Effect of copper oxide nanoparticles on gene expression of NMDA receptor

Cover Page

Cite item

Full Text

Abstract

Introduction. Copper plays an important role in the metabolism of the brain, but particles of copper, in the nanometer range, exhibit neurotoxic properties and cause malfunctioning of brain cells.

Material and methods. For 6 weeks, 3 times a week, the animals were injected with a suspension of NPs of copper oxide. The determination of the expression of the genes GRIN1, GRIN2a, and GRIN2b, encoding the proteins GluN1, GluN2a, and GluN2b, respectively, was carried out by real-time PCR with probes.

Results. A statistically significant decrease in the expression level of genes encoding NMDA receptor proteins was determined when exposed to 0.5 mg/ml CuO nanoparticles (ΔCt(GRIN1) = 0.813; ΔCt(GRIN2A) = 3.477; ΔCt(GRIN2B) = 1.37) in comparison with control group (ΔCt(GRIN1) = 6.301; ΔCt(GRIN2A) = 7.823; ΔCt(GRIN2B) = 4.747).

Conclusion. Evaluation of gene expression of the NMDA receptor may be present in a genetic marker to determine the toxic effect of copper oxide nanoparticles; however, further studies are needed, including behavioral tests to confirm the clinical manifestations of neurodegenerative disorders.

About the authors

Ivan Andreevich Sitnikov

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

Author for correspondence.
Email: sitnikovia@ymrc.ru
ORCID iD: 0000-0002-4109-9268

Junior Researcher, Department of Molecular Biology and Electron Microscopy, FBRI YMRC PHPIW of Rospotrebnadzor, 620014, Yekaterinburg, Russia.

e-mail: sitnikovia@ymrc.ru

Russian Federation

Daria Ramilevna Shaikhova

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

Email: darya.boo@mail.ru
ORCID iD: 0000-0002-7029-3406

Младший научный сотрудник отдела молекулярной биологии и электронной микроскопии ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора, 620014, г. Екатеринбург

e-mail: darya.boo@mail.ru

Russian Federation

Anna Mikhailovna Amromina

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

Email: amrominaam@ymrc.ru
ORCID iD: 0000-0001-8794-7288

Младший научный сотрудник отдела молекулярной биологии и электронной микроскопии ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора, 620014, г. Екатеринбург

e-mail: amrominaam@ymrc.ru

Russian Federation

Marina Petrovna Sutunkova

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

Email: sutunkova@ymrc.ru
ORCID iD: 0000-0002-1743-7642

Доктор медицинских наук, директор ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора, 620014, г. Екатеринбург

e-mail: sutunkova@ymrc.ru

Russian Federation

Yuliya Vladimirovna Ryabova

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

Email: ryabova@ymrc.ru
ORCID iD: 0000-0003-2677-0479

Младший научный сотрудник отдела токсикологии и биопрофилактики ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора, 620014, г. Екатеринбург

e-mail: ryabova@ymrc.ru

Russian Federation

Anastasiya Valerevna Tazhigulova

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

Email: vasilyevaav@ymrc.ru
ORCID iD: 0000-0001-9384-8550

Лаборант-исследователь отдела токсикологии и биопрофилактики ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора, 620014, г. Екатеринбург

e-mail: vasilyevaav@ymrc.ru

Russian Federation

Vadim Olegovich Ruzakov

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

Email: ruzakov@ymrc.ru
ORCID iD: 0000-0002-8902-0416

Помощник директора по развитию ФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» Роспотребнадзора, 620014, г. Екатеринбург

 e-mail: ruzakov@ymrc.ru

Russian Federation

References

  1. Ulanova T.S., Antipyeva M.V., Zabirova M.I., Volkova M.V. Determination of nanoscale particles in the air of working zone at the metallurgical production. Analiz riska zdorovyu. 2015; 1: 77–81. (in Russian)
  2. Gurvich V.B., Katznelson B.A., Ruzakov V.O., Privalova L.I., Bushueva T.V., Grebyonkina S.V. Biochemical effects of workers exposed to aerosols of metallurgical copper production containing nanoparticles. In: Proceedings of the All-Russian Scientific and Practical Conference with International Participation October 20–21, 2016 [Aktualnye gigienicheskie aspekty nanotoksikologii: teoreticheskie osnovy, identifikaciya opasnosti dlya zdorovya i puti ee snizheniya: Materialy mezhdunarodnoj konferencii 20–21 oktyabrya 2016 goda]. Ekaterinburg, 2016; 21–3. (in Russian)
  3. Minigalieva I.A., Katsnelson B.A., Panov V.G., Privalova L.I., Varaksin A.N., Gurvich V.B. et al. In vivo toxicity of copper oxide, lead oxide and zinc oxide nanoparticles acting in different combinations and its attenuation with a complex of innocuous bio-protectors. Toxicology. 2017; 380: 72–93.
  4. Khamidulina Kh.Kh., Davydova Yu.O. International approaches to the evaluation of the toxicity and hazards of nanoparticles and nanomaterials. Toksikologicheskii vestnik. 2011; 6: 53–7. (in Russian)
  5. Filatov B.N., Bocharova L.I., Klauchek V.V., Maslennikov A.A., Pocheptsov A.Ya., Tochilkina L.P. Production and use of nanomaterials (toxicological and hygienic problems). Farmakologiya. 2015; 16(1): 259–66. (in Russian)
  6. De Matteis V., Cascione M., Toma C.C., Pellegrino P., Rizzello L., Rinaldi R. Tailoring Cell Morphomechanical Perturbations Through Metal Oxide Nanoparticles. V. Nanoscale Res. Lett. 2019; 14(1): 109.
  7. Takenaka S., Karg E., Roth C., Schulz H., Ziesenis A., et al. Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect. 2001; 109: 547–51.
  8. Sharma H.S., Sharma A. Nanoparticles aggravate heat stress induced cognitive deficits, blood-brain barrier disruption, edema formation and brain pathology. Prog Brain Res. 2007; 162: 245–73.
  9. Linder M.C., Hazegh-Azam M. Copper biochemistry and molecular biology. Am. J. Clin. Nutr. 1996; 63: 797–811.
  10. Stys P.K., You H.T., Zamponi G.W. Copper-dependent regulation of NMDA receptors by cellular prion protein: implications for neurodegenerative disorders. J. Physiol. 2012; 590: 1357–68.
  11. Katsnelson B.A., Privalova L.I., Gurvich V.B., Makeev O.G., Shur V.J., Sutunkova M.P. et al. Method for prevention of adverse health effects of general toxic and genotoxic action of copper oxide nanoparticles. Patent RF; N 2560682 (in Russian).
  12. Valko M., Morris H., Cronin M.T.D. Metals, toxicity and oxidative stress. Curr. Med. Chem. 2005; 12: 1161–208.
  13. Pal A., Badyal R.K., Vasishta R.K., Attri S.V., Thapa B.R., Prasad R. Biochemical, histological, and memory impairment effects of chronic copper toxicity: a model for non-wilsonian brain copper toxicosis in wistar rat. Biol. Trace Elem. Res. 2013; 153: 257–68.
  14. Hung Y.H., Bush A.I., Cherny R.A. Copper in the brain and Alzheimer’s disease. J. Biol. Inorg. Chem. 2010; 15: 61–76.
  15. Huang Y., Shen W., Su J., Cheng B., Li D., Liu G., Zhou W.X., Zhang Y.X. Modulating the Balance of Synaptic and Extrasynaptic NMDA Receptors Shows Positive Effects against Amyloid-beta-Induced Neurotoxicity. J Alzheimers Dis. 2017; 57: 885–97.
  16. MacDonald J.F., Jackson M.F., Beazely M.A. Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors. Crit Rev Neurobiol. 2006; 18: 71–84.
  17. Schlief M.L., West T., Craig A.M., Holtzman D.M., Gitlin J.D. Role of the Menkes copper-transporting ATPase in NMDA receptor-mediated neuronal toxicity. Proc Natl Acad Sci U S A. 2006; 103: 14919–24.
  18. Kalia L.V., Kalia S.K., Salter M.W. NMDA receptors in clinical neurology: excitatory times ahead. Lancet Neurol. 2008; 7: 742–55.
  19. Kotermanski S.E., Johnson J.W. Mg2+ imparts NMDA receptor subtype selectivity to the Alzheimer’s drug memantine. J Neurosci. 2009; 29: 2774–9.
  20. Wang R., Reddy P.H. Role of Glutamate and NMDA Receptors in Alzheimer’s Disease. J Alzheimers Dis. 2017; 57: 1041–8.
  21. Trofimov A.N., Rotov A.Yu., Veniaminova E.A., Fomalont K., Schwarz 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. (in Russian)
  22. Gielen M., Retchless B.S., Mony L., Johnson J.W., Paoletti P. Mechanism of differential control of NMDA receptor activity by NR2 subunits. Nature. 2009; 459(7247): 703–7.
  23. Hansen K.B., Yi F., Perszyk R.E., Furukawa H., Wollmuth L.P., Gibb A.J., Traynelis S.F. Structure, function, and allosteric modulation of NMDA receptors. Journal of General Physiology. 2018; 150(8): 1081–105.
  24. Paoletti P., Bellone C., Zhou Q. NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat. Rev. Neurosci. 2013; 14: 383–400.
  25. Omelchenko I.A., Nelson C.S., Allen C.N. Lead inhibition of Nmethyl-D-aspartate receptors containing NR2A, NR2C and NR2D subunits. J Pharmacol Exp Ther. 1997; 282(3): 1458–64.
  26. Hong F., Sheng L., Ze Y., Hong J., Zhou Y., Wang L. et al. Suppression of neurite outgrowth of primary cultured hippocampal neurons is involved in impairment of glutamate metabolism and NMDA receptor function caused by nanoparticulate TiO2. Biomaterials. 2015; 53: 76–85.
  27. Li X., Sun W., An L. Nano-CuO impairs spatial cognition associated with inhibiting hippocampal long-term potentiation via affecting glutamatergic neurotransmission in rats. Toxicology and Industrial Health. 2018; 34(6): 409–21.
  28. Stark D.T., Bazan N.G. Synaptic and extrasynaptic NMDA receptors differentially modulate neuronal cyclooxygenase-2 function, lipid peroxidation, and neuroprotection. Journal of Neuroscience. 2011; 31(39): 13710–21.
  29. An L., Liu S., Yang Z. et al. Cognitive impairment in rats induced by nano-CuO and its possible mechanisms. Toxicology Letters. 2012; 213(2): 220–7.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2021 Sitnikov I.A., Shaikhova D.R., Amromina A.M., Sutunkova M.P., Ryabova Y.V., Tazhigulova A.V., Ruzakov V.O.



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 - 81728 от 11 декабря 2013.