Unitat de Recerca, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Dr. Antoni Pujadas, 42, 08830 Sant Boi de Llobregat, Barcelona, Spain.
J Psychiatr Res. 2013 Jul;47(7):926-34. doi: 10.1016/j.jpsychires.2013.03.004. Epub 2013 Mar 27.
Negative symptoms are the most resilient manifestations in schizophrenia. An imbalance in dopamine and glutamate pathways has been proposed for the emergence of these symptoms. SP1, SP3 and SP4 transcription factors regulate genes in these pathways, suggesting a possible involvement in negative symptoms. In this study, we characterized Sp factors in the brains of subjects with schizophrenia and explored a possible association with negative symptoms. We also included analysis of NR1, NR2A and DRD2 as Sp target genes. Postmortem cerebellum and prefrontal cortex from an antemortem clinically well-characterized and controlled collection of elderly subjects with chronic schizophrenia (n = 16) and control individuals (n = 14) were examined. We used the Positive and Negative Syndrome and the Clinical Global Impression Schizophrenia scales, quantitative PCR and immunoblot. SP1 protein and mRNA were reduced in the prefrontal cortex in schizophrenia whereas none of Sp factors were altered in the cerebellum. However, we found that SP1, SP3 and SP4 protein levels inversely correlated with negative symptoms in the cerebellum. Furthermore, NR2A and DRD2 mRNA levels correlated with negative symptoms in the cerebellum. In the prefrontal cortex, SP1 mRNA and NR1 and DRD2 inversely correlated with these symptoms while Sp protein levels did not. This pilot study not only reinforces the involvement of SP1 in schizophrenia, but also suggests that reduced levels or function of SP1, SP4 and SP3 may participate in negative symptoms, in part through the regulation of NMDA receptor subunits and/or Dopamine D2 receptor, providing novel information about the complex negative symptoms in this disorder.
阴性症状是精神分裂症中最顽固的表现。多巴胺和谷氨酸途径的不平衡被认为是这些症状出现的原因。SP1、SP3 和 SP4 转录因子调节这些途径中的基因，表明它们可能与阴性症状有关。在这项研究中，我们对精神分裂症患者大脑中的 Sp 因子进行了特征描述，并探索了它们与阴性症状之间可能存在的关联。我们还包括了对 Sp 靶基因 NR1、NR2A 和 DRD2 的分析。我们检查了来自老年慢性精神分裂症患者（n=16）和对照个体（n=14）的、经生前临床充分特征描述和控制的、死后小脑和前额叶皮质组织。我们使用阳性和阴性综合征量表和临床总体印象-精神分裂症量表、定量 PCR 和免疫印迹法进行分析。SP1 蛋白和 mRNA 在精神分裂症患者的前额叶皮质中减少，而小脑中没有 Sp 因子发生改变。然而，我们发现 SP1、SP3 和 SP4 蛋白水平与小脑中的阴性症状呈负相关。此外，NR2A 和 DRD2 mRNA 水平与小脑中的阴性症状相关。在前额叶皮质中，SP1 mRNA 和 NR1 和 DRD2 与这些症状呈负相关，而 Sp 蛋白水平则没有。这项初步研究不仅加强了 SP1 在精神分裂症中的作用，还表明 SP1、SP4 和 SP3 的水平降低或功能降低可能通过调节 NMDA 受体亚基和/或多巴胺 D2 受体参与阴性症状，为该疾病复杂的阴性症状提供了新的信息。
