The Effects of Direct Current Stimulation in Adult Tissues

直流电刺激对成人组织的影响

• 批准号: 10380856
• 负责人: Nestor J Oviedo
• 金额: $ 30.74万
• 依托单位: UNIVERSITY OF CALIFORNIA, MERCED
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-16 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380856
• 关键词: Address; Adopted; Adult; Affect; Alzheimer' s Disease; Behavior; Biological; Biological Models; Biophysics; Body Regions; Body part; Calcium Signaling; Cell Cycle; Cell Death; Cell Differentiation process; Cell Proliferation; Cells; Clinical; Cognition; Coin; Complex; Cues; DNA Repair; Disease; Early Gene Transcriptions; Electric Stimulation; Electrophysiology (science); Equipment; Exhibits; Genetic; Genetic Transcription; Genomics; Human; Ice; Immediate-Early Genes; Injury; Instruction; Intervention; Invertebrates; Knowledge; Lead; Measures; Mediating; Mediator of activation protein; Mental Depression; Methodology; Methods; Migraine; Mitosis; Mitotic; Modality; Molecular; Molecular Genetics; Monitor; Muscle Cells; Natural regeneration; Neurologic; Organism; Parkinson Disease; Patients; Pattern; Pharmacological Treatment; Pharmacology; Pharmacology Study; Pharyngeal structure; Photoreceptors; Physiologic pulse; Physiological; Planarians; Platyhelminths; Process; Protein Biosynthesis; Psyche structure; Radiation therapy; Recovery; Regulation; Research; Signal Pathway; Signal Transduction; Specific qualifier value; Spectrum Analysis; Stimulus; Testing; Time; Tissue Transplantation; Tissues; Transcriptional Activation; Transcriptional Regulation; Translating; Transplantation; WNT Signaling Pathway; Whole Organism; base; bone repair; cell behavior; cell type; cellular targeting; direct application; genetic information; improved; in vivo; insight; interdisciplinary approach; millisecond; multitask; nervous system disorder; novel; novel strategies; prevent; reconstitution; release of sequestered calcium ion into cytoplasm; replacement tissue; response; skills; stem cell biomarkers; stem cell differentiation; stem cell division; stem cell migration; stem cell proliferation; stem cells; tissue regeneration; tool; treatment duration

Project Summary/Abstract The exogenous application of electric currents is an effective method widely used to treat a plethora of clinical conditions and to enhance mental skills including multitasking capability and numerical cognition in healthy humans. Despite the wide use of localized direct current stimulation (DCS) in experimental, clinical and public settings, the molecular bases of its effects in various cell types are unknown. We seek to gain fundamental knowledge about the effects and signals mediating DCS in adult tissues. Therefore, we focus on basic electrophysiology research using a model system based on planarian flatworms, which is amenable to study various DCS modalities and their effects on tissues at systemic and cellular levels. We plan to merge molecular genetics and electrophysiology to define instructive mechanisms underlying cellular responses to DCS. Planarians activate stem cells (SCs) called neoblasts to continually renew adult tissues and are capable of regenerating any part of their body upon injury. Our research team developed a novel strategy based on the external application of DCS of physiological strength to the whole planarian body. We provide compelling evidence that it is possible to use DCS similar to the one used in humans to control collective neoblast behavior in vivo (i.e. regulation of transcription, cell cycle, cell death, differentiation), and induce permanent changes in adult tissue identity without using genetic or pharmacological treatments. The integration of biophysical and genetic information may provide a paradigm shift in the way we approach SC regulation in the adult body and by executing this project we expect to uncover mechanistic insights about this process. A major impact of these studies will be the elucidation of basic mechanisms mediating DCS effects in the complexity of the whole organism to enable the implementation of biomedical approaches to induce selective tissue replacements and control cellular behavior to prevent or treat disease.

项目概要/摘要 外源性施加电流是一种广泛应用于治疗多种临床疾病的有效方法。 并增强健康的心理技能，包括多任务处理能力和数字认知能力 人类。尽管局部直流电刺激 (DCS) 在实验、临床和公共领域得到广泛使用 在不同的细胞类型中，其作用的分子基础尚不清楚。我们寻求获得根本性的 了解成人组织中介导 DCS 的效应和信号。因此，我们重点关注基础 使用基于涡虫扁虫的模型系统进行电生理学研究，该模型值得研究 各种 DCS 模式及其对全身和细胞水平组织的影响。我们计划合并 分子遗传学和电生理学来定义细胞反应的指导机制 直流控制系统。涡虫激活称为新生细胞的干细胞 (SC) 来不断更新成体组织，并且能够 在受伤时再生身体的任何部分。我们的研究团队开发了一种新颖的策略 外用DCS将生理强度作用于涡虫全身。我们提供引人注目的 有证据表明可以使用类似于人类使用的 DCS 来控制集体新生细胞 体内行为（即转录、细胞周期、细胞死亡、分化的调节），并诱导永久性 在不使用遗传或药物治疗的情况下改变成人组织特性。的整合 生物物理和遗传信息可能会为我们处理 SC 调节的方式提供范式转变。 成人的身体，通过执行这个项目，我们希望揭示有关这个过程的机械见解。一个专业 这些研究的影响将是阐明调节 DCS 效应的复杂性的基本机制 整个有机体能够实施生物医学方法来诱导选择性组织 替代和控制细胞行为以预防或治疗疾病。

项目成果

Whole planarian chromosome squash.

整个涡虫染色体被挤压。

• 发表时间: 2021
• 作者: Barghouth, Paul G;Oviedo, Néstor J
• 通讯作者: Oviedo, Néstor J

How Ca2+ influx is attenuated in the heart during a "fight or flight" response.

在“战斗或逃跑”反应期间，心脏中的 Ca2 流入如何减弱。

• 发表时间: 2019-06-03
• 作者: Bazmi, Maedeh;Escobar, Ariel L
• 通讯作者: Escobar, Ariel L

TRAF-like Proteins Regulate Cellular Survival in the Planarian Schmidtea mediterranea.

TRAF 样蛋白调节涡虫 Schmidtea mediterranea 的细胞存活。

• 发表时间: 2020-11-20
• 影响因子: 5.8
• 作者: Ziman, Benjamin;Barghouth, Paul G;Maciel, Eli Isael;Oviedo, Néstor J
• 通讯作者: Oviedo, Néstor J

Phase 1 repolarization rate defines Ca2+ dynamics and contractility on intact mouse hearts.

第一相复极化率定义了完整小鼠心脏的 Ca2 动态和收缩性。

• 发表时间: 2019
• 作者: López Alarcón, María Micaela;Rodríguez de Yurre, Ainhoa;Felice, Juan Ignacio;Medei, Emiliano;Escobar, Ariel L
• 通讯作者: Escobar, Ariel L

Poly(ADP-Ribose) Polymerase-3 Regulates Regeneration in Planarians.

Poly(ADP-Ribose) Polymerase-3 调节涡虫的再生。

• 发表时间: 2020-01-29
• 影响因子: 5.6
• 作者: Barghouth, Paul G;Karabinis, Peter;Venegas, Andie;Oviedo, Néstor J
• 通讯作者: Oviedo, Néstor J