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Loss of\n                      <jats:styled-content style=\"fixed-case\">DMT<\/jats:styled-content>\n                      1 function results in microcytic anemia. While iron plays an important role in neural function, the behavioral consequences of\n                      <jats:styled-content style=\"fixed-case\">DMT<\/jats:styled-content>\n                      1 deficiency are largely unexplored. The goal of this study was to define the neurobehavioral and neurochemical phenotypes of homozygous Belgrade (\n                      <jats:italic>b\/b<\/jats:italic>\n                      ) rats that carry\n                      <jats:styled-content style=\"fixed-case\">DMT<\/jats:styled-content>\n                      1 mutation and explore potential mechanisms of these phenotypes. The\n                      <jats:italic>b\/b<\/jats:italic>\n                      rats (11\u201312\u00a0weeks old) and their healthy littermate heterozygous (\n                      <jats:italic>+\/b<\/jats:italic>\n                      ) Belgrade rats were subject to elevated plus maze tasks. The\n                      <jats:italic>b\/b<\/jats:italic>\n                      rats spent more time in open arms, entered open arms more frequently and traveled more distance in the maze than\n                      <jats:italic>+\/b<\/jats:italic>\n                      controls, suggesting increased impulsivity. Impaired emotional behavior was associated with down\u2010regulation of\n                      <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>\n                      in the hippocampus in\n                      <jats:italic>b\/b<\/jats:italic>\n                      rats. Also,\n                      <jats:italic>b\/b<\/jats:italic>\n                      rats showed increased\n                      <jats:styled-content style=\"fixed-case\">\n                        GABA\n                        <jats:sub>A<\/jats:sub>\n                      <\/jats:styled-content>\n                      receptor \u03b11 and\n                      <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>\n                      transporter, indicating altered\n                      <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>\n                      ergic function. Furthermore, metal analysis revealed that\n                      <jats:italic>b\/b<\/jats:italic>\n                      rats have decreased total iron, but normal non\u2010heme iron, in the brain. Interestingly,\n                      <jats:italic>b\/b<\/jats:italic>\n                      rats exhibited unusually high copper levels in most brain regions, including striatum and hippocampus. Quantitative\n                      <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\n                      analysis showed that both copper importer copper transporter 1 and exporter copper\u2010transporting ATPase 1 were up\u2010regulated in the hippocampus from\n                      <jats:italic>b\/b<\/jats:italic>\n                      rats. Finally,\n                      <jats:italic>b\/b<\/jats:italic>\n                      rats exhibited increased 8\u2010isoprostane levels and decreased glutathione\/glutathione disulfide ratio in the hippocampus, reflecting elevated oxidative stress. Combined, our results suggest that copper loading in\n                      <jats:styled-content style=\"fixed-case\">DMT<\/jats:styled-content>\n                      1 deficiency could induce oxidative stress and impair\n                      <jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>\n                      metabolism, which promote impulsivity\u2010like behavior.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13717-fig-0007-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                      Iron\u2010copper model: Mutations in the divalent metal transporter 1 (DMT1) decrease body iron status and up\u2010regulate copper absorption, which leads to copper loading in the brain and consequently increases metal\u2010induced oxidative stress. This event disrupts GABAergic neurotransmission and promotes impulsivity\u2010like behavior. Our model provides better understanding of physiological risks associated with imbalanced metal metabolism in mental function and, more specifically, the interactions with GABA and redox control in the treatment of emotional disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jnc.13717","type":"journal-article","created":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T17:09:18Z","timestamp":1466615358000},"page":"918-928","source":"Crossref","is-referenced-by-count":29,"title":["Loss of divalent metal transporter 1 function promotes brain copper accumulation and increases impulsivity"],"prefix":"10.1111","volume":"138","author":[{"given":"Murui","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeastern University Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JuOae","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of 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