Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression

Enzymatic biofuel cells (EBFCs) have excellent potential as components in bioelectronic devices, especially as active biointerfaces to regulate stem cell behavior for regenerative medicine applications. However, it remains unclear to what extent EBFC-generated electrical stimulation can regulate the functional behavior of human adipose-derived mesenchymal stem cells (hAD-MSCs) at the morphological and gene expression levels. Herein, we investigated the effect of EBFC-generated electrical stimulation on hAD-MSC cell morphology and gene expression using next-generation RNA sequencing. We tested three different electrical currents, 127 ± 9, 248 ± 15, and 598 ± 75 nA/cm2, in mesenchymal stem cells. We performed transcriptome profiling to analyze the impact of EBFC-derived electrical current on gene expression using next generation sequencing (NGS). We also observed changes in cytoskeleton arrangement and analyzed gene expression that depends on the electrical stimulation. The electrical stimulation of EBFC changes cell morphology through cytoskeleton re-arrangement. In particular, the results of whole transcriptome NGS showed that specific gene clusters were up- or down-regulated depending on the magnitude of applied electrical current of EBFC. In conclusion, this study demonstrates that EBFC-generated electrical stimulation can influence the morphological and gene expression properties of stem cells; such capabilities can be useful for regenerative medicine applications such as bioelectronic devices.

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SoxB1 Activity Regulates Sensory Neuron Regeneration, Maintenance, and Function in Planarians

Developmental Cell ◽

10.1016/j.devcel.2018.10.014 ◽

2018 ◽

Vol 47 (3) ◽

pp. 331-347.e5 ◽

Cited By ~ 10

Author(s):

Kelly G. Ross ◽

Alyssa M. Molinaro ◽

Celeste Romero ◽

Brian Dockter ◽

Katrina L. Cable ◽

...

Keyword(s):

Sensory Neuron ◽

Neuron Regeneration ◽

And Function

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Altered ROS production, NF-κB activation and interleukin-6 gene expression induced by electrical stimulation in dystrophic mdx skeletal muscle cells

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2015.03.012 ◽

2015 ◽

Vol 1852 (7) ◽

pp. 1410-1419 ◽

Cited By ~ 24

Author(s):

Carlos Henríquez-Olguín ◽

Francisco Altamirano ◽

Denisse Valladares ◽

José R. López ◽

Paul D. Allen ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Electrical Stimulation ◽

Interleukin 6 ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Ros Production

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Proteinase Inhibitor II Gene Expression Induced by Electrical Stimulation and Control of Photosynthetic Activity in Tomato Plants

Plant and Cell Physiology ◽

10.1093/oxfordjournals.pcp.a078816 ◽

1995 ◽

Cited By ~ 1

Keyword(s):

Gene Expression ◽

Electrical Stimulation ◽

Proteinase Inhibitor ◽

Photosynthetic Activity ◽

Tomato Plants ◽

Proteinase Inhibitor Ii ◽

And Control

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Changes in Gene Expression of the MCU Complex Are Induced by Electrical Stimulation in Adult Skeletal Muscle

Frontiers in Physiology ◽

10.3389/fphys.2020.601313 ◽

2021 ◽

Vol 11 ◽

Author(s):

Esteban R. Quezada ◽

Alexis Díaz-Vegas ◽

Enrique Jaimovich ◽

Mariana Casas

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Electrical Stimulation ◽

Muscle Fibers ◽

Low Frequency ◽

Extracellular Atp ◽

Mrna Levels ◽

Dependent Manner ◽

Adult Skeletal Muscle ◽

Muscle Plasticity

The slow calcium transient triggered by low-frequency electrical stimulation (ES) in adult muscle fibers and regulated by the extracellular ATP/IP3/IP3R pathway has been related to muscle plasticity. A regulation of muscular tropism associated with the MCU has also been described. However, the role of transient cytosolic calcium signals and signaling pathways related to muscle plasticity over the regulation of gene expression of the MCU complex (MCU, MICU1, MICU2, and EMRE) in adult skeletal muscle is completely unknown. In the present work, we show that 270 0.3-ms-long pulses at 20-Hz ES (and not at 90 Hz) transiently decreased the mRNA levels of the MCU complex in mice flexor digitorum brevis isolated muscle fibers. Importantly, when ATP released after 20-Hz ES is hydrolyzed by the enzyme apyrase, the repressor effect of 20 Hz on mRNA levels of the MCU complex is lost. Accordingly, the exposure of muscle fibers to 30 μM exogenous ATP produces the same effect as 20-Hz ES. Moreover, the use of apyrase in resting conditions (without ES) increased mRNA levels of MCU, pointing out the importance of extracellular ATP concentration over MCU mRNA levels. The use of xestospongin B (inhibitor of IP3 receptors) also prevented the decrease of mRNA levels of MCU, MICU1, MICU2, and EMRE mediated by a low-frequency ES. Our results show that the MCU complex can be regulated by electrical stimuli in a frequency-dependent manner. The changes observed in mRNA levels may be related to changes in the mitochondria, associated with the phenotypic transition from a fast- to a slow-type muscle, according to the described effect of this stimulation frequency on muscle phenotype. The decrease in mRNA levels of the MCU complex by exogenous ATP and the increase in MCU levels when basal ATP is reduced with the enzyme apyrase indicate that extracellular ATP may be a regulator of the MCU complex. Moreover, our results suggest that this regulation is part of the axes linking low-frequency stimulation with ATP/IP3/IP3R.

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Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles

Physiological Genomics ◽

10.1152/physiolgenomics.00210.2004 ◽

2005 ◽

Vol 22 (2) ◽

pp. 227-243 ◽

Cited By ~ 53

Author(s):

Tatiana Y. Kostrominova ◽

Douglas E. Dow ◽

Robert G. Dennis ◽

Richard A. Miller ◽

John A. Faulkner

Keyword(s):

Gene Expression ◽

Electrical Stimulation ◽

Mrna Expression ◽

Action Potentials ◽

Skeletal Muscles ◽

Microarray Study ◽

Number Of Genes ◽

Denervated Muscles ◽

And Control ◽

Stimulation Of

Loss of innervation in skeletal muscles leads to degeneration, atrophy, and loss of force. These dramatic changes are reflected in modifications of the mRNA expression of a large number of genes. Our goal was to clarify the broad spectrum of molecular events associated with long-term denervation of skeletal muscles. A microarray study compared gene expression profiles of 2-mo denervated and control extensor digitorum longus (EDL) muscles from 6-mo-old rats. The study identified 121 genes with increased and 7 genes with decreased mRNA expression. The expression of 107 of these genes had not been identified previously as changed after denervation. Many of the genes identified were genes that are highly expressed in skeletal muscles during embryonic development, downregulated in adults, and upregulated after denervation of muscle fibers. Electrical stimulation of denervated muscles preserved muscle mass and maximal force at levels similar to those in the control muscles. To understand the processes underlying the effect of electrical stimulation on denervated skeletal muscles, mRNA and protein expression of a number of genes, identified by the microarray study, was compared. The hypothesis was that loss of nerve action potentials and muscle contractions after denervation play the major roles in upregulation of gene expression in skeletal muscles. With electrical stimulation of denervated muscles, the expression levels for these genes were significantly downregulated, consistent with the hypothesis that loss of action potentials and/or contractions contribute to the alterations in gene expression in denervated skeletal muscles.

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