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Glutamate Excitotoxicity; a Possible Mechanism for Apoptosis of Motoneurons in Adult Mouse Spinal Cord Slices

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Neurophysiology Aims and scope

In experiments on mice spinal cord slices, it was found that intense apoptosis of motoneurons develops in these slices rather rapidly (6 hours). This process can be significantly suppressed by treatment with the NMDA glutamate receptor antagonist MK-801 (50 μM) and AMPA/kainite non-NMDA glutamate receptor antagonist CNQX (100 μM). Such treatment considerably increased the percentage of viable motoneurons in the ventral horns of the spinal cord. The results obtained confirm the statement that glutamate excitotoxicity could be a significant possible factor responsible for apoptosis of motoneurons under conditions of spinal cord impairment.

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References

  1. M. S. Beattie, S. L. Shuman, and J. C. Bresnahan, “Apoptosis and spinal cord injury,” Neuroscientist, 4, 163–171 (1998).

    Article  Google Scholar 

  2. H. Chi H, H.-Y- Chang, and T.-K. Sang, “Neuronal cell death mechanisms in major neurodegenerative diseases,” Int. J. Mol. Sci., 19, No. 10, 3082 (2018).

  3. M. J. Crowe, J. C. Bresnahan, S. L. Shuman, et al., “Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys,” Nat. Med., 3, No. 1, 73–76 (1997).

    Article  CAS  Google Scholar 

  4. S. Casha, W. R. Yu, and M. G. Fehlings, “FAS deficiency reduces apoptosis, spares axons and improves function after spinal cord injury,” Exp. Neurol., 196, No. 2, 390–400 (2005).

    Article  CAS  Google Scholar 

  5. H. R. Momeni and M. Kanje, “Calpain inhibitors delay injury-induced apoptosis in adult mouse spinal cord motor neurons,” Neuroreport, 17, No. 8, 761–765 (2006).

  6. H. R. Momeni, S. Azadi, and M. Kanje, “Calpain activation and apoptosis in motor neurons of cultured adult mouse spinal cord,” Funct. Neurol., 22, No. 2, 105–110 (2007).

    PubMed  Google Scholar 

  7. F. M. Maynard, “Immobilization hypercalcemia following spinal cord injury,” Arch. Phys. Med. Rehabil., 67, 41–44 (1986).

    CAS  PubMed  Google Scholar 

  8. I. Bezprozvanny, “Calcium signaling and neurodegenerative diseases,” Trends Mol. Med., 15, No. 3, 89–100 (2009).

    Article  CAS  Google Scholar 

  9. H. R. Momeni and M. Jarahzadeh, “Effects of a voltage sensitive calcium channel blocker and a sodium-calcium exchanger inhibitor on apoptosis of motor neurons in adult spinal cord slices,” Cell J. (Yakhteh), 14, No. 3, 171–176 (2012).

    CAS  Google Scholar 

  10. S. F. Traynelis, L. P. Wollmuth, C. J. McBain, et al., “Glutamate receptor ion channels: Structure, regulation, and function,” Pharmacol. Rev., 62, No. 3, 405–496 (2010).

    Article  CAS  Google Scholar 

  11. G. Akgül and C. J. McBain, “Diverse roles for ionotropic glutamate receptors on inhibitory interneurons in developing and adult brain,” J. Physiol., 594, No. 19, 5471–5490 (2016).

    Article  Google Scholar 

  12. X.-x. Dong, Y. Wang, and Z.-h. Qin, “Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases,” Acta Pharmacol. Sin., 30, No. 4, 379–387 (2009).

    Article  CAS  Google Scholar 

  13. C. Matute, E. Alberdi, G. Ibarretxe, and M. V. Sánchez-Gómez, “Excitotoxicity in glial cells,” Eur. J. Pharmacol., 447, No. 2–3, 239–246 (2002).

    Article  CAS  Google Scholar 

  14. G. Yu, F. Wu, and E.-S. Wang, “BQ-869, a novel NMDA receptor antagonist, protects against excitotoxicity and attenuates cerebral ischemic injury in stroke,” Int. J. Clin. Exp. Pathol., 8, No. 2, 1213–1225 (2015).

    PubMed  PubMed Central  Google Scholar 

  15. J. L. Cross, B. P. Meloni, A. J. Bakker, et al., “Modes of neuronal calcium entry and homeostasis following cerebral ischemia,” Stroke Res. Treat., 2010, 316862 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. M. G. Van Westerlaak, E. A. Joosten, A. A. Gribnau, et al., “Differential cortico-motoneuron vulnerability after chronic mitochondrial inhibition in vitro and the role of glutamate receptors,” Brain Res.,;922, No. 2, 243–249 (2001).

  17. A. V. Krassioukov, A. Ackery, G. Schwartz, et al., “An in vitro model of neurotrauma in organotypic spinal cord cultures from adult mice,” Brain Res. Brain Res. Protoc., 10, No. 2, 60–68 (2002).

    Article  Google Scholar 

  18. C. A. Connelly, L. C. Chen, and S. D. Colquhoun, “Metabolic activity of cultured rat brainstem, hippocampal and spinal cord slices,”. J. Neurosci. Methods, 99, Nos. 1–2, 1–7 (2000).

  19. J. M. Mouveroux E. A. Lakke, and E. Marani, “Lumbar spinal cord explants from neonatal rat display age-related decrease of outgrowth in culture,” Neurosci. Lett., 311, 69–72 (2001).

    Article  CAS  Google Scholar 

  20. A. J. Bruce, B. Malfroy, and M. Baudry, “Beta-amyloid toxicity in organotypic hippocampal cultures: Protection by EUK-8, a synthetic catalytic free radical scavenger,” Proc. Natl. Acad. Sci., 93, No. 6, 2312–2316 (1996).

    Article  CAS  Google Scholar 

  21. T. Mosmann, “Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays,” J. Immunol. Methods, 65, Nos. 1–2, 55–63 (1983).

  22. S. Elmore, “Apoptosis: A review of programmed cell death,” Toxicol. Pathol., 35, No. 4, 495–516 (2007).

    Article  CAS  Google Scholar 

  23. H. R. Momeni and M. Kanje, “The calpain inhibitor VI prevents apoptosis of adult motor neurons,” Neuroreport, 16, No. 10, 1065–1068 (2005).

  24. T. W. Lai, S. Zhang, and Y. T. Wang, “Excitotoxicity and stroke: Identifying novel targets for neuroprotection,” Prog. Neurobiol., 115, 157–188 (2014).

    Article  CAS  Google Scholar 

  25. M. K. Kutzing, V. Luo, and B. L. Firestein, “Protection from glutamate-induced excitotoxicity by memantine,” Ann. Biomed. Eng., 40, No. 5, 1170–1181 (2012).

    Article  Google Scholar 

  26. E. A. Sribnick, A. M. Del Re, S. K. Ray, et al., “Estrogen attenuates glutamate-induced cell death by inhibiting Ca2+ influx through L-type voltage-gated Ca2+ channels,” Brain Res., 1276, 159–170 (2009).

    Article  CAS  Google Scholar 

  27. G. Vallazza-Deschamps, C. Fuchs, D. Cia, et al., “Diltiazem-induced neuroprotection in glutamate excitotoxicity and ischemic insult of retinal neurons,” Doc. Ophthalmol., 110, No. 1, 25–35 (2005).

    Article  Google Scholar 

  28. H. R. Momeni, “Role of calpain in apoptosis,” Cell J. (Yakhteh), 13, No. 2, 65–72 (2011).

    CAS  Google Scholar 

  29. J. M. Wingrave, K. E. Schaecher, E. A. Sribnick, et al., “Early induction of secondary injury factors causing activation of calpain and mitochondria-mediated neuronal apoptosis following spinal cord injury in rats,” J. Neurosci. Res., 73, No. 1, 95–104 (2003).

    Article  CAS  Google Scholar 

  30. K. Ajiro, C. D. Bortner, J. Westmoreland, and J. A. Cidlowski, “An endogenous calcium-dependent, caspase-independent intranuclear degradation pathway in thymocyte nuclei: Antagonism by physiological concentrations of K+ ions,” Exp. Cell Res., 314, No. 6, 1237–1249 (2008).

    Article  CAS  Google Scholar 

  31. A. G. Yakovlev, G. Wang, B. A. Stoica, et al., “A role of the Ca2+/Mg2+-dependent endonuclease in apoptosis and its inhibition by Poly(ADP-ribose) polymerase,” J. Biol. Chem., 275, No. 28, 21302–21308 (2000).

    Article  CAS  Google Scholar 

  32. S. S. Smaili, Y.-T. Hsu, A. C. P. Carvalho, et al., “Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling,” Braz. J. Med. Biol. Res., 36, No. 2, 183–190 (2003).

    Article  CAS  Google Scholar 

  33. R. J. Gagliardi, “Neuroprotection, excitotoxicicity and NMDA antagonists,” Arq. Neuropsiquiatr., 58, No. 2B, 583–588 (2000).

    Article  CAS  Google Scholar 

  34. S.-Y. Jeong and D.-W. Seol, “The role of mitochondria in apoptosis,” BMB Rep., 41, No. 1, 11–22 (2008).

    Article  CAS  Google Scholar 

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  1. Biology Department, Faculty of Science, Arak University, Arak, Iran

    H. R. Momeni, M. Jarahzadeh & E. Farjad

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  1. H. R. Momeni
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  2. M. Jarahzadeh
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  3. E. Farjad
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Correspondence to H. R. Momeni.

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Momeni, H.R., Jarahzadeh, M. & Farjad, E. Glutamate Excitotoxicity; a Possible Mechanism for Apoptosis of Motoneurons in Adult Mouse Spinal Cord Slices. Neurophysiology 52, 408–414 (2020). https://doi.org/10.1007/s11062-021-09898-1

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  • DOI: https://doi.org/10.1007/s11062-021-09898-1

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