Reward-based hypertension control by a synthetic brain–dopamine interface
| Autor: | Katrin Rössger, Martin Fussenegger, Ghislaine Charpin-El Hamri |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Dopamine
Biology Cell Line Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dopamine receptor D1 Reward Dopamine receptor D3 Cyclic AMP medicine Animals Humans Cyclic adenosine monophosphate Cyclic AMP Response Element-Binding Protein Neurotransmitter Monitoring Physiologic 030304 developmental biology Drug Carriers 0303 health sciences Multidisciplinary Receptors Dopamine D1 Dopaminergic Biological Sciences Gene Expression Regulation chemistry Dopamine receptor Hypertension Synthetic gene circuits Prosthetic networks Gene regulation Gene switch Designer cells biology.protein Genetic Engineering CREB1 Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America, 110 (45) |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1312414110 |
| Popis: | 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. ISSN:0027-8424 ISSN:1091-6490 |
| Databáze: | OpenAIRE |
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