title: Nicotinamide adenine dinucleotide prevents neuroaxonal degeneration induced by manganese in cochlear organotypic cultures.
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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Center for Hearing and Deafness, University at Buffalo, Buffalo, NY 14214, United States.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, Buffalo, NY 14214, United States; Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Dalian
authors.initials: D
authors.lastname: Ding
authors.affiliation: Center for Hearing and Deafness, University at Buffalo, Buffalo, NY 14214, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Salvi
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY 14214, United States. Electronic address: jaroth@buffalo.edu.
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Roth
mesh_terms: D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology; D003056:Cochlear Nerve / Q000187:drug effects* / Q000473:pathology; D008345:Manganese / Q000633:toxicity*; D009243:NAD / Q000627:therapeutic use*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D009243:NAD; D008345:Manganese
keywords: Apoptosis; Hair cells; Manganese; NAD; Ototoxicity; Spiral ganglion neurons