Optogenetics stimulation in non-invasive skeletal muscle activation: biomarker identification via key gene expressions in calcium signaling pathway
Date
2020
Authors
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Publisher
University of Delaware
Abstract
Optogenetic stimulation which enables spatially sensitive, cell-type-specific, pain-free stimulation, is an emerging alternative to electrical stimulation. Optogenetics directly activates the nerves distal to the paralyzed/injured skeletal muscle via expression of light-sensitive Channelrhodopsin-2 (ChR2) on cell membranes, Skeletal muscle contracts in response to optogenetic stimulation by triggering an action potential that propagates and induces a global cellular calcium response. Rises in cytosolic calcium then stimulate downstream calcium-dependent signaling pathways to regulate skeletal muscle contractions. Recognizing that calcium signaling pathways plays a crucial role in skeletal muscle contractions, my thesis aims to identify the key genes/transcription factors in the calcium signaling pathway that mediate skeletal muscle contractions. I achieved this aim by comparing differentially expressed genes between optogenetically stimulated skeletal muscle (triceps-surae) to contralateral, unstimulated skeletal muscle of young mice. My results show that pro-inflammatory cytokines (Tnf, Il6) and growth factors (Egr1, Egr2), are up regulated in the optogenetic stimulated skeletal muscle compared with the contralateral unstimulated control. These targets can potentially be utilized to regulate the production of a biological drug in-situ, by repeatedly applying light to the tissue and inducing expression of therapeutic transgenes in skeletal muscle paralysis.
Description
Keywords
Optogenetic stimulation, Electrical stimulation, Channelrhodopsin-2, Mice