Melatonin salvages lead-induced neuro-cognitive shutdown, anxiety, and depressive-like symptoms via oxido-inflammatory and cholinergic mechanisms
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Date
2021-05-19
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Brain and Behavior published by Wiley Periodicals LLC
Abstract
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 pro-
cesses 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 + mela-
tonin 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 neu-
rological consequences of PbCl2 neurotoxicity by eliciting its properties against oxida-
tive and nonoxidative action of PbCl2.
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anxiety, cholinergic disturbance, cognition, depression, lead-toxicity, melatonin, neurogenesis, neuro-inflammation, oxidative stress