| 1. |
- Johnson Chacko, Lejo, et al.
(författare)
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Neurosensory Differentiation and Innervation Patterning in the Human Fetal Vestibular End Organs between the Gestational Weeks 8-12
- 2016
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Balance orientation depends on the precise operation of the vestibular end organs and the vestibular ganglion neurons. Previous research on the assemblage of the neuronal network in the developing fetal vestibular organ has been limited to data from animal models. Insights into the molecular expression profiles and signaling moieties involved in embryological development of the human fetal inner ear have been limited. We present an investigation of the cells of the vestibular end organs with specific focus on the hair cell differentiation and innervation pattern using an uninterrupted series of unique specimens from gestational weeks 8-12. Nerve fibers positive for peripherin innervate the entire fetal crista and utricle. While in rodents only the peripheral regions of the cristae and the extra-striolar region of the statolithic organs are stained. At week 9, transcription factors PAX2 and PAX8 were observed in the hair cells whereas PAX6 was observed for the first time among the supporting cells of the cristae and the satellite glial cells of the vestibular ganglia. Glutamine synthetase, a regulator of the neurotransmitter glutamate, is strongly expressed among satellite glia cells, transitional zones of the utricle and supporting cells in the sensory epithelium. At gestational week 11, electron microscopic examination reveals bouton contacts at hair cells and first signs of the formation of a protocalyx at type I hair cells. Our study provides first-hand insight into the fetal development of the vestibular end organs as well as their pattern of innervation by means of immunohistochemical and EM techniques, with the aim of contributing toward our understanding of balance development.
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| 2. |
- Liu, Wei, et al.
(författare)
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Possible role of gap junction intercellular channels and connexin 43 in satellite glial cells (SGCs) for preservation of human spiral ganglion neurons : A comparative study with clinical implications
- 2014
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 355:2, s. 267-278
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Tidskriftsartikel (refereegranskat)abstract
- Human spiral ganglion (SG) neurons show remarkable survival properties and maintain electric excitability for a long time after complete deafness and even separation from the organ of Corti, features essential for cochlear implantation. Here, we analyze and compare the localization and distribution of gap junction (GJ) intercellular channels and connexin 43 (Cx43) in cells surrounding SG cell bodies in man and guinea pig by using transmission electron microscopy and confocal immunohistochemistry. GJs and Cx43 expression has been recognized in satellite glial cells (SGCs) in non-myelinating sensory ganglia including the human SG. In man, SG neurons can survive as mono-polar or "amputated" cells with unbroken central projections following dendrite degeneration and consolidation of the dendrite pole. Cx43-mediated GJ signaling between SGCs is believed to play a key role in this "healing" process and could explain the unique preservation of human SG neurons and the persistence of cochlear implant function.
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| 3. |
- Luque, Maria, et al.
(författare)
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HCN channels in the mammalian cochlea : Expression pattern, subcellular location, and age-dependent changes
- 2021
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Ingår i: Journal of Neuroscience Research. - : John Wiley & Sons. - 0360-4012 .- 1097-4547. ; 99:2, s. 699-728
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal diversity in the cochlea is largely determined by ion channels. Among voltage-gated channels, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open with hyperpolarization and depolarize the cell until the resting membrane potential. The functions for hearing are not well elucidated and knowledge about localization is controversial. We created a detailed map of subcellular location and co-expression of all four HCN subunits across different mammalian species including CBA/J, C57Bl/6N, Ly5.1 mice, guinea pigs, cats, and human subjects. We correlated age-related hearing deterioration in CBA/J and C57Bl/6N with expression levels of HCN1, -2, and -4 in individual auditory neurons from the same cohort. Spatiotemporal expression during murine postnatal development exposed HCN2 and HCN4 involvement in a critical phase of hair cell innervation. The huge diversity of subunit composition, but lack of relevant heteromeric pairing along the perisomatic membrane and axon initial segments, highlighted an active role for auditory neurons. Neuron clusters were found to be the hot spots of HCN1, -2, and -4 immunostaining. HCN channels were also located in afferent and efferent fibers of the sensory epithelium. Age-related changes on HCN subtype expression were not uniform among mice and could not be directly correlated with audiometric data. The oldest mice groups revealed HCN channel up- or downregulation, depending on the mouse strain. The unexpected involvement of HCN channels in outer hair cell function where HCN3 overlaps prestin location emphasized the importance for auditory function. A better understanding may open up new possibilities to tune neuronal responses evoked through electrical stimulation by cochlear implants.
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| 4. |
- Pechriggl, Elisabeth J, et al.
(författare)
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Development of the innervation of the human inner ear
- 2015
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Ingår i: Developmental Neurobiology. - : Wiley. - 1932-8451 .- 1932-846X. ; 75:7, s. 683-702
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Tidskriftsartikel (refereegranskat)abstract
- Studies on the formation of neuronal structures of the human cochlea are rare, presumptively, due to the difficult accessibility of specimens, so that most investigations are performed on mouse models. By means of immunohistochemical and transmission electron microscopic techniques, we investigated an uninterrupted series of unique specimens from gestational week 8 to week 12. We were able to demonstrate the presence of nerve fibers in the prosensory domain at gestational week 8, followed by afferent synaptogenesis at week 11. We identified PAX2 as an early marker for hair cell differentiation. Glutamine synthetase-positive peripheral glial cells occurred at the beginning of week 8. Transcription factor MAF B was used to demonstrate maturation of the spiral ganglion neurons. The early expression of tyrosine hydroxylase could be assessed. This study provides insights in the early assembly of the neural circuit and organization in humans.
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