1. Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: implications for Alzheimer's disease.
- Author
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Tocco G, Freire-Moar J, Schreiber SS, Sakhi SH, Aisen PS, and Pasinetti GM
- Subjects
- Alzheimer Disease drug therapy, Amygdala enzymology, Amygdala pathology, Animals, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Apoptosis drug effects, Brain growth & development, Cells, Cultured, Cerebral Cortex enzymology, Cerebral Cortex pathology, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors pharmacology, Cyclooxygenase Inhibitors therapeutic use, 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 genetics, Kainic Acid pharmacology, Kainic Acid toxicity, Nerve Degeneration drug effects, Nerve Tissue Proteins genetics, Organ Specificity, Prostaglandin-Endoperoxide Synthases genetics, RNA, Messenger biosynthesis, RNA, Messenger genetics, Rats, Rats, Sprague-Dawley, Seizures chemically induced, Seizures enzymology, Seizures pathology, Alzheimer Disease enzymology, Brain enzymology, Isoenzymes biosynthesis, Nerve Tissue Proteins biosynthesis, Prostaglandin-Endoperoxide Synthases biosynthesis
- Abstract
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 corticohippocampal neurons confirmed the neuronal expression of COX-2 in vitro and 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.
- Published
- 1997
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