Morphofunctional characteristics of hippocampal neurons in glutamate excitotoxicity in vitro model and after α-ketoglutarate administration

Authors

  • O.A. Kostiuchenko
  • G.G. Skibo
  • I.V. Lushnikova

Keywords:

glutamate excitotoxicity, neuroprotection, α-ketoglutarate, mTOR.

Abstract

Background. The study of cellular mechanisms associated with damage to brain cells as a result of glutamate excitotoxicity, as well as the identification of endogenous neuroprotective factors for the development of effective therapeutic strategies is still relevant. Objective. To study morphofunctional changes of neurons in the context of neuroprotection by α-ketoglutarate in glutamate excitotoxicity in vitro model, as well as to reveal the relationship between α-ketoglutarate/mTOR-mediated mechanisms. Methods. The research was conducted using hippocampal cell cultures. Cell viability and immunoreactivity of synaptogenesis and autophagy markers were evaluated. To analyze α-ketoglutarate/mTOR-mediated signaling pathways under conditions of glutamate excitotoxicity, glutamate, α-ketoglutarate and the mTOR inhibitor - rapamycin were used. Results. Glutamate administration had a deleterious effect on neuronal viability and synaptogenesis in culture, which was reduced by the addition of α-ketoglutarate and rapamycin. Increased LC3+ immunoreactivity induced by α-ketoglutarate and rapamycin indicates activation of autophagy, which can be attributed to the protective factors in this model. Conclusion. The unidirectional action of α-ketoglutarate and rapamycin implies the involvement and interaction of α-ketoglutarate- and mTOR-mediated signaling pathways in endogenous neuroprotection. Thus, the results indicate a significant potential of α-ketoglutarate in mTOR modulation for the purpose of neuroprotection in glutamate excitotoxicity conditions.

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Published

2022-10-21

How to Cite

Kostiuchenko , O. ., Skibo, . G., & Lushnikova, . I. . (2022). Morphofunctional characteristics of hippocampal neurons in glutamate excitotoxicity in vitro model and after α-ketoglutarate administration. Морфологія / Morphologia / Morfologìâ, 16(3), 153–157. Retrieved from https://morphology.dma.edu.ua/article/view/282009

Issue

Vol. 16 No. 3 (2022)

Section

Статті

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