Audesirk T, Cabell L
Biology Department, University of Colorado at Denver, 80217-3364, USA.
Neurotoxicology. 1999 Aug;20(4):639-46.
We investigated the effects of nicotine and its metabolic byproduct cotinine on survival, differentiation and intracellular Ca2+ levels of cultured E18 rat hippocampal neurons. We used a range of concentrations from 1 nM to 10 microM, most of which are within the likely range of human fetal exposure from maternal smoking. Nicotine did not influence neuron survival or neurite production. However, at all concentrations tested, nicotine significantly increased branching of both axons and dendrites, an effect which was not reversed by co-culturing with alpha-bungarotoxin, which blocks the nicotinic acetylcholine receptors that predominate in hippocampal cultures (Alkondon and Albuquerque, 1993; Barrantes et al., 1995b). Cotinine at 100 nM and 1 microM significantly reduced neuron survival and neurite production of surviving neurons, but did not significantly alter axon or dendrite branching. These membrane-permeable compounds may work synergistically in the developing embryo to impair the survival and differentiation of hippocampal neurons via intracellular mechanisms.
我们研究了尼古丁及其代谢副产物可替宁对培养的E18大鼠海马神经元的存活、分化及细胞内钙离子水平的影响。我们使用了从1 nM到10 microM的一系列浓度，其中大多数处于人类胎儿因母亲吸烟而接触到的可能浓度范围内。尼古丁不影响神经元的存活或神经突的产生。然而，在所有测试浓度下，尼古丁均显著增加了轴突和树突的分支，与α-银环蛇毒素共培养并不能逆转这种效应，α-银环蛇毒素可阻断海马培养物中占主导地位的烟碱型乙酰胆碱受体（Alkondon和Albuquerque，1993年；Barrantes等人，1995年b）。100 nM和1 microM的可替宁显著降低了神经元的存活及存活神经元的神经突产生，但对轴突或树突分支没有显著影响。这些可透过细胞膜的化合物可能在发育中的胚胎中协同作用，通过细胞内机制损害海马神经元的存活和分化。
