7 results on '"Furness, David N"'
Search Results
2. Relative time course of degeneration of different cochlear structures in the CD/1 mouse model of accelerated aging.
- Author
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Mahendrasingam, Shanthini, MacDonald, Jamie, Furness, David, Macdonald, Jamie A, and Furness, David N
- Abstract
Presbycusis (age-related hearing loss) can result from various cochlear pathologies. We have studied the time course of degeneration in a mouse that shows accelerated presbycusis, the CD/1 mouse, as a possible model to investigate stem-cell strategies to prevent or ameliorate presbycusic changes. CD/1 mice from 0 to 72 weeks old were examined by light and electron microscopy. Early pathological changes were detected in basal turn spiral ligament fibrocytes and spiral ganglion, but the latter was variable as both satellite cells and neurons were normal in some cochleae. Light microscopic counts in the spiral ligament of 20-week-old mice revealed that of the five main types (types I-V), only type V fibrocytes showed no reduction in numbers compared with 3-week-old animals, and type IV showed the greatest losses. However, all types of fibrocyte showed subtle damage when examined using electron microscopy, in the form of swollen mitochondria, as early as 2 weeks. The extent of mitochondrial damage showed a degree of correspondence with the light microscopic pattern of fibrocyte loss in that types III and IV fibrocytes had the most abnormal mitochondria and type V the least, especially at early stages. By 10-15 weeks, ultrastructural features of fibrocyte damage were similar to longer term changes reported in gerbils. Stria vascularis, spiral ganglion and hair cells showed few consistent early signs of damage but became increasingly affected, lagging behind the fibrocyte damage. Our data suggest that fibrocyte pathology may precede other presbycusic changes; breakdown of homeostatic mechanisms to which they contribute may cause the subsequent degeneration of the hair cells. Overall, there were many similarities to presbycusic changes in other rodents and humans. Therefore, the features of accelerated aging in this mouse make it a suitable model for rapidly assessing possible strategies to prevent or ameliorate presbycusic changes. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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3. Synaptotagmin IV determines the linear Ca2+ dependence of vesicle fusion at auditory ribbon synapses.
- Author
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Johnson, Stuart L., Franz, Christoph, Kuhn, Stephanie, Furness, David N., Rüttiger, Lukas, Münkner, Stefan, Rivolta, Marcelo N., Seward, Elizabeth P., Herschman, Harvey R., Engel, Jutta, Knipper, Marlies, and Marcotti, Walter
- Subjects
HAIR cells ,COCHLEA ,MAMMALS ,SYNAPSES ,NEURAL transmission ,SYNAPTIC vesicles ,RODENTS ,OLFACTORY receptors - Abstract
Mammalian cochlear inner hair cells (IHCs) are specialized for the dynamic coding of continuous and finely graded sound signals. This ability is largely conferred by the linear Ca
2+ dependence of neurotransmitter release at their synapses, which is also a feature of visual and olfactory systems. The prevailing hypothesis is that linearity in IHCs occurs through a developmental change in the Ca2+ sensitivity of synaptic vesicle fusion from the nonlinear (high order) Ca2+ dependence of immature spiking cells. However, the nature of the Ca2+ sensor(s) of vesicle fusion at hair cell synapses is unknown. We found that synaptotagmin IV was essential for establishing the linear exocytotic Ca2+ dependence in adult rodent IHCs and immature outer hair cells. Moreover, the expression of the hitherto undetected synaptotagmins I and II correlated with a high-order Ca2+ dependence in IHCs. We propose that the differential expression of synaptotagmins determines the characteristic Ca2+ sensitivity of vesicle fusion at hair cell synapses. [ABSTRACT FROM AUTHOR]- Published
- 2010
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4. Distribution of the Glutamate/Aspartate Transporter GLAST in Relation to the Afferent Synapses of Outer Hair Cells in the Guinea Pig Cochlea.
- Author
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Furness, David N., Hulme, Julie A., Lawton, D., and Hackney, Carole M.
- Abstract
The glutamate/aspartate transporter GLAST is known to occur in the plasma membrane of supporting cells and their glialike processes around the synaptic region of inner hair cells of the mammalian cochlea. Its function there is presumably to take up glutamate following the release of this putative amino acid neurotransmitter from the inner hair cells. In this study, we have investigated whether GLAST is also associated with the outer hair cells using postembedding immunogold labeling. This is interesting because it is uncertain whether the outer hair cells have a functional synapse at which glutamate may be released. However, earlier ultrastructural studies of the afferent synapses in outer hair cells in several mammalian species have shown features normally associated with synaptic activity. These observations are confirmed and extended here in guinea pig where these afferent synapses have presynaptic bodies, putative synaptic vesicles, and coated pits associated with them. Immunoreactivity for GLAST was found along the plasma membranes of Deiters' cells, especially around the synaptic region of the hair cell, on processes wrapped around approaching nerve fibers. Semiquantitative analysis of the distribution of immunogold labeling of Deiters' cells confirmed that it was densest in the region adjacent to the synapses. There was also more labeling in apical than in basal regions of the cochlea in three of the four animals examined, suggesting an association with the number of afferent synapses, which are more numerous in apical regions. Interestingly, labeling also occurred in other regions of the cell membrane away from the afferent terminals. This suggests that glutamate uptake is also required away from the immediate vicinity of synapses, perhaps as a consequence of glutamate dispersal resulting from the mechanical displacement of the cochlear partition during stimulation. Nonetheless, the particular association of GLAST with the synaptic region of the outer hair cell implies that the latter have active afferent synapses at which glutamate is released. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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5. Immunoreactivity of sensory hair bundles of the guinea-pig cochlea to antibodies against elastin and keratan sulphate.
- Author
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Katori, Yukio, Hackney, Carole M., and Furness, David N.
- Abstract
The stereociliary bundles of hair cells contain cross-linking extracellular filaments which have been suggested to play a role in mechanoelectrical transduction. To investigate the composition of these filaments, antibodies to the extracellular matrix molecules elastin and keratan sulphate have been used for light- and electron-microscopic immunocytochemistry of the guinea-pig organ of Corti. With the antibody to elastin, no immunoreactivity was found in hair bundles. This implies either that the epitope recognised by this antibody is not present in the links or that it is obscured. The antibody to keratan sulphate labelled the stereociliary bundles of both inner and outer hair cells but not supporting cells. The tips of the tallest stereocilia, especially on outer hair cells, the tips of the shorter stereocilia where the tip links attach to the stereociliary membrane, and the attachments of the lateral links, were labelled. This suggests that the links contain keratan sulphate proteoglycans, molecules which in other tissues are known to maintain structural integrity and fibrillar spacing, and to influence the microenvironment of the cell surface. [ABSTRACT FROM AUTHOR]
- Published
- 1996
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6. Ultrastructural localization of the likely mechanoelectrical transduction channel protein, transmembrane-like channel 1 (TMC1) during development of cochlear hair cells.
- Author
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Mahendrasingam, Shanthini and Furness, David N.
- Abstract
Transmembrane channel like protein 1 (TMC1) is likely to be a pore-forming subunit of the transduction channel of cochlear hair cells that is mechanically gated by tension on tip links in the stereocilia bundle. To localise TMC1 precisely, we labelled mice cochleae of different ages using custom-made polyclonal antibodies to TMC1 for light and transmission electron microscopy (TEM). Immunofluorescence revealed stereocilia labelling at P9 but not at P3 in apical hair cells. Immunogold labelling for TEM confirmed that labelling was absent at P3, and showed weak labelling at P6 with no stereocilia tip labelling, increasing at P9, with specific tip labelling on shorter stereocilia and some throughout the bundle. At P12 and P21, labelling was refined mostly to stereocilia tips. Quantification showed that labelling overall reached maximum by P12, labelling per tip was relatively constant from P9 to P21, but percent tips labelled was reduced from 16% to 8%. Tmc1−/− showed no labelling. Thus TMC1 occurs at the lower end of the tip link, supporting its presence in the MET complex and likely the channel. Tip localisation from P9 onwards coincides with lipoma HMGIC fusion partner-like 5 (LHFPL5), a protein that may be involved in acquiring/maintaining TMC1 localisation. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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7. Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation.
- Author
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Corns, Laura F., Johnson, Stuart L., Roberts, Terri, Ranatunga, Kishani M., Hendry, Aenea, Ceriani, Federico, Safieddine, Saaid, Steel, Karen P., Forge, Andy, Petit, Christine, Furness, David N., Kros, Corné J., and Marcotti, Walter
- Abstract
In the adult auditory organ, mechanoelectrical transducer (MET) channels are essential for transducing acoustic stimuli into electrical signals. In the absence of incoming sound, a fraction of the MET channels on top of the sensory hair cells are open, resulting in a sustained depolarizing current. By genetically manipulating the in vivo expression of molecular components of the MET apparatus, we show that during pre-hearing stages the MET current is essential for establishing the electrophysiological properties of mature inner hair cells (IHCs). If the MET current is abolished in adult IHCs, they revert into cells showing electrical and morphological features characteristic of pre-hearing IHCs, including the re-establishment of cholinergic efferent innervation. The MET current is thus critical for the maintenance of the functional properties of adult IHCs, implying a degree of plasticity in the mature auditory system in response to the absence of normal transduction of acoustic signals. Mechanoelectrical transducer (MET) channels on the tips of inner hair cells are essential for transducing auditory sensory information. Here, the authors show that disrupting MET channel function also prevents the preservation of normal inner hair cell identity in adult mice. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
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