Ethanol Exposure Induces Microglia Activation and Neuroinflammation through TLR4 Activation and SENP6 Modulation in the Adolescent Rat Hippocampus
Identifieur interne : 000772 ( Pmc/Checkpoint ); précédent : 000771; suivant : 000773Ethanol Exposure Induces Microglia Activation and Neuroinflammation through TLR4 Activation and SENP6 Modulation in the Adolescent Rat Hippocampus
Auteurs : Qing Li [République populaire de Chine] ; Dexiang Liu [République populaire de Chine] ; Fang Pan [République populaire de Chine] ; Cyrus S. H. Ho [Singapour] ; Roger C. M. Ho [Singapour]Source :
- Neural Plasticity [ 2090-5904 ] ; 2019.
Abstract
The ethanol-induced toll-like receptor 4 (TLR4) signal activation of microglia and neuroinflammation are observed in both adolescent and adult rat brains, but the regulatory mechanisms of some TLR4 signaling-related factors in this process are still unclear. SUMO-specific protease 6 (SENP6) inhibits neuroinflammation by dampening nuclear factor kappa-B (NF-
Url:
DOI: 10.1155/2019/1648736
PubMed: 31781182
PubMed Central: 6874951
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Ethanol Exposure Induces Microglia Activation and Neuroinflammation through TLR4 Activation and SENP6 Modulation in the Adolescent Rat Hippocampus</title><author><name sortKey="Li, Qing" sort="Li, Qing" uniqKey="Li Q" first="Qing" last="Li">Qing Li</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Dexiang" sort="Liu, Dexiang" uniqKey="Liu D" first="Dexiang" last="Liu">Dexiang Liu</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Pan, Fang" sort="Pan, Fang" uniqKey="Pan F" first="Fang" last="Pan">Fang Pan</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Ho, Cyrus S H" sort="Ho, Cyrus S H" uniqKey="Ho C" first="Cyrus S. H." last="Ho">Cyrus S. H. Ho</name><affiliation wicri:level="4"><nlm:aff id="I2">Department of Psychological Medicine, National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Psychological Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Ho, Roger C M" sort="Ho, Roger C M" uniqKey="Ho R" first="Roger C. M." last="Ho">Roger C. M. Ho</name><affiliation wicri:level="4"><nlm:aff id="I2">Department of Psychological Medicine, National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Psychological Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="I3">Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Institute for Health Innovation and Technology (iHealthtech), National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31781182</idno><idno type="pmc">6874951</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874951</idno><idno type="RBID">PMC:6874951</idno><idno type="doi">10.1155/2019/1648736</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000731</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000731</idno><idno type="wicri:Area/Pmc/Curation">000731</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000731</idno><idno type="wicri:Area/Pmc/Checkpoint">000772</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000772</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Ethanol Exposure Induces Microglia Activation and Neuroinflammation through TLR4 Activation and SENP6 Modulation in the Adolescent Rat Hippocampus</title><author><name sortKey="Li, Qing" sort="Li, Qing" uniqKey="Li Q" first="Qing" last="Li">Qing Li</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Dexiang" sort="Liu, Dexiang" uniqKey="Liu D" first="Dexiang" last="Liu">Dexiang Liu</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Pan, Fang" sort="Pan, Fang" uniqKey="Pan F" first="Fang" last="Pan">Fang Pan</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Ho, Cyrus S H" sort="Ho, Cyrus S H" uniqKey="Ho C" first="Cyrus S. H." last="Ho">Cyrus S. H. Ho</name><affiliation wicri:level="4"><nlm:aff id="I2">Department of Psychological Medicine, National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Psychological Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Ho, Roger C M" sort="Ho, Roger C M" uniqKey="Ho R" first="Roger C. M." last="Ho">Roger C. M. Ho</name><affiliation wicri:level="4"><nlm:aff id="I2">Department of Psychological Medicine, National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Psychological Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="I3">Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Institute for Health Innovation and Technology (iHealthtech), National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author></analytic><series><title level="j">Neural Plasticity</title><idno type="ISSN">2090-5904</idno><idno type="eISSN">1687-5443</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The ethanol-induced toll-like receptor 4 (TLR4) signal activation of microglia and neuroinflammation are observed in both adolescent and adult rat brains, but the regulatory mechanisms of some TLR4 signaling-related factors in this process are still unclear. SUMO-specific protease 6 (SENP6) inhibits neuroinflammation by dampening nuclear factor kappa-B (NF-<italic>κ</italic>B) activation via the de-SUMOylation of NF kappa-B essential modulator (NEMO). This study investigates the effects of long-term ethanol consumption on neuroinflammation in the hippocampus of adolescent rats and the regulatory roles of TLR4 and SENP6. Twenty-one days of ethanol exposure in adolescent rats were used to develop an animal model. The number of microglia, microglial activation, and the expression of TLR4 in the hippocampus of adolescent rats were examined by immunoreactivity. The levels of TLR4, activation of NF-<italic>κ</italic>B including IkB-<italic>α</italic> and p-NF-<italic>κ</italic>B-p65, and SENP6 were measured by western blotting. Proinflammatory cytokines including TNF-<italic>α</italic>, IL-1<italic>β</italic>, and IL-6 were measured by enzyme-linked immunosorbent assay. The NF-<italic>κ</italic>B activation and proinflammatory cytokines released in overexpressed SENP6 and siRNA targeting SENP6 microglial cells after treatment with ethanol were estimated in vitro. This study found that alcohol exposure increased the number of activated microglia and the levels of p-NF-<italic>κ</italic>B-p65 and proinflammatory cytokines, while it decreased the SENP6 level in wild-type rats, but not in TLR4 knockout rats. The ethanol-induced increases of p-NF-<italic>κ</italic>B-p65, TNF-<italic>α</italic>, and IL-1<italic>β</italic> were dampened by overxpression of SENP6 and enhanced in SENP6-siRNA microglia. Our data suggest that ethanol exposure during adolescence induces the microglia-mediated neuroinflammation via TLR4 activation, and SENP6 plays an essential role in dampening NF-<italic>κ</italic>B activation and neuroinflammation.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Foxcroft, D R" uniqKey="Foxcroft D">D. R. Foxcroft</name></author><author><name sortKey="Coombes, L" uniqKey="Coombes L">L. Coombes</name></author><author><name sortKey="Wood, S" uniqKey="Wood S">S. Wood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ji, Z" uniqKey="Ji Z">Z. Ji</name></author><author><name sortKey="Yuan, L" uniqKey="Yuan L">L. Yuan</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X. Lu</name></author><author><name sortKey="Ding, H" uniqKey="Ding H">H. Ding</name></author><author><name sortKey="Luo, J" uniqKey="Luo J">J. Luo</name></author><author><name sortKey="Ke, Z J" uniqKey="Ke Z">Z. J. Ke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Curlik, D M" uniqKey="Curlik D">D. M. Curlik</name></author><author><name sortKey="Difeo, G" uniqKey="Difeo G">G. DiFeo</name></author><author><name sortKey="Shors, T J" uniqKey="Shors T">T. J. Shors</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pascual, M" uniqKey="Pascual M">M. Pascual</name></author><author><name sortKey="Boix, J" uniqKey="Boix J">J. Boix</name></author><author><name sortKey="Felipo, V" uniqKey="Felipo V">V. Felipo</name></author><author><name sortKey="Guerri, C" uniqKey="Guerri C">C. Guerri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vetreno, R P" uniqKey="Vetreno R">R. P. Vetreno</name></author><author><name sortKey="Broadwater, M" uniqKey="Broadwater M">M. Broadwater</name></author><author><name sortKey="Liu, W" uniqKey="Liu W">W. Liu</name></author><author><name sortKey="Spear, L P" uniqKey="Spear L">L. P. Spear</name></author><author><name sortKey="Crews, F T" uniqKey="Crews F">F. T. Crews</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="White, A M" uniqKey="White A">A. M. White</name></author><author><name sortKey="Swartzwelder, H S" uniqKey="Swartzwelder H">H. S. Swartzwelder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schweinsburg, A D" uniqKey="Schweinsburg A">A. D. Schweinsburg</name></author><author><name sortKey="Mcqueeny, T" uniqKey="Mcqueeny T">T. McQueeny</name></author><author><name sortKey="Nagel, B J" uniqKey="Nagel B">B. J. Nagel</name></author><author><name sortKey="Eyler, L T" uniqKey="Eyler L">L. T. Eyler</name></author><author><name sortKey="Tapert, S F" uniqKey="Tapert S">S. F. Tapert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sircar, R" uniqKey="Sircar R">R. Sircar</name></author><author><name sortKey="Basak, A K" uniqKey="Basak A">A. K. Basak</name></author><author><name sortKey="Sircar, D" uniqKey="Sircar D">D. Sircar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vetreno, R P" uniqKey="Vetreno R">R. P. Vetreno</name></author><author><name sortKey="Lawrimore, C J" uniqKey="Lawrimore C">C. J. Lawrimore</name></author><author><name sortKey="Rowsey, P J" uniqKey="Rowsey P">P. J. Rowsey</name></author><author><name sortKey="Crews, F T" uniqKey="Crews F">F. T. Crews</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vetreno, R P" uniqKey="Vetreno R">R. P. Vetreno</name></author><author><name sortKey="Crews, F T" uniqKey="Crews F">F. T. Crews</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zahr, N M" uniqKey="Zahr N">N. M. Zahr</name></author><author><name sortKey="Kaufman, K L" uniqKey="Kaufman K">K. L. Kaufman</name></author><author><name sortKey="Harper, C G" uniqKey="Harper C">C. G. Harper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reynolds, A R" uniqKey="Reynolds A">A. R. Reynolds</name></author><author><name sortKey="Berry, J N" uniqKey="Berry J">J. N. Berry</name></author><author><name sortKey="Sharrett Field, L" uniqKey="Sharrett Field L">L. Sharrett-Field</name></author><author><name sortKey="Prendergast, M A" uniqKey="Prendergast M">M. A. Prendergast</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, L" uniqKey="Qin L">L. Qin</name></author><author><name sortKey="He, J" uniqKey="He J">J. He</name></author><author><name sortKey="Hanes, R N" uniqKey="Hanes R">R. N. Hanes</name></author><author><name sortKey="Pluzarev, O" uniqKey="Pluzarev O">O. Pluzarev</name></author><author><name sortKey="Hong, J S" uniqKey="Hong J">J. S. Hong</name></author><author><name sortKey="Crews, F T" uniqKey="Crews F">F. T. Crews</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crews, F T" uniqKey="Crews F">F. T. Crews</name></author><author><name sortKey="Vetreno, R P" uniqKey="Vetreno R">R. P. Vetreno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Montesinos, J" uniqKey="Montesinos J">J. Montesinos</name></author><author><name sortKey="Alfonso Loeches, S" uniqKey="Alfonso Loeches S">S. Alfonso-Loeches</name></author><author><name sortKey="Guerri, C" uniqKey="Guerri C">C. Guerri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alfonso Loeches, S" uniqKey="Alfonso Loeches S">S. Alfonso-Loeches</name></author><author><name sortKey="Urena Peralta, J" uniqKey="Urena Peralta J">J. Urena-Peralta</name></author><author><name sortKey="Morillo Bargues, M J" uniqKey="Morillo Bargues M">M. J. Morillo-Bargues</name></author><author><name sortKey="Gomez Pinedo, U" uniqKey="Gomez Pinedo U">U. Gomez-Pinedo</name></author><author><name sortKey="Guerri, C" uniqKey="Guerri C">C. Guerri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, Y N" uniqKey="Zhao Y">Y. N. Zhao</name></author><author><name sortKey="Wang, F" uniqKey="Wang F">F. Wang</name></author><author><name sortKey="Fan, Y X" uniqKey="Fan Y">Y. X. Fan</name></author><author><name sortKey="Ping, G F" uniqKey="Ping G">G. F. Ping</name></author><author><name sortKey="Yang, J Y" uniqKey="Yang J">J. Y. Yang</name></author><author><name sortKey="Wu, C F" uniqKey="Wu C">C. F. Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bryant, C E" uniqKey="Bryant C">C. E. Bryant</name></author><author><name sortKey="Symmons, M" uniqKey="Symmons M">M. Symmons</name></author><author><name sortKey="Gay, N J" uniqKey="Gay N">N. J. Gay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liaunardy Jopeace, A" uniqKey="Liaunardy Jopeace A">A. Liaunardy-Jopeace</name></author><author><name sortKey="Gay, N J" uniqKey="Gay N">N. J. Gay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawasaki, T" uniqKey="Kawasaki T">T. Kawasaki</name></author><author><name sortKey="Kawai, T" uniqKey="Kawai T">T. Kawai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crews, F T" uniqKey="Crews F">F. T. Crews</name></author><author><name sortKey="Qin, L" uniqKey="Qin L">L. Qin</name></author><author><name sortKey="Sheedy, D" uniqKey="Sheedy D">D. Sheedy</name></author><author><name sortKey="Vetreno, R P" uniqKey="Vetreno R">R. P. Vetreno</name></author><author><name sortKey="Zou, J" uniqKey="Zou J">J. Zou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crews, F T" uniqKey="Crews F">F. T. Crews</name></author><author><name sortKey="Vetreno, R P" uniqKey="Vetreno R">R. P. Vetreno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Robinson, G" uniqKey="Robinson G">G. Robinson</name></author><author><name sortKey="Most, D" uniqKey="Most D">D. Most</name></author><author><name sortKey="Ferguson, L B" uniqKey="Ferguson L">L. B. Ferguson</name></author><author><name sortKey="Mayfield, J" uniqKey="Mayfield J">J. Mayfield</name></author><author><name sortKey="Harris, R A" uniqKey="Harris R">R. A. Harris</name></author><author><name sortKey="Blednov, Y A" uniqKey="Blednov Y">Y. A. Blednov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alfonso Loeches, S" uniqKey="Alfonso Loeches S">S. Alfonso-Loeches</name></author><author><name sortKey="Pascual Lucas, M" uniqKey="Pascual Lucas M">M. Pascual-Lucas</name></author><author><name sortKey="Blanco, A M" uniqKey="Blanco A">A. M. Blanco</name></author><author><name sortKey="Sanchez Vera, I" uniqKey="Sanchez Vera I">I. Sanchez-Vera</name></author><author><name sortKey="Guerri, C" uniqKey="Guerri C">C. Guerri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fernandez Lizarbe, S" uniqKey="Fernandez Lizarbe S">S. Fernandez-Lizarbe</name></author><author><name sortKey="Pascual, M" uniqKey="Pascual M">M. Pascual</name></author><author><name sortKey="Guerri, C" uniqKey="Guerri C">C. Guerri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Montesinos, J" uniqKey="Montesinos J">J. Montesinos</name></author><author><name sortKey="Pascual, M" uniqKey="Pascual M">M. Pascual</name></author><author><name sortKey="Rodriguez Arias, M" uniqKey="Rodriguez Arias M">M. Rodriguez-Arias</name></author><author><name sortKey="Minarro, J" uniqKey="Minarro J">J. Minarro</name></author><author><name sortKey="Guerri, C" uniqKey="Guerri C">C. Guerri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bajo, M" uniqKey="Bajo M">M. Bajo</name></author><author><name sortKey="Montgomery, S E" uniqKey="Montgomery S">S. E. Montgomery</name></author><author><name sortKey="Cates, L N" uniqKey="Cates L">L. N. Cates</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Narayanan, K B" uniqKey="Narayanan K">K. B. Narayanan</name></author><author><name sortKey="Park, H H" uniqKey="Park H">H. H. Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, E D" uniqKey="Tang E">E. D. Tang</name></author><author><name sortKey="Wang, C Y" uniqKey="Wang C">C. Y. Wang</name></author><author><name sortKey="Xiong, Y" uniqKey="Xiong Y">Y. Xiong</name></author><author><name sortKey="Guan, K L" uniqKey="Guan K">K. L. Guan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tokunaga, F" uniqKey="Tokunaga F">F. Tokunaga</name></author><author><name sortKey="Sakata, S" uniqKey="Sakata S">S. Sakata</name></author><author><name sortKey="Saeki, Y" uniqKey="Saeki Y">Y. Saeki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kovalenko, A" uniqKey="Kovalenko A">A. Kovalenko</name></author><author><name sortKey="Chable Bessia, C" uniqKey="Chable Bessia C">C. Chable-Bessia</name></author><author><name sortKey="Cantarella, G" uniqKey="Cantarella G">G. Cantarella</name></author><author><name sortKey="Israel, A" uniqKey="Israel A">A. Israel</name></author><author><name sortKey="Wallach, D" uniqKey="Wallach D">D. Wallach</name></author><author><name sortKey="Courtois, G" uniqKey="Courtois G">G. Courtois</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, X" uniqKey="Liu X">X. Liu</name></author><author><name sortKey="Chen, W" uniqKey="Chen W">W. Chen</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Li, L" uniqKey="Li L">L. Li</name></author><author><name sortKey="Wang, C" uniqKey="Wang C">C. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Long, Y" uniqKey="Long Y">Y. Long</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X. Liu</name></author><author><name sortKey="Wang, N" uniqKey="Wang N">N. Wang</name></author><author><name sortKey="Zhou, H" uniqKey="Zhou H">H. Zhou</name></author><author><name sortKey="Zheng, J" uniqKey="Zheng J">J. Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferguson, C" uniqKey="Ferguson C">C. Ferguson</name></author><author><name sortKey="Mckay, M" uniqKey="Mckay M">M. McKay</name></author><author><name sortKey="Harris, R A" uniqKey="Harris R">R. A. Harris</name></author><author><name sortKey="Homanics, G E" uniqKey="Homanics G">G. E. Homanics</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccarthy, K D" uniqKey="Mccarthy K">K. D. McCarthy</name></author><author><name sortKey="De Vellis, J" uniqKey="De Vellis J">J. de Vellis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, A W" uniqKey="Jones A">A. W. Jones</name></author><author><name sortKey="Sternebring, B" uniqKey="Sternebring B">B. Sternebring</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, L" uniqKey="Sun L">L. Sun</name></author><author><name sortKey="Li, Q" uniqKey="Li Q">Q. Li</name></author><author><name sortKey="Li, Q" uniqKey="Li Q">Q. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Block, M L" uniqKey="Block M">M. L. Block</name></author><author><name sortKey="Zecca, L" uniqKey="Zecca L">L. Zecca</name></author><author><name sortKey="Hong, J S" uniqKey="Hong J">J. S. Hong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, J Y" uniqKey="Yang J">J. Y. Yang</name></author><author><name sortKey="Xue, X" uniqKey="Xue X">X. Xue</name></author><author><name sortKey="Tian, H" uniqKey="Tian H">H. Tian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walter, T J" uniqKey="Walter T">T. J. Walter</name></author><author><name sortKey="Crews, F T" uniqKey="Crews F">F. T. Crews</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drew, P D" uniqKey="Drew P">P. D. Drew</name></author><author><name sortKey="Johnson, J W" uniqKey="Johnson J">J. W. Johnson</name></author><author><name sortKey="Douglas, J C" uniqKey="Douglas J">J. C. Douglas</name></author><author><name sortKey="Phelan, K D" uniqKey="Phelan K">K. D. Phelan</name></author><author><name sortKey="Kane, C J M" uniqKey="Kane C">C. J. M. Kane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ahlers, K E" uniqKey="Ahlers K">K. E. Ahlers</name></author><author><name sortKey="Karacay, B" uniqKey="Karacay B">B. Karacay</name></author><author><name sortKey="Fuller, L" uniqKey="Fuller L">L. Fuller</name></author><author><name sortKey="Bonthius, D J" uniqKey="Bonthius D">D. J. Bonthius</name></author><author><name sortKey="Dailey, M E" uniqKey="Dailey M">M. E. Dailey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pascual, M" uniqKey="Pascual M">M. Pascual</name></author><author><name sortKey="Balino, P" uniqKey="Balino P">P. Balino</name></author><author><name sortKey="Aragon, C M" uniqKey="Aragon C">C. M. Aragon</name></author><author><name sortKey="Guerri, C" uniqKey="Guerri C">C. Guerri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boschen, K E" uniqKey="Boschen K">K. E. Boschen</name></author><author><name sortKey="Ruggiero, M J" uniqKey="Ruggiero M">M. J. Ruggiero</name></author><author><name sortKey="Klintsova, A Y" uniqKey="Klintsova A">A. Y. Klintsova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jian, H" uniqKey="Jian H">H. Jian</name></author><author><name sortKey="Zhao, Y" uniqKey="Zhao Y">Y. Zhao</name></author><author><name sortKey="Liu, B" uniqKey="Liu B">B. Liu</name></author><author><name sortKey="Lu, S" uniqKey="Lu S">S. Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jian, H" uniqKey="Jian H">H. Jian</name></author><author><name sortKey="Zhao, Y" uniqKey="Zhao Y">Y. Zhao</name></author><author><name sortKey="Liu, B" uniqKey="Liu B">B. Liu</name></author><author><name sortKey="Lu, S" uniqKey="Lu S">S. Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Inoki, K" uniqKey="Inoki K">K. Inoki</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Zhu, T" uniqKey="Zhu T">T. Zhu</name></author><author><name sortKey="Wu, J" uniqKey="Wu J">J. Wu</name></author><author><name sortKey="Guan, K L" uniqKey="Guan K">K. L. Guan</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Neural Plast</journal-id><journal-id journal-id-type="iso-abbrev">Neural Plast</journal-id><journal-id journal-id-type="publisher-id">NP</journal-id><journal-title-group><journal-title>Neural Plasticity</journal-title></journal-title-group><issn pub-type="ppub">2090-5904</issn><issn pub-type="epub">1687-5443</issn><publisher><publisher-name>Hindawi</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31781182</article-id><article-id pub-id-type="pmc">6874951</article-id><article-id pub-id-type="doi">10.1155/2019/1648736</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Ethanol Exposure Induces Microglia Activation and Neuroinflammation through TLR4 Activation and SENP6 Modulation in the Adolescent Rat Hippocampus</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Li</surname><given-names>Qing</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Dexiang</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0002-6782-9759</contrib-id><name><surname>Pan</surname><given-names>Fang</given-names></name><email>panfang@sdu.edu.cn</email><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ho</surname><given-names>Cyrus S. H.</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ho</surname><given-names>Roger C. M.</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref><xref ref-type="aff" rid="I3"><sup>3</sup></xref></contrib></contrib-group><aff id="I1"><sup>1</sup>Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China</aff><aff id="I2"><sup>2</sup>Department of Psychological Medicine, National University of Singapore, Singapore</aff><aff id="I3"><sup>3</sup>Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore</aff><author-notes><fn fn-type="other"><p>Academic Editor: Tara Walker</p></fn></author-notes><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>12</day><month>11</month><year>2019</year></pub-date><volume>2019</volume><elocation-id>1648736</elocation-id><history><date date-type="received"><day>28</day><month>4</month><year>2019</year></date><date date-type="accepted"><day>5</day><month>8</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019 Qing Li et al.</copyright-statement><copyright-year>2019</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>The ethanol-induced toll-like receptor 4 (TLR4) signal activation of microglia and neuroinflammation are observed in both adolescent and adult rat brains, but the regulatory mechanisms of some TLR4 signaling-related factors in this process are still unclear. SUMO-specific protease 6 (SENP6) inhibits neuroinflammation by dampening nuclear factor kappa-B (NF-<italic>κ</italic>B) activation via the de-SUMOylation of NF kappa-B essential modulator (NEMO). This study investigates the effects of long-term ethanol consumption on neuroinflammation in the hippocampus of adolescent rats and the regulatory roles of TLR4 and SENP6. Twenty-one days of ethanol exposure in adolescent rats were used to develop an animal model. The number of microglia, microglial activation, and the expression of TLR4 in the hippocampus of adolescent rats were examined by immunoreactivity. The levels of TLR4, activation of NF-<italic>κ</italic>B including IkB-<italic>α</italic> and p-NF-<italic>κ</italic>B-p65, and SENP6 were measured by western blotting. Proinflammatory cytokines including TNF-<italic>α</italic>, IL-1<italic>β</italic>, and IL-6 were measured by enzyme-linked immunosorbent assay. The NF-<italic>κ</italic>B activation and proinflammatory cytokines released in overexpressed SENP6 and siRNA targeting SENP6 microglial cells after treatment with ethanol were estimated in vitro. This study found that alcohol exposure increased the number of activated microglia and the levels of p-NF-<italic>κ</italic>B-p65 and proinflammatory cytokines, while it decreased the SENP6 level in wild-type rats, but not in TLR4 knockout rats. The ethanol-induced increases of p-NF-<italic>κ</italic>B-p65, TNF-<italic>α</italic>, and IL-1<italic>β</italic> were dampened by overxpression of SENP6 and enhanced in SENP6-siRNA microglia. Our data suggest that ethanol exposure during adolescence induces the microglia-mediated neuroinflammation via TLR4 activation, and SENP6 plays an essential role in dampening NF-<italic>κ</italic>B activation and neuroinflammation.</p></abstract><funding-group><award-group><funding-source>National Natural Science Foundation of China</funding-source><award-id>31771220</award-id><award-id>31371036</award-id></award-group></funding-group></article-meta></front><floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Effect of ethanol exposure on the number of microglia (Iba-1 staining) in the hippocampus. Representative photomicrographs of level-matched coronal sections of CA1 (a, A–H), CA2/3 (b, A–H), and DG (c, A–H) from WT (A, E), WT+EtOH (B, F), KO (C, G), and KO+EtOH (D, H) rats. White arrows indicate Iba-1<sup>+</sup> microglia. Regions of interest (framed areas) in A–D are presented in E–H. Scale bar: 100 <italic>μ</italic>m in A–D; 20 <italic>μ</italic>m in E–H. WT = control rats without ethanol; WT+EtOH = control rats with ethanol; KO = TLR4 knockout rats without ethanol; KO+EtOH = TLR4 knockout rats with ethanol. CA1 = field CA1 of the hippocampus; CA2/3 = field CA2-3 of the hippocampus; DG = dentate gyrus of the hippocampus. Quantifications of Iba-1<sup>+</sup> microglia from WT, WT+EtOH, KO, and KO+EtOH rats are shown in (a, I) (CA1), (b, I) (CA2/3), and (c, I) (DG). The number of Iba-1<sup>+</sup> microglia was averaged from five random areas across each region in consecutive three sections of each rat. Data are presented as the mean number of Iba-1<sup>+</sup>cells/mm<sup>2</sup> ± S.E.M. (<italic>n</italic> = 4). <sup>∗∗</sup><italic>p</italic> < 0.01, <sup>∗∗∗</sup><italic>p</italic> < 0.001.</p></caption><graphic xlink:href="NP2019-1648736.001"></graphic></fig><fig id="fig2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Effect of ethanol exposure on the extent of microglial activation (ED-1 staining) and colocalization of ED-1 with TLR4 (ED-1/TLR4 colabeling) in the hippocampus. Representative photomicrographs of level-matched coronal sections of CA1 (a, A–P), CA2/3 (b, A–P), and DG (c, A–P) from WT (A, E, I, M), WT+EtOH (B, F, J, N), KO (C, J, K, O), and KO+EtOH (D, H, L, P) rats. White arrows indicate ED-1<sup>+</sup> (F) or ED-1<sup>+</sup>/TLR4<sup>+</sup> (N) cells. Regions of interest (framed areas) in A–D are presented in E–H for ED-1 staining and in I–L are presented in M–P for ED-1/TLR4 colabeling. Scale bar: 100 <italic>μ</italic>m in A–D, I–L); 20 <italic>μ</italic>m in E–H, M–P. WT = control rats without ethanol; WT+EtOH = control rats with ethanol; KO = TLR4 knockout rats without ethanol; KO+EtOH = TLR4 knockout rats with ethanol. CA1 = field CA1 of the hippocampus; CA2/3 = field CA2-3 of the hippocampus; DG = dentate gyrus of the hippocampus.</p></caption><graphic xlink:href="NP2019-1648736.002"></graphic></fig><fig id="fig3" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Effect of ethanol exposure on the TLR4 expression in the hippocampus. Representative photomicrographs of level-matched coronal sections of CA1 (a, A–H), CA2/3 (b, A–H), and DG (c, A–H) from WT (A, E), WT+EtOH (B, F), KO (C, G), and KO+EtOH (D, H) rats. White arrows indicate TLR4<sup>+</sup> cells. Regions of interest (framed areas) in A–D are presented in E–H. Scale bar: 100 <italic>μ</italic>m in A–D; 20 <italic>μ</italic>m in E–H. WT = control rats without ethanol; WT+EtOH = control rats with ethanol; KO = TLR4 knockout rats without ethanol; KO+EtOH = TLR4 knockout rats with ethanol. CA1 = field CA1 of the hippocampus; CA2/3 = field CA2-3 of the hippocampus; DG = dentate gyrus of the hippocampus. Quantifications of TLR4<sup>+</sup> cells from WT and WT+EtOH rats are shown in (d) (CA1), (e) (CA2/3), and (f) (DG). The number of TLR4<sup>+</sup> cells was averaged from five random areas across each region in consecutive three sections of each rat. Data are presented as the mean number of Iba-1<sup>+</sup>cells/mm<sup>2</sup> ± S.E.M. (<italic>n</italic> = 4). <sup>∗∗∗</sup><italic>p</italic> < 0.001. The hippocampal protein level of TLR4 (g) was measured by WB, and quantitative analyses were normalized to GADPH. Data are presented as the mean ± S.E.M. <sup>∗∗∗</sup><italic>p</italic> < 0.001.</p></caption><graphic xlink:href="NP2019-1648736.003"></graphic></fig><fig id="fig4" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Effects of ethanol exposure on the levels of SENP6, IkB-<italic>α</italic>, p-NF-<italic>κ</italic>B-p65, and proinflammatory cytokines in the hippocampus. The hippocampal levels of SENP6 (a), IkB-<italic>α</italic> (b), and p-NF-<italic>κ</italic>B-p65 (c) of the WT, WT+EtOH, KO, and KO+EtOH rats were measured by WB. And the levels of TNF-<italic>α</italic> (d), IL-1<italic>β</italic> (e), and IL-6 (f) proteins were measured by ELISA. WT = control rats without ethanol; WT+EtOH = control rats with ethanol; KO = TLR4 knockout rats without ethanol; KO+EtOH = TLR4 knockout rats with ethanol. Quantitative analyses were normalized to <italic>β</italic>-actin (for SENP6), GADPH (for IkB-<italic>α</italic>), or Lamin A/C (for p-NF-<italic>κ</italic>B-p65) for WB. Cytokine concentrations were normalized to the total protein content. Data are presented as the mean ± S.E.M. <sup>∗∗</sup><italic>p</italic> < 0.01, <sup>∗∗∗</sup><italic>p</italic> < 0.001.</p></caption><graphic xlink:href="NP2019-1648736.004"></graphic></fig><fig id="fig5" orientation="portrait" position="float"><label>Figure 5</label><caption><p>The modulatory effect of SENP6 in ethanol-induced neuroinflammation. (a) The statistical analyses of SENP6 levels in cultured microglial cells treated with different doses of ethanol (0, 10, 30, 50, and 100 mM) for 24 h. (b) The transfection efficiency by comparing the SENP6 level of the SENP6 and siSENP6 groups to Scr group. (c–g) The levels of IkB-<italic>α</italic>, p-NF-<italic>κ</italic>B-p65, TNF-<italic>α</italic>, IL-1<italic>β</italic>, and IL-6 in microglial cells of the Scr group with nonethanol treatment and of Scr, SENP6, and siSENP6 groups after treatment with ethanol at100mM for 24 h. Scr-Con = scrambled sequence group with nonethanol treatment; Scr-E = scrambled sequence group with 100 mM ethanol treatment; SENP6-E = overexpressed SENP6 group with 100 mM ethanol treatment; siSENP6-E = siRNA against SENP6 group with 100 mM ethanol treatment. Quantitative analyses were normalized to <italic>β</italic>-actin (for SENP6), GADPH (for IkB-<italic>α</italic>), or Lamin A/C (for p-NF-<italic>κ</italic>B-p65) for WB. And cytokine concentrations were normalized to the total protein content. Data are presented as the mean ± S.E.M. <sup>∗</sup><italic>p</italic> < 0.05, <sup>∗∗</sup><italic>p</italic> < 0.01, <sup>∗∗∗</sup><italic>p</italic> < 0.001.</p></caption><graphic xlink:href="NP2019-1648736.005"></graphic></fig></floats-group></pmc><affiliations><list><country><li>République populaire de Chine</li><li>Singapour</li></country><orgName><li>Université nationale de Singapour</li></orgName></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Li, Qing" sort="Li, Qing" uniqKey="Li Q" first="Qing" last="Li">Qing Li</name></noRegion><name sortKey="Liu, Dexiang" sort="Liu, Dexiang" uniqKey="Liu D" first="Dexiang" last="Liu">Dexiang Liu</name><name sortKey="Pan, Fang" sort="Pan, Fang" uniqKey="Pan F" first="Fang" last="Pan">Fang Pan</name></country><country name="Singapour"><noRegion><name sortKey="Ho, Cyrus S H" sort="Ho, Cyrus S H" uniqKey="Ho C" first="Cyrus S. H." last="Ho">Cyrus S. H. Ho</name></noRegion><name sortKey="Ho, Roger C M" sort="Ho, Roger C M" uniqKey="Ho R" first="Roger C. M." last="Ho">Roger C. M. Ho</name><name sortKey="Ho, Roger C M" sort="Ho, Roger C M" uniqKey="Ho R" first="Roger C. M." last="Ho">Roger C. M. Ho</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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