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Cerebral ischemic injury decreases α-synuclein expression in brain tissue and glutamate-exposed HT22 cells

Abstract

α-Synuclein is abundantly expressed in neuronal tissue, plays an essential role in the pathogenesis of neurodegenerative disorders, and exerts a neuroprotective effect against oxidative stress. Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. In this study, we examined α-synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical operation was performed on male Sprague-Dawley rats, and brain samples were isolated 24 hours after MCAO. We confirmed neurological behavior deficit, infarction area, and histopathological changes following MCAO injury. A proteomic approach and Western blot analysis demonstrated a decrease in α-synuclein in the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced neuronal cell death and decreased α-synuclein expression in a hippocampal-derived cell line in a dose-dependent manner. It is known that α-synuclein regulates neuronal survival, and low levels of α-synuclein expression result in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads to a reduction in α-synuclein and consequently causes serious brain damage.

References

  1. 1.

    Schaller B, Graf R. Cerebral ischemia and reperfusion: the pathophysiologic concept as a basis for clinical therapy. J Cereb Blood Flow Metab 2004; 24(4): 351–371.

    Article  Google Scholar 

  2. 2.

    Min D, Mao X, Wu K, Cao Y, Guo F, Zhu S, Xie N, Wang L, Chen T, Shaw C, Cai J. Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils. Neurosci Lett 2012; 510(1): 29–33.

    CAS  Article  Google Scholar 

  3. 3.

    Sims NR, Muyderman H. Mitochondria, oxidative metabolism and cell death in stroke. Biochim Biophys Acta 2010; 1802(1): 80–91.

    CAS  Article  Google Scholar 

  4. 4.

    Starkov AA, Chinopoulos C, Fiskum G. Mitochondrial calcium and oxidative stress as mediators of ischemic brain injury. Cell Calcium 2004; 36(3-4): 257–264.

    CAS  Article  Google Scholar 

  5. 5.

    Rink C, Khanna S. MicroRNA in ischemic stroke etiology and pathology. Physiol Genomics. 2011; 43(10): 521–528.

    CAS  Article  Google Scholar 

  6. 6.

    Hayashi T, Abe K. Ischemic neuronal cell death and organellae damage. Neurol Res 2004; 26(8): 827–834.

    CAS  Article  Google Scholar 

  7. 7.

    Sidhu A, Wersinger C, Vernier P. Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse? FASEB J 2004; 18(6): 637–647.

    CAS  Article  Google Scholar 

  8. 8.

    Zhu M, Qin ZJ, Hu D, Munishkina LA, Fink AL. Alpha-synuclein can function as an antioxidant preventing oxidation of unsaturated lipid in vesicles. Biochemistry 2006; 45(26): 8135–8142.

    CAS  Article  Google Scholar 

  9. 9.

    Zhu M, Li W, Lu C. Role of alpha-synuclein protein levels in mitochondrial morphology and cell survival in cell lines. PLoS One 2012; 7(4): e36377.

    CAS  Article  Google Scholar 

  10. 10.

    Adibhatla MR, Hatcher JF. Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radic Biol Med 2006; 40(3): 376–387.

    Article  Google Scholar 

  11. 11.

    Adibhatla RM, Hatcher JF. Phospholipase A(2), reactive oxygen species, and lipid peroxidation in CNS pathologies. BMB Rep 2008: 41(8): 560–567.

    CAS  Article  Google Scholar 

  12. 12.

    Angelova PR, Horrocks MH, Klenerman D, Gandhi S. Abramov AY, Shchepinov MS. Lipid peroxidation is essential for α-synuclein-induced cell death. J Neurochem 2015; 133(4): 582–589.

    CAS  Article  Google Scholar 

  13. 13.

    Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989; 20(1): 84–91.

    CAS  Article  Google Scholar 

  14. 14.

    Maher P, Davis JB. The role of monoamine metabolism in oxidative glutamate toxicity. J Neurosci 1996; 16(20): 6394–6401.

    CAS  Article  Google Scholar 

  15. 15.

    Ferrer I, Planas AM. Signaling of cell death and cell survival following focal cerebral ischemia: life and death struggle in the penumbra. J Neuropathol Exp Neurol 2003; 62(4): 329–339.

    Article  Google Scholar 

  16. 16.

    Li Y, Chopp M, Powers C, Jiang N. Apoptosis and protein expression after focal cerebral ischemia in rat. Brain Res 1997; 765(2): 301–312.

    CAS  Article  Google Scholar 

  17. 17.

    Kaplan B, Ratner V, Haas E. Alpha-synuclein: its biological function and role in neurodegenerative diseases. J Mol Neurosci 2003; 20(2): 83–92.

    CAS  Article  Google Scholar 

  18. 18.

    Ma QL, Chan P, Yoshii M, Uéda K. Alpha-synuclein aggregation and neurodegenerative diseases. J Alzheimers Dis 2003; 5(2): 139–148.

    CAS  Article  Google Scholar 

  19. 19.

    Zarranz JJ, Alegre J, Gómez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atarés B, Llorens V, Gomez Tortosa E, del Ser T, Muñoz DG, de Yebenes JG. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 2004; 55(2): 164–173.

    CAS  Article  Google Scholar 

  20. 20.

    Lee M, Hyun D, Halliwell B, Jenner P. Effect of the overexpression of wild-type or mutant alpha-synuclein on cell susceptibility to insult. J Neurochem 2001; 76(4): 998–1009.

    CAS  Article  Google Scholar 

  21. 21.

    Pompella A, Visvikis A, Paolicchi A, De Tata V, Casini AF. The changing faces of glutathione, a cellular protagonist. Biochem Pharmacol 2003; 66(8): 1499–1503.

    CAS  Article  Google Scholar 

  22. 22.

    Seo JH, Rah JC, Choi SH, Shin JK, Min K, Kim HS, Park CH, Kim S, Kim EM, Lee SH, Lee S, Suh SW, Suh YH. Alpha-synuclein regulates neuronal survival via Bcl-2 family expression and PI3/Akt kinase pathway. FASEB J 2002; 16(13): 1826–1828.

    CAS  Article  Google Scholar 

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Koh, PO. Cerebral ischemic injury decreases α-synuclein expression in brain tissue and glutamate-exposed HT22 cells. Lab Anim Res 33, 244–250 (2017). https://doi.org/10.5625/lar.2017.33.3.244

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  • DOI: https://doi.org/10.5625/lar.2017.33.3.244

Keywords

  • α-synuclein
  • cerebral ischemia
  • hippocampal-derived cell line
  • MCAO