Torres K C L, Souza B R, Miranda D M, Nicolato R, Neves F S, Barros A G A, Dutra W O, Gollob K J, Correa H, Romano-Silva M A
Laboratório de Neurociência, Departamento de Saúde Mental, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av Alfredo Balena, 190; Belo Horizonte-MG, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):214-9. doi: 10.1016/j.pnpbp.2008.10.020. Epub 2008 Nov 8.
Bipolar disorder (BPD) and schizophrenia (SCZ) are severe disorders representing an enormous social, familiar and individual burden, being SCZ the most disabling psychiatric disorder characterized by psychosis and cognitive impairment. It is well known that SCZ and BPD are associated with abnormalities in dopamine signaling pathway. Recent data in the literature have demonstrated altered expression levels of some proteins involved in the modulation of this pathway in both brain and peripheral tissues. It was shown that protein and mRNA levels of dopamine and cAMP regulated phosphoprotein (DARPP-32) were downregulated in dorsolateral prefrontal cortex (DLPFC) of patients with SCZ or BPD when compared to controls. Due to the difficulty to access brain tissue and the absence of objective laboratory tests for bio-markers, we measured DARPP-32 expression in blood cell sub-populations (CD4+ T lymphocytes, CD56+ NK cells, CD19+ B lymphocytes and CD14+ monocytes) taking advantage of the close relation of nervous and immune systems. Using flow cytometry as the analytical method, our results have shown that the DARPP-32 expression was diminished in CD4+ T lymphocytes, CD19+ B lymphocytes and CD14+ monocytes of BPD patients and was also decreased in CD4+ T lymphocytes and CD56+ NK cells of SCZ patients. These results showed that DARPP-32 expression in immune cells agrees with reports of reduced DARPP-32 protein in the DLPFC of BPD or SCZ patients. Our data suggest that DARPP-32 expression in PBMC could be used as a source of bio-markers to help in the treatment response of neuropsychiatry disorders as a window to the changes in the brain of those patients.
双相情感障碍（BPD）和精神分裂症（SCZ）是严重的疾病，给社会、家庭和个人带来了巨大负担，其中SCZ是最具致残性的精神疾病，其特征为精神病性症状和认知障碍。众所周知，SCZ和BPD与多巴胺信号通路异常有关。文献中的最新数据表明，参与该通路调节的一些蛋白质在大脑和外周组织中的表达水平发生了改变。研究表明，与对照组相比，SCZ或BPD患者背外侧前额叶皮质（DLPFC）中多巴胺和cAMP调节磷蛋白（DARPP - 32）的蛋白质和mRNA水平下调。由于获取脑组织困难且缺乏生物标志物的客观实验室检测方法，我们利用神经和免疫系统的密切关系，测量了血细胞亚群（CD4 + T淋巴细胞、CD56 + NK细胞、CD19 + B淋巴细胞和CD14 + 单核细胞）中DARPP - 32的表达。使用流式细胞术作为分析方法，我们的结果表明，BPD患者的CD4 + T淋巴细胞、CD19 + B淋巴细胞和CD14 + 单核细胞中DARPP - 32表达降低，SCZ患者的CD4 + T淋巴细胞和CD56 + NK细胞中DARPP - 32表达也降低。这些结果表明，免疫细胞中DARPP - 32的表达与BPD或SCZ患者DLPFC中DARPP - 32蛋白减少的报道一致。我们的数据表明，外周血单核细胞中DARPP - 32的表达可作为生物标志物的来源，有助于了解神经精神疾病的治疗反应，作为观察这些患者大脑变化的一个窗口。
