Institute of Developmental Biology RAS, Institute of Normal Physiology RAMS, Moscow, Russia.
J Chem Neuroanat. 2009 Dec;38(4):241-56. doi: 10.1016/j.jchemneu.2009.08.004. Epub 2009 Aug 19.
Besides the dopaminergic (DA-ergic) neurons possessing the whole set of enzymes of DA synthesis from l-tyrosine and the DA membrane transporter (DAT), the neurons partly expressing the DA-ergic phenotype have been first discovered two decades ago. Most of the neurons express individual enzymes of DA synthesis, tyrosine hydroxylase (TH) or aromatic l-amino acid decarboxylase (AADC) and lack the DAT. A list of the neurons partly expressing the DA-ergic phenotype is not restricted to so-called monoenzymatic neurons, e.g. it includes some neurons co-expressing both enzymes of DA synthesis but lacking the DAT. In contrast to true DA-ergic neurons, monoenzymatic neurons and bienzymatic non-dopaminergic neurons lack the vesicular monoamine transporter 2 (VMAT2) that raises a question about the mechanisms of storing and release of their final synthetic products. Monoenzymatic neurons are widely distributed all through the brain in adulthood being in some brain regions even more numerous than DA-ergic neurons. Individual enzymes of DA synthesis are expressed in these neurons continuously or transiently in norm or under certain physiological conditions. Monoenzymatic neurons, particularly those expressing TH, appear to be even more numerous and more widely distributed in the brain during ontogenesis than in adulthood. Most populations of monoenzymatic TH neurons decrease in number or even disappear by puberty. Functional significance of monoenzymatic neurons remained uncertain for a long time after their discovery. Nevertheless, it has been shown that most monoenzymatic TH neurons and AADC neurons are capable to produce l-3,4-dihydroxyphenylalanine (L-DOPA) from l-tyrosine and DA from L-DOPA, respectively. L-DOPA produced in monoenzymatic TH neurons is assumed to play a role of a neurotransmitter or neuromodulator acting on target neurons via catecholamine receptors. Moreover, according to our hypothesis L-DOPA released from monoenzymatic TH neurons is captured by monoenzymatic AADC neurons for DA synthesis. Such cooperative synthesis of DA is considered as a compensatory reaction under a failure of DA-ergic neurons, e.g. in neurodegenerative diseases like hyperprolactinemia and Parkinson's disease.Thus, a substantial number of the brain neurons express partly the DA-ergic phenotype, mostly individual complementary enzymes of DA synthesis, serving to produce DA in cooperation that is supposed to be a compensatory reaction under the failure of DA-ergic neurons.
除了多巴胺能（DA-ergic）神经元拥有从 l-酪氨酸合成 DA 的全套酶和 DA 膜转运体（DAT）之外，大约二十年前首次发现了部分表达 DA-ergic 表型的神经元。大多数神经元表达 DA 合成的单个酶，如酪氨酸羟化酶（TH）或芳香族 l-氨基酸脱羧酶（AADC），而缺乏 DAT。部分表达 DA-ergic 表型的神经元列表不仅限于所谓的单酶神经元，例如，它包括一些同时表达两种 DA 合成酶但缺乏 DAT 的神经元。与真正的 DA-ergic 神经元相比，单酶神经元和双酶非多巴胺能神经元缺乏囊泡单胺转运体 2（VMAT2），这引发了关于其最终合成产物储存和释放机制的问题。单酶神经元广泛分布于整个大脑中，在某些脑区甚至比 DA-ergic 神经元更为丰富。在正常情况下或在某些生理条件下，这些神经元中持续或短暂地表达 DA 合成的单个酶。在个体发生过程中，这些神经元中表达 DA 合成的单个酶，特别是表达 TH 的神经元，比成年期更为丰富和广泛分布。大多数单酶 TH 神经元的数量在青春期减少甚至消失。在其发现后的很长一段时间内，单酶神经元的功能意义仍不确定。然而，已经表明大多数单酶 TH 神经元和 AADC 神经元分别能够从 l-酪氨酸和 L-DOPA 中产生 l-3,4-二羟基苯丙氨酸（L-DOPA）和 DA。单酶 TH 神经元产生的 L-DOPA 被认为是一种神经递质或神经调质，通过儿茶酚胺受体作用于靶神经元。此外，根据我们的假设，单酶 TH 神经元释放的 L-DOPA 被单酶 AADC 神经元捕获用于 DA 合成。这种 DA 的协同合成被认为是 DA-ergic 神经元衰竭时的代偿反应，例如在高泌乳素血症和帕金森病等神经退行性疾病中。因此，大量的脑神经元部分表达 DA-ergic 表型，主要是互补的 DA 合成单个酶，用于合作产生 DA，这被认为是 DA-ergic 神经元衰竭时的代偿反应。
