Sensory SystemResearch PaperQuantitative analysis of the expression of the glutamate–aspartate transporter and identification of functional glutamate uptake reveal a role for cochlear fibrocytes in glutamate homeostasis
Section snippets
Animals
CD-1 mice, pigmented guinea pigs and rats have been used in this study. Five-week old CD-1 mice were used to investigate the distribution of GLAST in different fibrocyte types and cochlear regions by immunofluorescence and quantitative immunogold electron microscopy. Relative levels of glutamate were also assessed in CD-1 mouse fibrocytes. The relative amount of GLAST was determined in different cochlear sub-regions, by dot blotting of guinea-pig tissue, which have four cochlear turns, as
Results
The anatomical landmarks relevant to this study are illustrated in Fig. 1A which shows a cross-section of the cochlear duct. Fibrocytes which contain GLAST are located in the lateral wall and on the perilymphatic surface of the spiral limbus. Other regions known to contain GLAST are the spiral ganglion and organ of Corti.
Discussion
The present study was aimed primarily at determining whether lateral wall fibrocytes in the cochlea exhibit a functional glutamate uptake process based on the expression of GLAST. Our data show that (i) the lateral wall expresses the greater proportion of cochlear GLAST compared with spiral ganglion and organ of Corti in guinea pig; (ii) at the cellular level in mice, type II and type V fibrocytes express the most GLAST and this expression is achieved by an increased surface area and not by
Conclusion
Our data show that lateral wall fibrocytes express GLAST in the relative amount type II>type V>type IV>type I>type III, that the fibrocytes possess functional uptake capacity based on GLAST and can accumulate a glutamate analogue. Type V has the highest glutamate levels and is most exposed to perilymph. Spiral limbus fibrocytes also express high levels of GLAST relative to other types and have strong uptake currents. These data all suggest that the fibrocytes perform a role in glutamate
Acknowledgments
Supported by Deafness Research UK. D.J.J. is a Royal Society University Research Fellow.
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2022, American Journal of Human GeneticsCitation Excerpt :For instance, using 1,100 proprioceptive neurons and Smart-seq2, Wu et al. detected 11,000 genes per cell and identified 8 cell types,76 while previous studies using 10X Genomics favoring a higher number of cells but with lower coverage could not differentiate proprioceptive neurons in any subtypes.77 In the study from Milon et al., only one type of fibrocyte was identified, whereas there are 5 known types of fibrocytes (type I–V) present in both man and experimental animals, but that have quite different function and molecular expression.78,79 Thus, new sequencing technologies may offer increased resolution and statistical power to reveal more accurate predictions of the involvement of more specific cells in hearing loss.
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2022, Hearing ResearchCitation Excerpt :Deterioration of EP and subsequent lateral wall degeneration may reflect specific patterns of hearing impairment, such as those associated with metabolic hearing loss (Lang et al., 2010; Dubno et al., 2013; Saremi and Stenfelt, 2013). There are five main types of fibrocyte, Types I – V which differ in location in the spiral ligament and in morphology (Spicer and Schulte, 1996; Furness et al., 2009). They are connected together by gap junctions in a syncytial network and are thought to perform roles in ion transfer (in generating the EP), water balance, inflammation and basilar membrane tensioning (see review by Furness, 2019).
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2021, Progress in Brain ResearchImmunohistochemical localization of Nrf2 in the human cochlea
2018, Brain ResearchCitation Excerpt :Sensory and non-sensory cells in the inner ear are exposed to ototoxicants and noise during the life time of an individual. Glutamate is the major neurotransmitter in the cochlea and vestibule (Furness et al., 2009; Sadeghi et al., 2014). Excessive noise or ototoxicants can evoke excessive release of glutamate.
The expression of glutamate aspartate transporter (GLAST) within the human cochlea and its distribution in various patient populations
2013, Brain ResearchCitation Excerpt :The spiral ligament contains an extracellular matrix that has five regionally and morphologically distinct types of fibrocytes, types I–V (Spicer and Schulte, 1996). Fibrocytes are also found over the perilymphatic surface of the spiral limbus, a ridge of tissue on the osseous spiral lamina that runs internal to the Organ of Corti (Furness et al., 2009). These cells contain Na+/K+ ATPase and other ion pumps, allowing them to contribute to the maintenance of ion homeostasis.
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2012, Hearing ResearchCitation Excerpt :It should be noted, however, that GS expression was examined in whole cochlear lysates, and therefore may not reflect processes occurring specifically at the afferent synapse. Recent work demonstrated activity of the excitatory amino acid transporter GLAST in fibrocytes lining the lateral wall and suggests a role for these cells in regulating glutamate homeostasis (Furness et al., 2009). It follows that glutamine synthetase may also be expressed in these cells as well to regulate glutamate recycling.