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The neuroprotective effect of melatonin is well known, but the effect of its interaction with lead in the brain remains inconclusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To assess the therapeutic role of melatonin on cognitive deficit, anxiety and depressive\u2010like symptoms in matured male Wistar rats exposed to a subchronic lead chloride (PbCl\n                      <jats:sub>2<\/jats:sub>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Twenty male Wistar rats were blindly randomized into four groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05\/group): group 1 to 4 underwent intragastric administration of physiological saline (10\u00a0ml\/kg; vehicle), PbCl\n                      <jats:sub>2<\/jats:sub>\n                      (50\u00a0mg\/kg), melatonin (10\u00a0mg\/kg) and PbCl\n                      <jats:sub>2<\/jats:sub>\n                      + melatonin respectively for a period of 4 weeks during which neurobehavioral data were extracted, followed by neurochemical and histopathological evaluations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Exposure to PbCl\n                      <jats:sub>2<\/jats:sub>\n                      reduced cognitive performance by increasing the escape latency and average proximity to the platform zone border, decreasing average path length in the platform zone, cognitive score, and time spent in probing. It raised the thigmotaxis percentage, time spent in rearing, number of pellet\u2010like feces, and time spent in the dark compartment of a bright\/dark box which are predictors of anxiety. It also induced depressive\u2010like behavior as immobility time was enhanced. PbCl\n                      <jats:sub>2<\/jats:sub>\n                      deranged neurochemicals; malondialdehyde, interlukin\u20101\u03b2, and tumor necrotic factor\u2010\u03b1 were increased while superoxide dismutase and acetylcholinesterase were decreased without remarkable alteration in reduced glutathione and nitric oxide. Administration of PbCl\n                      <jats:sub>2<\/jats:sub>\n                      further disrupted neuronal settings of hippocampal proper and dentate gyrus. In contrast, the supplementation of melatonin reversed all the neurological consequences of PbCl\n                      <jats:sub>2<\/jats:sub>\n                      neurotoxicity by eliciting its properties against oxidative and nonoxidative action of PbCl\n                      <jats:sub>2<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that melatonin down\u2010regulates neurotoxicant interplays in the brain systems. Therefore, this study suggests the use of melatonin as an adjuvant therapy in neuropathological disorders\/dysfunctions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.2227","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T18:31:24Z","timestamp":1622831484000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Melatonin salvages lead\u2010induced neuro\u2010cognitive shutdown, anxiety, and depressive\u2010like symptoms via oxido\u2010inflammatory and cholinergic mechanisms"],"prefix":"10.1002","volume":"11","author":[{"given":"Noah A.","family":"Omeiza","sequence":"first","affiliation":[{"name":"Neuropharmacology and Toxicology Unit Department of Pharmacology and Therapeutics College of Medicine University of Ibadan  Ibadan Oyo State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halimat A.","family":"Abdulrahim","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry College of Health Sciences University of Ilorin  Ilorin Kwara State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5462-9950","authenticated-orcid":false,"given":"Abdullateef I.","family":"Alagbonsi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biology (Physiology) School of Medicine and Pharmacy College of Medicine and Health Sciences University of Rwanda  Huye Southern Province Republic of Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Precious U.","family":"Ezurike","sequence":"additional","affiliation":[{"name":"Neuropharmacology and Toxicology Unit Department of Pharmacology and Therapeutics College of Medicine University of Ibadan  Ibadan Oyo State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talha K.","family":"Soluoku","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Faculty of Medicine American University of Beirut  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Happy","family":"Isiabor","sequence":"additional","affiliation":[{"name":"Neuropharmacology and Toxicology Unit Department of Pharmacology and Therapeutics College of Medicine University of Ibadan  Ibadan Oyo State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulmusawwir A.","family":"Alli\u2010oluwafuyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics College of Health Sciences University of Ilorin  Ilorin Kwara State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24220"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.12816\/0006042"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1515\/intox\u20102015\u20100009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2018.06.023"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23010238"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gexplo.2020.106493"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891\u20105849(96)00352\u20108"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2015.06.040"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204\u2010008\u20100313\u2010y"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2015.07.025"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants8030071"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.7860\/JCDR\/2016\/20273.8261"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3316\/informit.251867577313676"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u2010079X.2010.00847.x"},{"issue":"2","key":"e_1_2_9_16_1","first-page":"33","article-title":"Thirty\u2010four years since the discovery","volume":"59","author":"Bubenik G. 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