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

Details

• Personal Author:
  Ding D ; Roth JA ; Salvi R ; Wang L
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Manganese Minerals Nervous System Nervous System Disorders Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Auditory-nerve Auditory-system Cell-biology Cell-function Cellular-function Central-nervous-system Central-nervous-system-disorders Exposure-levels Injuries Manganese-compounds Nerve-fibers Nerve-function Nerves Neurotoxic-effects Ototoxicity Risk-factors

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• ISSN:
  0161-813X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  65-74
• Volume:
  40
• NIOSHTIC Number:
  nn:20045111
• Citation:
  Neurotoxicology 2014 Jan; 40:65-74
• Contact Point Address:
  Jerome A. Roth, Department of Pharmacology and Toxicology, University at Buffalo, 11 Cary Hall, Buffalo, NY 14214
• Email:
  jaroth@buffalo.edu
• CAS Registry Number:
  Manganese (CAS RN 7439-96-5)
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  State University of New York - Buffalo
• Peer Reviewed:
  True
• Start Date:
  20120901
• Source Full Name:
  Neurotoxicology
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:414239c9e835b9e12a3ab4bc27792392eb3dd9b55b9791cc75bd0cb46799d08e8c21b4499b3ff034ed31477383b182ad2d1bf625abbbb48f5a4a0428c09d8430
• Download URL:
  https://stacks.cdc.gov/view/cdc/200638/cdc_200638_DS1.pdf
• File Type:
  [PDF - 3.07 MB ]