Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations

Zhang, Lijie; Tu, Runqi; Wang, Yawei; Hu, Yazhen; Li, Xing; Cheng, Xuemin; Yin, Yong; Li, Wenjie; Huang, Hui

doi:10.3389/fphys.2017.00446

Cited by 52 publications

(33 citation statements)

References 49 publications

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“…The most significant and important finding in our study was the discovery of memory loss in adult zebrafish induced by chronic PbCl 2 exposure at a concentration of 50 ppb. This finding is consistent with previous publications about the neurotoxicity and memory impairment induced by chronic lead exposure in rodents [28][29][30]. On the other hand, the study done by Chen et al also showed that the 25 to 50 ppb lead acetate exposure of 8 to 120 hpf zebrafish induced memory deficiency at the adult stage (determined at 150 dpf), which was tested by food reward-based T-maze [6].…”

Section: Discussionsupporting

confidence: 91%

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Thi

Audira

et al. 2020

IJMS

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Lead and lead-derived compounds have been extensively utilized in industry, and their chronic toxicity towards aquatic animals has not been thoroughly addressed at a behavioral level. In this study, we assessed the risk of exposure to lead at a waterborne environmental concentration in adult zebrafish by behavioral and biochemical analyses. Nine tests, including three-dimension (3D) locomotion, novel tank exploration, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and a short-term memory test, were performed to assess the behavior of adult zebrafish after the exposure to 50 ppb PbCl 2 for one month. The brain tissues were dissected and subjected to biochemical assays to measure the relative expression of stress biomarkers and neurotransmitters to elucidate the underlying mechanisms for behavioral alterations. The results of the behavioral tests showed that chronic exposure to lead could elevate the stress and anxiety levels characterized by elevated freezing and reduced exploratory behaviors. The chronic exposure to PbCl 2 at a low concentration also induced a sharp reduction of aggressiveness and short-term memory. However, no significant change was found in predator avoidance, social interaction, shoaling, or color preference. The biochemical assays showed elevated cortisol and reduced serotonin and melatonin levels in the brain, thus, altering the behavior of the PbCl 2 -exposed zebrafish. In general, this study determined the potential ecotoxicity of long-term lead exposure in adult zebrafish through multiple behavioral assessments. The significant findings were that even at a low concentration, long-term exposure to lead could impair the memory and cause a decrease in the aggressiveness and exploratory activities of zebrafish, which may reduce their survival fitness.(EC10/NOEC-usually more than 14 days) on fish range from 18 to 1559 µg/L and 44 to 437 µg/L, respectively [3,4].More evidence has shown the detrimental impacts of lead on human health, especially at a neurobehavioral level. The neurotoxicity of chronic exposure to low concentrations of lead can impair cognitive performance in childhood through to adulthood [5][6][7][8][9]. Some studies demonstrated the correlation between the exposure to lead at low concentrations and attention-deficit/hyperactivity disorder (ADHD) in children [10]. The development of the central nervous system can be disrupted when children are exposed to low concentrations of lead for a long period of time (blood lead level below 10 mg/dL) [11]. Therefore, lead toxicity has become a serious issue for human health and environmental protection [6]. According to previous studies, the effect of lead on the nervous system includes the disruption of key molecules during neuronal migration and differentiation, interference with synapse formation mediated by a reduction in neuronal sialic acid production and premature differentiation of glial cells, interference with neurotransmitter release, and disruption of the...

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Section: Discussionsupporting

confidence: 91%

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Thi

Audira

et al. 2020

IJMS

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“…This result indicates that Pb treatment may have affected the ability of the animals to learn or remember the location of the dark box earlier than expected after several trial period. This finding supported several earlier reports that implicated Pb EAHT exposure as an agent of cognitive impairment, particularly in a developing brain [13,[33][34][35]. This result further indicates that the treatment of Vitexin alongside Pb treatment will attenuate the possible cognitive impairment caused by Pb.…”

Section: Discussionsupporting

confidence: 91%

“…Exposure to Pb, even in low doses, results in various adverse consequences, particularly in the brain [8]. Pb, as a neurotoxicant, crosses the blood-brain barrier to cause oxidative stress [9], morphologic damage, neurodegeneration and cognitive impairment in the brain, particularly that of developing brain [10][11][12][13]. The prefrontal cortex (PFC), which accounts for one-third of the human cerebral cortex, is responsible for working memory, higher reasoning, decision making and many other executive functions [14,15].…”

Section: Introductionmentioning

confidence: 99%

Lead acetate-induced neurodegenerative changes in the dorsolateral prefrontal cortex of mice: the role of Vitexin

Amedu

Omotoso

2020

Environ Anal Health Toxicol

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This study was aimed at investigating the neuroprotective effect of Vitexin against lead (Pb) induced neurodegenerative changes in the dorsolateral prefrontal cortex (DLPFC) and working memory in mice. Thirty-two adolescent male albino mice were divided into four groups (n=8). Control group received 0.2 mL of normal saline; Pb group received 100 mg/kg of Pb acetate for 14 days, Vitexin group received 1mg/kg of Vitexin for 14 days, and Pb+Vitexin group received 100 mg/kg of Pb acetate and 1 mgkg of Vitexin for 14 days. Barnes maze test and novel object recognition test were done to ascertain working memory. Histoarchitectural assessment of DLPFC was done with haematoxylin and eosin (H&E), cresyl fast violet and congo red stains. Furthermore, cell count and other morphometric measurements were done. There was significant decline in working memory in the Pb group, but a combination of Pb+Vitexin improved the working memory. Vitexin significantly reduced neuronal death and chromatolysis caused by Pb. Amyloid aggregation was not observed in any of the groups. This study has shown that concurrent administration of Vitexin and Pb will significantly reduce neurodegeneration and improve working memory. However, Pb treatment or Pb+Vitexin treatment does not have any effect on intercellular distance, neuronal length and the cross-sectional area of neurons in layer III of DLPFC.

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“…lead is a heavy metal widely used in various industries, its release can permanently pollute the environment [1] .It has been well documented that lead exposure can develop multiple systemic adverse effects, including decreased intelligence quotient (IQ) [2,3] cognitive impairment [4][5][6] memory decline [7,8] and de cient attention [9][10][11] as well as known hematological toxicities.. In addition, recent studies have reported that lead exposure may aggravate neurodegenerative disorders, such as Alzheimer's and Parkinson's disease.…”

Section: Introductionmentioning

confidence: 99%

Lead Exposure Induced Copper Clearance Disorder of Blood-CSF Barrier

Wang

et al. 2020

Preprint

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Lead is a heavy metal commonly found in the environment with known neurotoxicity, hematological and other toxicities. It has been found that lead exposure can disturb partial metal regulatory function in the blood-CSF barrier (BCB). Copper, which play an important role in maintaining normal brain function, can accumulate in brain after lead exposure. The studies of Alzheimer's disease (AD) indicated that abnormal copper homeostasis in cerebrospinal fluid (CSF) may be involved in the pathogenesis. However, the mechanism of copper disturbance in the brain caused by lead is still unknown. This study was designed to investigate copper clearance by the BCB in central nervous system after lead exposure, with focus on copper transporter protein CTR1/ATP7A. Inductively coupled plasma mass spectrometry (ICP-MS) and principal component analysis (PCA) were used to identify the changes of heavy metal level in hippocampus and CSF after lead exposure. It was found that the change in copper level was most pronounced in the brain between 3 to 12 weeks post lead exposure. Ventriculo-cisternal (VC) perfusion in Sprague Dawley (SD) rat suggested that the ability of BCB to deliver copper from the CSF to blood was decreased after lead exposure. Confocal microscope showed evidence of the presence of excess copper in the choroid plexus cells leading to CTR1/ATP7A shifting toward the apical microvilli facing the CSF after lead exposure. Finally, transmission electron microscopy (TEM) was used for observation of the microstructure of choroid plexus showed altered mitochondrial morphology with decreased microvilli after lead exposure. Our data suggested that lead exposure may alter BCB cellular microscopic structure and its copper transport, clearance function that might further cause brain injury.

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Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations

Cited by 52 publications

References 49 publications

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Lead acetate-induced neurodegenerative changes in the dorsolateral prefrontal cortex of mice: the role of Vitexin

Lead Exposure Induced Copper Clearance Disorder of Blood-CSF Barrier

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