Mapping dopaminergic deficiencies in the substantia nigra/ventral tegmental area in schizophrenia.
Mapping dopaminergic deficiencies in the substantia nigra/ventral tegmental area in schizophrenia.
复制标题
绘制精神分裂症黑质/腹侧被盖区的多巴胺能缺陷。
DOI：
10.1007/s00429-014-0901-y
复制
发表时间：
2016
影响因子：
3.1
通讯作者：
Perez-Costas,Emma
中科院分区：
文献类型：
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作者：
Rice,MatthewW;Roberts,RosalindaC;Melendez-Ferro,Miguel;Perez-Costas,Emma
我们实验室以前的工作表明，精神分裂症患者黑质/腹侧被盖区（SN/VTA）内酪氨酸羟化酶蛋白表达不足。然而，我们对SN/VTA内这些缺陷的性质和具体位置知之甚少。本研究有两个目的：（1）测试酪氨酸羟化酶缺陷是否可以解释为神经元损失的结果;（2）评估酪氨酸羟化酶缺陷是否在SN/VTA内具有亚区域特异性，因此可能影响特定的多巴胺能通路。为实现这些目标：（1）我们获得了匹配的SN/VTA精神分裂症和对照样本中多巴胺能神经元数量、神经元总数及其比例的估计值;（2）我们对SN/VTA精神分裂症和对照匹配样本进行了定性评估，同时进行了酪氨酸羟化酶免疫组织化学处理。我们没有发现任何显着差异的神经元总数，多巴胺能神经元，或它们的比例。我们的TH表达的定性研究表明，在SN/VTA内的神经元过程和细胞体的标记显着减少，这是亚区域特异性的。SN/VTA的背侧间脑多巴胺能神经元TH标记下降最明显。这些数据支持存在特定于途径的多巴胺能缺陷，这会影响皮质的多巴胺输入，而不会出现显着的神经元损失。有趣的是，这些研究结果支持早期报告的减少酪氨酸羟化酶标记的目标领域，这种多巴胺能输入在前额叶和内嗅皮层。最后，我们的研究结果支持酪氨酸羟化酶缺陷可能导致精神分裂症皮质区观察到的多巴胺能低下状态。
Previous work from our laboratory showed deficits in tyrosine hydroxylase protein expression within the substantia nigra/ventral tegmental area (SN/VTA) in schizophrenia. However, little is known about the nature and specific location of these deficits within the SN/VTA. The present study had two aims: (1) test if tyrosine hydroxylase deficits could be explained as the result of neuronal loss; (2) assess if deficits in tyrosine hydroxylase are sub-region specific within the SN/VTA, and thus, could affect specific dopaminergic pathways. To achieve these objectives: (1) we obtained estimates of the number of dopaminergic neurons, total number of neurons, and their ratio in matched SN/VTA schizophrenia and control samples; (2) we performed a qualitative assessment in SN/VTA schizophrenia and control matched samples that were processed simultaneously for tyrosine hydroxylase immunohistochemistry. We did not find any significant differences in the total number of neurons, dopaminergic neurons, or their ratio. Our qualitative study of TH expression showed a conspicuous decrease in labeling of neuronal processes and cell bodies within the SN/VTA, which was sub-region specific. Dorsal diencephalic dopaminergic populations of the SN/VTA presented the most conspicuous decrease in TH labeling. These data support the existence of pathway-specific dopaminergic deficits that would affect the dopamine input to the cortex without significant neuronal loss. Interestingly, these findings support earlier reports of decreases in tyrosine hydroxylase labeling in the target areas for this dopaminergic input in the prefrontal and entorhinal cortex. Finally, our findings support that tyrosine hydroxylase deficits could contribute to the hypodopaminergic state observed in cortical areas in schizophrenia.