PUBLICATION

Beneficial impacts of neuromuscular electrical stimulation on muscle structure and function in the zebrafish model of Duchenne muscular dystrophy

Authors

Kilroy, E.A., Ignacz, A.C., Brann, K.L., Schaffer, C.E., Varney, D., Alrowaished, S.S., Silknitter, K.J., Miner, J.N., Almaghasilah, A., Spellen, T.L., Lewis, A.D., Tilbury, K., King, B.L., Kelley, J.B., Henry, C.A.

ID

ZDB-PUB-220325-8

Date

2022

Source

eLIFE 11: (Journal)

Registered Authors

Henry, Clarissa A.

Keywords

developmental biology, dystroglycanopathies, neuromuscular development, skeletal muscle, zebrafish

Datasets

GEO:GSE155465

MeSH Terms

Animals
Electric Stimulation
Neuromuscular Junction/physiology
Muscle, Skeletal/physiology
Muscular Dystrophy, Duchenne*/genetics
Muscular Dystrophy, Duchenne*/therapy
Humans
Zebrafish

(all 8)

PubMed

35324428 Full text @ Elife

Abstract

Neuromuscular electrical stimulation (NMES) allows activation of muscle fibers in the absence of voluntary force generation. NMES could have the potential to promote muscle homeostasis in the context of muscle disease, but the impacts of NMES on diseased muscle are not well understood. We used the zebrafish Duchenne muscular dystrophy (dmd) mutant and a longitudinal design to elucidate the consequences of NMES on muscle health. We designed four neuromuscular stimulation paradigms loosely based on weightlifting regimens. Each paradigm differentially affected neuromuscular structure, function, and survival. Only endurance neuromuscular stimulation (eNMES) improved all outcome measures. We found that eNMES improves muscle and neuromuscular junction morphology, swimming, and survival. Heme oxygenase and integrin alpha7 are required for eNMES-mediated improvement. Our data indicate that neuromuscular stimulation can be beneficial, suggesting that the right type of activity may benefit patients with muscle disease.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
CFP	dmd^{ta222a/ta222a}; fb122Tg/fb122Tg; i104Tg/i104Tg	electric field	Long-pec to Day 6	trunk musculature myosin filament	IFL	Figure 7.
CFP	dmd^{ta222a/ta222a}; fb122Tg/fb122Tg; i104Tg/i104Tg	standard conditions	Long-pec to Day 6	trunk musculature myosin filament	IFL	Figure 7.
EGFP	dmd^{ta222a/ta222a}; fb122Tg/fb122Tg; i104Tg/i104Tg	standard conditions	Long-pec to Day 6	trunk musculature myosin filament	IFL	Figure 7.
EGFP	dmd^{ta222a/ta222a}; fb122Tg/fb122Tg; i104Tg/i104Tg	electric field	Long-pec to Day 6	trunk musculature myosin filament	IFL	Figure 7.
hmox1a	dmd^{ta222a/ta222a}	electric field	Long-pec to Days 7-13	whole organism	RNA-Seq	Figure 8.
hmox1a	dmd^{ta222a/ta222a}	standard conditions	Long-pec to Days 7-13	whole organism	RNA-Seq	Figure 8.
hmox1a	WT	electric field	Long-pec to Days 7-13	whole organism	RNA-Seq	Figure 8.
hmox1a	WT	standard conditions	Long-pec to Days 7-13	whole organism	RNA-Seq	Figure 8.
postnb	dmd^{ta222a/ta222a}	standard conditions	Days 7-13	whole organism	RNA-Seq	Figure 9.
postnb	dmd^{ta222a/ta222a}	electric field	Days 7-13	whole organism	RNA-Seq	Figure 9.

1 - 10 of 14

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	electric field	Long-pec	caudal fin muscle contraction increased frequency, abnormal	Figure 1.
WT	electric field	Long-pec	trunk musculature detection of wounding normal process quality, normal	Figure 1.
WT	electric field	Long-pec to Days 7-13	trunk musculature actin filament organized, normal	Figure 3.
WT	electric field	Long-pec to Days 7-13	trunk musculature sarcolemma organized, normal	Figure 2.
WT	electric field	Long-pec to Days 7-13	trunk musculature sarcolemma organized, normal	Figure 3.
WT	electric field	Long-pec to Days 7-13	whole organism hmox1a expression increased amount, abnormal	Figure 8.
WT	electric field	Protruding-mouth to Days 7-13	whole organism regulation of gene expression rate of occurence, normal	Figure 8.
WT	electric field	Days 7-13	trunk musculature actin filament organized, normal	Figure 9.
WT	electric field	Days 7-13	trunk musculature connective tissue replacement involved in inflammatory response wound healing decreased occurrence, abnormal	Figure 9.
WT	electric field	Days 7-13	trunk musculature sarcolemma organized, normal	Figure 9.

1 - 10 of 74

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
fb121Tg	Tg(myog:Hsa.HIST1H2BJ-mRFP)	Transgenic Insertion
fb122Tg	Tg(mylpfa:LY-CFP)	Transgenic Insertion
i104Tg	Tg(smyhc1:EGFP)	Transgenic Insertion
mai18		Small Deletion	itga7
ta222a		Point Mutation	dmd

1 - 5 of 5

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Human Disease / Model

Human Disease	Fish	Conditions	Evidence
Duchenne muscular dystrophy	dmd^{ta222a/ta222a}	electric field	TAS

Sequence Targeting Reagents

Target	Reagent	Reagent Type
hmox1a	MO1-hmox1a	MRPHLNO

Fish

Fish
dmd^{ta222a/ta222a}
dmd^{ta222a/ta222a}; fb122Tg/fb122Tg; i104Tg/i104Tg
dmd^{ta222a/ta222a} + MO1-hmox1a
fb122Tg/fb122Tg; i104Tg/i104Tg
itga7^mai18/mai18
WT

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab-SV2	monoclonal		IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
CFP	EFG	CFP
EGFP	EFG	EGFP
mRFP	EFG	mRFP

Mapping

Kilroy et al., 2022 ZDB-PUB-220325-8 PMID:35324428

Beneficial impacts of neuromuscular electrical stimulation on muscle structure and function in the zebrafish model of Duchenne muscular dystrophy

Kilroy et al., 2022

ZDB-PUB-220325-8
PMID:35324428