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Nicotinamide adenine dinucleotide prevents neuroaxonal degeneration induced by manganese in cochlear organotypic cultures.

Wang L; Ding D; Salvi R; Roth JA

Neurotoxicology 2014 Jan; 40:65-74

https://doi.org/10.1016/j.neuro.2013.11.007

20045111

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.

Manganese-compounds; Minerals; Exposure-levels; Risk-factors; Nerves; Nerve-function; Auditory-nerve; Auditory-system; Injuries; Nerve-fibers; Cell-biology; Cell-function; Cellular-function; Neurotoxic-effects; Ototoxicity; Central-nervous-system; Central-nervous-system-disorders

Jerome A. Roth, Department of Pharmacology and Toxicology, University at Buffalo, 11 Cary Hall, Buffalo, NY 14214

NRTXDN

7439-96-5

20140101

Journal Article

jaroth@buffalo.edu

Grant

2014

Grant-Number-R01-OH-010235; M092014

0161-813X

Manufacturing

Neurotoxicology

NY

State University of New York - Buffalo