Belluardo Natale, Mudò Giuseppa, Blum Mariann, Itoh Nobuyuki, Agnati Luigi, Fuxe Kjell
Department of Experimental Medicine, Division of Human Physiology, University of Palermo, Corso Tukory 129, I-91134 Palermo, Italy.
Neurobiol Aging. 2004 Nov-Dec;25(10):1333-42. doi: 10.1016/j.neurobiolaging.2004.01.002.
Indirect trophic actions of nicotine on brain during aging are suggested from observations describing nicotine as a cognitive enhancer, increasing vigilance and improving learning and memory, and both in vitro and in vivo models have demonstrated neuroprotective effects of nAChR agonists. Previously, we have reported that an acute intermittent (-)nicotine treatment significantly increases fibroblast growth factor-2 (FGF-2) mRNA and protein in several brain regions of rat brain. The present study was designed to analyse if nicotine-induced FGF-2 expression in the rat brain was preserved during aging. Using in situ hybridization and quantitative RNase protection assay the present paper reports that during aging (12- and 24-month-old rats) the response of FGF-2 gene expression in the rat brain to nAChR stimulation by (-)nicotine is fully effective and involves both neurons and glial cells. The investigation was extended to other members of the FGF family, such as FGF-5 and -20, but this expression was not influenced by the (-)nicotine treatment at any age studied. Similarly following (-)nicotine treatment no changes were observed in FGF receptors (FGFR 1-3) mRNA levels in adult and aged rats. Taken together, the present and previous data support the hypothesis that neuroprotective effects of (-)nicotine and the potential beneficial effects of (-)nicotine agonists in the treatment of Alzheimer's and Parkinson's diseases, may at least in part involve an activation of the neuronal and glial FGF-2 signalling. Work is in progress to analyse the mechanism(s) linking nAChR activation to the up-regulation of FGF-2.
从将尼古丁描述为一种认知增强剂、可提高警觉性并改善学习和记忆的观察结果中，提示了尼古丁在衰老过程中对大脑的间接营养作用，并且体外和体内模型均已证明烟碱型乙酰胆碱受体（nAChR）激动剂具有神经保护作用。此前，我们曾报道急性间歇性（-）尼古丁处理可显著增加大鼠脑几个区域中的成纤维细胞生长因子-2（FGF-2）的mRNA和蛋白质。本研究旨在分析在衰老过程中大鼠脑中尼古丁诱导的FGF-2表达是否得以保留。本文采用原位杂交和定量核糖核酸酶保护试验报告称，在衰老过程中（12月龄和24月龄大鼠），大鼠脑内FGF-2基因表达对（-）尼古丁刺激nAChR的反应是完全有效的，且涉及神经元和神经胶质细胞。该研究扩展至FGF家族的其他成员，如FGF-5和-20，但在所研究的任何年龄阶段，这种表达均不受（-）尼古丁处理的影响。同样，在（-）尼古丁处理后，成年和老年大鼠的FGF受体（FGFR 1 - 3）mRNA水平未观察到变化。综上所述，目前和先前的数据支持以下假说：（-）尼古丁的神经保护作用以及（-）尼古丁激动剂在治疗阿尔茨海默病和帕金森病中的潜在有益作用，可能至少部分涉及神经元和神经胶质细胞FGF-2信号的激活。目前正在进行工作以分析将nAChR激活与FGF-2上调联系起来的机制。
