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

Shen H, Matsui JI, Lei D, Han L, Ohlemiller KK, Bao J - Mol Neurodegener (2010)

Bottom Line: Age-related decline of neuronal function is associated with age-related structural changes.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otolaryngology, Washington University School of Medicine, St, Louis, MO, 63110, USA. jbao@wustl.edu.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Comparison of age-related hearing loss between wild-type and bcl-2 transgenic mice. Mean (+SD) ABR thresholds were measured in wild type and BCL-2 transgenic mice versus age (2 and 9 months) and stimulus frequency. Five female mice were used for each group. No significant threshold protection effect of the BCL-2 transgene was apparent.
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Figure 2: Comparison of age-related hearing loss between wild-type and bcl-2 transgenic mice. Mean (+SD) ABR thresholds were measured in wild type and BCL-2 transgenic mice versus age (2 and 9 months) and stimulus frequency. Five female mice were used for each group. No significant threshold protection effect of the BCL-2 transgene was apparent.

Mentions: To address whether overexpression of Bcl-2 in hair cells and SGNs during aging might delay age-related hearing loss, we compared ABR thresholds in wild type and transgenic mice at 2 and 9 months. Consistent with the C57 Ahl background [5], hearing thresholds increased with age, beginning with high frequencies. No significant effect of genotype was apparent (Figure 2A). To assess whether age-related loss of hair cells was delayed by over-expression of human Bcl-2, we examined the number of hair cells in both wild type and transgenic mice from 18- and 24-month-old mice. Figure 3 compares hair cell densities of wild type and transgenic mice at four basal-apical locations. Pooled counts from two-month-old animals provided normal densities for comparison. Both inner and outer hair cells progressively degenerated with age, following a basal-to-apical pattern. Counts obtained at 18 and 24 months revealed no indication that survival of either inner or outer hair cells was greater in transgenic mice. Trends suggested by the data, including better survival of OHCs in wild types at 18 months and better survival of OHCs in transgenic at 24 months, were not significant.


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

Shen H, Matsui JI, Lei D, Han L, Ohlemiller KK, Bao J - Mol Neurodegener (2010)

Comparison of age-related hearing loss between wild-type and bcl-2 transgenic mice. Mean (+SD) ABR thresholds were measured in wild type and BCL-2 transgenic mice versus age (2 and 9 months) and stimulus frequency. Five female mice were used for each group. No significant threshold protection effect of the BCL-2 transgene was apparent.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2914024&req=5

Figure 2: Comparison of age-related hearing loss between wild-type and bcl-2 transgenic mice. Mean (+SD) ABR thresholds were measured in wild type and BCL-2 transgenic mice versus age (2 and 9 months) and stimulus frequency. Five female mice were used for each group. No significant threshold protection effect of the BCL-2 transgene was apparent.
Mentions: To address whether overexpression of Bcl-2 in hair cells and SGNs during aging might delay age-related hearing loss, we compared ABR thresholds in wild type and transgenic mice at 2 and 9 months. Consistent with the C57 Ahl background [5], hearing thresholds increased with age, beginning with high frequencies. No significant effect of genotype was apparent (Figure 2A). To assess whether age-related loss of hair cells was delayed by over-expression of human Bcl-2, we examined the number of hair cells in both wild type and transgenic mice from 18- and 24-month-old mice. Figure 3 compares hair cell densities of wild type and transgenic mice at four basal-apical locations. Pooled counts from two-month-old animals provided normal densities for comparison. Both inner and outer hair cells progressively degenerated with age, following a basal-to-apical pattern. Counts obtained at 18 and 24 months revealed no indication that survival of either inner or outer hair cells was greater in transgenic mice. Trends suggested by the data, including better survival of OHCs in wild types at 18 months and better survival of OHCs in transgenic at 24 months, were not significant.

Bottom Line: Age-related decline of neuronal function is associated with age-related structural changes.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otolaryngology, Washington University School of Medicine, St, Louis, MO, 63110, USA. jbao@wustl.edu.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus