The Wistar Audiogenic Rat (WAR) is a well-characterized seizure-prone, inbred rodent strain that, when acutely stimulated with high-intensity sounds, develops brainstem-dependent tonic-clonic seizures that can evolve to limbic-like, myoclonic (forebrain) seizures when the acoustic stimuli are presented chronically (audiogenic kindling). In order to investigate possible mechanisms underlying WAR susceptibility to seizures, we evaluated Na,K-ATPase activity, Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and oxidative stress markers in whole forebrain and whole brainstem samples of naïve WAR, as compared to samples from control Wistar rats. We also evaluated the expression levels of α1 and α3 isoforms of Na,K-ATPase in forebrain samples. We observed increased Na,K-ATPase activity in forebrain samples and increased oxidative stress markers (lipid peroxidation, glutathione peroxidase and superoxide dismutase) in brainstem samples of WAR. The Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and expression levels of α1 and α3 isoforms of Na,K-ATPase were unaltered. In view of previous data showing that the membrane potentials from naïve WAR’s neurons are less negative than that from neurons from Wistar rats, we suggest that Na,K-ATPase increased activity might be involved in a compensatory mechanism necessary to maintain WAR’s brains normal activity. Additionally, ongoing oxidative stress in the brainstem could bring Na,K-ATPase activity back to normal levels, which may explain why WAR’s present increased susceptibility to seizures triggered by high-intensity sound stimulation.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>29225049</pmid><doi>10.1016/j.brainres.2017.12.001</doi><tpages>8</tpages></addata></record> |
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| subjects | Acoustic Stimulation - adverse effects Adenosine Triphosphatases - metabolism Animals Audiogenic seizures Brain Stem - enzymology Brain Stem - pathology Disease Models, Animal Glutathione Peroxidase - metabolism K-ATPase Kindling, Neurologic - physiology Lipid composition Lipid Peroxidation Neurons - enzymology Oxidative stress Oxidative Stress - physiology Prosencephalon - enzymology Prosencephalon - pathology Protein Isoforms - metabolism Rats Rats, Wistar Seizures - etiology Seizures - metabolism Seizures - pathology Sodium-Potassium-Exchanging ATPase - metabolism Wistar audiogenic rats |
| title | Oxidative stress and Na,K-ATPase activity differential regulation in brainstem and forebrain of Wistar Audiogenic rats may lead to increased seizure susceptibility |
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