Display options
Share it on

Iran J Pharm Res. 2015;14(3):811-24.

Ameliorating of Memory Impairment and Apoptosis in Amyloid β-Injected Rats Via Inhibition of Nitric Oxide Synthase: Possible Participation of Autophagy.

Iranian journal of pharmaceutical research : IJPR

Marjan Shariatpanahi, Fariba Khodagholi, Ghorbangol Ashabi, Azar Aghazadeh Khasraghi, Leila Azimi, Mohammad Abdollahi, Mohammad Hossein Ghahremani, Seyed Nasser Ostad, Farshid Noorbakhsh, Mohammad Sharifzadeh

Affiliations

  1. Department of Toxicology and Pharmacology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  2. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Neuro Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  3. Department of Physiology, School of Medicine, Physiology Research center, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran.
  4. Tehran University of Medical Sciences, International Campus, Tehran, Iran.
  5. Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  6. Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  7. Department of Toxicology and Pharmacology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. ; Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

PMID: 26330869 PMCID: PMC4518109

Abstract

It has been proposed that appearance of amyloid beta (Aβ) in hippocampus is one of the characteristic features of Alzheimer's disease (AD). The role of Nitric oxide (NO) in neurodegenerative disorders is controversy in different contexts. Here, we examined the effect of NO on spatial memory. For this purpose, we compared the effects of three different concentrations of L-NG-Nitroarginine Methyl Ester (L-NAME) as a nitric oxide synthase (NOS) inhibitor. We used Morris water maze (MWM) for evaluation of behavioral alterations. We also assessed the apoptosis and autophagy markers as two possible interfering pathways with NO signaling by western blot method. We found that in Aβ pretreated rats, intra-hippocampal injection of 1or 2 (μg/side) of L-NAME caused a significant reduction in escape latency and traveled distance comparing to Aβ-treatment group. Our molecular findings revealed that L-NAME could induce autophagy and attenuate apoptosis dose dependently. The protective role of autophagy and the deteriorative role of apoptosis is the hypothesis that can vindicate our findings. Thus using NOS inhibitors at low concentrations can be one of the therapeutic approaches in the future studies.

Keywords: Alzheimer’s disease; Apoptosis; Autophagy; L-NAME; MWM

References

  1. Cell Death Differ. 2009 Jan;16(1):46-56 - PubMed
  2. Neuromolecular Med. 2014 Mar;16(1):175-90 - PubMed
  3. Mol Med. 2012 Mar 27;18:201-8 - PubMed
  4. Iran J Pharm Res. 2010 Summer;9(3):313-20 - PubMed
  5. Mol Cell Biol. 2005 Feb;25(3):1025-40 - PubMed
  6. Behav Brain Res. 2012 Jun 15;232(1):165-73 - PubMed
  7. Arterioscler Thromb Vasc Biol. 1999 Jan;19(1):140-6 - PubMed
  8. Acta Physiol (Oxf). 2013 Aug;208(4):410-21 - PubMed
  9. Mol Aspects Med. 2005 Feb-Apr;26(1-2):67-96 - PubMed
  10. Neuropsychopharmacology. 2010 Nov;35(12):2357-66 - PubMed
  11. Int J Biochem Cell Biol. 2004 Dec;36(12):2376-91 - PubMed
  12. Int Immunol. 2009 Nov;21(11):1199-204 - PubMed
  13. J Biol Chem. 2007 Feb 16;282(7):4585-600 - PubMed
  14. Nat Genet. 2005 Jul;37(7):771-6 - PubMed
  15. Behav Brain Res. 2011 Oct 10;224(1):140-4 - PubMed
  16. J Clin Invest. 2008 Jun;118(6):2015-8 - PubMed
  17. Behav Brain Res. 2006 Nov 1;174(1):49-55 - PubMed
  18. Neuroimage. 2013 Nov 1;81:96-109 - PubMed
  19. Neuroscience. 2011 Mar 10;176:12-9 - PubMed
  20. Neurosci Lett. 2010 Jan 4;468(2):151-5 - PubMed
  21. Prog Neurobiol. 2013 Jul-Aug;106-107:33-54 - PubMed
  22. Chin J Physiol. 1998 Sep 30;41(3):175-9 - PubMed
  23. Free Radic Biol Med. 2013 Oct;63:207-21 - PubMed
  24. Iran J Pharm Res. 2013 Summer;12(3):457-69 - PubMed
  25. PLoS One. 2010 Mar 23;5(3):e9819 - PubMed
  26. Neurobiol Learn Mem. 2012 Sep;98 (2):130-8 - PubMed
  27. FEBS Lett. 2013 Aug 19;587(16):2643-8 - PubMed
  28. Mol Neurobiol. 2010 Jun;41(2-3):55-72 - PubMed
  29. In Vivo. 2004 May-Jun;18(3):325-33 - PubMed
  30. Curr Med Chem. 2003 Oct;10(20):2147-74 - PubMed
  31. Nat Rev Drug Discov. 2007 Apr;6(4):304-12 - PubMed
  32. Neurosci Res. 2009 Feb;63(2):129-37 - PubMed
  33. Toxicol Appl Pharmacol. 2013 Nov 15;273(1):180-8 - PubMed
  34. Mol Cell. 2011 Jul 8;43(1):19-32 - PubMed
  35. Nitric Oxide. 2013 Feb 28;29:46-52 - PubMed
  36. Ann Neurol. 1992 Sep;32(3):297-311 - PubMed
  37. Anal Biochem. 1976 May 7;72:248-54 - PubMed
  38. Behav Brain Res. 2006 Jul 15;171(1):147-53 - PubMed
  39. Neurosci Lett. 2010 Feb 12;470(2):106-10 - PubMed
  40. Iran J Pharm Res. 2012 Spring;11(2):661-9 - PubMed
  41. Free Radic Biol Med. 2008 Jul 1;45(1):18-31 - PubMed
  42. Pharmacol Biochem Behav. 2011 Mar;98 (1):67-75 - PubMed

Publication Types