Neurobiology & Development (UPR3294), Institute of Neurobiology Alfred Fessard, Centre National de la Recherche Scientifique, 91198 CNRS Gif-sur-Yvette, France.
J Comp Neurol. 2011 Feb 15;519(3):576-98. doi: 10.1002/cne.22535.
Although the simultaneous presence of tyrosine hydroxylase (TH), aromatic amino acid decarboxylase (AADC), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) is considered as a phenotypic signature of dopamine (DA) neurons, it has been suggested that they are not uniformly expressed in all dopaminergic brain nuclei. Moreover, in nonmammalian vertebrates, two tyrosine hydroxylase genes (TH1 and TH2) are found, and they exhibit different expression patterns in zebrafish brains. Here we present a detailed description of the distribution of TH1, TH2, AADC, DAT, and VMAT2 transcripts, in relation to TH and DA immunoreactivity to better characterize dopaminergic nuclei in the adult zebrafish forebrain. TH2-positive cells in the hypothalamus are strongly DA immunoreactive (DAir), providing direct evidence that they are dopaminergic. DAir cells are also found in most TH1-positive or TH-immunoreactive (THir) nuclei. However, the DAir signal was weaker than THir in the olfactory bulb, telencephalon, ventral thalamus, pretectum, and some posterior tubercular and preoptic nuclei. These cell populations also exhibited low levels of VMAT2 transcripts, suggesting that low DA is due to a lower vesicular DA accumulation. In contrast, cell populations with low levels of AADC did not always have low levels of DA. DAT transcripts were abundantly expressed in most of the TH1- or TH2-positive territories. In addition, DAT and/or VMAT2 transcripts were found in some periventricular cell populations such as in the telencephalon without TH1 or TH2 expression. Thus, expression patterns of dopaminergic cell markers are not homogeneous, suggesting that the gene regulatory logic determining the dopaminergic phenotype is unexpectedly complex.
虽然同时存在酪氨酸羟化酶 (TH)、芳香族氨基酸脱羧酶 (AADC)、多巴胺转运体 (DAT) 和囊泡单胺转运体 2 (VMAT2) 被认为是多巴胺 (DA) 神经元的表型特征，但有人认为它们并非在所有多巴胺能脑核中均匀表达。此外，在非哺乳动物脊椎动物中，发现了两种酪氨酸羟化酶基因 (TH1 和 TH2)，它们在斑马鱼大脑中表现出不同的表达模式。在这里，我们详细描述了 TH1、TH2、AADC、DAT 和 VMAT2 转录本的分布情况，以及与 TH 和 DA 免疫反应性的关系，以便更好地描述成年斑马鱼前脑的多巴胺能核。下丘脑的 TH2 阳性细胞强烈表达 DA（DAir），这提供了它们是多巴胺能细胞的直接证据。DAir 细胞也存在于大多数 TH1 阳性或 TH 免疫阳性（THir）核中。然而，在嗅球、端脑、腹侧丘脑、顶盖和一些后结节和视前核中，DAir 信号比 THir 弱。这些细胞群也表现出低水平的 VMAT2 转录本，表明低 DA 是由于囊泡 DA 积累较低。相比之下，AADC 水平低的细胞群并不总是 DA 水平低。DAT 转录本在大多数 TH1 或 TH2 阳性区域中大量表达。此外，在一些脑室周围细胞群中发现了 DAT 和/或 VMAT2 转录本，例如在没有 TH1 或 TH2 表达的端脑中。因此，多巴胺能细胞标志物的表达模式并不均匀，这表明决定多巴胺能表型的基因调控逻辑出乎意料地复杂。
