Smits Simone M, Ponnio Tiia, Conneely Orla M, Burbach J Peter H, Smidt Marten P
Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Eur J Neurosci. 2003 Oct;18(7):1731-8. doi: 10.1046/j.1460-9568.2003.02885.x.
The mesencephalic dopaminergic (mesDA) system is involved in many brain functions including motor control and motivated behaviour, and is of clinical importance because of its implication in psychiatric disorders and Parkinson's disease. Nurr1, a member of the nuclear hormone receptor superfamily of transcription factors, is essential for establishing the dopaminergic phenotype, because expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, requires Nurr1. In addition, Nurr1 plays an important role in the maintenance of mesDA neurons. Neonatal Nurr1 knockout mice lack expression of the dopamine transporter (DAT), the vesicular monoamine transporter 2 (VMAT2) and l-aromatic amino acid decarboxylase (AADC) in addition to TH specifically in mesDA neurons. It is unclear whether the lack of expression of these dopaminergic markers is caused by a maintenance defect or whether the induction of these markers depends on Nurr1 expression. To address this problem, the expression of DAT, VMAT2 and AADC was analysed at embryonic day 12.5 and 14.5. Here we demonstrate that induction of VMAT2 and DAT specifically in mesDA neurons requires Nurr1 expression, whereas AADC expression in mesDA neurons is induced independently of Nurr1 function.
中脑多巴胺能（mesDA）系统参与多种脑功能，包括运动控制和动机行为，并且因其与精神疾病和帕金森病有关而具有临床重要性。Nurr1是转录因子核激素受体超家族的成员，对于建立多巴胺能表型至关重要，因为多巴胺合成中的限速酶酪氨酸羟化酶（TH）的表达需要Nurr1。此外，Nurr1在mesDA神经元的维持中起重要作用。新生Nurr1基因敲除小鼠除了在mesDA神经元中特异性缺乏TH外，还缺乏多巴胺转运体（DAT）、囊泡单胺转运体2（VMAT2）和L-芳香族氨基酸脱羧酶（AADC）的表达。目前尚不清楚这些多巴胺能标志物表达的缺乏是由维持缺陷引起的，还是这些标志物的诱导依赖于Nurr1的表达。为了解决这个问题，在胚胎第12.5天和14.5天分析了DAT、VMAT2和AADC的表达。在这里，我们证明了在mesDA神经元中特异性诱导VMAT2和DAT需要Nurr1的表达，而mesDA神经元中AADC的表达是独立于Nurr1功能诱导的。
