Chemical neurobiology of ventral mesencephalon: mechanisms underlying neuronal death in Parkinsonism.

帕金森病是一种神经退行性疾病，对澳大利亚社区有深远的影响。它影响着大约1%的50岁以上的人和大约50,000名澳大利亚人。脑细胞会在许多年后死亡，最终大脑协调运动控制的部分会造成严重的损失，导致无法控制的运动发生。这种情况的原因尚不清楚，尽管药物可以在大约5年的时间内控制运动障碍，但最终会出现越来越多的残疾，最终完全依赖。这种情况对患者的家庭和澳大利亚的医疗保健系统都有深远的影响。显然，最重要的是了解脑细胞在这种衰弱的神经状况下是如何死亡的，因为一旦了解了这种死亡机制，就可以制定策略来保护处于危险之中的脑细胞，从而可以开发新的药物来防止疾病的发生和发展。由于对人脑的尸检研究表明，帕金森病的细胞是通过程序性细胞死亡的过程死亡的(即，未知的刺激通过涉及基因激活的确切机制向细胞发出死亡信息)，我们将研究这种独特的脑细胞死亡形式的参与，并试图确定是什么因素启动了这一过程。通过建立培养大鼠脑细胞的实验模型，我们计划测试多种因素如何启动死亡级联，以及可能的治疗方法如何预防。这些评估将通过测量细胞生化和电活动来进行。我们还希望研究如何拯救和刺激处于危险中的脑细胞生长，以重建正常的大脑回路。总体而言，该方案旨在了解疾病的过程，以便揭示其管理的新方向。

Parkinson's disease (PD) is a neurodegenerative disease which has profound effects on the Australian community. It affects about 1% of individuals aged more than 50 years and approximately 50,000 Australians. Brain cells die over many years and eventually the loss is so bad from the parts of the brain that coordinate motor control that uncontrollable motor movements occur. The cause of the condition is unknown and although drugs can control the motor disorders for some 5 years, eventually increasing disability occurs and finally complete dependency. The condition has profound effects on the families of the sufferers and the Australian health care system. Clearly, it is most important to understand how brain cells die in this debilitating neurological condition because once this death mechanism is understood then strategies can be devised to protect at risk brain cells so that new drugs can be developed to prevent the onset and progression of the disease. Since post-mortem studies on human brain suggest that cells in Parkinson's disease die by a process of programmed cell death (i.e. an unknown stimulus gives the cells a message to die by an exact mechanism involving gene activation), we shall examine the involvement of this unique form of brain cell death and attempt to determine what factors initiate the process. By establishing experimental models where rat brain cells are cultured, we plan to test how multiple factors could start the death cascade and how possible treatments may be preventitive. These assessments will be performed by measuring cellular biochemistry and electrical activity. We also hope to examine how at risk brain cells can be rescued and stimulated to grow to re-establish normal brain circuits. Overall, the programme aims to understand the disease process such that new directions for its management will be revealed.