Journal of Molecular Neuroscience

, Volume 45, Issue 1, pp 10–21 | Cite as

Cyclooxygenase (COX)-1 Activity Precedes the COX-2 Induction in Aβ-Induced Neuroinflammation

  • Leila Dargahi
  • Shiva Nasiraei-Moghadam
  • Azadeh Abdi
  • Leila Khalaj
  • Fatemeh Moradi
  • Abolhassan AhmadianiEmail author


Two different isoforms of cyclooxygenases, COX-1 and COX-2, are constitutively expressed under normal physiological conditions of the central nervous system, and accumulating data indicate that both isoforms may be involved in different pathological conditions. However, the distinct role of COX-1 and COX-2 and the probable interaction between them in neuroinflammatory conditions associated with Alzheimer’s disease are conflicting issues. The aim of this study was to elucidate the comparable role of each COX isoform in neuroinflammatory response induced by β-amyloid peptide (Aβ). Using histological and biochemical methods, 13 days after stereotaxic injection of Aβ into the rat prefrontal cortex, hippocampal neuroinflammation and neuronal injury were confirmed by increased expression of tumor necrosis factor-alpha (TNF-α) and COX-2, elevated levels of prostaglandin E2 (PGE2), astrogliosis, activation of caspase-3, and neuronal cell loss. Selective COX-1 or COX-2 inhibitors, SC560 and NS398, respectively, were chronically used to explore the role of COX-1 and COX-2. Treatment with either COX-1 or COX-2 selective inhibitor or their combination equally decreased the level of TNF-α, PGE2, and cleaved caspase-3 and attenuated astrogliosis and neuronal cell loss. Interestingly, treatment with COX-1 selective inhibitor or the combined COX inhibitors prevented the induction of COX-2. These results indicate that the activity of both isoforms is detrimental in neuroinflammatory conditions associated with Aβ, but COX-1 activity is necessary for COX-2 induction and COX-2 activity seems to be the main source of PGE2 increment.


β-Amyloid peptide Neuroinflammation Cyclooxygenase-1 Cyclooxygenase-2 Prostaglandin E2 



The authors are grateful to T. Al-Tarihi, M. Motevalian, and F. Khodagholi for their valuable help and to Neuroscience Research Center of Shahid Beheshti University of Medical Sciences for financial support.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Leila Dargahi
    • 1
    • 2
  • Shiva Nasiraei-Moghadam
    • 1
  • Azadeh Abdi
    • 1
    • 2
  • Leila Khalaj
    • 1
    • 2
  • Fatemeh Moradi
    • 1
  • Abolhassan Ahmadiani
    • 1
    • 2
    Email author
  1. 1.Neuroscience Research CenterShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of PharmacologySchool of Medicine, Shahid Beheshti University of Medical SciencesTehranIran

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