Meador-Woodruff J H, Haroutunian V, Powchik P, Davidson M, Davis K L, Watson S J
Department of Psychiatry, University of Michigan, Ann Arbor, USA.
Arch Gen Psychiatry. 1997 Dec;54(12):1089-95. doi: 10.1001/archpsyc.1997.01830240045007.
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.
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.
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).
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.
多巴胺受体新亚型的鉴定重新引发了人们对多巴胺能机制参与精神分裂症的兴趣。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情况。
对16例精神分裂症患者和9例对照者的尸检脑样本中编码5种多巴胺受体的信使RNA分子水平进行了定量分析。取自前额叶皮质、初级视皮质和纹状体多个区域的样本进行原位杂交，随后进行定量图像分析。
精神分裂症患者与对照者在纹状体或视皮质中多巴胺受体转录本的表达没有差异。在前额叶皮质中发现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，且定位于布罗德曼第11区（眶额叶皮质）。
在精神分裂症中，皮质多巴胺能神经传递可能在受体表达水平受到破坏。前额叶皮质中D3和D4信使RNA表达似乎存在局灶性异常，两者均下调，这与精神分裂症中前额叶皮质多巴胺能功能减退一致。
