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

帕金森S病通常与多巴胺细胞的丧失有关，多巴胺细胞将神经从黑质输送到纹状体。然而，我们在10例帕金森S病患者的死后纹状体组织中发现了大量明显新的多巴胺能细胞，而在5例年龄匹配的对照组中未发现。我们的目标是首先通过建立它们的神经化学和形态特征来确定这些细胞是否真的是多巴胺能神经元。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以及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活动还是将其影响扩展到大脑的更大区域非常重要。其次，我们将评估它们在人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S病的损害严重程度有关，或者大多数患者接受的L-多巴疗法是否对他们的外表起到了作用。这些实验将为我们确定这些细胞是有益的还是有害的奠定基础。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，但具有新的功能，或者它们是否实际上是最近诞生的新细胞。如果我们想要改变他们的数量以改善对帕金森S病的治疗，这些知识是必不可少的。我们估计在帕金森S病患者的每个纹状体中有多达66,000个这样的多巴胺能细胞。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，让大脑在更长时间内保持基本功能，也可能是有害的，无论是在帕金森S病本身的发生中发挥作用，还是在L多巴疗法的有害副作用中发挥作用。

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.