Age-related loss of neuronal nicotinic receptor expression in the aging mouse hippocampus corresponds with cyclooxygenase-2 and PPARγ expression and is altered by long-term NS398 administration
Age-related loss of neuronal nicotinic receptor expression in the aging mouse hippocampus corresponds with cyclooxygenase-2 and PPARγ expression and is altered by long-term NS398 administration
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DOI：
10.1002/neu.20106
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发表时间：
2005-03-01
期刊：
影响因子：
--
通讯作者：
Rogers, SW
中科院分区：
文献类型：
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作者：
Gahring, LC;Persiyanov, K;Rogers, SW
哺乳动物背侧海马区的年龄相关变化与神经元烟碱型乙酰胆碱受体(NAChR)的表达减少有关，这在与痴呆相关的病理中尤其严重，包括阿尔茨海默病。由于小鼠是基底前脑和边缘系统nAChR表达随年龄增长而下降的有用模型，我们使用免疫组织化学方法检测了长期(12个月)口服尼古丁和/或偏爱非类固醇抗炎药(NSAID)NS398的环氧合酶-2(COX-2)对C57BL/6小鼠nAChRalpha4、Alpha5、Alpha7和Beta4表达的影响。在背侧海马区，表达nAChRs的抑制性神经元也表达COX-2和PPARGamma2，后者也是NS398的靶标。服用NS398与nAChRalpha4和nAChRbeta4的滞留有关，但与nAChRalpha5或alpha7无关，但尼古丁没有类似的效果。尼古丁和NS398联合给药消除了NS398对nAChRalpha4保留的相关影响。这些结果提供了证据，表明在衰老过程中，口服尼古丁和非甾体抗炎药之间的相互作用并不是直接的，当联合使用时，甚至可能是拮抗的。(C)2004年威利期刊公司。
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 nAChRalpha4, 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 (PPARgamma2) which is also a target of NS398. Administration of NS398 correlated with retention of nAChRalpha4 and to a lesser extent nAChRbeta4, but not nAChRalpha5 or alpha7, but nicotine exhibited no similar effect. Nicotine and NS398 co-administration abolished the NS398-related effect on nAChRalpha4 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. (C) 2004 Wiley Periodicals, Inc.