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Acute lead acetate induces neurotoxicity through decreased synaptic plasticity-related protein expression and disordered dendritic formation in nerve cells

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Abstract

Lead (Pb) is a widespread environmental heavy metal that can damage the cerebral cortex and hippocampus, and reduce the learning and memory ability in humans and animals. In vivo and in vitro models of acute lead acetate exposure were established to further study the mechanism of neurons injury. In this study, 4-week-old female Kunming mice were randomly divided into four groups. Each group was treated with distilled water with different Pb concentrations (0, 2.4, 4.8 and 9.6 mM). Mice were killed, and brain tissues were collected to detect the changes in synaptic plasticity-related protein expression. Furthermore, Neuro-2A cells were treated with 0, 5, 25 and 50 μM lead acetate for 24 h to observe the changes in cell morphology and function. In in vivo experiment, results showed that the expression levels of cytoskeleton-associated and neural function-related proteins decreased in a dose-dependent manner in the mouse brain tissue. In in vitro experiment, compared with the control group, Pb treatment groups were observed with smaller and round cells, decreased cell density and number of synapses. In the Pb exposure group, the survival rate of nerve cells decreased evidently, and the permeability of the cell membrane was increased. Western blot results showed that the expression of cytoskeleton-associated and function-related proteins decreased gradually with increased Pb exposure dose. Confocal laser scanning microscopy results revealed the morphological and volumetric changes in Neuro-2A cells, and a dose-dependent reduction in the number of axon and dendrites. These results suggested that abnormal neural structures and inhibiting expression of synaptic plasticity-related proteins might be the possible mechanisms of Pb-induced mental retardation in human and animals, thereby laying a foundation for the molecular mechanism of Pb neurotoxicity.

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Acknowledgements

This work was supported by the National Science Foundation of China (32002352), the Nature and Scientific Foundation of Henan Province in China (202300410165), the Key Research Projects in Colleges of Henan province (22A330001 and 22A230007) and the Scientific and Technological Foundation of Henan Province in China (212102110102).

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  1. Lingli Chen and Yuye Liu contributed equally to this work.

Authors and Affiliations

  1. College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, Henan, 453003, People’s Republic of China

    Lingli Chen, Yuye Liu, Penghuan Jia, Hongli Zhang, Zhihong Yin, Dongfang Hu, Hongmei Ning & Yaming Ge

  2. Postdoctoral Research and Development Base, Henan Institute of Science and Technology, Xinxiang, Henan, People’s Republic of China

    Lingli Chen, Zhihong Yin & Dongfang Hu

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  1. Lingli Chen
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Contributions

Lingli Chen contributed to design and data analysis, Yuye Liu wrote the manuscript, Penghuan Jia and Hongli Zhang carried out the experiments and collected the data, Zhihong Yin, Dongfang Hu and Hongmei Ning contributed to revise the manuscript, and Yaming Ge managed the project.

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Correspondence to Yaming Ge.

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Chen, L., Liu, Y., Jia, P. et al. Acute lead acetate induces neurotoxicity through decreased synaptic plasticity-related protein expression and disordered dendritic formation in nerve cells. Environ Sci Pollut Res 29, 58927–58935 (2022). https://doi.org/10.1007/s11356-022-20051-1

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