Granulocyte-Colony-Stimulating Factor Alters the Proteomic Landscape of the Ventral Tegmental Area.
Granulocyte-Colony-Stimulating Factor Alters the Proteomic Landscape of the Ventral Tegmental Area.
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DOI：
10.3390/proteomes6040035
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发表时间：
2018-09-23
期刊：
影响因子：
3.3
通讯作者：
Kiraly DD
中科院分区：
文献类型：
--
作者：
Mervosh NL;Wilson R;Rauniyar N;Hofford RS;Kutlu MG;Calipari ES;Lam TT;Kiraly DD
可卡因成瘾的特征是中脑边缘多巴胺回路的异常可塑性，导致寻求和服用药物的动机失调。尽管可卡因使用障碍给社会造成了重大损失，但目前没有可用的药物治疗。我们最近已经确定了粒细胞集落刺激因子（G-CSF）作为一种可溶性细胞因子，改变可卡因的行为反应，并增加多巴胺从腹侧被盖区（VTA）的释放。尽管这些已知的行为和神经生理学的影响，G-CSF影响脑功能的分子机制尚不清楚。在这项研究中，小鼠反复注射G-CSF，可卡因或组合治疗，并使用无偏倚的蛋白质组学方法检查VTA中蛋白质表达的变化。反复G-CSF处理导致与突触可塑性和神经元形态相关的多种信号通路的改变。虽然治疗组的作用有明显的重叠，但注射可卡因和可卡因与G-CSF的组合导致显著调节的蛋白质的不同模式。这些实验提供了有价值的信息的分子途径，G-CSF激活在一个重要的边缘脑区，并将有助于指导G-CSF功能的进一步表征和评估作为一个可能的翻译目标。
Cocaine addiction is characterized by aberrant plasticity of the mesolimbic dopamine circuit, leading to dysregulation of motivation to seek and take drug. Despite the significant toll that cocaine use disorder exacts on society, there are currently no available pharmacotherapies. We have recently identified granulocyte-colony stimulating factor (G-CSF) as a soluble cytokine that alters the behavioral response to cocaine and which increases dopamine release from the ventral tegmental area (VTA). Despite these known effects on behavior and neurophysiology, the molecular mechanisms by which G-CSF affects brain function are unclear. In this study mice were treated with repeated injections of G-CSF, cocaine or a combination and changes in protein expression in the VTA were examined using an unbiased proteomics approach. Repeated G-CSF treatment resulted in alterations in multiple signaling pathways related to synaptic plasticity and neuronal morphology. While the treatment groups had marked overlap in their effect, injections of cocaine and the combination of cocaine and G-CSF lead to distinct patterns of significantly regulated proteins. These experiments provide valuable information as to the molecular pathways that G-CSF activates in an important limbic brain region and will help to guide further characterization of G-CSF function and evaluation as a possible translational target.