Laboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, Switzerland.
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Malta; Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, UK.
J Neurosci Methods. 2018 Oct 1;308:205-218. doi: 10.1016/j.jneumeth.2018.08.012. Epub 2018 Aug 11.
Parkinson's disease is a common neurodegenerative disease characterized by a widely variety of motor and non-motor symptoms. While the motor deficits are only visible following a severe dopamine depletion, neurodegenerative process and some non-motor symptoms are manifested years before the motor deficits. Importantly, chronic degeneration of dopaminergic neurons leads to the development of compensatory mechanisms that play roles in the progression of the disease and the response to anti-parkinsonian therapies. The identification of these mechanisms will be of great importance for improving our understanding of factors with important contributions to the disease course and the underlying adaptive process. To date, most of the data obtained from animal models reflect the late, chronic, dopamine-depleted states, when compensatory mechanisms have already been established. Thus, adequate animal models with which researchers are able to dissect early- and late-phase mechanisms are necessary. Here, we reviewed the literature related to animal models of early-stage PD and pharmacological treatments capable of inducing acute dopamine impairments and/or depletion, such as reserpine, haloperidol and tetrodotoxin. We highlighted the advantages, limitations and the future prospective uses of these models, as well as their applications in the identification of novel agents for treating this neurological disorder.
帕金森病是一种常见的神经退行性疾病，其特征是广泛存在运动和非运动症状。虽然运动缺陷仅在多巴胺严重耗竭后才可见，但神经退行性过程和一些非运动症状在运动缺陷出现多年前就已经表现出来。重要的是，多巴胺能神经元的慢性退化导致了代偿机制的发展，这些机制在疾病的进展和对抗帕金森病疗法的反应中发挥作用。这些机制的鉴定对于改善我们对疾病过程和潜在适应过程中具有重要贡献的因素的理解将非常重要。迄今为止，大多数从动物模型中获得的数据反映了晚期、慢性、多巴胺耗竭的状态，此时已经建立了代偿机制。因此，研究人员需要具有能够剖析早期和晚期阶段机制的合适的动物模型。在这里，我们回顾了与早期帕金森病动物模型和能够诱导急性多巴胺损伤和/或耗竭的药理学治疗相关的文献，如利血平、氟哌啶醇和河豚毒素。我们强调了这些模型的优点、局限性和未来的应用前景，以及它们在鉴定治疗这种神经退行性疾病的新型药物中的应用。
