{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:58:25Z","timestamp":1791122305176,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T00:00:00Z","timestamp":1364428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:p>\n                    Parkinson's disease is characterized by a progressive degeneration of substantia nigra (SN) dopaminergic neurons with age. We previously found that a single systemic lipopolysaccharide (LPS, 5 mg\/kg, i.p.) injection caused a slow progressive loss of tyrosine hydroxylase immunoreactive (TH+IR) neurons in SN associated with increasing motor dysfunction. In this study, we investigated the role of NADPH oxidase (NOX) in inflammation\u2010mediated SN neurotoxicity. A comparison of control (NOX2\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) mice with NOX subunit gp91\n                    <jats:sup>phox<\/jats:sup>\n                    \u2010deficient (NOX2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice 10 months after LPS administration (5 mg\/kg, i.p.) resulted in a 39% (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.01) loss of TH+IR neurons in NOX2\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice, whereas NOX2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice did not show a significant decrease. Microglia (Iba1+IR) showed morphological activation in NOX2\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice, but not in NOX2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice at 1 hr. Treatment of NOX2\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice with LPS resulted in a 12\u2010fold increase in NOX2 mRNA in midbrain and 5.5\u20136.5\u2010fold increases in NOX2 protein (+IR) in SN compared with the saline controls. Brain reactive oxygen species (ROS), determined using diphenyliodonium histochemistry, was increased by LPS in SN between 1 hr and 20 months. Diphenyliodonium (DPI), an NOX inhibitor, blocked LPS\u2010induced activation of microglia and production of ROS, TNF\u03b1, IL\u20101\u03b2, and MCP\u20101. Although LPS increased microglial activation and ROS at all ages studied, saline control NOX2\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice showed age\u2010related increases in microglial activation, NOX, and ROS levels at 12 and 22 months of age. Together, these results suggest that NOX contributes to persistent microglial activation, ROS production, and dopaminergic neurodegeneration that persist and continue to increase with age. \u00a9 147.\n                  <\/jats:p>","DOI":"10.1002\/glia.22479","type":"journal-article","created":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T05:19:13Z","timestamp":1364447953000},"page":"855-868","source":"Crossref","is-referenced-by-count":247,"title":["NADPH oxidase and aging drive microglial activation, oxidative stress, and dopaminergic neurodegeneration following systemic LPS administration"],"prefix":"10.1002","volume":"61","author":[{"given":"Liya","family":"Qin","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Pharmacology School of Pharmaceutical Sciences Hebei University People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jau\u2010Shyong","family":"Hong","sequence":"additional","affiliation":[{"name":"Neuropharmacology Section NIEHS Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulton T.","family":"Crews","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina School of Medicine Chapel Hill North Carolina"},{"name":"Department of Psychiatry University of North Carolina School of Medicine Chapel Hill North Carolina"},{"name":"Department of Pharmacology University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-04-01324.1996"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2005.06.004"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0351127"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-009-9164-4"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(04)00081-3"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.03.003"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0109fje"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.016"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80139-2"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70062-6"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(98)00040-0"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2004.10.003"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2008.02.014"},{"key":"e_1_2_6_16_1","first-page":"83","article-title":"Inflammation in Parkinson's disease","volume":"86","author":"McGeer PL","year":"2001","journal-title":"Adv Neurol"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-01-00205.1998"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01463655"},{"key":"e_1_2_6_19_1","volume-title":"The mouse brain in sterotaxic coordinates","author":"Paxinos G","year":"2004"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0295-202"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0428-1"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-5"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-10"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307657200"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20467"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0556-6"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0937239100"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0983fje"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.10.031"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.22479","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.22479","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T12:26:16Z","timestamp":1698668776000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.22479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,28]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1002\/glia.22479"],"URL":"https:\/\/doi.org\/10.1002\/glia.22479","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,28]]}}}