Effect of Gestational Diabetes in Female Rats on the Functions of Brain Astrocytes in Their Offspring

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Abstract

Gestational diabetes mellitus (GDM) in the mother may impair fetal brain development through epigenetic mechanisms and metabolic dysregulation of glial cells. The present study aims to investigate functional changes in astrocytes derived from the brains of neonatal rats born from mothers with GDM. It was found that maternal GDM not only led to hypoglycemia in newborn pups but also increased the proliferation of primary cortical astrocytes under glucose deprivation compared to controls. Astrocyte proliferation in response to activation of protease-activated receptor 1 (PAR1) by a peptide agonist did not differ in the GDM and control groups. Astrocyte proliferation was increased in glucose-containing medium, while glucose deprivation either had no effect or suppressed proliferation. Interestingly, noticeable lipopolysaccharide (LPS)-induced activation of primary astrocytes observed in the control group was completely abolished in the GDM group, as indicated by IL-6 secretion levels. These findings suggest that intrauterine exposure to GDM may program long-term alterations in the metabolic and immune activity of fetal astrocytes.

About the authors

I. I. Bakbina

Pirogov Russian National Research Medical University

Moscow, Russia

I. G. Savinkova

Pirogov Russian National Research Medical University

Moscow, Russia

A. S. Artyukhov

Pirogov Russian National Research Medical University

Moscow, Russia

L. R. Gorbacheva

Lomonosov Moscow State University

Email: gorbi67@mail.ru
Moscow, Russia

References

  1. Rodolaki K., Pergialiotis V., Iakovidou N., Boutsikou T., Iliodromiti Z., Kanaka-Gantenbein C. // Frontiers in Endocrinology. 2023. V. 14. P. 1125628.
  2. Vuong B., Odero G., Rozbacher S., Stevenson M., Kereliuk S.M., Pereira T.J., Dolinsky V.W., Kauppinen T.M. // Journal of Neuroinflammation. 2017. V. 14. № 1. P. 80.
  3. Garza-Martínez M.J., Á Hernández-Mariano J., Hurtado-Salgado E.M., Cupul-Uicab L.A. // Journal of Psychiatric Research. 2025. V. 182. P. 100–115.
  4. Pretorius R.A., Avraam D., Guxens M., Julvez J., Harris J.R., Nader J.T., Cadman T., Elhakeem A., Strandberg-Larsen K., Marroun H.E., Defina S., Yang T.C., McEachan R., Wright J., Ibarluzea J., Santa-Marina L., Delgado J.M., Rebagliato M., Charles M.-A. // BMC pediatrics. 2025. V. 25. № 1. P. 76.
  5. Aviel-Shekler K., Hamshawi Y., Sirhan W., Getselter D., Srikanth K.D., Malka A., Piran R., Elliott E. // Translational Psychiatry. 2020. V. 10. № 1. P. 412.
  6. Yamamoto J.M., Benham J.L., Dewey D., Sanchez J.J., Murphy H.R., Feig D.S., Donovan L.E. // Diabetologia. 2019. V. 62. № 9. P. 1561–1574.
  7. Persson B. // Seminars in Fetal & Neonatal Medicine. 2009. V. 14. № 2. P. 106–110.
  8. Verkhratsky A., Nedergaard M. // Physiological Reviews. 2018. V. 98. № 1. P. 239–389.
  9. Zhang Y., Qi Y., Gao Y., Chen W., Zhou T., Zang Y., Li J. // Frontiers in Neuroscience. 2023. V. 17.
  10. Meza-León A., Montoya-Estrada A., Reyes-Muñoz E., Romo-Yáñez J. // Biomedicines. 2024. V. 12. № 2. P. 351.
  11. Shamsad A., Gautam T., Singh R., Banerjee M. // World Journal of Clinical Pediatrics. 2025. V. 14. № 1. P. 99231.
  12. Słupecka-Ziemilska M., Wychowański P., Puzianowska-Kuznicka M. // Nutrients. 2020. V. 12. № 9. P. 2792.
  13. Lehnen H., Zechner U., Haaf T. // Molecular Human Reproduction. 2013. V. 19. № 7. P. 415–422.
  14. Zhang X., Qiu W., Huang J., Pang X., Su Y., Ye J., Zhou S., Tang Z., Wang R., Su R. // Journal of Diabetes and Its Complications. 2024. V. 38. № 9. P. 108805.
  15. Kong L., Gu P.-P., Tang Z.-Z., Gou L.-S., Liu Y.-W. // Fundamental & Clinical Pharmacology. 2022. V. 36. № 3. P. 509–517.
  16. Festoff B.W., Dockendorff C. // Biomolecules. 2021. V. 11. № 11. P. 1558.
  17. Gorbacheva L.R., Pinelis V.G., Reiser G., Strukova S.M. // Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology. 2012. V. 6. № 1. P. 56–66.
  18. Иванова А.Е., Горбачева Л.Р., Струкова С.М., Пинелис В.Г., Рейзер Г. // Биологические Мембраны. 2013. Т. 30. № 5–6. С. 387.
  19. Wang H., Ubl J.J., Stricker R., Reiser G., Reiser G. // Am. J. Physiol. Cell Physiol. 2002. V. 283. P. 1351–1364.
  20. Babkina I., Savinkova I., Molchanova T., Sidorova M., Surin A., Gorbacheva L. // International Journal of Molecular Sciences. 2024. V. 25. № 2. P. 1221.
  21. Bao X., Hua Y., Keep R.F., Xi G. // Conditioning Medicine. 2018. V. 1. № 2. P. 57–63.
  22. Festoff B.W., Citron B.A. // Frontiers in Neurology. 2019. V. 10. № 59.
  23. American Diabetes Association // Diabetes Care. 2014. V. 37. № 1. P. S14–80.
  24. Abdul Aziz S.H., John C.M., Mohamed Yusof N.I.S., Nordin M., Ramasamy R., Adam A., Mohd Fauzi F. // BioMed Research International. 2016. V. 2016. P. 9704607.
  25. Preston C.C., Larsen T.D., Eclov J.A., Louwagie E.J., Gandy T.C.T., Faustino R.S., Baack M.L. // Frontiers in Endocrinology. 2020. V. 11. P. 570846.
  26. Furman B.L. // Current Protocols in Pharmacology. 2015. V. 70. P. 5.47.1–5.47.20.
  27. Hou L., Liu Y., Wang X., Ma H., He J., Zhang Y., Yu C., Guan W., Ma Y. // In Vitro Cellular & Developmental Biology. Animal. 2011. V. 47. № 8. P. 573–580.
  28. Chen F., Ge L., Jiang X., Lai Y., Huang P., Hua J., Lin Y., Lin Y., Jiang X. // PLOS ONE. 2022. V. 17. № 9. P. e0273703.
  29. Brekke E., Morken T.S., Sonnewald U. // Neurochemistry International. 2015. V. 82. P. 33–41.
  30. Márquez-Valadez B., Valle-Bautista R., García-López G., Díaz N.F., Molina-Hernández A. // Frontiers in Endocrinology. 2018. V. 9. P. 664.
  31. Gong L., Jiang S., Tian J., Li Y., Yu W., Zhang L., Xiao D. // Reproductive Toxicology. 2024. V. 123. P. 108494.
  32. Brown A.M., Ransom B.R. // Metabolic Brain Disease. 2015. V. 30. № 1. P. 233–239.
  33. Abramov E.A., Ivanova A.E., Dashinimaev E.B., Kamkin A.G., Gorbacheva L.R. // Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology. 2022. V. 16. № 1. P. 63–71.
  34. Wei W., Yu Z., Xie M., Wang W., Luo X. // Journal of Molecular Neuroscience. 2017. V. 61. № 1. P. 105–114.
  35. Yoo B.K., Choi J.W., Han B.H., Kim W.-K., Kim H.-C., Ko K.H. // Neuroscience Letters. 2005. V. 376. № 3. P. 171–176.
  36. Yung H.W., Tolkovsky A.M. // Journal of Neurochemistry. 2003. V. 86. № 5. P. 1281–1288.
  37. Abdyeva A., Kurtova E., Savinkova I., Galkov M., Gorbacheva L. // International Journal of Molecular Sciences. 2024. V. 25. № 2. P. 1122.
  38. Chistyakov D.V., Goriainov S.V., Astakhova A.A., Sergeeva M.G. // Metabolites. 2021. V. 11. № 5. P. 311.
  39. Morozova M.P., Savinkova I.G., Gorbacheva L.R. // Journal of Evolutionary Biochemistry and Physiology. 2024. V. 60. № 4. P. 1531–1545.
  40. Li L., Acioglu C., Heary R.F., Elkabes S. // Brain, Behavior, and Immunity. 2021. V. 91. P. 740–755.
  41. Cai D., Yuan M., Frantz D.F., Melendez P.A., Hansen L., Lee J., Shoelson S.E. // Nature Medicine. 2005. V. 11. № 2. P. 183–190.
  42. Wang Y., Qian Y., Fang Q., Zhong P., Li W., Wang L., Fu W., Zhang Y., Xu Z., Li X., Liang G. // Nature Communications. 2018. V. 9. № 1. P. 16185.
  43. Coughlin S.R. // Nature. 2000. V. 407. № 6801. P. 258–264.
  44. Liu Y., Tang Z.-Z., Zhang Y.-M., Kong L., Xiao W.-F., Ma T.-F., Liu Y.-W. // Biochemical Pharmacology. 2020. V. 175. P. 113849.
  45. Aye I.L.M.H., Powell T.L., Jansson T. // Placenta. 2013. V. 34. P. S40–45.
  46. Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., Wu M., Ventre J., Doebber T., Fujii N., Musi N., Hirshman M.F., Goodyear L.J., Moller D.E. // The Journal of Clinical Investigation. 2001. V. 108. № 8. P. 1167–1174.
  47. Burda J.E., Sofroniew M.V. // Neuron. 2014. V. 81. № 2. P. 229–248.

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