TY - JOUR
T1 - Maturational regulation and regional induction of cyclooxygenase-2 in rat brain
T2 - Implications for Alzheimer's disease
AU - Tocco, G.
AU - Freire-Moar, J.
AU - Schreiber, S. S.
AU - Sakhi, S. H.
AU - Aisen, P. S.
AU - Pasinetti, G. M.
N1 - Funding Information:
This work was supported by AG13799, AG14239, and ADRC of New York (AG05138) pilot project grant to G.M.P. The authors thank Dr. Michel Baudry for helpful discussions and support. We also thank Mr. Brian Kramer, Ms. Hoong-San Chen, and Dr. Wei Yi for their technical assistance and comments.
PY - 1997/4
Y1 - 1997/4
N2 - 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- 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.
AB - 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- 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.
UR - http://www.scopus.com/inward/record.url?scp=0031127741&partnerID=8YFLogxK
U2 - 10.1006/exnr.1997.6429
DO - 10.1006/exnr.1997.6429
M3 - Article
C2 - 9168834
AN - SCOPUS:0031127741
SN - 0014-4886
VL - 144
SP - 339
EP - 349
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -