Dexamethasone reduces cytokine mRNA levels and microglial activity in the brainstem of newborn rats

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Resumo

During the perinatal period of ontogenesis microglia, take part functions as a critical key-regulator of the angio-, neuro- and synaptogenesis processes. Under normal development, without inflammation induction, administration of the glucocorticoid hormone dexamethasone (0.2 mg/kg) caused a rapid decrease in the mRNA levels of both pro- and anti-inflammatory cytokines in the brainstem of neonatal rat pups. A decrease in the expression of the Il1b, Tnfa genes was observed within 1 hour, and Il10, Tgfb1 4 hours after the administration of the hormone to 3-day-old rat pups. Suppression of cytokine mRNA levels was accompanied by a decrease in the number of cells expressing the microglia marker protein IBA1 in the locus coeruleus region of the brain stem in 6 hours after glucocorticoid administration. The identified features of the dexamethasone action can weaken the participation of microglia in the processes of neuroplasticity in the developing brain, which may be one of the reasons for long-term changes in brain functioning.

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Sobre autores

T. Kalinina

Federal research center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University

Autor responsável pela correspondência
Email: kalin@bionet.nsc.ru
Rússia, Novosibirsk; Novosibirsk

V. Bulygina

Federal research center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: kalin@bionet.nsc.ru
Rússia, Novosibirsk

D. Lanshakov

Federal research center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University

Email: kalin@bionet.nsc.ru
Rússia, Novosibirsk; Novosibirsk

E. Sukhareva

Federal research center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: kalin@bionet.nsc.ru
Rússia, Novosibirsk

N. Dygalo

Federal research center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University

Email: kalin@bionet.nsc.ru
Rússia, Novosibirsk; Novosibirsk

Bibliografia

  1. Sapolsky R.M., Romero L.M., Munck A.U. // Endocr. Rev. 2000. V. 21. P. 55–89.
  2. Sorrells S.F., Sapolsky R.M. // Brain Behav. Immun. 2007. V. 21. P. 259–272.
  3. Manuela Z., Julien P., Elodie B., Olivier B., Jérôme M. // Curr Neuropharmacol. 2021. V. 19. P. 2188–2204.
  4. Sarid E.B., Stoopler M.L., Morency A.M., Garfinkle J. // Pediatr. Res. 2022. V. 92. P. 1225–1239.
  5. Melan N., Pradat P., Godbert I., Pastor-Diez B., Basson E., Picaud J.C. // Eur. J. Pediatr. 2024. V. 183. P. 677–687.
  6. Zheng B., Zheng Y., Hu W., Chen Z. //Arch. Toxicol. 2024. V. 98. P. 1975–1990. doi: 10.1007/s00204-024-03733-2. Epub 2024 Apr 6. PMID: 38581585.
  7. Тишкина А.О., Степаничев М.Ю., Аниол В.А., Гуляева Н.В. // Успехи физиологических наук. 2014. Т. 45. №4. С. 3–18.
  8. Thion M.S., Ginhoux F., Garel S. // Science. 2018. V. 362. P. 185–189.
  9. Zengeler K.E., Lukens J.R. // Trends in Immunology. – 2024.
  10. Bilbo S.D., Smith S.H., Schwarz J.M. // J. Neuroimmune Pharmacol. 2012. V. 7. P. 24–41.
  11. Bilbo S.D., Block C.L., Bolton J.L., Hanamsagar R., Tran P.K. // Exp. Neurol. 2018. V. 299. P. 241–251.
  12. Walker D.J., Spencer K.A. // Gen. Comp. Endocrinol. 2018. V. 256. P. 80–88.
  13. Wang H., He Y., Sun Z., Ren S., Liu M., Wang G., Yang J. // J Neuroinflammation. 2022. V. 19. P. 132.
  14. Shishkina G.T., Kalinina T.S., Dygalo N.N. // Neuroscience. 2004. V. 129. P. 521–528.
  15. Kalinina T.S., Shishkina G.T., Dygalo N.N. // Neurochem. Res. 2012. V. 37. P. 811–818.
  16. Lanshakov D.A., Sukhareva E.V., Kalinina T.S., Dygalo N.N. // Neurobiol. Dis. 2016. V. 91. P. 1–9.
  17. Дыгало Н.Н., Науменко Е.В. //Докл. АН СССР. Сер. биол. 1983. Т. 271. № 4. С. 1003.
  18. Дыгало Н.Н., Юдин Н.С., Калинина Т.С., Науменко Е.В. // Онтогенетические и генетико-эволюционные аспекты нейроэндокринной регуляции стресса. Новосибирск: Наука. 1990. С. 136–148.
  19. Kreider M.L., Tate C.A., Cousins M.M., Oliver C.A., Seidler F.J., Slotkin T.A. // Neuropsychopharmacology. 2006. V. 31. P. 12–35.
  20. Slotkin T.A., Ko A., Seidler F.J. // Toxicology. 2018. V. 408. P. 11–21.
  21. Tsiarli M.A., Rudine A., Kendall N., Pratt M.O., Krall R., Thiels E., DeFranco D.B., Monaghan A.P. // Transl. Psychiatry. 2017. V. 7. e1153
  22. O’Donnell K.J., Meaney M.J. // Am. J. Psychiatry. 2017. V. 174. P. 319–328. doi: 10.1176/appi.ajp.2016.16020138. Epub 2016 Nov 14. PMID: 27838934.
  23. Scheinost D., Sinha R., Cross S.N., Kwon S.H., Sze G., Constable R.T., Ment L.R. // Pediatr. Res. 2017. V. 81. P. 214–226.
  24. Meyer J.S. // Physiol. Rev. 1985. V. 65. P. 946–1020.
  25. Park K.W., Lee H.G., Jin B.K., Lee Y.B. // Exp. Mol. Med. 2007. V. 39. P. 812–819.
  26. Bedolla A., Wegman E., Weed M., Paranjpe A., Alkhimovitch A., Ifergan I., McClain L., Luo Y. // bioRxiv [Preprint]. 2023. 2023.07.05.547814.
  27. Spittau B., Dokalis N., Prinz M. //Trends Immunol. 2020. V. 41. P. 836–848.
  28. Butovsky O., Jedrychowski M.P., Moore C.S., Cialic R., Lanser A.J., Gabriely G., Koeglsperger T., Dake B., Wu P.M., Doykan C.E., Fanek Z., Liu L., Chen Z., Rothstein J.D., Ransohoff R.M., Gygi S.P., Antel J.P., Weiner H.L. // Nat. Neurosci. 2014. V. 17. P. 131–143.
  29. Hui B., Yao X., Zhang L., Zhou Q. // Naunyn Schmiedebergs Arch. Pharmacol. 2020. V. 393. P. 1761–1768.
  30. Shishkina G.T., Kalinina T.S., Popova N.K., Dygalo N.N. // Behav. Neurosci. 2004. V. 118. P. 1285–1292.
  31. Dygalo N.N., Kalinina T.S., Shishkina G.T. // Ann. N. Y. Acad. Sci. 2008. V. 1148. P. 409–414.
  32. Sukhareva E.V., Kalinina T.S., Bulygina V.V., Dygalo N.N. // Russian Journal of Genetics: Applied Research. 2017. V. 7. P. 226–234.
  33. Kalinina T.S., Sukhareva E.V., Bulygina V.V., Lanshakov D.A., Egorova K.V., Dygalo N.N. // European Neuropsychopharmacology. 2019. V. 29. P. S166–S167.
  34. Liu Y.U., Ying Y., Li Y., Eyo U.B., Chen T., Zheng J., Umpierre A.D., Zhu J., Bosco D.B., Dong H., Wu L.J. // Nat. Neurosci. 2019. V. 22. P. 1771–1781.
  35. Mercan D., Heneka M.T. // Nat. Neurosci. 2019. V. 22. P. 1745–1746.
  36. Stowell R.D., Sipe G.O., Dawes R.P., Batchelor H.N., Lordy K.A., Whitelaw B.S., Stoessel M.B., Bidlack J.M., Brown E., Sur M., Majewska A.K. // Nat. Neurosci. 2019. V. 22. P. 1782–1792.
  37. Zou H.L., Li J., Zhou J.L., Yi X., Cao S. // Ibrain. 2021. V. 7. P. 309–317.
  38. Cronk J.C., Kipnis J. // F1000Prime Rep. 2013. V. 5. P. 53.
  39. Barry-Carroll L., Gomez-Nicola D. // Nat. Rev. Neurosci. 2024. V. 25. P. 414–427.

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2. Fig. 1. Interleukin 1B (Il1b) (a) and tumor necrosis factor-alpha (Tnfa) (b) mRNA levels in the brainstem of 3-day-old rat pups 30, 60, 120, 240, and 360 minutes after administration of 0.2 mg/kg dexamethasone (curve No. 2) as a percentage of the administration of saline (curve No. 1). “0” on the abscissa axis – intact same-age rat pups, *p < 0.05 compared to control animals of the same time interval.

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3. Fig. 2. Interleukin 10 (Il10) (a) and transforming growth factor beta (Tgfb) (b) mRNA levels in the brainstem of 3-day-old rat pups 30, 60, 120, 240, and 360 minutes after administration of 0.2 mg/kg dexamethasone (curve No. 2) as a percentage of the administration of saline (curve No. 1). “0” on the abscissa axis – intact same-age rat pups, *p < 0.05 compared to control animals of the same time interval.

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4. Fig. 3. (a) Representative micrographs of IBA1 staining in the brainstem of 3-day-old control rats (1) and 6 hours after dexamethasone administration (2). Microglial cells are indicated by arrows, LC(TH) is the Locus Coeruleus area of ​​the brainstem stained for tyrosine hydroxylase (TH). (b) The number of IBA1-expressing cells and their diameter in the brainstem of control (1) and 0.2 mg/kg dexamethasone-treated (2) 3-day-old rats 6 hours after exposure. *p < 0.05 compared to the control group.

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