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

Abstract

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.