Age-related loss of neuronal nicotinic receptor expression in the aging mouse hippocampus corresponds with cyclooxygenase-2 and PPAR gamma expression and is altered by long-term NS398 administration.
Age-related changes in the mammalian dorsal hippocampus are associated with diminished expression of neuronal nicotinic acetylcholine receptors (nAChR), which is particularly severe in pathologies such as those associated with dementias, including Alzheimer's disease. Because the mouse is a useful model for age-related decline in nAChR expression in the basal forebrain and limbic system, we used immunohistochemistry to examine the influence of long-term (12-month) oral administration of nicotine and/or the cyclooxygenase-2 (COX-2) preferring non-steroidal anti-inflammatory drug (NSAID) NS398 on nAChR alpha4, alpha5, alpha7, and beta4 expression in the C57BL/6 mouse. Inhibitory neurons of the dorsal hippocampus that express nAChRs also constitutively express COX-2 and the peroxisome proliferator-antagonist receptor subtype gamma-2 (PPAR gamma2) which is also a target of NS398. Administration of NS398 correlated with retention of nAChR alpha4 and to a lesser extent nAChR beta4, but not nAChR alpha5 or alpha7, but nicotine exhibited no similar effect. Nicotine and NS398 co-administration abolished the NS398-related effect on nAChR alpha4 retention. These results provide evidence that the interaction during aging between oral administration of nicotine and NSAIDs are not straightforward and could even be antagonistic when combined.
Gahring
Lorise C
LC
Salt Lake City VA-Geriatrics Research, Education and Clinical Center, Salt Lake City, Utah, USA.
Persiyanov
Karina
K
Days
Emily L
EL
Rogers
Scott W
SW
D000375:Aging / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009578:Nitrobenzenes / Q000008:administration & dosage*; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D011978:Receptors, Nicotinic / Q000096:biosynthesis*; D013449:Sulfonamides / Q000008:administration & dosage*; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D047495:PPAR gamma; D011978:Receptors, Nicotinic; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases