Mr. Sarah Chen Profile

Sarah Chen

at Univ. of California, San Diego

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Proceedings Article | 5 October 2023 Poster + Paper

Effects of H2O2 and high doses of nicotinamide on laser-induced neuronal degeneration in mouse model of Huntington’s disease

Sophia Barber, Sarah Chen, Veronica Gomez, Chengbiao Wu, Linda Shi

Proceedings Volume 12649, 126490V (2023) https://doi.org/10.1117/12.2677626

KEYWORDS: Axons, Neurons, Shrinkage, Neurological disorders, Nervous system, Laser cutting, Resistance, Brain diseases, Laser induced damage, Control systems

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Axonal degeneration is a key component of neurodegenerative diseases such as Huntington’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis (ALS). (NAm), an NAD+ precursor, has long since been implicated in axonal protection and reduction of degeneration. On the other hand, hydrogen peroxide (H₂O₂) has been implicated in oxidative stress and axonal degeneration. The effects of laser-induced axonal damage in wild-type (WT) and Huntington’s disease(HD) mouse dorsal root ganglion neurons (DRGs) treated with NAm or H₂O₂ were investigated and the cell body width, axon width, axonal strength, and axon shrinkage post laser-induced injury were measured. We found that HD mouse DRGs have increased strength against laser damage compared to wild-type DRGs. We additionally found that treatment with NAm reduces the neuronal strength against laser damage in both WT and HD DRGs. Interestingly, when comparing HD DRGs treated with H₂O₂ and WT DRGs treated with H₂O₂, we found that treatment with H₂O₂ reduced the time required for the RoboLase laser system to cut through HD DRGs. We additionally found that both NAm and H₂O₂ treatments resulted in morphological changes in both WT and HD DRG cell bodies, respectively. We did not find any difference in shrinkage across the models. Ultimately, our results suggest that H₂O₂ at the same concentration may have less damaging effects on WT neurons than previously expected. Our results additionally indicate that higher concentrations of NAm, previously deemed to be safe, may have a neurotoxic effect rather than an axonal protective effect on HD and WT DRGs.

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