Comparative impact analysis of neuronal and glial progenitors conditioned medium on cerebellar neurons under glutamate exitotoxicity



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Abstract

One of the main causes of cell death in neurodegenerative diseases is excitotoxicity. Today the potential directions of treatment neurodegenerative diseases are including cell therapy, the purpose of which is to replace lost nerve tissue with donor cells. Transplanted cells along with replaced lost tissues have a paracrine effect, which requires careful study. The aim of this work was to study the effect of conditioned media, obtaining from neuronal and glial progenitor cells, on a primary culture of cerebellar neurons in a model of glutamate excitotoxicity. The cell viability, expression of marker genes for apoptosis and neuritogenesis, and the number of necrotic and apoptotic cells were determined in the culture of cerebellar neurons. The composition of the studied conditioned media was analyzed for the content of neurotrophins. A comparative analysis was revealed differences in the secretion of neurotrophins between the obtained cultures: the amount of brain-derived neurotrophic factor, nerve growth factor, ciliary neurotrophic factor and glial neurotrophic factor was higher in the secretion of glial progenitors. It was shown that the addition of conditioned media from neuronal cells does not significantly affect the viability of cerebellar neurons, whereas preincubation with media from glial progenitors has a neuroprotective effect by increasing the viability of cerebellar neurons, and during long-term cultivation promotes the growth of neurites by increasing the expression level of MAP2 and GAP43 genes.

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About the authors

D. I Salikhova

N.P. Bochkov Medical Genetic Research Center; Research Institute of Human Morphology

Email: diana_salikhova@bk.ru
Moscow, Russia

G. E Leonov

N.P. Bochkov Medical Genetic Research Center

Email: diana_salikhova@bk.ru
Moscow, Russia

T. B Bukharova

N.P. Bochkov Medical Genetic Research Center

Email: diana_salikhova@bk.ru
Moscow, Russia

Z. V Kornienko

N.P. Bochkov Medical Genetic Research Center

Email: diana_salikhova@bk.ru
Moscow, Russia

N. V Bulatenko

N.P. Bochkov Medical Genetic Research Center

Email: diana_salikhova@bk.ru
Moscow, Russia

A. S Efremova

N.P. Bochkov Medical Genetic Research Center

Email: diana_salikhova@bk.ru
Moscow, Russia

O. V Makhnach

N.P. Bochkov Medical Genetic Research Center

Email: diana_salikhova@bk.ru
Moscow, Russia

A. V Makarov

Research Institute of Human Morphology

Email: diana_salikhova@bk.ru
Moscow, Russia

AV. V Elchaninov

Research Institute of Human Morphology

Email: diana_salikhova@bk.ru
Moscow, Russia

T. H Fathudinov

Research Institute of Human Morphology; Peoples' Friendship University of Russia

Email: diana_salikhova@bk.ru
Moscow, Russia

D. V Goldshtein

N.P. Bochkov Medical Genetic Research Center; Peoples' Friendship University of Russia

Email: diana_salikhova@bk.ru
Moscow, Russia

References

  1. Kim S.U., Lee H.J. Human Neural Stem Cell-Based Cell-and Gene-Therapy for Neurological Diseases. Stem Cells and Cell Therapy 2014; 8: 21-48.
  2. Kim S.U., De Vellis J. Stem cell-based cell therapy in neurological diseases: a review. Journal of neuroscience research 2009; 87(10): 2183-200.
  3. Baraniak P.R., McDevitt T.C. Stem cell paracrine actions and tissue regeneration. Regenerative medicine 2010; 5(1): 121-43.
  4. Breton R.R., Rodriguez J.C. Excitotoxicity and oxidative stress in acute ischemic stroke. Acute ischemic stroke 2012; 200: 29-58.
  5. Hynd M.R., Scott H.L., Dodd P.R. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease. Neurochemistry international 2004; 45(5): 583-95.
  6. Yang H., Wang C., Chen H. et al. Neural Stem Cell-Conditioned Medium Ameliorated Cerebral Ischemia-Reperfusion Injury in Rats. Stem cells international 2018; 2018: 1-7.
  7. Liang P., Liu J., Xiong J. et al. Neural stem cell-conditioned medium protects neurons and promotes propriospinal neurons relay neural circuit reconnection after spinal cord injury. Cell transplantation 2014; 23(1): 45-56.
  8. Kume T., Nishikawa H., Tomioka H. et al. p75-mediated neuroprotection by NGF against glutamate cytotoxicity in cortical cultures. Brain research 2000; 852(2): 279-89.
  9. Vedunova M.V., Sakharnova Т.А., Mitroshina E.V. et al. Antihypoxic and neuroprotective properties of BDNF and GDNF in vitro and in vivo under hypoxic conditions. Modern technologies in medicine 2014; 6(4): 38-44.
  10. Almeida R.D., Manadas B.J., Melo C.V. et al. Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell death and differentiation 2005; 12(10): 1329-43.
  11. Fumagalli F., Racagni G., Riva M.A. The expanding role of BDNF: a therapeutic target for Alzheimer's disease. The pharmacogenomics journal 2006; 6(1): 8-15.
  12. Bilimoria P.M., Bonni A. Cultures of cerebellar granule neurons. Cold Spring Harbor Protocols 2008; 2008(12): 5107.
  13. Chambers S.M., Fasano C.A., Papapetrou E.P. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nature biotechnology 2009; 27(3): 275-80.
  14. Shutova M.V., Chestkov I.V., Bogomazov A.N. et al. Generation of iPS cells from human umbilical vein endothelial cells by lentiviral transduction and their differentiation to neuronal lineage. Human Embryonic and Induced Pluripotent Stem Cells 2011: 133-49.
  15. Krencik R., Zhang S.C. Directed differentiation of functional astroglial subtypes from human pluripotent stem cells. Nature protocols 2011; 6(11): 1710-7.
  16. Emdad L., D'Souza S.L., Kothari H.P. et al. Efficient differentiation of human embryonic and induced pluripotent stem cells into functional astrocytes. Stem cells and development 2011; 21(3): 404-10.
  17. Савинкова И.Г., Горбачева Л.Р., Струкова C.M. и др. Нейропротекторное действие при глутаматной эксайтотоксичности пептидов-аналогов привязанного лиганда, освобождаемого активированным протеином С. Биологические мембраны: Журнал мембранной и клеточной биологии 2013; 30(5-6): 468.
  18. Nishihara T., Okahashi N., Ueda N. Activin A induces apoptotic cell death. Biochemical and biophysical research communications 1993; 197(2): 985-91.
  19. Liu Y., Tao L., Fu X. et al. BDNF protects retinal neurons from hyperglycemia through the TrkB/ERK/MAPK pathway. Molecular medicine reports 2013; 7(6): 1773-8.
  20. Anitha M., Gondha C., Sutliff R. et al. GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation of the PI3K/Akt pathway. The Journal of clinical investigation 2006; 116(2): 344-56.
  21. Kim M.S., Shutov L.P., Gnanasekaran A. et al. Nerve growth factor (NGF) regulates activity of nuclear factor of activated T-cells (NFAT) in neurons via the phosphatidylinositol 3-kinase (PI3K)-Akt-glycogen synthase kinase 3p (GSK3p) pathway. Journal of Biological Chemistry 2014; 289(45): 31349-60.
  22. Pierchala B.A., Ahrens R.C., Paden A.J. et al. Nerve growth factor promotes the survival of sympathetic neurons through the cooperative function of the protein kinase C and phosphatidylinositol 3-kinase pathways. Journal of Biological Chemistry 2004; 279(27): 27986-93.
  23. Lu S., Lu C., Han Q. et al. Adipose-derived mesenchymal stem cells protect PC12 cells from glutamate excitotoxicity induced apoptosis by upregulation of XIAP through PI3-K/Akt activation. Toxicology 2011; 279(1-3): 189-95.
  24. Tan B., Luan Z., Wei X. et al. AMP-activated kinase mediates adipose stem cell-stimulated neuritogenesis of PC12 cells. Neuroscience 2011; 181: 40-7.
  25. Hao P., Liang Z., Piao H. et al. Conditioned medium of human adipose-derived mesenchymal stem cells mediates protection in neurons following glutamate excitotoxicity by regulating energy metabolism and GAP-43 expression. Metabolic brain disease 2014; 29(1): 193-205.
  26. Wei X., Du Z., Zhao L. et al. IFATS collection: The conditioned media of adipose stromal cells protect against hypoxia-ischemia-induced brain damage in neonatal rats. Stem cells 2009; 27(2): 478-88.
  27. Wilkins A., Kemp K., Ginty M. et al. Human bone marrow derived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro. Stem cell research 2009; 3(1): 63-70.

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