Court J A, Lloyd S, Thomas N, Piggott M A, Marshall E F, Morris C M, Lamb H, Perry R H, Johnson M, Perry E K
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, UK.
Neuroscience. 1998 Nov;87(1):63-78. doi: 10.1016/s0306-4522(98)00088-8.
Reports of a reduction in the risk of developing Parkinson's disease and Alzheimer's disease in tobacco smokers, together with the loss of high-affinity nicotine binding in these diseases, suggest that consequences of nicotinic cholinergic transmission may be neuroprotective. Changes in brain dopaminergic parameters and nicotinic receptors in response to tobacco smoking have been assessed in this study of autopsy samples from normal elderly individuals with known smoking histories and apolipoprotein E genotype. The ratio of homovanillic acid to dopamine, an index of dopamine turnover, was reduced in elderly smokers compared with age matched non-smokers (P<0.05) in both the caudate and putamen. Dopamine levels were significantly elevated in the caudate of smokers compared with non-smokers (P<0.05). However there was no significant change in the numbers of dopamine (D1, D2 and D3) receptors or the dopamine transporter in the striatum, or for dopamine D1 and D2 receptors in the hippocampus in smokers compared with non-smokers or ex-smokers. The density of high-affinity nicotine binding was higher in smokers than non-smokers in the hippocampus, entorhinal cortex and cerebellum (elevated by 51-221%) and to a lesser extent in the striatum (25-55%). The density of high-affinity nicotine binding in ex-smokers was similar to that of the non-smokers in all the areas investigated. The differences in high-affinity nicotine binding between smokers and the non- and ex-smokers could not be explained by variation in apolipoprotein E genotype. There were no differences in alpha-bungarotoxin binding, measured in hippocampus and cerebellum, between any of the groups. These findings suggest that chronic cigarette smoking is associated with a reduction of the firing of nigrostriatal dopaminergic neurons in the absence of changes in the numbers of dopamine receptors and the dopamine transporter. Reduced dopamine turnover associated with increased numbers of high-affinity nicotine receptors is consistent with attenuated efficacy of these receptors in smokers. A decrease in striatal dopamine turnover may be a mechanism of neuroprotection in tobacco smokers that could delay basal ganglia pathology. The current findings are also important in the interpretation of measurements of nicotinic receptors and dopaminergic parameters in psychiatric conditions such as schizophrenia, in which there is a high prevalence of cigarette smoking.
有报告称吸烟者患帕金森病和阿尔茨海默病的风险降低，同时在这些疾病中高亲和力尼古丁结合丧失，这表明烟碱型胆碱能传递的后果可能具有神经保护作用。在这项对有已知吸烟史和载脂蛋白E基因型的正常老年人尸检样本的研究中，评估了吸烟对脑多巴胺能参数和烟碱型受体的影响。与年龄匹配的非吸烟者相比，老年吸烟者尾状核和壳核中高香草酸与多巴胺的比值（多巴胺周转率指标）降低（P<0.05）。与非吸烟者相比，吸烟者尾状核中的多巴胺水平显著升高（P<0.05）。然而，与非吸烟者或已戒烟者相比，吸烟者纹状体中多巴胺（D1、D2和D3）受体数量或多巴胺转运体，以及海马体中多巴胺D1和D2受体数量均无显著变化。吸烟者海马体、内嗅皮质和小脑中高亲和力尼古丁结合密度高于非吸烟者（升高51%-221%），在纹状体中升高程度较小（25%-55%）。在所有研究区域，已戒烟者的高亲和力尼古丁结合密度与非吸烟者相似。吸烟者与非吸烟者和已戒烟者之间高亲和力尼古丁结合的差异无法用载脂蛋白E基因型的差异来解释。任何组之间海马体和小脑中测量的α-银环蛇毒素结合均无差异。这些发现表明，慢性吸烟与黑质纹状体多巴胺能神经元放电减少有关，而多巴胺受体数量和多巴胺转运体无变化。多巴胺周转率降低与高亲和力尼古丁受体数量增加相关，这与吸烟者中这些受体的效能减弱一致。纹状体多巴胺周转率降低可能是吸烟者神经保护的一种机制，可延迟基底神经节病变。目前的发现对于解释精神疾病如精神分裂症中烟碱型受体和多巴胺能参数的测量也很重要，在精神分裂症中吸烟率很高。
