Cases O, Lebrand C, Giros B, Vitalis T, De Maeyer E, Caron M G, Price D J, Gaspar P, Seif I
Department of Physiology, Medical School, Teviot Place, Edinburgh EH8 9AG, Scotland.
J Neurosci. 1998 Sep 1;18(17):6914-27. doi: 10.1523/JNEUROSCI.18-17-06914.1998.
Genetic loss or pharmacological inhibition of monoamine oxidase A (MAOA) in mice leads to a large increase in whole-brain levels of serotonin (5-HT). Excess 5-HT in mouse neonates prevents the normal barrel-like clustering of thalamic axons in the somatosensory cortex. Projection fields of other neuron populations may develop abnormally. In the present study, we have analyzed the localization of 5-HT immunolabeling in the developing brain of MAOA knock-out mice. We show numerous atypical locations of 5-HT during embryonic and postnatal development. Catecholaminergic cells of the substantia nigra, ventral tegmental area, hypothalamus, and locus ceruleus display transient 5-HT immunoreactivity. Pharmacological treatments inhibiting specific monoamine plasma membrane transporters and genetic crosses with mice lacking the dopamine plasma membrane transporter show that the accumulation of 5-HT in these catecholaminergic cells is attributable to 5-HT uptake via the dopamine or the norepinephrine plasma membrane transporter. In the telencephalon, transient 5-HT immunolabeling is observed in neurons in the CA1 and CA3 fields of the hippocampus, the central amygdala, the indusium griseum, and the deep layers of the anterior cingulate and retrosplenial cortices. In the diencephalon, primary sensory nuclei, as well as the mediodorsal, centrolateral, oval paracentral, submedial, posterior, and lateral posterior thalamic nuclei, are transiently 5-HT immunolabeled. The cortical projections of these thalamic nuclei are also labeled. In the brainstem, neurons in the lateral superior olivary nucleus and the anteroventral cochlear nucleus are transiently 5-HT immunolabeled. None of these structures appear to express the monoamine biosynthetic enzyme L-aromatic amino acid decarboxylase. The administration of monoamine plasma membrane transporter inhibitors indicates that the 5-HT immunolabeling in these structures is attributable to an uptake of 5-HT by the 5-HT plasma membrane transporter. This points to neuron populations that form highly precise projection maps that could be affected by 5-HT during specific developmental stages.
小鼠体内单胺氧化酶A（MAOA）的基因缺失或药物抑制会导致全脑血清素（5-HT）水平大幅升高。小鼠新生儿体内过量的5-HT会阻止丘脑轴突在体感皮层中正常形成桶状聚集。其他神经元群体的投射场可能会异常发育。在本研究中，我们分析了MAOA基因敲除小鼠发育中的大脑中5-HT免疫标记的定位。我们发现，在胚胎期和出生后发育过程中，5-HT存在许多非典型定位。黑质、腹侧被盖区、下丘脑和蓝斑的儿茶酚胺能细胞显示出短暂的5-HT免疫反应性。抑制特定单胺质膜转运体的药物治疗以及与缺乏多巴胺质膜转运体的小鼠进行基因杂交实验表明，这些儿茶酚胺能细胞中5-HT的积累归因于通过多巴胺或去甲肾上腺素质膜转运体摄取5-HT。在端脑，海马CA1和CA3区、中央杏仁核、灰被、前扣带回和压后皮质深层的神经元中观察到短暂的5-HT免疫标记。在间脑，主要感觉核以及丘脑背内侧核、中央外侧核、椭圆形中央旁核、内侧下核、后核和丘脑后外侧核都有短暂的5-HT免疫标记。这些丘脑核的皮质投射也被标记。在脑干，外侧上橄榄核和前腹侧耳蜗核的神经元有短暂的5-HT免疫标记。这些结构似乎都不表达单胺生物合成酶L-芳香族氨基酸脱羧酶。单胺质膜转运体抑制剂的给药表明，这些结构中的5-HT免疫标记归因于5-HT质膜转运体对5-HT的摄取。这表明在特定发育阶段，形成高度精确投射图谱的神经元群体可能会受到5-HT的影响。
