Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia.
Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia.
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DOI：
10.1001/archpsyc.1997.01830240045007
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发表时间：
1997-12
影响因子：
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通讯作者：
J. Meador-Woodruff;V. Haroutunian;P. Powchik;M. Davidson;Kenneth L. Davis;Stanley J. Watson
中科院分区：
文献类型：
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作者：
J. Meador-Woodruff;V. Haroutunian;P. Powchik;M. Davidson;Kenneth L. Davis;Stanley J. Watson
背景多巴胺受体新亚型的发现重新引起了人们对精神分裂症中多巴胺能机制的兴趣。我们测定了精神分裂症患者大脑中编码多巴胺受体的转录本的表达。方法对16例精神分裂症患者和9例正常对照脑组织中编码5种多巴胺受体的信使RNA分子进行定量检测。对来自前额叶皮质、初级视觉皮质和纹状体多个区域的样本进行了原位杂交，然后进行了定量图像分析。结果精神分裂症患者与对照组纹状体和视皮层多巴胺受体转录本的表达差异无统计学意义。在前额叶皮质，多巴胺受体转录本显著减少，但这些变化仅限于D3和D4受体，并局限于Brodmann区11(眶前皮质)。结论精神分裂症患者皮质多巴胺能神经传递可能从受体表达水平受到干扰。前额叶皮质D3和D4信使RNA表达出现局灶性异常，两者表达下调，与精神分裂症前额叶皮质低多巴胺反应一致。
BACKGROUND The identification of novel subtypes of the dopamine receptors has renewed interest in the involvement of dopaminergic mechanisms in schizophrenia. We determined the expression of transcripts encoding the dopamine receptors in the brains of schizophrenic patients. METHODS The levels of the messenger RNA molecules encoding the 5 dopamine receptors were quantified in postmortem brain samples from 16 schizophrenic patients and 9 control subjects. Samples from multiple regions of the prefrontal cortex, primary visual cortex, and striatum were subjected to in situ hybridization followed by quantitative image analysis. RESULTS Expression of dopamine receptor transcripts did not differ between schizophrenic patients and controls in striatum or visual cortex. Dramatic decreases of dopamine receptor transcripts were found in the prefrontal cortex, but these changes were restricted to the D3 and D4 receptors, and localized to Brodmann area 11 (orbitofrontal cortex). CONCLUSIONS Cortical dopaminergic neurotransmission may be disrupted in schizophrenia at the level of receptor expression. There appears to be a focal abnormality of D3 and D4 messenger RNA expression in the prefrontal cortex, with down-regulation of both, consistent with prefrontal cortical hypodopaminergia in schizophrenia.