Electrical stimulation alters DNA methylation and promotes neurite outgrowth

Electrical stimulation (ES) influences neural regeneration and functionality. We here investigate whether ES regulates DNA demethylation, a critical epigenetic event known to influence nerve regeneration. Retinal ganglion cells (RGCs) have long served as a standard model for central nervous system n...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2023-10, Vol.124 (10), p.1530-1545
Main Authors: Ashok, Ajay, Tai, Wai Lydia, Lennikov, Anton, Chang, Karen, Chen, Julie, Li, Boyuan, Cho, Kin‐Sang, Utheim, Tor Paaske, Chen, Dong Feng
Format: Article
Language:English
Subjects:
Axonogenesis
Central nervous system
Demethylation
Developmental stages
DNA methylation
Electrical stimuli
Epigenetics
Explants
Histones
Immunohistochemistry
Lysine
Nerves
Neurons
Optic nerve
Phenotypes
Pheochromocytoma cells
Regeneration
Retina
Retinal ganglion cells
Stimulation
Translocation
Tubulin
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Summary:Electrical stimulation (ES) influences neural regeneration and functionality. We here investigate whether ES regulates DNA demethylation, a critical epigenetic event known to influence nerve regeneration. Retinal ganglion cells (RGCs) have long served as a standard model for central nervous system neurons, whose growth and disease development are reportedly affected by DNA methylation. The current study focuses on the ability of ES to rescue RGCs and preserve vision by modulating DNA demethylation. To evaluate DNA demethylation pattern during development, RGCs from mice at different stages of development, were analyzed using qPCR for ten‐eleven translocation (TETs) and immunostained for 5 hydroxymethylcytosine (5hmc) and 5 methylcytosine (5mc). To understand the effect of ES on neurite outgrowth and DNA demethylation, cells were subjected to ES at 75 µAmp biphasic ramp for 20 min and cultured for 5 days. ES increased TETs mediated neurite outgrowth, DNA demethylation, TET1 and growth associated protein 43 levels significantly. Immunostaining of PC12 cells following ES for histone 3 lysine 9 trimethylation showed cells attained an antiheterochromatin configuration. Cultured mouse and human retinal explants stained with β‐III tubulin exhibited increased neurite growth following ES. Finally, mice subjected to optic nerve crush injury followed by ES exhibited improved RGCs function and phenotype as validated using electroretinogram and immunohistochemistry. Our results point to a possible therapeutic regulation of DNA demethylation by ES in neurons.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.30462