Manganese (Mn) is an essential
trace mineral for normal growth and development. Persistent exposures to high atmospheric levels of Mn have deleterious effects on CNS and peripheral nerves including those associated with the auditory system.
Nicotinamide adenine dinucleotide (
NAD) is a
coenzyme which functions in the electron transfer system within the mitochondria. One of the most notable protective functions of
NAD is to delay axonal degenerations caused by various neurodegenerative
injuries. We hypothesized that
NAD might also protect auditory nerve fibers (
ANF) and SGN from Mn injury. To test this hypothesis, cochlear organotypic cultures were treated with different doses of Mn (0.5-3.0 mM) alone or combined with 20 mM
NAD. Results demonstrate that the percentage of hair cells,
ANF and SGN decreased with increasing Mn concentration. The addition of 20 mM
NAD did not significantly reduce hair cells loss in the presence of Mn, whereas the density of
ANF and SGN increased significantly in the presence of
NAD.
NAD suppressed Mn-induced TUNEL staining and
caspase activation suggesting it prevents apoptotic cell death. These results suggest that excess Mn has ototoxic and neurotoxic effects on the auditory system and that
NAD may prevent Mn-induced axonal degeneration and avoid or delay
hearing loss caused by excess Mn exposure.