首发精神病患者外周血单个核细胞中转录因子特异性蛋白4的磷酸化水平升高。
Phosphorylation of transcription factor specificity protein 4 is increased in peripheral blood mononuclear cells of first-episode psychosis.
作者信息
Pinacho Raquel, Saia Gregory, Fusté Montserrat, Meléndez-Pérez Iria, Villalta-Gil Victoria, Haro Josep Maria, Gill Grace, Ramos Belén
机构信息
Unitat de recerca, Fundació Sant Joan de Déu, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America; Cell, Molecular and Developmental Biology Program, Sackler School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
出版信息
PLoS One. 2015 Apr 27;10(4):e0125115. doi: 10.1371/journal.pone.0125115. eCollection 2015.
BACKGROUND
Altered expression of transcription factor specificity protein 4 (SP4) has been found in the postmortem brain of patients with psychiatric disorders including schizophrenia and bipolar disorder. Reduced levels of SP4 protein have recently been reported in peripheral blood mononuclear cells in first-episode psychosis. Also, SP4 levels are modulated by lithium treatment in cultured neurons. Phosphorylation of SP4 at S770 is increased in the cerebellum of bipolar disorder subjects and upon inhibition of NMDA receptor signaling in cultured neurons. The aim of this study was to investigate whether SP4 S770 phosphorylation is increased in lymphocytes of first-episode psychosis patients and the effect of lithium treatment on this phosphorylation.
METHODS
A cross-sectional study of S770 phosphorylation relative to total SP4 immunoreactivity using specific antibodies in peripheral blood mononuclear cells in first-episode psychosis patients (n = 14, treated with lithium or not) and matched healthy controls (n = 14) by immunoblot was designed. We also determined the effects of the prescribed drugs lithium, olanzapine or valproic acid on SP4 phosphorylation in rat primary cultured cerebellar granule neurons.
RESULTS
We found that SP4 S770 phosphorylation was significantly increased in lymphocytes in first-episode psychosis compared to controls and decreased in patients treated with lithium compared to patients who did not receive lithium. Moreover, incubation with lithium but not olanzapine or valproic acid reduced SP4 phosphorylation in rat cultured cerebellar granule neurons.
CONCLUSIONS
The findings presented here indicate that SP4 S770 phosphorylation is increased in lymphocytes in first-episode psychosis which may be reduced by lithium treatment in patients. Moreover, our study shows lithium treatment prevents this phosphorylation in vitro in neurons. This pilot study suggests that S770 SP4 phosphorylation could be a peripheral biomarker of psychosis, and may be regulated by lithium treatment in first-episode psychosis.
背景
在包括精神分裂症和双相情感障碍在内的精神疾病患者的尸检大脑中，已发现转录因子特异性蛋白4（SP4）的表达发生改变。最近有报道称，首发精神病患者外周血单核细胞中SP4蛋白水平降低。此外，在培养的神经元中，锂治疗可调节SP4水平。双相情感障碍患者小脑以及培养的神经元中NMDA受体信号受到抑制时，SP4在S770位点的磷酸化增加。本研究的目的是调查首发精神病患者淋巴细胞中SP4 S770磷酸化是否增加，以及锂治疗对这种磷酸化的影响。
方法
设计了一项横断面研究，通过免疫印迹法，使用特异性抗体检测首发精神病患者（n = 14，接受或未接受锂治疗）和匹配的健康对照者（n = 14）外周血单核细胞中相对于总SP4免疫反应性的S770磷酸化情况。我们还确定了处方药物锂、奥氮平或丙戊酸对大鼠原代培养小脑颗粒神经元中SP4磷酸化的影响。
结果
我们发现，与对照组相比，首发精神病患者淋巴细胞中SP4 S770磷酸化显著增加，与未接受锂治疗的患者相比，接受锂治疗的患者该磷酸化水平降低。此外，用锂孵育可降低大鼠培养小脑颗粒神经元中SP4的磷酸化，而用奥氮平或丙戊酸孵育则无此作用。
结论
本研究结果表明，首发精神病患者淋巴细胞中SP4 S770磷酸化增加，锂治疗可能会降低这种磷酸化。此外，我们的研究表明锂治疗在体外可防止神经元中的这种磷酸化。这项初步研究表明，S770 SP4磷酸化可能是精神病的外周生物标志物，且在首发精神病中可能受锂治疗的调节。
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