New dopaminergic neurons in the Parkinson's disease striatum: Establishment of phenotype, function and origin.

帕金森氏症通常与将神经从黑质传递到纹状体的多巴胺细胞的丧失有关。然而，我们在10名帕金森病患者的纹状体死后组织中发现了大量明显新的多巴胺能细胞，但在5名年龄匹配的对照中却没有发现。我们的目的首先是通过建立这些细胞的神经化学和形态特征来确定它们是否确实是多巴胺能神经元。这是确定这些明显的多巴胺能细胞是否确实产生神经递质多巴胺和确定它们属于哪一类神经元所必需的。后者对于确定它们是在纹状体局部起作用还是将其影响扩展到大脑的更大区域很重要。其次，我们将评估它们在人类和大鼠组织中的功能。我们将确定它们的数量是否与帕金森病损伤的严重程度有关，或者大多数患者接受的左旋多巴治疗是否对它们的外观起作用。这些实验将为我们确定这些细胞是有益还是有害打下基础。最后，我们将确定这些细胞来自哪里。我们将确定它们是否一直存在，只是承担了一种新的功能，还是它们实际上是最近诞生的新细胞。如果我们要改变它们的数量来改善帕金森病的治疗，这些知识是必不可少的。我们估计帕金森病患者的每个纹状体中有多达66,000个这种多巴胺能细胞。这足以对疾病的表现产生重大影响。这些细胞可能是有益的，可以让大脑维持更长时间的基本功能，也可能是有害的，在帕金森病本身的发展中起作用，或者在左旋多巴治疗的有害副作用中起作用。

Parkinson s disease is usually associated with loss of dopamine cells that send nerves from the substantia nigra to the striatum. However, we have found large numbers of apparently new dopaminergic cells in post mortem tissue from the striatum of 10 patients with Parkinson s disease but not in 5 age-matched controls. Our aims are firstly to determine whether these cells are indeed dopaminergic neurons by establishing their neurochemical and morphological profiles. This is required to determine whether these apparently dopaminergic cells do indeed produce the neurotransmitter dopamine and to determine to what class of neuron they belong. The latter is important to establish whether they act locally in the striatum or extend their influence over a larger area of the brain. Secondly we shall assess their function in human and rat tissue. We shall determine whether their number is related to the severity of damage in Parkinson s disease, or whether L-DOPA therapy, which most patients receive, plays any role in their appearance. These experiments will lay the ground work to allow us to determine whether these cells are beneficial or harmful. Lastly, we shall determine where these cells come from. We shall determine whether they have always been present but have taken on a new function, or whether they are in fact new cells which have been born recently. This knowledge is essential if we are to be able to change their numbers to improve treatment of Parkinson s disease. We estimate that there are up to 66,000 of these dopaminergic cells in each striatum of patients with Parkinson s disease. This is enough to have a significant impact on the manifestation of the disease. These cells might be beneficial, allowing the brain to maintain essential functions for longer or they might be harmful playing a role in either development of Parkinson s disease itself or the harmful side effects of L-DOPA therapy.