Age-related loss of neuronal nicotinic receptor expression in the aging mouse hippocampus corresponds with cyclooxygenase-2 and PPAR? expression and is altered by long-term NS398 administration
✍ Scribed by Gahring, Lorise C. ;Persiyanov, Karina ;Days, Emily L. ;Rogers, Scott W.
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 709 KB
- Volume
- 62
- Category
- Article
- ISSN
- 0022-3034
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✦ Synopsis
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 agerelated 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␣4, ␣5, ␣7, and 4 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␥2) which is also a target of NS398. Administration of NS398 correlated with retention of nAChR␣4 and to a lesser extent nAChR4, but not nAChR␣5 or ␣7, but nicotine exhibited no similar effect. Nicotine and NS398 co-administration abolished the NS398-related effect on nAChR␣4 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.