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PNAS:一种由多巴胺触发的用于控制血压的植入物

来源:Eurekalert 2013-10-16 11:28

科研人员制造出了一个基于人类细胞的植入物,当它被注入高血压小鼠体内的时候,它接触在性唤起期释放的多巴胺的情况下产生了一种降低血压的化合物,因此也就把这种动物的血压降低到了正常范围。这种神经递质多巴胺在大脑中自然释放,对诸如食物、毒品和性等愉悦的刺激做出应答,并且通过外周神经泄露到血液中。Martin Fussenegger及其同事对一个人类细胞系进行了重新编程,从而在接触多巴胺的时候制造出一种容易识别的蛋白质,称为SEAP。在描述了这些细胞在体外对多巴胺做出反应的特征之后,这组作者把这些细胞放入了半渗透微胶囊中,然后把它们植入了小鼠体内。在接触引发释放多巴胺的刺激——包括食物、甲基苯丙胺或者性唤起——的时候,有这种植入物的小鼠表现出了血流中的SEAP浓度提高。这组作者对这些细胞进行了重新改造,从而对于多巴胺做出应答,产生心房利钠肽(ANP),这是一种降低血压的化合物。然后把这种植入物注射到了高血压的雄性小鼠体内。当让它与一只雌性小鼠一起生活的时候,有这种植入物的这种动物表现出了血流中的心房利钠肽(ANP)浓度增加和血压下降。这组作者说,这些发现可能有助于开发由自动的、潜意识生理活动控制的治疗装置。(生物谷Bioon.com)

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PNAS          doi: 10.1073/pnas.1312414110

Reward-based hypertension control by a synthetic brain–dopamine interface

Katrin Rossgera, Ghislaine Charpin-El Hamrib, and Martin Fussenegger

Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal’s reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

 

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