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Dendrogenin A and B two new steroidal alkaloids increasing neural responsiveness in the deafened guinea pig.

Fransson A, de Medina P, Paillasse MR, Silvente-Poirot S, Poirot M, Ulfendahl M - Front Aging Neurosci (2015)

Bottom Line: Following immediate or delayed Dendrogenin treatment the electrical responsiveness was significantly maintained, in a similar extent as has been shown using neurotrophic factors.Histological analysis showed that the spiral ganglion neurons density was only slightly higher than the untreated group.That electrical responsiveness was maintained despite a significantly reduced neural population suggests that the efficacy of cochlear implants is more related to the functional state of the spiral ganglion neurons than merely their number.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.

ABSTRACT

Aim: To investigate the therapeutic potential for treating inner ear damage of two new steroidal alkaloid compounds, Dendrogenin A and Dendrogenin B, previously shown to be potent inductors of cell differentiation.

Methods: Guinea pigs, unilaterally deafened by neomycin infusion, received a cochlear implant followed by immediate or a 2-week delayed treatment with Dendrogenin A, Dendrogenin B, and, as comparison artificial perilymph and glial cell-line derived neurotrophic factor. After a 4-week treatment period the animals were sacrificed and the cochleae processed for morphological analysis. Electrically-evoked auditory brainstem responses (eABRs) were measured weekly throughout the experiment.

Results: Following immediate or delayed Dendrogenin treatment the electrical responsiveness was significantly maintained, in a similar extent as has been shown using neurotrophic factors. Histological analysis showed that the spiral ganglion neurons density was only slightly higher than the untreated group.

Conclusions: Our results suggest that Dendrogenins constitute a new class of drugs with strong potential to improve cochlear implant efficacy and to treat neuropathy/synaptopathy related hearing loss. That electrical responsiveness was maintained despite a significantly reduced neural population suggests that the efficacy of cochlear implants is more related to the functional state of the spiral ganglion neurons than merely their number.

No MeSH data available.


Related in: MedlinePlus

The spiral ganglion neuron density in different experimental groups. In Study I, the cell density in the GDNF study was significantly higher (p < 0.001) compared to both Dendrogenin groups. There was no significant difference, neither between the DDA and DDB groups, nor between the control group (AP) and DDA. There was a significant difference (p < 0.05) between the DDB and the control group. Study II displayed no difference between the two Dendrogenin groups and the control group. DDA, Dendrogenin A; DDB, Dendrogenin B; GDNF, Glial cell-line derived neurotrophic factor.
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Figure 3: The spiral ganglion neuron density in different experimental groups. In Study I, the cell density in the GDNF study was significantly higher (p < 0.001) compared to both Dendrogenin groups. There was no significant difference, neither between the DDA and DDB groups, nor between the control group (AP) and DDA. There was a significant difference (p < 0.05) between the DDB and the control group. Study II displayed no difference between the two Dendrogenin groups and the control group. DDA, Dendrogenin A; DDB, Dendrogenin B; GDNF, Glial cell-line derived neurotrophic factor.

Mentions: As shown in Figure 3, illustrating both studies, the density of spiral ganglion neurons was significantly reduced in all experimental groups compared to the normal inner ear (Normal; not deafened and not treated). In the first study, the cell density in the GDNF group was significantly higher (p < 0.001) compared to both Dendrogenin groups (DDA, DDB). There were no significant differences neither between the DDA group and the control group nor between the DDA and DDB group. The spiral ganglion cell density was slightly but significantly higher in the DDB group compared to the control group (p < 0.05). Note that even with GDNF treatment, there was a significant loss of spiral ganglion neurons compared to the normal group. The results of delayed treatment in the second study (Figure 2) were similar. Again, there was no difference in spiral ganglion density between the Dendrogenin groups and the control group. Consistently with spiral ganglion numeration, histological analysis showed a greater loss of spiral ganglion neuron of the Rosenthal’s canal for AP, DDA and DDB compared to the GDNF group (Figure 3). In Figure 4 the eABR thresholds are shown as a function of spiral ganglion neuron density for all groups. In Study I there was no difference between the Dendrogenin groups, both showing slightly increased eABR thresholds compared to the GDNF group. However, the spiral ganglion neuron density for the Dendrogenin groups were very low compared to the GDNF treated group. In Study II the DDA group show very high (or not measurable) eABR thresholds and with the same spiral ganglion neuron density as in Study I. DDB on the other hand displayed slightly higher eABR thresholds compared to Study I but still very low spiral ganglion neuron densities.


Dendrogenin A and B two new steroidal alkaloids increasing neural responsiveness in the deafened guinea pig.

Fransson A, de Medina P, Paillasse MR, Silvente-Poirot S, Poirot M, Ulfendahl M - Front Aging Neurosci (2015)

The spiral ganglion neuron density in different experimental groups. In Study I, the cell density in the GDNF study was significantly higher (p < 0.001) compared to both Dendrogenin groups. There was no significant difference, neither between the DDA and DDB groups, nor between the control group (AP) and DDA. There was a significant difference (p < 0.05) between the DDB and the control group. Study II displayed no difference between the two Dendrogenin groups and the control group. DDA, Dendrogenin A; DDB, Dendrogenin B; GDNF, Glial cell-line derived neurotrophic factor.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4513558&req=5

Figure 3: The spiral ganglion neuron density in different experimental groups. In Study I, the cell density in the GDNF study was significantly higher (p < 0.001) compared to both Dendrogenin groups. There was no significant difference, neither between the DDA and DDB groups, nor between the control group (AP) and DDA. There was a significant difference (p < 0.05) between the DDB and the control group. Study II displayed no difference between the two Dendrogenin groups and the control group. DDA, Dendrogenin A; DDB, Dendrogenin B; GDNF, Glial cell-line derived neurotrophic factor.
Mentions: As shown in Figure 3, illustrating both studies, the density of spiral ganglion neurons was significantly reduced in all experimental groups compared to the normal inner ear (Normal; not deafened and not treated). In the first study, the cell density in the GDNF group was significantly higher (p < 0.001) compared to both Dendrogenin groups (DDA, DDB). There were no significant differences neither between the DDA group and the control group nor between the DDA and DDB group. The spiral ganglion cell density was slightly but significantly higher in the DDB group compared to the control group (p < 0.05). Note that even with GDNF treatment, there was a significant loss of spiral ganglion neurons compared to the normal group. The results of delayed treatment in the second study (Figure 2) were similar. Again, there was no difference in spiral ganglion density between the Dendrogenin groups and the control group. Consistently with spiral ganglion numeration, histological analysis showed a greater loss of spiral ganglion neuron of the Rosenthal’s canal for AP, DDA and DDB compared to the GDNF group (Figure 3). In Figure 4 the eABR thresholds are shown as a function of spiral ganglion neuron density for all groups. In Study I there was no difference between the Dendrogenin groups, both showing slightly increased eABR thresholds compared to the GDNF group. However, the spiral ganglion neuron density for the Dendrogenin groups were very low compared to the GDNF treated group. In Study II the DDA group show very high (or not measurable) eABR thresholds and with the same spiral ganglion neuron density as in Study I. DDB on the other hand displayed slightly higher eABR thresholds compared to Study I but still very low spiral ganglion neuron densities.

Bottom Line: Following immediate or delayed Dendrogenin treatment the electrical responsiveness was significantly maintained, in a similar extent as has been shown using neurotrophic factors.Histological analysis showed that the spiral ganglion neurons density was only slightly higher than the untreated group.That electrical responsiveness was maintained despite a significantly reduced neural population suggests that the efficacy of cochlear implants is more related to the functional state of the spiral ganglion neurons than merely their number.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.

ABSTRACT

Aim: To investigate the therapeutic potential for treating inner ear damage of two new steroidal alkaloid compounds, Dendrogenin A and Dendrogenin B, previously shown to be potent inductors of cell differentiation.

Methods: Guinea pigs, unilaterally deafened by neomycin infusion, received a cochlear implant followed by immediate or a 2-week delayed treatment with Dendrogenin A, Dendrogenin B, and, as comparison artificial perilymph and glial cell-line derived neurotrophic factor. After a 4-week treatment period the animals were sacrificed and the cochleae processed for morphological analysis. Electrically-evoked auditory brainstem responses (eABRs) were measured weekly throughout the experiment.

Results: Following immediate or delayed Dendrogenin treatment the electrical responsiveness was significantly maintained, in a similar extent as has been shown using neurotrophic factors. Histological analysis showed that the spiral ganglion neurons density was only slightly higher than the untreated group.

Conclusions: Our results suggest that Dendrogenins constitute a new class of drugs with strong potential to improve cochlear implant efficacy and to treat neuropathy/synaptopathy related hearing loss. That electrical responsiveness was maintained despite a significantly reduced neural population suggests that the efficacy of cochlear implants is more related to the functional state of the spiral ganglion neurons than merely their number.

No MeSH data available.


Related in: MedlinePlus