Prostaglandin G/H synthase-2 (cyclooxygenase-2) mRNA expression is decreased in Alzheimer's disease.
Recent evidence suggests that the use of nonsteroidal anti-inflammatory drugs (NSAIDS) is beneficial for therapy or prevention of Alzheimer's disease (AD). The major anti-inflammatory action of NSAIDS is to inhibit prostaglandin G/H synthase-2 (PGHS-2), the first committed enzymatic step for prostaglandin biosynthesis. We have previously shown that PGHS-2 message is induced by Interleukin-1 beta and other inflammatory mediators in primary cultures of rodent astrocytes. To determine whether similar elevations of PGHS-2 occur as part of the gliosis in AD, we quantified PGHS-2 mRNA levels in control and AD brain by Northern hybridization analysis. To our surprise we found that PGHS-2 mRNA levels were reduced threefold in AD neocortex relative to control brain tissue. In contrast, levels were not reduced in putamen, an area that is relatively spared in AD. To localize PGHS-2 mRNA production in control and AD brain, sections of neocortex and hippocampus were hybridized with a 35S-labeled riboprobe for human PGHS-2 followed by immunocytochemistry with antibodies against neuron specific enolase (NSE) or glial fibrillary acidic protein (GFAP). Our findings indicate that PGHS-2 message is primarily localized to cells that stain for NSE rather than GFAP. Furthermore, in the three cases we examined, PGHS-2 hybridization per neuron appeared to be reduced in AD. Thus, the decrease we observe in overall PGSH-2 mRNA levels is likely to reflect both the known decline in numbers of neurons in AD as well as a lowered capacity for neuronal synthesis of PGHS-2, perhaps due to dysfunction or a loss of synaptic input.
Department of Neurobiology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
J W
JW
Chang
P D
PD
Coleman
M K
MK
O'Banion
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015536:Down-Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008970:Molecular Weight; D009457:Neuroglia / Q000201:enzymology; D009693:Nucleic Acid Hybridization; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010751:Phosphopyruvate Hydratase