Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects
Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects
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DOI：
10.1176/ajp.156.10.1580
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发表时间：
1999-10-01
影响因子：
17.7
通讯作者：
Lewis, DA
中科院分区：
文献类型：
--
作者：
Akil, M;Pierri, JN;Lewis, DA
目的：前额叶皮层多巴胺神经传递障碍与精神分裂症的病理生理有关。然而，在这种疾病中，多巴胺投射到前额皮质的完整性还没有被直接检查。方法：作者采用免疫细胞化学方法和酪氨酸羟化酶，多巴胺生物合成的限速酶，和多巴胺膜转运蛋白的抗体，检查多巴胺轴突的背内侧前额叶皮层（9区）从16对精神分裂症和匹配的对照组。结果如下：与对照组相比，酪氨酸羟化酶免疫反应阳性轴突的总长度在精神分裂症患者的浅层和中层中没有变化，但在第6层中平均减少了33.6%。第6层酪氨酸羟化酶阳性轴突的总长度在13例精神分裂症患者中与对照组相比有所减少。轴突的多巴胺膜转运蛋白的免疫反应表现出类似的变化模式。与此相反，标记为5-羟色胺转运体的轴突在精神分裂症患者和对照组之间的任何层检查没有差异。此外，含酪氨酸羟化酶轴突的密度在长期接受氟哌啶醇治疗的猴子和匹配的对照动物之间没有差异。结论：这些研究结果表明，精神分裂症是与改变多巴胺神经支配的前额叶皮层区9是板层和神经递质特异性的，似乎不是一个结果的药物治疗。总之，这些数据为精神分裂症患者前额叶皮层多巴胺神经传递障碍提供了直接证据。
Objective: Abnormalities in dopamine neurotransmission in the prefrontal cortex have been implicated in the pathophysiology of schizophrenia. However, the integrity of the dopamine projections to the prefrontal cortex in this disorder has not been directly examined. Method: The authors employed immunocytochemical methods and antibodies against tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis, and the dopamine membrane transporter to examine dopamine axons in the dorsomedial prefrontal cortex (area 9) from 16 pairs of schizophrenic and matched control subjects. Results: Compared to the control subjects, the total length of tyrosine hydroxylase-immunoreactive axons was unchanged in the superficial and middle layers of the schizophrenic subjects but was reduced by an average of 33.6% in layer 6. The total length of tyrosine hydroxylase-positive axons in layer 6 was decreased in 13 of the schizophrenic subjects compared to their control subjects. Axons immunoreactive for the dopamine membrane transporter showed a similar pattern of change. In contrast, axons labeled for the serotonin transporter did not differ between schizophrenic and control subjects in any layer examined. In addition, the density of tyrosine hydroxylase-containing axons did not differ between monkeys chronically treated with haloperidol and matched control animals. Conclusions: These findings reveal that schizophrenia is associated with an altered dopamine innervation of prefrontal cortex area 9 that is lamina- and neurotransmitter-specific and that does not appear to be a consequence of pharmacological treatment. Together, these data provide direct evidence for a disturbance in dopamine neurotransmission in the prefrontal cortex of schizophrenic subjects.