Some neurotoxic effects of lead nanoparticles on NMDA glutamate receptor gene expression and behavioral responses in Wistar rats

Introduction. Industrial pollution of the workplace air and the environment with lead oxide nanoparticles (PbO NPs) poses the risk of neurodegenerative diseases in workers of lead and copper smelters and the population living around these enterprises. Various studies showed the involvement of N-methyl-D-aspartate (NMDA) receptor expression in the mechanisms of lead toxicity.

Materials and methods. During two months, outbred female rats were exposed to lead nanoparticles (PbO NPs) at a concentration of 0.2 mg/m³ in a “nose-only” inhalation exposure system. The behavioral responses of the rats were assessed using the open field and the elevated plus maze tests. Quantitative expression of the NMDA receptor genes (GRIN1, GRIN2A, GRIN2B) in the rat hippocampus was assessed using a real-time PCR. Statistical data analysis was carried out using the Mann–Whitney U test.

Results. The neurotoxic effect of PbO NPs manifested itself in the suppression of GRIN2A gene expression in the hippocampus of experimental rats. The expression of the GRIN1 gene also showed a tendency to decrease in rats under effect of PbO NPs, while the expression of the GRIN2B gene did not change. The results of the open field test did not reveal any differences between the experimental and control groups of rats. The elevated plus maze test revealed a significant decrease in the number of entries into the open arms of the maze in rats from the experimental group.

Limitations. This work was performed on female Wistar rats and does not take into account possible inter-gender differences.

Conclusion. The results of the experiment demonstrated the neurotoxic effect of PbO NPs including the reduced expression level of the GRIN2A gene of the NMDA receptor and a decrease in the proportion of time spent in the open arms in the elevated plus maze test.

Compliance with ethical standards. Conclusion of the local ethics committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers: the maintenance, nutrition, care of animals and their removal from the experiment was carried out in accordance with the requirements of the Declaration of Helsinki and “International guiding principles for biomedical research involving animals”, developed by the Council for International Organizations of Medical Sciences and the International Council for Laboratory Animal Science (2012). The studies were approved by the Local Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol No. 4 dated July 12, 2022).

Contribution:
Amromina A.M., Shaikhova D.R., Bereza I.A. — data collection and processing, statistical analysis, draft manuscript preparation and editing;
Tazhigulova A.V., Solovyeva S.N. — data collection, manuscript editing;
Minigalieva I.A. — research conception and design, manuscript editing;
Butakova I.V. — data processing, manuscript editing;
Gurvich V.B., Sutunkova M.P. — research conception and design.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version. 

Conflict of interest. The authors declare no conflict of interest. 

Acknowledgement. The study had no sponsorship. 

Received: October 10, 2022 / Accepted: December 8, 2022 / Published: January 12, 2023