Melatonin salvages lead‐induced neuro‐cognitive shutdown, anxiety, and depressive‐like symptoms via oxido‐inflammatory and cholinergic mechanisms
Abstract Introduction Lead is the most used nonphysiological neurotoxic heavy metal in the world that has been indicated to interfere with the cognitive and noncognitive processes via numerous mechanisms. The neuroprotective effect of melatonin is well known, but the effect of its interaction with l...
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| Format: | Article |
| Language: | English |
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Wiley
2021-08-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.2227 |
| _version_ | 1827877400705236992 |
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| author | Noah A. Omeiza Halimat A. Abdulrahim Abdullateef I. Alagbonsi Precious U. Ezurike Talha K. Soluoku Happy Isiabor Abdulmusawwir A. Alli‐oluwafuyi |
| author_facet | Noah A. Omeiza Halimat A. Abdulrahim Abdullateef I. Alagbonsi Precious U. Ezurike Talha K. Soluoku Happy Isiabor Abdulmusawwir A. Alli‐oluwafuyi |
| author_sort | Noah A. Omeiza |
| collection | DOAJ |
| description | Abstract Introduction Lead is the most used nonphysiological neurotoxic heavy metal in the world that has been indicated to interfere with the cognitive and noncognitive processes via numerous mechanisms. The neuroprotective effect of melatonin is well known, but the effect of its interaction with lead in the brain remains inconclusive. Objective To assess the therapeutic role of melatonin on cognitive deficit, anxiety and depressive‐like symptoms in matured male Wistar rats exposed to a subchronic lead chloride (PbCl2). Methods Twenty male Wistar rats were blindly randomized into four groups (n = 5/group): group 1 to 4 underwent intragastric administration of physiological saline (10 ml/kg; vehicle), PbCl2 (50 mg/kg), melatonin (10 mg/kg) and PbCl2 + melatonin respectively for a period of 4 weeks during which neurobehavioral data were extracted, followed by neurochemical and histopathological evaluations. Results Exposure to PbCl2 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‐like feces, and time spent in the dark compartment of a bright/dark box which are predictors of anxiety. It also induced depressive‐like behavior as immobility time was enhanced. PbCl2 deranged neurochemicals; malondialdehyde, interlukin‐1β, and tumor necrotic factor‐α were increased while superoxide dismutase and acetylcholinesterase were decreased without remarkable alteration in reduced glutathione and nitric oxide. Administration of PbCl2 further disrupted neuronal settings of hippocampal proper and dentate gyrus. In contrast, the supplementation of melatonin reversed all the neurological consequences of PbCl2 neurotoxicity by eliciting its properties against oxidative and nonoxidative action of PbCl2. Conclusion These findings suggest that melatonin down‐regulates neurotoxicant interplays in the brain systems. Therefore, this study suggests the use of melatonin as an adjuvant therapy in neuropathological disorders/dysfunctions. |
| first_indexed | 2024-03-12T17:35:47Z |
| format | Article |
| id | doaj.art-9f2fd59e1712486eb3013b738cb4b144 |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-03-12T17:35:47Z |
| publishDate | 2021-08-01 |
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| series | Brain and Behavior |
| spelling | doaj.art-9f2fd59e1712486eb3013b738cb4b1442023-08-04T10:56:25ZengWileyBrain and Behavior2162-32792021-08-01118n/an/a10.1002/brb3.2227Melatonin salvages lead‐induced neuro‐cognitive shutdown, anxiety, and depressive‐like symptoms via oxido‐inflammatory and cholinergic mechanismsNoah A. Omeiza0Halimat A. Abdulrahim1Abdullateef I. Alagbonsi2Precious U. Ezurike3Talha K. Soluoku4Happy Isiabor5Abdulmusawwir A. Alli‐oluwafuyi6Neuropharmacology and Toxicology Unit Department of Pharmacology and Therapeutics College of Medicine University of Ibadan Ibadan Oyo State NigeriaDepartment of Medical Biochemistry College of Health Sciences University of Ilorin Ilorin Kwara State NigeriaDepartment of Clinical Biology (Physiology) School of Medicine and Pharmacy College of Medicine and Health Sciences University of Rwanda Huye Southern Province Republic of RwandaNeuropharmacology and Toxicology Unit Department of Pharmacology and Therapeutics College of Medicine University of Ibadan Ibadan Oyo State NigeriaDepartment of Neuroscience Faculty of Medicine American University of Beirut Beirut LebanonNeuropharmacology and Toxicology Unit Department of Pharmacology and Therapeutics College of Medicine University of Ibadan Ibadan Oyo State NigeriaDepartment of Pharmacology and Therapeutics College of Health Sciences University of Ilorin Ilorin Kwara State NigeriaAbstract Introduction Lead is the most used nonphysiological neurotoxic heavy metal in the world that has been indicated to interfere with the cognitive and noncognitive processes via numerous mechanisms. The neuroprotective effect of melatonin is well known, but the effect of its interaction with lead in the brain remains inconclusive. Objective To assess the therapeutic role of melatonin on cognitive deficit, anxiety and depressive‐like symptoms in matured male Wistar rats exposed to a subchronic lead chloride (PbCl2). Methods Twenty male Wistar rats were blindly randomized into four groups (n = 5/group): group 1 to 4 underwent intragastric administration of physiological saline (10 ml/kg; vehicle), PbCl2 (50 mg/kg), melatonin (10 mg/kg) and PbCl2 + melatonin respectively for a period of 4 weeks during which neurobehavioral data were extracted, followed by neurochemical and histopathological evaluations. Results Exposure to PbCl2 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‐like feces, and time spent in the dark compartment of a bright/dark box which are predictors of anxiety. It also induced depressive‐like behavior as immobility time was enhanced. PbCl2 deranged neurochemicals; malondialdehyde, interlukin‐1β, and tumor necrotic factor‐α were increased while superoxide dismutase and acetylcholinesterase were decreased without remarkable alteration in reduced glutathione and nitric oxide. Administration of PbCl2 further disrupted neuronal settings of hippocampal proper and dentate gyrus. In contrast, the supplementation of melatonin reversed all the neurological consequences of PbCl2 neurotoxicity by eliciting its properties against oxidative and nonoxidative action of PbCl2. Conclusion These findings suggest that melatonin down‐regulates neurotoxicant interplays in the brain systems. Therefore, this study suggests the use of melatonin as an adjuvant therapy in neuropathological disorders/dysfunctions.https://doi.org/10.1002/brb3.2227anxietycholinergic disturbancecognitiondepressionlead‐toxicitymelatonin |
| spellingShingle | Noah A. Omeiza Halimat A. Abdulrahim Abdullateef I. Alagbonsi Precious U. Ezurike Talha K. Soluoku Happy Isiabor Abdulmusawwir A. Alli‐oluwafuyi Melatonin salvages lead‐induced neuro‐cognitive shutdown, anxiety, and depressive‐like symptoms via oxido‐inflammatory and cholinergic mechanisms Brain and Behavior anxiety cholinergic disturbance cognition depression lead‐toxicity melatonin |
| title | Melatonin salvages lead‐induced neuro‐cognitive shutdown, anxiety, and depressive‐like symptoms via oxido‐inflammatory and cholinergic mechanisms |
| title_full | Melatonin salvages lead‐induced neuro‐cognitive shutdown, anxiety, and depressive‐like symptoms via oxido‐inflammatory and cholinergic mechanisms |
| title_fullStr | Melatonin salvages lead‐induced neuro‐cognitive shutdown, anxiety, and depressive‐like symptoms via oxido‐inflammatory and cholinergic mechanisms |
| title_full_unstemmed | Melatonin salvages lead‐induced neuro‐cognitive shutdown, anxiety, and depressive‐like symptoms via oxido‐inflammatory and cholinergic mechanisms |
| title_short | Melatonin salvages lead‐induced neuro‐cognitive shutdown, anxiety, and depressive‐like symptoms via oxido‐inflammatory and cholinergic mechanisms |
| title_sort | melatonin salvages lead induced neuro cognitive shutdown anxiety and depressive like symptoms via oxido inflammatory and cholinergic mechanisms |
| topic | anxiety cholinergic disturbance cognition depression lead‐toxicity melatonin |
| url | https://doi.org/10.1002/brb3.2227 |
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