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

封面

如何引用文章

全文:

详细

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 

作者简介

Anna Amromina

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

编辑信件的主要联系方式.
Email: amrominaam@ymrc.ru
ORCID iD: 0000-0001-8794-7288

Junior Researcher, Department of Molecular Biology and Electron Microscopy, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation.

e-mail: amrominaam@ymrc.ru

俄罗斯联邦

Daria Shaikhova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: noemail@neicon.ru
ORCID iD: 0000-0002-7029-3406
俄罗斯联邦

Ivan Bereza

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: noemail@neicon.ru
ORCID iD: 0000-0002-4109-9268
俄罗斯联邦

Anastasiya Tazhigulova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: noemail@neicon.ru
ORCID iD: 0000-0001-9384-8550
俄罗斯联邦

Ilzira Minigalieva

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: noemail@neicon.ru
ORCID iD: 0000-0002-1871-8593
俄罗斯联邦

Svetlana Solovyeva

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: noemail@neicon.ru
ORCID iD: 0000-0001-8580-403X
俄罗斯联邦

Inna Butakova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: noemail@neicon.ru
ORCID iD: 0000-0002-9871-9712
俄罗斯联邦

Vladimir Gurvich

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: noemail@neicon.ru
ORCID iD: 0000-0002-6475-7753
俄罗斯联邦

Marina Sutunkova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: noemail@neicon.ru
ORCID iD: 0000-0002-1743-7642
俄罗斯联邦

参考

  1. Dumková J., Smutná T., Vrlíková L., Le Coustumer P., Večeřa Z., Dočekal B., et al. Sub-chronic inhalation of lead oxide nanoparticles revealed their broad distribution and tissue-specific subcellular localization in target organs. Part. Fibre Toxicol. 2017; 14(1): 55. https://doi.org/10.1186/s12989-017-0236-y
  2. Sutunkova M.P., Solovyeva S.N., Chernyshov I.N., Klinova S.V., Gurvich V.B., Shur V.Ya., et al. Manifestation of systemic toxicity in rats after a short-time inhalation of lead oxide nanoparticles. Int. J. Mol. Sci. 2020; 21(3): 690. https://doi.org/10.3390/ijms21030690
  3. Wani A.L., Ara A., Usmani J.A. Lead toxicity: a review. Interdiscip. Toxicol. 2015; 8(2): 55–64. https://doi.org/10.1515/intox-2015-0009
  4. Xu J., Yan H.C., Yang B., Tong L.S., Zou Y.X., Tian Y. Effects of lead exposure on hippocampal metabotropic glutamate receptor subtype 3 and 7 in developmental rats. J. Negat. Results Biomed. 2009; 8: 5. https://doi.org/10.1186/1477-5751-8-5
  5. Rocha A., Trujillo K.A. Neurotoxicity of low-level lead exposure: History, mechanisms of action, and behavioral effects in humans and preclinical models. Neurotoxicology. 2019; 73: 58–80. https://doi.org/10.1016/j.neuro.2019.02.021
  6. Neal A.P., Guilarte T.R. Molecular neurobiology of lead (Pb(2+)): effects on synaptic function. Mol. Neurobiol. 2010; 42(3): 151–60. https://doi.org/10.1007/s12035-010-8146-0
  7. Lau C.G., Zukin R.S. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat. Rev. Neurosci. 2007; 8(6): 413–26. https://doi.org/10.1038/nrn2153
  8. Mony L., Kew J.N., Gunthorpe M.J., Paoletti P. Allosteric modulators of NR2B-containing NMDA receptors: Molecular mechanisms and therapeutic potential. Br. J. Pharmacol. 2009; 157(8): 1301–17. https://doi.org/10.1111/j.1476-5381.2009.00304.x
  9. Endele S., Rosenberger G., Geider K., Popp B., Tamer C., Stefanova I., et al. Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. Nat. Genet. 2010; 42(11): 1021–6. https://doi.org/10.1038/ng.677
  10. Ramos A., Pereira E., Martins G.C., Wehrmeister T.D., Izídio G.S. Integrating the open field, elevated plus maze and light/dark box to assess different types of emotional behaviors in one single trial. Behav. Brain Res. 2008; 193(2): 277–88. https://doi.org/10.1016/j.bbr.2008.06.007
  11. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001; 25(4): 402–8. https://doi.org/10.1006/meth.2001.1262
  12. Trofimov A.N., Rotov A.Yu., Veniaminova E.A., Fomalont K., Shvarts A.P., Zubareva O.E. Behavioral alterations of adult rats evoked by neonatal LPS injections are associated with changes of ionotropic glutamate receptors gene expression in the brain. Rossiyskiy fiziologicheskiy zhurnal im. I.M. Sechenova. 2020; 106(3): 356–72. https://doi.org/10.31857/S0869813920030097 (in Russian)
  13. Hansen K.B., Yi F., Perszyk R.E., Furukawa H., Wollmuth L.P., Gibb A.J., et al. Structure, function, and allosteric modulation of NMDA receptors. J. Gen. Physiol. 2018; 150(8): 1081–105. https://doi.org/10.1085/jgp.201812032
  14. Traynelis S.F., Wollmuth L.P., McBain C.J., Menniti F.S., Vance K.M., Ogden K.K., et al. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol. Rev. 2010; 62(3): 405–96. https://doi.org/10.1124/pr.109.002451
  15. Monyer H., Burnashev N., Laurie D.J., Sakmann B., Seeburg P.H. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron. 1994; 12(3): 529–40. https://doi.org/10.1016/0896-6273(94)90210-0
  16. Wu Y., Wang Y., Wang M., Sun N., Li C. GRIN2A polymorphisms and expression levels are associated with lead-induced neurotoxicity. Toxicol. Ind. Health. 2016; 33(4): 332–39. https://doi.org/10.1177/0748233716647636
  17. Wang T., Guan R.L., Liu M.C., Shen X.F., Chen J.Y., Zhao M.G., et al. Lead exposure impairs hippocampus related learning and memory by altering synaptic plasticity and morphology during juvenile period. Mol. Neurobiol. 2016; 53(6): 3740–52. https://doi.org/10.1007/s12035-015-9312-1
  18. Zhu X., Liu X., Wei F., Wang F., Merzenich M.M., Schreiner C.E., et al. Perceptual training restores impaired cortical temporal processing due to lead exposure. Cereb. Cortex. 2016; 26(1): 334–45. https://doi.org/10.1093/cercor/bhu258
  19. Katsnel’son B.A., Privalova L.I., Degtyareva T.D., Kuz’min S.V., Sutunkova M.P., Minigalieva I.A., et al. Comparative characterization of the biological aggressivity of particles having different dimensions in nano- and micrometric ranges. Zdorov’e naseleniya i sreda obitaniya – ZNiSO. 2011; (5): 32–6. (in Russian)
  20. Gavazzo P., Zanardi I., Baranowska-Bosiacka I., Marchetti C. Molecular determinants of Pb2+ interaction with NMDA receptor channels. Neurochem. Int. 2008; 52(1–2): 329–37. https://doi.org/10.1016/j.neuint.2007.07.003
  21. Forrest D., Yuzaki M., Soares H.D., Ng L., Luk D.C., Sheng M., et al. Targeted disruption of NMDAR receptor 1 gene abolishes NMDA response and results in neonatal death. Neuron. 1994; 13(2): 325–38. https://doi.org/10.1016/0896-6273(94)90350-6
  22. Tang Y.P., Shimizu E., Dube G.R., Rampon C., Kerchner G.A., Zhuo M., et al. Genetic enhancement of learning and memory in mice. Nature. 1999; 401(6748): 63–9. https://doi.org/10.1038/43432
  23. Zhou Q., Sheng M. NMDA receptors in nervous system diseases. Neuropharmacology. 2013; 74: 69–75. https://doi.org/10.1016/j.neuropharm.2013.03.030
  24. Tartaglione A.M., Serafini M.M., Raggi A., Iacoponi F., Zianni E., Scalfari A., et al. Sex-dependent effects of developmental lead exposure in Wistar rats: evidence from behavioral and molecular correlates. Int. J. Mol. Sci. 2020; 21(8): 2664. https://doi.org/10.3390/ijms21082664
  25. Kazlauckas V., Schuh J., Dall’Igna O.P., Pereira G.S., Bonan C.D., Lara D.R. Behavioral and cognitive profile of mice with high and low exploratory phenotypes. Behav. Brain Res. 2005; 162(2): 272–8. https://doi.org/10.1016/j.bbr.2005.03.021
  26. Griffin A.S., Guillette L.M., Healy S.D. Cognition and personality: an analysis of an emerging field. Trends Ecol. Evol. 2015; 30(4): 207–14. https://doi.org/10.1016/j.tree.2015.01.012
  27. Shilova O.B., Markina N.V., Perepelkina O.V., Gichenok I.V., Korochkin L.I., Poletaeva I.I. Neonatal semax and saline injections induce open-field behavior changes in mice of different genotypes. Zhurnal vysshey nervnoy deyatel’nosti im. I.P. Pavlova. 2004; 54(6): 785–94. (in Russian)
  28. Bogdanova S.A., Frolova G.A. Effect of pharmacological stimulation of the activity of the dopaminergic system by “deprenyl” on the behavior of low-anxiety rats. In: Donetsk Readings 2019: Education, Science, Innovations, Culture and Challenges of Our Time: Proceedings of the Fourth International Scientific Conference [Donetskie chteniya 2019: obrazovanie, nauka, innovatsii, kul’tura i vyzovy sovremennosti: materialy IV Mezhdunarodnoy nauchnoy konferentsii]. Donetsk; 2019: 364–66. (in Russian)
  29. Pavlova I.V., Rysakova M.P. Features of conditioned reflex fear in active and passive rabbits. Zhurnal vysshey nervnoy deyatel’nosti im. I.P. Pavlova. 2015; 65(6): 720. https://doi.org/10.7868/S0044467715050123 (in Russian)
  30. Kraeuter A.K., Guest P.C., Sarnyai Z. The elevated plus maze test for measuring anxiety-like behavior in rodents. Methods Mol. Biol. 2019; 1916: 69–74. https://doi.org/10.1007/978-1-4939-8994-2_4

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Amromina A.M., Shaikhova D.R., Bereza I.A., Tazhigulova A.V., Minigalieva I.A., Solovyeva S.N., Butakova I.V., Gurvich V.B., Sutunkova M.P., 2023


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 37884 от 02.10.2009.