scholarly journals Comparison of Methods for the Histological Evaluation of Odontocete Spiral Ganglion Cells

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 683 ◽  
Author(s):  
Tania Ramírez ◽  
Simona Sacchini ◽  
Yania Paz ◽  
Rubén S. Rosales ◽  
Nakita Câmara ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Auditory Pathway ◽  
Histological Evaluation ◽  
Anatomical Location ◽  
Tissue Samples ◽  
Edta Solution ◽  
Ganglion Neurons ◽  
Hearing System

Cetaceans greatly depend on their hearing system to perform many vital activities. The spiral ganglion is an essential component of the auditory pathway and can even be associated with injuries caused by anthropogenic noise. However, its anatomical location, characterized by surrounding bony structures, makes the anatomical and anatomopathological study of the spiral ganglion a difficult task. In order to obtain high-quality tissue samples, a perfect balance between decalcification and the preservation of neural components must be achieved. In this study, different methodologies for spiral ganglion sample preparation and preservation were evaluated. Hydrochloric acid had the shortest decalcification time but damaged the tissue extensively. Both formic acid and EDTA decalcification solutions had a longer decalcification time but exhibited better preservation of the neurons. However, improved cell morphology and staining were observed on ears pretreated with EDTA solution. Therefore, we suggest that decalcifying methodologies based on EDTA solutions should be used to obtain the highest quality samples for studying cell morphology and antigenicity in cetacean spiral ganglion neurons.

Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons

Development ◽  
2001 ◽  
Vol 128 (13) ◽  
pp. 2421-2432 ◽  
Author(s):  
Eric J. Huang ◽  
Wei Liu ◽  
Bernd Fritzsch ◽  
Lynne M. Bianchi ◽  
Louis F. Reichardt ◽  
...  
Keyword(s):  
Inner Ear ◽  
Ganglion Cells ◽  
Substantial Reduction ◽  
Spiral Ganglion ◽  
Neurotrophin Receptor ◽  
Axon Pathfinding ◽  
Target Field ◽  
Afferent Fibers ◽  
Soma Size ◽  
Ganglion Neurons

The POU domain transcription factors Brn3a, Brn3b and Brn3c are required for the proper development of sensory ganglia, retinal ganglion cells, and inner ear hair cells, respectively. We have investigated the roles of Brn3a in neuronal differentiation and target innervation in the facial-stato-acoustic ganglion. We show that absence of Brn3a results in a substantial reduction in neuronal size, abnormal neuronal migration and downregulation of gene expression, including that of the neurotrophin receptor TrkC, parvalbumin and Brn3b. Selective loss of TrkC neurons in the spiral ganglion of Brn3a−/− cochlea leads to an innervation defect similar to that of TrkC−/− mice. Most remarkably, our results uncover a novel role for Brn3a in regulating axon pathfinding and target field innervation by spiral and vestibular ganglion neurons. Loss of Brn3a results in severe retardation in development of the axon projections to the cochlea and the posterior vertical canal as early as E13.5. In addition, efferent axons that use the afferent fibers as a scaffold during pathfinding also show severe misrouting. Interestingly, despite the well-established roles of ephrins and EphB receptors in axon pathfinding, expression of these molecules does not appear to be affected in Brn3a−/− mice. Thus, Brn3a must control additional downstream genes that are required for axon pathfinding.

scholarly journals Neural Tissue Degeneration in Rosenthal’s Canal and Its Impact on Electrical Stimulation of the Auditory Nerve by Cochlear Implants: An Image-Based Modeling Study

2020 ◽  
Vol 21 (22) ◽  
pp. 8511
Author(s):  
Kiran Kumar Sriperumbudur ◽  
Revathi Appali ◽  
Anthony W. Gummer ◽  
Ursula van Rienen
Keyword(s):  
Cochlear Implant ◽  
Cochlear Implants ◽  
Auditory Nerve ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Sensorineural Deafness ◽  
Neural Tissue ◽  
Neural Degeneration ◽  
Tissue Degeneration ◽  
Ganglion Neurons

Sensorineural deafness is caused by the loss of peripheral neural input to the auditory nerve, which may result from peripheral neural degeneration and/or a loss of inner hair cells. Provided spiral ganglion cells and their central processes are patent, cochlear implants can be used to electrically stimulate the auditory nerve to facilitate hearing in the deaf or severely hard-of-hearing. Neural degeneration is a crucial impediment to the functional success of a cochlear implant. The present, first-of-its-kind two-dimensional finite-element model investigates how the depletion of neural tissues might alter the electrically induced transmembrane potential of spiral ganglion neurons. The study suggests that even as little as 10% of neural tissue degeneration could lead to a disproportionate change in the stimulation profile of the auditory nerve. This result implies that apart from encapsulation layer formation around the cochlear implant electrode, tissue degeneration could also be an essential reason for the apparent inconsistencies in the functionality of cochlear implants.

scholarly journals Intrinsically Self-renewing Neuroprogenitors From the A/J Mouse Spiral Ganglion as Virtually Unlimited Source of Mature Auditory Neurons

2020 ◽  
Vol 14 ◽  
Author(s):  
Francis Rousset ◽  
Vivianne B. C. Kokje ◽  
Rebecca Sipione ◽  
Dominik Schmidbauer ◽  
German Nacher-Soler ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Progenitor Cells ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Specific Cell ◽  
Auditory Neurons ◽  
Self Renewal ◽  
Starting Point ◽  
Ganglion Neurons

Nearly 460 million individuals are affected by sensorineural hearing loss (SNHL), one of the most common human sensory disorders. In mammals, hearing loss is permanent due to the lack of efficient regenerative capacity of the sensory epithelia and spiral ganglion neurons (SGN). Sphere-forming progenitor cells can be isolated from the mammalian inner ear and give rise to inner ear specific cell types in vitro. However, the self-renewing capacities of auditory progenitor cells from the sensory and neuronal compartment are limited to few passages, even after adding powerful growth factor cocktails. Here, we provide phenotypical and functional characterization of a new pool of auditory progenitors as sustainable source for sphere-derived auditory neurons. The so-called phoenix auditory neuroprogenitors, isolated from the A/J mouse spiral ganglion, exhibit robust intrinsic self-renewal properties beyond 40 passages. At any passage or freezing–thawing cycle, phoenix spheres can be efficiently differentiated into mature spiral ganglion cells by withdrawing growth factors. The differentiated cells express both neuronal and glial cell phenotypic markers and exhibit similar functional properties as mouse spiral ganglion primary explants and human sphere-derived spiral ganglion cells. In contrast to other rodent models aiming at sustained production of auditory neurons, no genetic transformation of the progenitors is needed. Phoenix spheres therefore represent an interesting starting point to further investigate self-renewal in the mammalian inner ear, which is still far from any clinical application. In the meantime, phoenix spheres already offer an unlimited source of mammalian auditory neurons for high-throughput screens while substantially reducing the numbers of animals needed.

scholarly journals Gene therapy as a possible option to treat hereditary hearing loss

2020 ◽  
Vol 32 (2) ◽  
pp. 149-159
Author(s):  
Michael Morgan ◽  
Juliane W. Schott ◽  
Axel Rossi ◽  
Christian Landgraf ◽  
Athanasia Warnecke ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Middle Ear ◽  
Hearing Aids ◽  
Spiral Ganglion ◽  
Primary Auditory Cortex ◽  
Auditory Pathway ◽  
Therapeutic Strategies ◽  
Sound Waves ◽  
Ganglion Neurons

Abstract The process of hearing involves a series of events. The energy of sound is captured by the outer ear and further transferred through the external auditory canal to the middle ear. In the middle ear, sound waves are converted into movements of the tympanic membrane and the ossicles, thereby amplifying the pressure so that it is sufficient to cause movement of the cochlear fluid. The traveling wave within the cochlea leads to depolarization of the inner ear hair cells that, in turn, release the neurotransmitter glutamate. Thereby, the spiral ganglion neurons are activated to transfer the signals via the auditory pathway to the primary auditory cortex. This complex combination of mechanosensory and physiological mechanisms involves many distinct types of cells, the function of which are impacted by numerous proteins, including those involved in ion channel activity, signal transduction and transcription. In the last 30 years, pathogenic variants in over 150 genes were found to be linked to hearing loss. Hearing loss affects over 460 million people world-wide, and current treatment approaches, such as hearing aids and cochlear implants, serve to improve hearing capacity but do not address the underlying genetic cause of hearing loss. Therefore, therapeutic strategies designed to correct the genetic defects causative for hearing loss offer the possibility to treat these patients. In this review, we will discuss genetic causes of hearing loss, novel gene therapeutic strategies to correct hearing loss due to gene defects and some of the preclinical studies in hearing loss animal models as well as the clinical translation of gene therapy approaches to treat hearing loss patients.

scholarly journals ISL1 is an essential determinant of structural and functional tonotopic representation of sound

2021 ◽  
Author(s):  
Iva Filova ◽  
Kateryna Pysanenko ◽  
Mitra Tavakoli ◽  
Simona Vochyanova ◽  
Martina Dvorakova ◽  
...  
Keyword(s):  
Auditory Processing ◽  
Acoustic Startle ◽  
Spiral Ganglion ◽  
Auditory Pathway ◽  
Acoustic Startle Reflex ◽  
Mutant Mice ◽  
Spiral Ganglion Neurons ◽  
Auditory Neurons ◽  
Frequency Map ◽  
Ganglion Neurons

A cardinal feature of the auditory pathway is frequency selectivity, represented in the form of a tonotopic map from the cochlea to the cortex. The molecular determinants of the auditory frequency map are unknown. Here, we discovered that the transcription factor ISL1 regulates molecular and cellular features of auditory neurons, including the formation of the spiral ganglion, and peripheral and central processes that shape the tonotopic representation of the auditory map. We selectively knocked out Isl1 in auditory neurons using Neurod1Cre strategies. In the absence of Isl1, spiral ganglion neurons migrate into the central cochlea and beyond, and the cochlear wiring is profoundly reduced and disrupted. The central axons of Isl1 mutants lose their topographic projections and segregation at the cochlear nucleus. Transcriptome analysis of spiral ganglion neurons shows that Isl1 regulates neurogenesis, axonogenesis, migration, neurotransmission-related machinery, and synaptic communication patterns. We show that peripheral disorganization in the cochlea affects the physiological properties of hearing in the midbrain and auditory behavior. Surprisingly, auditory processing features are preserved despite the significant hearing impairment, revealing central auditory pathway resilience and plasticity in Isl1 mutant mice. Mutant mice have a reduced acoustic startle reflex, altered prepulse inhibition, and characteristics of compensatory neural hyperactivity centrally. Our findings show that ISL1 is one of the obligatory factors required to sculpt auditory structural and functional tonotopic maps. Still, upon Isl1 deletion, the ensuing central compensatory plasticity of the auditory pathway does not suffice to overcome developmentally induced peripheral dysfunction of the cochlea.

scholarly journals Estrogen inhibits the apoptosis of spiral ganglion cells in C57BL/6J mice with presbycusis by downregulating AQP4.

2020 ◽  
Author(s):  
Long Chen ◽  
Yu-qi Yang ◽  
Xue-rui Li ◽  
Zi-yi Feng ◽  
Zi-wei Han ◽  
...  
Keyword(s):  
Protective Effect ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Hearing Threshold ◽  
The Elderly ◽  
Control Group ◽  
Aqp4 Expression ◽  
Cochlear Spiral Ganglion ◽  
Ganglion Neurons ◽  
Group D

Abstract BackgroundEstrogen has a protective effect on age-related hearing loss (ARHL), but the mechanism has not been elucidated. Cochlear spiral ganglion neurons (SGN) are an important link between the cochlear hair cells and the auditory center. This study used C57BL/6J mice as models of elderly individuals to observe the protective effect of estrogen against cochlear spiral ganglion cell apoptosis.MethodsFifty mice were divided into the following five groups (10 mice/group): the young group at 3 months of age (3 m), the elderly group at 12 months of age (12 m), the ovariectomized group at 12 months of age (12 m ovx), the ovariectomized group at 12 months of age + estrogen treatment for 1 month (E2 1 m), and the ovariectomized group at 12 months of age + estrogen treatment for 2 months (E2 2 m). The auditory brain stem response (ABR) was analyzed to detect changes in the hearing threshold, enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum estrogen levels,Hematoxylin eosin (HE) staining and transmission electron microscopy (TEM) were used to observe the morphological changes in the cochlea spiral ganglion neurons (SGN), and TUNEL staining was used to observe the apoptosis of SGN. The expression of AQP4 was observed by immunofluorescence, and the mRNA expression levels of AQP4, Caspase-3, Bax and Bcl-2 in the cochlea spiral ganglion were determined by qRT-PCR. Cell experiments: Primary cultures of spiral ganglion cells were divided into a control group (SGC), DMSO group, D-gal group, D-gal + E2 group, D-gal + TGN020 group and D-gal + E2 + TGN020 group. Immunofluorescence was used to observe the AQP4 expression, qRT-PCR was used to observe the AQP4, Caspase-3, Bax and Bcl-2 mRNA expression levels, and flow cytometry was used to observe the apoptosis rate.ResultsAn increased hearing threshold was observed in the elderly mice (P < 0.001). After removal of the ovaries, the hearing threshold of the mice in the 12 m ovx group was higher than it was in the 12 m control group (P < 0.05), and this increased threshold was accompanied by an increased loss of spiral ganglion cells, increased apoptosis (P < 0.01), and increased AQP4 expression (P < 0.001). Treatment with exogenous estrogen reversed all these changes. Cell experiments: D-gal increased the apoptosis rate (P < 0.001) and AQP4 expression (P < 0.001). Estrogen and the AQP4 inhibitor TGN020 both reduced the apoptosis rate and AQP4 expression.ConclusionEstrogen inhibited apoptosis of cochlear spiral ganglion cells in aged C57BL/6J mice by downregulating AQP4, thus achieving a protective effect on ARHL.

scholarly journals Minocycline Protection of Neomycin Induced Hearing Loss in Gerbils

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Alan M. Robinson ◽  
Irena Vujanovic ◽  
Claus-Peter Richter
Keyword(s):  
Hearing Loss ◽  
Spiral Ganglion ◽  
Hearing Threshold ◽  
Organ Of Corti ◽  
Aminoglycoside Antibiotic ◽  
Histological Evaluation ◽  
Spiral Ganglion Neuron ◽  
Spiral Ganglion Neurons ◽  
Simultaneous Application ◽  
Ganglion Neurons

This animal study was designed to determine if minocycline ameliorates cochlear damage is caused by intratympanic injection of the ototoxic aminoglycoside antibiotic neomycin. Baseline auditory-evoked brainstem responses were measured in gerbils that received 40 mM intratympanic neomycin either with 0, 1.2, or 1.5 mg/kg intraperitoneal minocycline. Four weeks later auditory-evoked brainstem responses were measured and compared to the baseline measurements. Minocycline treatments of 1.2 mg/kg and 1.5 mg/kg resulted in significantly lower threshold increases compared to 0 mg/kg, indicating protection of hearing loss between 6 kHz and 19 kHz. Cochleae were processed for histology and sectioned to allow quantification of the spiral ganglion neurons and histological evaluation of organ of Corti. Significant reduction of spiral ganglion neuron density was demonstrated in animals that did not receive minocycline, indicating that those receiving minocycline demonstrated enhanced survival of spiral ganglion neurons, enhanced survival of sensory hairs cells and spiral ganglion neurons, and reduced hearing threshold elevation correlates with minocycline treatment demonstrating that neomycin induced hearing loss can be reduced by the simultaneous application of minocycline.

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