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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 loss of hair cells and SGNs between wild-type and Bax-/- mice. (A) Mean (+SD) inner and outer hair cell density at four basal-apical locations from the same mice tested in Figure 5. (B) Comparison of SGN numbers between wild-type and Bax-/- mice. The number of SGNs were counted and compared at both the apex and base region from the same 5 month-old mice.
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Figure 6: Comparison of age-related loss of hair cells and SGNs between wild-type and Bax-/- mice. (A) Mean (+SD) inner and outer hair cell density at four basal-apical locations from the same mice tested in Figure 5. (B) Comparison of SGN numbers between wild-type and Bax-/- mice. The number of SGNs were counted and compared at both the apex and base region from the same 5 month-old mice.

Mentions: No delay of age-related loss of hair cells and SGNs was also found in Bax-/- mice [22], and Bax is another key member of Bcl-2 family. We also determined whether there was no delay of age-related hearing loss in Bax-/- mice with assessment of hearing threshold by ABR to tone stimuli at 5, 10, 20, 28.3, and 40 kHz. As expected, there were no significant differences in ABR thresholds between Bax-/- and control mice at five months old (Figure 5). Furthermore, there were no significant differences in the number of inner hair cells (IHCs), outer hair cells (OHCs), and SGNs between the control and Bax-/- mice (Figure 6A and 6B). We noted that there tended to be more OHCs at the hook region for the Bax mice, however, this difference was not statistically significant. Most interestingly, there tended to be more SGNs in the control mice instead. Thus, consistent with the previous study [22], Bax targeted deletion did not delay age-related loss of hair cells and SGNs.


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 loss of hair cells and SGNs between wild-type and Bax-/- mice. (A) Mean (+SD) inner and outer hair cell density at four basal-apical locations from the same mice tested in Figure 5. (B) Comparison of SGN numbers between wild-type and Bax-/- mice. The number of SGNs were counted and compared at both the apex and base region from the same 5 month-old mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Comparison of age-related loss of hair cells and SGNs between wild-type and Bax-/- mice. (A) Mean (+SD) inner and outer hair cell density at four basal-apical locations from the same mice tested in Figure 5. (B) Comparison of SGN numbers between wild-type and Bax-/- mice. The number of SGNs were counted and compared at both the apex and base region from the same 5 month-old mice.
Mentions: No delay of age-related loss of hair cells and SGNs was also found in Bax-/- mice [22], and Bax is another key member of Bcl-2 family. We also determined whether there was no delay of age-related hearing loss in Bax-/- mice with assessment of hearing threshold by ABR to tone stimuli at 5, 10, 20, 28.3, and 40 kHz. As expected, there were no significant differences in ABR thresholds between Bax-/- and control mice at five months old (Figure 5). Furthermore, there were no significant differences in the number of inner hair cells (IHCs), outer hair cells (OHCs), and SGNs between the control and Bax-/- mice (Figure 6A and 6B). We noted that there tended to be more OHCs at the hook region for the Bax mice, however, this difference was not statistically significant. Most interestingly, there tended to be more SGNs in the control mice instead. Thus, consistent with the previous study [22], Bax targeted deletion did not delay age-related loss of hair cells and SGNs.

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