Góngora-Alfaro José Luis
Universidad Autonoma de Yucatan, Merida, Mexico.
Rev Neurol. 2010;50(4):221-9.
Prospective epidemiologic studies performed in large cohorts of men (total: 374,003 subjects) agree in which the risk of suffering Parkinson's disease diminishes progressively as the consumption of coffee and other caffeinated beverages increases. In the case of women (total: 345,184 subjects) the protective effect of caffeine is only observed in menopausal women which do not receive estrogen replacement therapy. Studies with models of acute parkinsonism in rodents have shown that caffeine reduces the loss of nigrostriatal dopaminergic neurons induced with the neurotoxins 6-hidroxidopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, effect that seems to be mediated through blockade of A(2A) adenosine receptors. Recently, it was shown that male rats treated with moderate doses of caffeine (5 mg/kg/day) during six months, followed by a withdrawal period of at least two weeks, developed a greater resistance to the catalepsy induced with the dopaminergic antagonist haloperidol, which was possibly mediated by an increase of dopaminergic transmission in the corpus striatum.
More studies are needed to demonstrate unequivocally that caffeine prevents the degeneration of dopaminergic neurons in animal models of moderate, chronic, and progressive parkinsonism, since it could lead to the discovery of more effective drugs for the prevention of aging-related degenerative diseases of the central nervous system.
在大量男性队列（总计374,003名受试者）中进行的前瞻性流行病学研究一致表明，帕金森病的患病风险会随着咖啡和其他含咖啡因饮料摄入量的增加而逐渐降低。对于女性（总计345,184名受试者）而言，咖啡因的保护作用仅在未接受雌激素替代疗法的绝经后女性中观察到。对啮齿动物急性帕金森病模型的研究表明，咖啡因可减少由神经毒素6 - 羟基多巴胺和1 - 甲基 - 4 - 苯基 - 1,2,3,6 - 四氢吡啶诱导的黑质纹状体多巴胺能神经元的损失，这种作用似乎是通过阻断A(2A)腺苷受体介导的。最近，研究表明雄性大鼠连续六个月接受中等剂量咖啡因（5毫克/千克/天）治疗，随后至少停药两周，对多巴胺能拮抗剂氟哌啶醇诱导的僵住症具有更强的抵抗力，这可能是由纹状体中多巴胺能传递增加介导的。
需要更多研究来明确证明咖啡因可预防中度、慢性和进行性帕金森病动物模型中多巴胺能神经元的退化，因为这可能会促成发现更有效的药物来预防与衰老相关的中枢神经系统退行性疾病。
