Maturational Regulation and Regional Induction of Cyclooxygenase-2 in Rat Brain: Implications for Alzheimer's Disease

• Published in: Experimental neurology Vol. 144; no. 2; pp. 339 - 349
• Main Authors: Tocco, G., Freire-Moar, J., Schreiber, S.S., Sakhi, S.H., Aisen, P.S., Pasinetti, G.M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.04.1997; Elsevier
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - enzymology; Amygdala - enzymology; Amygdala - pathology; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Brain - enzymology; Brain - growth & development; Cells, Cultured; Cerebral Cortex - enzymology; Cerebral Cortex - pathology; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase Inhibitors - therapeutic use; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Enzyme Induction - drug effects; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Agonists - toxicity; Gene Expression Regulation, Developmental - drug effects; Hippocampus - enzymology; Hippocampus - pathology; Isoenzymes - biosynthesis; Isoenzymes - genetics; Kainic Acid - pharmacology; Kainic Acid - toxicity; Medical sciences; Nerve Degeneration - drug effects; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neurology; Organ Specificity; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - genetics; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Seizures - chemically induced; Seizures - enzymology; Seizures - pathology; Cell culture; Animal model; Nervous system diseases; Rat; Enzyme; Alzheimer disease; Pathogenesis; Rodentia; Cerebral disorder; Ripening; Oxygenase; Vertebrata; Regulation(control); Mammalia; Animal; Central nervous system disease; Degenerative disease; Oxidoreductases; Hippocampus; Apoptosis
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.1997.6429

We explored the constitutive expression, maturational regulation, and relation to kainic-acid-induced apoptosis of cyclooxygenase (COX)-2 mRNA in rat brain. In adult rats, COX-2 mRNA was expressed primarily in limbic structures. Constitutive COX-2 mRNA expression increased markedly between Postnatal Day 7 (P7) and P14, reaching adult levels by P21. Despite intense KA-induced seizures, no COX-2 mRNA induction was found before P14 in any brain region examined. During response to KA-induced seizures in adult brain, COX-2 mRNA induction paralleled temporally and overlapped anatomically the appearance of cellular morphological features of apoptosis in subsets of cells of the pyramidal neuron layer of the hippocampal formation, amygdaloid complex, and pyriform cortex. While COX-2 mRNA showed KA-induced elevation in the granule cell layer of the dentate gyrus, no detectable morphological features of apoptosis were found in this region. Finally, monotypic culture of rat cortico-hippocampal neurons confirmed the neuronal expression of COX-2in vitroand revealed that COX-2 is induced during response to glutamate treatment, leading to neuron death. These studies may provide novel insights into the role of COX-2 and mechanisms of action of nonsteroidal anti-inflammatory drugs in Alzheimer's disease.