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Research
Ming Chao Liu
Fourth Military Medical University: Air Force Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0771-3930
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Lead and manganese are common neurotoxins. However, individuals are subject to co-exposures in real life, and it is therefore important to study these metals in combination.
Methods: Weaning Sprague-Dawley rats were given ad libitum access to drinking water solutions containing lead (100 ppm), manganese (2.5 mg/mL) or a mixture, and each treatment has its own minocycline (50 mg/Kg.d) supplement group.
Results: The results showed a significant difference in spatial memory and the induction levels of hippocampal long-term potentiation (LTP) in all exposure groups when compared with controls. The combined exposure group exhibited the most pronounced effect when compared with each of the single metal exposure groups. Microglia displayed activation at day 3 after exposure alone or in combination, while astrocytes showed activation at day 5, accompanied by decreased expression levels of glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), and glutamine synthetase (GS). Furthermore, the levels of the glutamate in the synaptic cleft increased significantly. When microglial activation was inhibited by minocycline, the activation of astrocytes, and the expression of GLAST, GLT-1, and GS were both reversed. In addition, upon minocycline treatment, the hippocampal LTP impairment and the cognitive injury were significantly alleviated in each of the exposure groups.
Conclusions: These results suggest that combined exposure to lead and manganese can cause greater effects on cognition and synaptic plasticity when compared to single metal exposure groups. And the reason may involve in microglia abnormal activation leading to an excessive regulation of astrocytes, resulting in glutamate reuptake dysfunction in astrocytes and lead to perturbed cognition and synaptic plasticity.
Keywords
lead, manganese, microglia, astrocyte, learning and memory
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- figs1BWandBPbandBMn.tif
SUPPORTING INFORMATION LEGENDS Fig. S1. SD-rat body weight and blood leads and manganese level. SD rats were divided to 4 groups: 0 ppm lead acetate and 0mg/ml manganese chloride; 100 ppm lead acetate; 2.5 mg/ml manganese chloride; 100 ppm lead acetate and 2.5 mg/ml manganese chloride. The lead acetate and manganese chloride were dissolved in distilled water. Rats were exposure from PND 24 to PND 80. Data are expressed as mean ± SD (n= 6). B and C: *P < 0.05 vs. Con. (A) There were no significant differences between the four groups in body weights (P > 0.05).
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This is a preprint. It has not completed peer review.
Research
Ming Chao Liu
Fourth Military Medical University: Air Force Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0771-3930
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 05 Jan, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Lead and manganese are common neurotoxins. However, individuals are subject to co-exposures in real life, and it is therefore important to study these metals in combination.
Methods: Weaning Sprague-Dawley rats were given ad libitum access to drinking water solutions containing lead (100 ppm), manganese (2.5 mg/mL) or a mixture, and each treatment has its own minocycline (50 mg/Kg.d) supplement group.
Results: The results showed a significant difference in spatial memory and the induction levels of hippocampal long-term potentiation (LTP) in all exposure groups when compared with controls. The combined exposure group exhibited the most pronounced effect when compared with each of the single metal exposure groups. Microglia displayed activation at day 3 after exposure alone or in combination, while astrocytes showed activation at day 5, accompanied by decreased expression levels of glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), and glutamine synthetase (GS). Furthermore, the levels of the glutamate in the synaptic cleft increased significantly. When microglial activation was inhibited by minocycline, the activation of astrocytes, and the expression of GLAST, GLT-1, and GS were both reversed. In addition, upon minocycline treatment, the hippocampal LTP impairment and the cognitive injury were significantly alleviated in each of the exposure groups.
Conclusions: These results suggest that combined exposure to lead and manganese can cause greater effects on cognition and synaptic plasticity when compared to single metal exposure groups. And the reason may involve in microglia abnormal activation leading to an excessive regulation of astrocytes, resulting in glutamate reuptake dysfunction in astrocytes and lead to perturbed cognition and synaptic plasticity.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
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