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No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

By Haiyan Shen, Jonathan I Matsui, Debin Lei, Lirong Han, Kevin K Ohlemiller and Jianxin Bao


Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs) is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family

Topics: Research Article
Publisher: BioMed Central
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  1. (2000). AF: Vulnerability to noise-induced hearing loss in 'middle-aged' and young adult mice: a dose-response approach in CBA, C57BL, and BALB inbred strains. Hear Res
  2. (2003). Aging and hippocampal/cortical circuits in rodents. Alzheimer Dis Assoc Disord
  3. (2001). Apoptosis and aging: role of the mitochondria.
  4. (1972). AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
  5. (2007). Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis. Neurobiol Aging
  6. (1996). Cochlear spiral ganglion cell degeneration in wild-caught mice as a function of age. Hear Res
  7. (2003). Degterev A: Diversity in the mechanisms of neuronal cell death. Neuron
  8. (1998). Dezso B: Apoptosis in the human inner ear. Detection by in situ end-labeling of fragmented DNA and correlation with other markers. Hear Res
  9. (2003). Erway LC: Genetic influences in individual susceptibility to noise: a review. Noise Health
  10. (2002). EW: bcl-2 Overexpression eliminates deprivation-induced cell death of brainstem auditory neurons.
  11. (2004). EW: Overexpression of bcl2 prevents neomycin-induced hair cell death and caspase-9 activation in the adult mouse utricle in vitro.
  12. (1993). Gacek MR: Cochlear pathology in presbycusis. Ann Otol Rhinol Laryngol
  13. (2004). Horvitz HR: A first insight into the molecular mechanisms of apoptosis. Cell
  14. (1994). Horvitz HR: C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell
  15. (1998). Horvitz HR: Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet
  16. (1997). Hosokawa M: Cell death in the inner ear associated with aging is apoptosis? Brain Res
  17. (1993). HR: The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin1 beta-converting enzyme. Cell
  18. (1996). Ischemia-induced neuronal apoptosis. Curr Opin Neurobiol
  19. (2010). Korneluk RG, Robertson GS: Over-expression of X-linked inhibitor of apoptosis protein slows presbycusis in C57BL/6J mice. Neurobiol Aging
  20. (2004). Men are but worms: neuronal cell death in C elegans and vertebrates. Cell Death Differ
  21. (2002). Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev
  22. (2002). Molecular mechanisms of age-related hearing loss. Ageing Res Rev
  23. (2001). Momoi T: Caspase-3-deficiency induces hyperplasia of supporting cells and degeneration of sensory cells resulting in the hearing loss. Brain Res
  24. (1999). Motor neuron degeneration is attenuated in bax-deficient neurons in vitro.
  25. (2000). Nadol JB: Pattern of degeneration of the spiral ganglion cell and its processes in the C57BL/6J mouse. Hear Res
  26. (2003). Neurons, glia, and plasticity in normal brain aging. Neurobiol Aging
  27. (2002). Noakes PG: Elucidating the molecular mechanisms that underlie the target control of motoneuron death.
  28. (2010). Ohlemiller K: Age-related loss of spiral ganglion neurons. Hearing Res
  29. (2003). Oppenheim RW: Response of motoneurons to neonatal sciatic nerve axotomy in Bax-knockout mice. Mol Cell Neurosci
  30. (1994). Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron
  31. (2009). Prolla TA: Age-related hearing loss in C57BL/6J mice is mediated by BAK-dependent mitochondrial apoptosis. PNAS
  32. (1996). RA: Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice.
  33. (2006). RamirezCamacho R: Ageing evokes an intrinsic pro-apoptotic signalling pathway in rat cochlea. Acta Otolaryngol
  34. (2000). Rao KS: Apoptosis and the nervous system.
  35. (2005). Role LW: Requirement of nicotinic acetylcholine receptor subunit 2 in the maintenance of spiral ganglion neurons during aging.
  36. (1996). SJ: BAX is required for neuronal death after trophic factor deprivation and during development. Neuron
  37. (1990). SJ: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature
  38. (1990). SJ: Deregulated Bcl-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M and D-expressing B-cell population. Mol Cell Biol
  39. (1992). Skilleter DN: Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation.
  40. (2002). Structural changes that occur during normal aging of primate cerebral hemispheres. Neurosci Biobehav Rev
  41. (2001). The expression of apoptosis-related proteins in the aged cochlea of Mongolian gerbils. Laryngoscope
  42. (1998). WD: Widespread elimination of naturally occurring neuronal death in Baxdeficient mice.
  43. (1993). Youle RJ: In situ labeling of granule cells for apoptosis-associated DNA fragmentation reveals different mechanisms of cell loss in developing cerebellum. Neuron