Gaspar P, Berger B, Febvret A, Vigny A, Henry J P
Inserm U106, Hôpital Salpêtriere, Paris, France.
J Comp Neurol. 1989 Jan 8;279(2):249-71. doi: 10.1002/cne.902790208.
The organization of the cortical monoamine systems, dopamine (DA), and noradrenaline (NA), which have been studied extensively in the rat and more recently in the monkey, had not yet been investigated directly in the human brain. We report here the first systematic account of the regional and laminar distributions of the catecholamine fibers in the human cerebral cortex, using immunohistochemistry of the catecholamine biosynthetic enzymes, tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH) in 13 cytoarchitectonic areas (4, 6, 9, 3b, 5, 40, 17, 18, 23, 24, 29, insula, and hippocampus) sampled postmortem. The noradrenergic (NA) innervation, mapped with DBH-immunoreactivity (DBH-IR), displayed a characteristic density gradient in the neocortex (highest in the primary sensorimotor areas, decreasing rostrally and caudally) that contrasted with the more uniform density in the limbic cortices (24, 23, 29, insula, hippocampus). NA axons were present in all cortical layers and were least numerous in layer I. The DBH-IR fibers were only partly TH-immunostained (10-50%, on double-labeled sections), suggesting a heterogeneity of the cortical NA axons. The putative dopaminergic (DA) fibers were identified by comparing alternate or double-immunolabeled (DBH-TH) sections, as the TH-IR fibers which contain no DBH-IR. A DA-like innervation was present in all cortical areas, with major regional differences in density and laminar distribution, which closely paralleled cytoarchitectural buildups: 1) the DA-like innervation was densest in the agranular areas, primary and secondary motor areas, anterior cingulate, and insula; it distributed throughout layers I-VI; 2) density was lower in the granular cortices, areas 9 (prefrontal cortex), 23, 3b, 5, 40, and 18, displaying a bilaminar pattern in layers I and V-VI. In all areas, DA-like fibers were most abundant in the molecular layer, with a predominant distribution in its deepest part. Convoluted and coily fibers represented a unique morphologic aspect of the CA innervation in the human cortex. These findings are in agreement with findings in nonhuman primates and demonstrate major evolutionary changes in the organization of the cortical aminergic input as compared with rodents. The most striking features are the expansion of the DA innervation to the whole cortex and the peak of highest density in the motor areas. The regional differentiation of NA innervation is also accentuated. Slight differences were found in the laminar distributions of the amines in humans and primates. These data seem quite promising and open new research fields in neurologic and psychiatric diseases.
在大鼠以及最近在猴子身上得到广泛研究的皮质单胺系统，即多巴胺（DA）和去甲肾上腺素（NA）系统，尚未在人类大脑中进行直接研究。我们在此报告，利用13个细胞构筑学区域（4区、6区、9区、3b区、5区、40区、17区、18区、23区、24区、29区、脑岛和海马体）的死后样本，通过对儿茶酚胺生物合成酶酪氨酸羟化酶（TH）和多巴胺-β-羟化酶（DBH）进行免疫组织化学，首次系统阐述了儿茶酚胺纤维在人类大脑皮质中的区域和分层分布情况。用DBH免疫反应性（DBH-IR）标记的去甲肾上腺素能（NA）神经支配在新皮质中呈现出特征性的密度梯度（在主要感觉运动区最高，向头端和尾端递减），这与边缘皮质（24区、23区、29区、脑岛、海马体）中较为均匀的密度形成对比。NA轴突存在于所有皮质层，在第I层数量最少。DBH-IR纤维仅有部分被TH免疫染色（在双标记切片上为10%-50%），表明皮质NA轴突具有异质性。通过比较交替或双免疫标记（DBH-TH）切片，将不含DBH-IR的TH-IR纤维鉴定为假定的多巴胺能（DA）纤维。所有皮质区域均存在类似DA的神经支配，在密度和分层分布上存在主要的区域差异，这与细胞构筑结构密切平行：1）类似DA的神经支配在无颗粒区、主要和次要运动区、前扣带回和脑岛最密集；它分布于I-VI层；2）在颗粒皮质，即9区（前额叶皮质）、23区、3b区、5区、40区和18区，密度较低，在I层以及V-VI层呈现双分层模式。在所有区域，类似DA的纤维在分子层最为丰富，主要分布在其最深部。盘绕和卷曲的纤维代表了人类皮质中儿茶酚胺能神经支配独特的形态学特征。这些发现与非人灵长类动物的研究结果一致，并表明与啮齿动物相比，皮质胺能输入组织发生了重大的进化变化。最显著的特征是DA神经支配扩展至整个皮质，且在运动区密度最高。NA神经支配的区域分化也更为明显。在人类和灵长类动物中，胺类的分层分布存在细微差异。这些数据似乎很有前景，并为神经和精神疾病开辟了新的研究领域。
