Neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, in the hippocampus of patients with schizophrenia.
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 Abeta 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.
Yokota
Osamu
O
Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, 700-8558, Japan. oyokota1@yahoo.co.jp
Terada
Seishi
S
Ishihara
Takeshi
T
Nakashima
Hanae
H
Kugo
Aki
A
Ujike
Hiroshi
H
Tsuchiya
Kuniaki
K
Ikeda
Kenji
K
Saito
Yuko
Y
Murayama
Shigeo
S
Ishizu
Hideki
H
Kuroda
Shigetoshi
S
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000096:biosynthesis; D001344:Autopsy; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins; D009474:Neurons / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011569:Psychiatric Status Rating Scales; D011720:Pyrazoles; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology*; D013449:Sulfonamides / Q000494:pharmacology*; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib