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Cyclooxygenase 2 RNA message abundance, stability, and hypervariability in sporadic alzheimer neocortex
Author(s) -
Lukiw Walter J.,
Bazan Nicolas G.
Publication year - 1997
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19971215)50:6<937::aid-jnr4>3.0.co;2-e
Subject(s) - neocortex , abundance (ecology) , rna , cyclooxygenase , biology , neuroscience , genetics , enzyme , ecology , biochemistry , gene
Long‐term treatment by nonsteroidal anti‐inflammatory drugs has been shown to decrease the incidence of Alzheimer's disease (AD). Both platelet‐activating factor and interleukin‐1β, potent mediators of the inflammatory and immune response, strongly induce transcription of the cyclooxygenase‐2 (COX‐2) gene in brain cells. Using Northern and RT‐PCR analysis, we have determined in 15 control and 10 sporadic AD human neocortical samples (age range, 60–82 yr; postmortem interval [PMI] range, 0.7–16.0 hr) the levels of COX‐2 RNA in relation to the constitutively expressed COX‐1 and β‐actin RNA message levels. Our results indicate that in short PMI brain, COX‐1 and COX‐2 transcripts are relatively low abundance RNA messages, ranging from a mean of 6.8% of the β‐actin signal in controls to 8.5% of the β‐actin signal in AD‐affected brain. A large variation in the signal intensity for COX‐2 RNA was noted in both control and AD; although there was a trend for higher COX‐2 RNA message abundance in AD neocortex to +11.5% of that of controls, it did not reach statistical significance (ANOVA = 0.45). Several human tissues, including heart, skeletal muscle, lung, kidney, and spinal cord, displayed 4.6‐ and 2.8‐kb COX‐2 RNA message isoforms; however, the 4.6‐kb COX‐2 RNA predominated in the hippocampus and association neocortex. COX‐2 RNA message was found to be degraded at similar rates in both control and AD tissues, and a strong positive correlation between the PMI and the intensity of the COX‐2 RNA signal was noted (ANOVA = 0.006). Linear regression analysis indicated that the 4.6‐kb COX‐2 RNA is an unstable short‐lived RNA species with a half‐life of not more than 3.5 hr, a feature characteristic of immediate early gene transcripts. Individual hypervariability in COX‐2 RNA message abundance may reflect various degrees of expression of AD‐related inflammatory processes. J. Neurosci. Res. 50:937–945, 1997. © 1997 Wiley‐Liss, Inc.