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

Authors
Wang-L; Ding-D; Salvi-R; Roth-JA
Source
Neurotoxicology 2014 Jan; 40:65-74
NIOSHTIC No.
20045111
Abstract
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.
Keywords
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
Contact
Jerome A. Roth, Department of Pharmacology and Toxicology, University at Buffalo, 11 Cary Hall, Buffalo, NY 14214
CODEN
NRTXDN
CAS No.
7439-96-5
Publication Date
20140101
Document Type
Journal Article
Email Address
jaroth@buffalo.edu
Funding Type
Grant
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-010235; M092014
ISSN
0161-813X
Source Name
Neurotoxicology
State
NY
Performing Organization
State University of New York - Buffalo
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