The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Srdjan M Vlajkovic - One of the best experts on this subject based on the ideXlab platform.
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Developmentally regulated expression of ectonucleotidases NTPDase5 and NTPDase6 and UDP-responsive P2Y receptors in the rat Cochlea
Histochemistry and Cell Biology, 2010Co-Authors: Mary G. O’keeffe, Gary D Housley, Peter R Thorne, Simon C. Robson, Srdjan M VlajkovicAbstract:Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) regulate complex extracellular P2 receptor signalling pathways in mammalian tissues by hydrolysing extracellular nucleotides to the respective nucleosides. All enzymes from this family (NTPDase1-8) are expressed in the adult rat Cochlea. This study reports the changes in expression of NTPDase5 and NTPDase6 in the developing rat Cochlea. These two intracellular members of the E-NTPDase family can be released in a soluble form and show preference for nucleoside 5′-diphosphates, such as UDP and GDP. Here, we demonstrate differential spatial and temporal patterns for NTPDase5 and NTPDase6 expression during Cochlear development, which are indicative of both cytosolic and extracellular action via pyrimidines. NTPDase5 is noted during the early postnatal period in developing sensory hair cells and supporting Deiters’ cells of the organ of Corti, and primary auditory neurons located in the spiral ganglion. In contrast, NTPDase6 is confined to the embryonic and early postnatal hair cell bundles. NTPDase6 immunolocalisation in the developing Cochlea underpins its putative role in hair cell bundle development, probably via cytosolic action, whilst NTPDase5 may have a broader extracellular role in the development of sensory and neural tissues in the rat Cochlea. Both NTPDase5 and NTPDase6 colocalize with UDP-preferring P2Y_4, P2Y_6 and P2Y_14 receptors during Cochlear development, but this strong association was lost in the adult Cochlea. Spatiotemporal topographic expression of NTPDase5 and NTPDase6 and P2Y receptors in adult and developing Cochlear tissues provide strong support for the role of pyrimidinergic signalling in Cochlear development.
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Post exposure administration of A1 adenosine receptor agonists attenuates noise-induced hearing loss
Hearing Research, 2010Co-Authors: Ann Chi Yan Wong, Rita Gupta, Gary D Housley, Peter R Thorne, Srdjan M VlajkovicAbstract:Abstract Adenosine is a constitutive cell metabolite with a putative role in protection and regeneration in many tissues. This study was undertaken to determine if adenosine signalling pathways are involved in protection against noise injury. A1 adenosine receptor expression levels were altered in the Cochlea exposed to loud sound, suggesting their involvement in the development of noise injury. Adenosine and selective adenosine receptor agonists (CCPA, CGS-21680 and Cl-IB-MECA) were applied to the round window membrane of the Cochlea 6 h after noise exposure. Auditory brainstem responses measured 48 h after drug administration demonstrated partial recovery of hearing thresholds (up to 20 dB) in the Cochleae treated with adenosine (non-selective adenosine receptor agonist) or CCPA (selective A1 adenosine receptor agonist). In contrast, the selective A2A adenosine receptor agonist CGS-21680 and A3 adenosine receptor agonist Cl-IB-MECA did not protect the Cochlea from hearing loss. Sound-evoked Cochlear potentials in control rats exposed to ambient noise were minimally altered by local administration of the adenosine receptor agonists used in the noise study. Free radical generation in the Cochlea exposed to noise was reduced by administration of adenosine and CCPA. This study pinpoints A1 adenosine receptors as attractive targets for pharmacological interventions to reduce noise-induced Cochlear injury after exposure.
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Post exposure administration of A(1) adenosine receptor agonists attenuates noise-induced hearing loss.
Hearing research, 2009Co-Authors: Ann Chi Yan Wong, Rita Gupta, Gary D Housley, Peter R Thorne, Srdjan M VlajkovicAbstract:Adenosine is a constitutive cell metabolite with a putative role in protection and regeneration in many tissues. This study was undertaken to determine if adenosine signalling pathways are involved in protection against noise injury. A(1) adenosine receptor expression levels were altered in the Cochlea exposed to loud sound, suggesting their involvement in the development of noise injury. Adenosine and selective adenosine receptor agonists (CCPA, CGS-21680 and Cl-IB-MECA) were applied to the round window membrane of the Cochlea 6h after noise exposure. Auditory brainstem responses measured 48h after drug administration demonstrated partial recovery of hearing thresholds (up to 20dB) in the Cochleae treated with adenosine (non-selective adenosine receptor agonist) or CCPA (selective A(1) adenosine receptor agonist). In contrast, the selective A(2A) adenosine receptor agonist CGS-21680 and A(3) adenosine receptor agonist Cl-IB-MECA did not protect the Cochlea from hearing loss. Sound-evoked Cochlear potentials in control rats exposed to ambient noise were minimally altered by local administration of the adenosine receptor agonists used in the noise study. Free radical generation in the Cochlea exposed to noise was reduced by administration of adenosine and CCPA. This study pinpoints A(1) adenosine receptors as attractive targets for pharmacological interventions to reduce noise-induced Cochlear injury after exposure.
Gary D Housley - One of the best experts on this subject based on the ideXlab platform.
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Developmentally regulated expression of ectonucleotidases NTPDase5 and NTPDase6 and UDP-responsive P2Y receptors in the rat Cochlea
Histochemistry and Cell Biology, 2010Co-Authors: Mary G. O’keeffe, Gary D Housley, Peter R Thorne, Simon C. Robson, Srdjan M VlajkovicAbstract:Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) regulate complex extracellular P2 receptor signalling pathways in mammalian tissues by hydrolysing extracellular nucleotides to the respective nucleosides. All enzymes from this family (NTPDase1-8) are expressed in the adult rat Cochlea. This study reports the changes in expression of NTPDase5 and NTPDase6 in the developing rat Cochlea. These two intracellular members of the E-NTPDase family can be released in a soluble form and show preference for nucleoside 5′-diphosphates, such as UDP and GDP. Here, we demonstrate differential spatial and temporal patterns for NTPDase5 and NTPDase6 expression during Cochlear development, which are indicative of both cytosolic and extracellular action via pyrimidines. NTPDase5 is noted during the early postnatal period in developing sensory hair cells and supporting Deiters’ cells of the organ of Corti, and primary auditory neurons located in the spiral ganglion. In contrast, NTPDase6 is confined to the embryonic and early postnatal hair cell bundles. NTPDase6 immunolocalisation in the developing Cochlea underpins its putative role in hair cell bundle development, probably via cytosolic action, whilst NTPDase5 may have a broader extracellular role in the development of sensory and neural tissues in the rat Cochlea. Both NTPDase5 and NTPDase6 colocalize with UDP-preferring P2Y_4, P2Y_6 and P2Y_14 receptors during Cochlear development, but this strong association was lost in the adult Cochlea. Spatiotemporal topographic expression of NTPDase5 and NTPDase6 and P2Y receptors in adult and developing Cochlear tissues provide strong support for the role of pyrimidinergic signalling in Cochlear development.
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TRPC3 ion channel subunit immunolocalization in the Cochlea
Histochemistry and Cell Biology, 2010Co-Authors: Sherif F. Tadros, Patrick A. B. Phan, Lutz Birnbaumer, Gary D HousleyAbstract:Canonical transient receptor potential (TRPC) subunits assemble as tetramers to form ion channels with high calcium (Ca^2+) permeability. Here, we investigated the possibility that TRPC3 ion channels are broadly expressed in the adult guinea pig and mouse Cochleae. Using immunofluorescence, pronounced labeling occurred in the spiral ganglion (SG) neurons, inner hair cells (IHC), outer hair cells (OHC) and epithelial cells lining scala media. TRPC3 expression was homogeneous in the SG throughout the Cochlea. In contrast, there was marked spatial variation in the immunolabeling in the Cochlear hair cells with respect to location. This likely relates to the tonotopy of these cells. TRPC3 immunolabeling was more pronounced in the IHC than OHC. Both basal region IHC and OHC had higher TRPC3 expression levels than the corresponding cells from the apical region of the Cochlea. These data suggest that TRPC3 ion channels contribute to Ca^2+ homeostasis associated with the hair cells, with higher ion fluxes in more basal regions of the Cochlea, and may also be a significant pathway for Ca^2+ entry associated with auditory neurotransmission via the SG neurons. TRPC3 expression was also identified within the spiral limbus region, inner and outer sulcus, but without evidence for spatial variation in expression level. Expression in these gap junction-coupled epithelial cells lining scala media is indicative of a contribution of TRPC3 channels to Cochlear electrochemical homeostasis.
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Post exposure administration of A1 adenosine receptor agonists attenuates noise-induced hearing loss
Hearing Research, 2010Co-Authors: Ann Chi Yan Wong, Rita Gupta, Gary D Housley, Peter R Thorne, Srdjan M VlajkovicAbstract:Abstract Adenosine is a constitutive cell metabolite with a putative role in protection and regeneration in many tissues. This study was undertaken to determine if adenosine signalling pathways are involved in protection against noise injury. A1 adenosine receptor expression levels were altered in the Cochlea exposed to loud sound, suggesting their involvement in the development of noise injury. Adenosine and selective adenosine receptor agonists (CCPA, CGS-21680 and Cl-IB-MECA) were applied to the round window membrane of the Cochlea 6 h after noise exposure. Auditory brainstem responses measured 48 h after drug administration demonstrated partial recovery of hearing thresholds (up to 20 dB) in the Cochleae treated with adenosine (non-selective adenosine receptor agonist) or CCPA (selective A1 adenosine receptor agonist). In contrast, the selective A2A adenosine receptor agonist CGS-21680 and A3 adenosine receptor agonist Cl-IB-MECA did not protect the Cochlea from hearing loss. Sound-evoked Cochlear potentials in control rats exposed to ambient noise were minimally altered by local administration of the adenosine receptor agonists used in the noise study. Free radical generation in the Cochlea exposed to noise was reduced by administration of adenosine and CCPA. This study pinpoints A1 adenosine receptors as attractive targets for pharmacological interventions to reduce noise-induced Cochlear injury after exposure.
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Post exposure administration of A(1) adenosine receptor agonists attenuates noise-induced hearing loss.
Hearing research, 2009Co-Authors: Ann Chi Yan Wong, Rita Gupta, Gary D Housley, Peter R Thorne, Srdjan M VlajkovicAbstract:Adenosine is a constitutive cell metabolite with a putative role in protection and regeneration in many tissues. This study was undertaken to determine if adenosine signalling pathways are involved in protection against noise injury. A(1) adenosine receptor expression levels were altered in the Cochlea exposed to loud sound, suggesting their involvement in the development of noise injury. Adenosine and selective adenosine receptor agonists (CCPA, CGS-21680 and Cl-IB-MECA) were applied to the round window membrane of the Cochlea 6h after noise exposure. Auditory brainstem responses measured 48h after drug administration demonstrated partial recovery of hearing thresholds (up to 20dB) in the Cochleae treated with adenosine (non-selective adenosine receptor agonist) or CCPA (selective A(1) adenosine receptor agonist). In contrast, the selective A(2A) adenosine receptor agonist CGS-21680 and A(3) adenosine receptor agonist Cl-IB-MECA did not protect the Cochlea from hearing loss. Sound-evoked Cochlear potentials in control rats exposed to ambient noise were minimally altered by local administration of the adenosine receptor agonists used in the noise study. Free radical generation in the Cochlea exposed to noise was reduced by administration of adenosine and CCPA. This study pinpoints A(1) adenosine receptors as attractive targets for pharmacological interventions to reduce noise-induced Cochlear injury after exposure.
Peter R Thorne - One of the best experts on this subject based on the ideXlab platform.
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Developmentally regulated expression of ectonucleotidases NTPDase5 and NTPDase6 and UDP-responsive P2Y receptors in the rat Cochlea
Histochemistry and Cell Biology, 2010Co-Authors: Mary G. O’keeffe, Gary D Housley, Peter R Thorne, Simon C. Robson, Srdjan M VlajkovicAbstract:Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) regulate complex extracellular P2 receptor signalling pathways in mammalian tissues by hydrolysing extracellular nucleotides to the respective nucleosides. All enzymes from this family (NTPDase1-8) are expressed in the adult rat Cochlea. This study reports the changes in expression of NTPDase5 and NTPDase6 in the developing rat Cochlea. These two intracellular members of the E-NTPDase family can be released in a soluble form and show preference for nucleoside 5′-diphosphates, such as UDP and GDP. Here, we demonstrate differential spatial and temporal patterns for NTPDase5 and NTPDase6 expression during Cochlear development, which are indicative of both cytosolic and extracellular action via pyrimidines. NTPDase5 is noted during the early postnatal period in developing sensory hair cells and supporting Deiters’ cells of the organ of Corti, and primary auditory neurons located in the spiral ganglion. In contrast, NTPDase6 is confined to the embryonic and early postnatal hair cell bundles. NTPDase6 immunolocalisation in the developing Cochlea underpins its putative role in hair cell bundle development, probably via cytosolic action, whilst NTPDase5 may have a broader extracellular role in the development of sensory and neural tissues in the rat Cochlea. Both NTPDase5 and NTPDase6 colocalize with UDP-preferring P2Y_4, P2Y_6 and P2Y_14 receptors during Cochlear development, but this strong association was lost in the adult Cochlea. Spatiotemporal topographic expression of NTPDase5 and NTPDase6 and P2Y receptors in adult and developing Cochlear tissues provide strong support for the role of pyrimidinergic signalling in Cochlear development.
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Post exposure administration of A1 adenosine receptor agonists attenuates noise-induced hearing loss
Hearing Research, 2010Co-Authors: Ann Chi Yan Wong, Rita Gupta, Gary D Housley, Peter R Thorne, Srdjan M VlajkovicAbstract:Abstract Adenosine is a constitutive cell metabolite with a putative role in protection and regeneration in many tissues. This study was undertaken to determine if adenosine signalling pathways are involved in protection against noise injury. A1 adenosine receptor expression levels were altered in the Cochlea exposed to loud sound, suggesting their involvement in the development of noise injury. Adenosine and selective adenosine receptor agonists (CCPA, CGS-21680 and Cl-IB-MECA) were applied to the round window membrane of the Cochlea 6 h after noise exposure. Auditory brainstem responses measured 48 h after drug administration demonstrated partial recovery of hearing thresholds (up to 20 dB) in the Cochleae treated with adenosine (non-selective adenosine receptor agonist) or CCPA (selective A1 adenosine receptor agonist). In contrast, the selective A2A adenosine receptor agonist CGS-21680 and A3 adenosine receptor agonist Cl-IB-MECA did not protect the Cochlea from hearing loss. Sound-evoked Cochlear potentials in control rats exposed to ambient noise were minimally altered by local administration of the adenosine receptor agonists used in the noise study. Free radical generation in the Cochlea exposed to noise was reduced by administration of adenosine and CCPA. This study pinpoints A1 adenosine receptors as attractive targets for pharmacological interventions to reduce noise-induced Cochlear injury after exposure.
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Post exposure administration of A(1) adenosine receptor agonists attenuates noise-induced hearing loss.
Hearing research, 2009Co-Authors: Ann Chi Yan Wong, Rita Gupta, Gary D Housley, Peter R Thorne, Srdjan M VlajkovicAbstract:Adenosine is a constitutive cell metabolite with a putative role in protection and regeneration in many tissues. This study was undertaken to determine if adenosine signalling pathways are involved in protection against noise injury. A(1) adenosine receptor expression levels were altered in the Cochlea exposed to loud sound, suggesting their involvement in the development of noise injury. Adenosine and selective adenosine receptor agonists (CCPA, CGS-21680 and Cl-IB-MECA) were applied to the round window membrane of the Cochlea 6h after noise exposure. Auditory brainstem responses measured 48h after drug administration demonstrated partial recovery of hearing thresholds (up to 20dB) in the Cochleae treated with adenosine (non-selective adenosine receptor agonist) or CCPA (selective A(1) adenosine receptor agonist). In contrast, the selective A(2A) adenosine receptor agonist CGS-21680 and A(3) adenosine receptor agonist Cl-IB-MECA did not protect the Cochlea from hearing loss. Sound-evoked Cochlear potentials in control rats exposed to ambient noise were minimally altered by local administration of the adenosine receptor agonists used in the noise study. Free radical generation in the Cochlea exposed to noise was reduced by administration of adenosine and CCPA. This study pinpoints A(1) adenosine receptors as attractive targets for pharmacological interventions to reduce noise-induced Cochlear injury after exposure.
Tibor Zelles - One of the best experts on this subject based on the ideXlab platform.
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purinergic signaling and Cochlear injury targeting the immune system
International Journal of Molecular Sciences, 2019Co-Authors: Laszlo Koles, Judit Szepesy, Eszter Berekmeri, Tibor ZellesAbstract:Hearing impairment is the most common sensory deficit, affecting more than 400 million people worldwide. Sensorineural hearing losses currently lack any specific or efficient pharmacotherapy largely due to the insufficient knowledge of the pathomechanism. Purinergic signaling plays a substantial role in Cochlear (patho)physiology. P2 (ionotropic P2X and the metabotropic P2Y) as well as adenosine receptors expressed on Cochlear sensory and non-sensory cells are involved mostly in protective mechanisms of the Cochlea. They are implicated in the sensitivity adjustment of the receptor cells by a K+ shunt and can attenuate the Cochlear amplification by modifying Cochlear micromechanics. Cochlear blood flow is also regulated by purines. Here, we propose to comprehend this field with the purine-immune interactions in the Cochlea. The role of harmful immune mechanisms in sensorineural hearing losses has been emerging in the horizon of Cochlear pathologies. In addition to decreasing hearing sensitivity and increasing Cochlear blood supply, influencing the immune system can be the additional avenue for pharmacological targeting of purinergic signaling in the Cochlea. Elucidating this complexity of purinergic effects on Cochlear functions is necessary and it can result in development of new therapeutic approaches in hearing disabilities, especially in the noise-induced ones.
Mark E Warchol - One of the best experts on this subject based on the ideXlab platform.
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fractalkine signaling regulates macrophage recruitment into the Cochlea and promotes the survival of spiral ganglion neurons after selective hair cell lesion
The Journal of Neuroscience, 2015Co-Authors: Tejbeer Kaur, Darius Zamani, Ling Tong, Edwin W Rubel, Kevin K Ohlemiller, Keiko Hirose, Mark E WarcholAbstract:Macrophages are recruited into the Cochlea in response to injury caused by acoustic trauma or ototoxicity, but the nature of the interaction between macrophages and the sensory structures of the inner ear remains unclear. The present study examined the role of fractalkine signaling in regulating the injury-evoked behavior of macrophages following the selective ablation of Cochlear hair cells. We used a novel transgenic mouse model in which the human diphtheria toxin receptor (huDTR) is selectively expressed under the control of Pou4f3 , a hair cell-specific transcription factor. Administration of diphtheria toxin (DT) to these mice resulted in nearly complete ablation of Cochlear hair cells, with no evident pathology among supporting cells, spiral ganglion neurons, or cells of the Cochlear lateral wall. Hair cell death led to an increase in macrophages associated with the sensory epithelium of the Cochlea. Their numbers peaked at 14 days after DT and then declined at later survival times. Increased macrophages were also observed within the spiral ganglion, but their numbers remained elevated for (at least) 56 d after DT. To investigate the role of fractalkine signaling in macrophage recruitment, we crossed huDTR mice to a mouse line that lacks expression of the fractalkine receptor (CX 3 CR1). Disruption of fractalkine signaling reduced macrophage recruitment into both the sensory epithelium and spiral ganglion and also resulted in diminished survival of spiral ganglion neurons after hair cell death. Our results suggest a fractalkine-mediated interaction between macrophages and the neurons of the Cochlea. SIGNIFICANCE STATEMENT It is known that damage to the inner ear leads to recruitment of inflammatory cells (macrophages), but the chemical signals that initiate this recruitment and the functions of macrophages in the damaged ear are unclear. Here we show that fractalkine signaling regulates macrophage recruitment into the Cochlea and also promotes the survival of Cochlear afferents after selective hair cell lesion. Because these afferent neurons carry sound information from the Cochlea to the auditory brainstem, their survival is a key determinant of the success of Cochlear prosthetics. Our data suggest that fractalkine signaling in the Cochlea is neuroprotective, and reveal a previously uncharacterized interaction between cells of the Cochlea and the innate immune system.
