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Front Cell Neurosci. 2014 Jan 30;8:14. doi: 10.3389/fncel.2014.00014. eCollection 2014.

Different effects of anesthetic isoflurane on caspase-3 activation and cytosol cytochrome c levels between mice neural progenitor cells and neurons.

Frontiers in cellular neuroscience

Yiying Zhang, Chuxiong Pan, Xu Wu, Yuanlin Dong, Deborah J Culley, Gregory Crosby, Tianzuo Li, Zhongcong Xie

Affiliations

  1. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School Charlestown, MA, USA.
  2. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School Charlestown, MA, USA ; Department of Anesthesia, Beijing Tongren Hospital, Capital Medical University Beijing, China.
  3. Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School Charlestown, MA, USA ; Department of Forensic Pathology, Faculty of Forensic Medicine, China Medical University , Shenyang, China.
  4. Department of Anesthesia, Brigham and Women's Hospital and Harvard Medical School Boston, MA, USA.
  5. Department of Anesthesia, Beijing Tongren Hospital, Capital Medical University Beijing, China.

PMID: 24523673 PMCID: PMC3906516 DOI: 10.3389/fncel.2014.00014

Abstract

Commonly used anesthetic isoflurane has been reported to promote Alzheimer's disease (AD) neuropathogenesis by inducing caspase-3 activation. However, the up-stream mechanisms of isoflurane's effects remain largely to be determined. Specifically, there is a lack of a good model/system to elucidate the underlying mechanism of the isoflurane-induced caspase-3 activation. We therefore set out to assess and compare the effects of isoflurane on caspase-3 activation in neural progenitor cells (NPCs) and in primary neurons from wild-type (WT) and AD transgenic (Tg) mice. The NPCs and neurons were obtained, cultured and then treated with either 2% isoflurane or under control condition for 6 h. The NPCs or neurons were harvested at the end of the treatment and were subjected to Western blot analysis. Here we showed for the first time that the isoflurane treatment induced caspase-3 activation in neurons, but not in NPCs, from either WT or AD Tg mice. Consistently, the isoflurane treatment increased cytosol levels of cytochrome c, a potential up-stream mechanism of isoflurane-induced caspase-3 activation in the mice neurons, but not NPCs. Finally, the isoflurane treatment induced a greater casapse-3 activation in the neurons, but not the NPCs, from AD Tg mice as compared to the WT mice. These data demonstrated that investigation and comparison of isoflurane's effects between mice NPCs and neurons would serve as a model/system to determine the underlying mechanism by which isoflurane induces caspase-3 activation. These findings would promote more research to investigate the effects of anesthetics on AD neuropathogenesis and the underlying mechanisms.

Keywords: Alzheimer’s disease; anesthesia; caspase-3; cytochrome c; isoflurane; neural progenitor cells; neurons

References

  1. Anesthesiology. 2004 Sep;101(3):703-9 - PubMed
  2. Anesthesiology. 2012 Mar;116(3):603-12 - PubMed
  3. Anesthesiology. 2009 Oct;111(4):741-52 - PubMed
  4. J Alzheimers Dis. 2005 Aug;7(4):319-24 - PubMed
  5. Ann Neurol. 2012 May;71(5):687-98 - PubMed
  6. Neurosci Bull. 2011 Aug;27(4):221-32 - PubMed
  7. J Neurosci. 2007 Feb 7;27(6):1247-54 - PubMed
  8. Nature. 2011 Apr 21;472(7343):319-24 - PubMed
  9. Anesthesiology. 1995 Jan;82(1):305-7 - PubMed
  10. Ann Neurol. 2008 Dec;64(6):618-27 - PubMed
  11. Alzheimers Dement. 2014 Mar;10(2):196-204 - PubMed
  12. Am J Med Sci. 2013 May;345(5):355-60 - PubMed
  13. J Am Geriatr Soc. 1994 Feb;42(2):198-201 - PubMed
  14. Curr Mol Med. 2013 Nov;13(9):1446-54 - PubMed
  15. Anesthesiology. 2006 May;104(5):988-94 - PubMed
  16. J Biol Chem. 2010 Feb 5;285(6):4025-4037 - PubMed
  17. Mayo Clin Proc. 2013 Jun;88(6):552-61 - PubMed
  18. Anesthesiology. 2008 Feb;108(2):251-60 - PubMed
  19. Lancet. 1998 Mar 21;351(9106):857-61 - PubMed
  20. Br J Psychiatry. 2014 Mar;204(3):188-93 - PubMed
  21. J Gerontol A Biol Sci Med Sci. 2006 Dec;61(12):1300-6 - PubMed
  22. Anesthesiology. 2009 Nov;111(5):964-70 - PubMed
  23. Mayo Clin Proc. 2011 Sep;86(9):885-93 - PubMed
  24. Neurobiol Dis. 2006 Dec;24(3):516-24 - PubMed
  25. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Dec 2;47:121 - PubMed
  26. Anesthesiology. 2010 Jun;112(6):1404-16 - PubMed
  27. J Neurosci Res. 2005 Nov 1;82(3):295-305 - PubMed
  28. Int J Neurosci. 1994 Aug;77(3-4):181-5 - PubMed
  29. Neurology. 2005 Oct 11;65(7):986-90 - PubMed
  30. Anesthesiology. 2005 Jun;102(6):1147-57 - PubMed

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