Neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, in the hippocampus of patients with schizophrenia

Osamu Yokota, Seishi Terada, Takeshi Ishihara, Hanae Nakashima, Aki Kugo, Hiroshi Ujike, Kuniaki Tsuchiya, Kenji Ikeda, Yuko Saito, Shigeo Murayama, Hideki Ishizu, Shigetoshi Kuroda

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Several types of evidence suggesting that the inflammatory response system is associated with pathophysiology of schizophrenia have been accumulated. Recently, a prospective double-blind study demonstrated that supplementary treatment with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, produced significantly greater improvement in scores on the Positive and Negative Syndrome Scale (PANSS) and on all subscales during the acute phase in patients with schizophrenia compared with risperidone alone therapy. The therapeutic effect of celecoxib on the psychopathology of schizophrenia is speculated to be based on COX activity inhibition; however, the detailed pharmacological mechanisms are unclear. To clarify whether or not COX-2 expression is altered in schizophrenia, we examined neuronal COX-2 expression in the hippocampus from cases of schizophrenia (n=17), normal controls (n=22), and cases of Alzheimer's disease (AD) as a positive control (n=17). Quantitative immunohistochemical analysis demonstrated that neuronal COX-2 expression was significantly up-regulated in each CA1-4 region in Alzheimer's disease compared with controls, and that the mean COX-2 immunointensity in CA1-4 was significantly correlated with Aβ load in cases of Alzheimer's disease. In contrast, COX-2 expression was not up-regulated in any subdivision of the hippocampus in the schizophrenia group. These results suggest that celecoxib may affect the pathophysiology of schizophrenia through COX-2-independent actions rather than by inhibiting activity of up-regulated COX-2 protein.

Original languageEnglish
Pages (from-to)715-721
Number of pages7
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Issue number4
Publication statusPublished - Jul 2004


  • AD
  • Alzheimer's disease
  • AβMTL phase
  • Celecoxib
  • Cyclooxygenase-2
  • Hippocampus
  • Inflammation
  • Schizophrenia
  • Selective cyclooxygenase-2 inhibitor
  • analysis of variance
  • phase of Aβ deposition in the medial temporal lobe
  • β-amyloid

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry


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