Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regenera...Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.展开更多
The damage to spiral organs related to age and sex in guinea pigs was studied by the surface preparation technique. Hair cell loss of spiral organs of the following four age groups: 8month, 1, 2, and 2.5-year old pig...The damage to spiral organs related to age and sex in guinea pigs was studied by the surface preparation technique. Hair cell loss of spiral organs of the following four age groups: 8month, 1, 2, and 2.5-year old pigs, was assessed. Each group was divided Into two subgroups according to different sexes. The decrease of hair cell population was linearly related to age, but not related to sex. The damage rate was greater in outer hair cells than in inner hair calls. In all of animals of different ages and both sexes, outer hair cell loss was prominent at the apex of cochlea. Less damage to outer hair cell was found at the base of cochlea. Damage to inner hair cell was also increased with age, but to a lesser extent.展开更多
Prestin has been identified as a motor protein responsible for outer hair cell (OHC) electromotility and is expressed on the OHC surface. Previous studies revealed that OHC electromotility and its associated nonlinear...Prestin has been identified as a motor protein responsible for outer hair cell (OHC) electromotility and is expressed on the OHC surface. Previous studies revealed that OHC electromotility and its associated nonlinear capacitance were mainly located at the OHC lateral wall and absent at the apical cuticular plate and the basal nucleus region. Immunofluorescent staining for prestin also failed to demonstrate prestin expression at the OHC basal ends in whole-mount preparation of the organ of Corti. However, there lacks a definitive demonstration of the pattern of prestin distribution. The OHC lateral wall has a trilaminate organization and is composed of the plasma membrane, cortical lattice, and subsurface cisternae. In this study, the location of prestin proteins in dissociated OHCs was examined using immunofluorescent staining and confocal microscopy. We found that prestin was uniformly expressed on the basolateral surface, including the basal pole. No staining was seen on the cuticular plate and stereocilia. When co-stained with a membrane marker di-8-ANEPPS, prestin-labeling was found to be in the outer layer of the OHC lateral wall. After separating the plasma membrane from the underlying subsurface cisternae using a hypotonic extracellular solution, prestin-labeling was found to be in the plasma membrane, not the subsurface cisternae. The data show that prestin is expressed in the plasma membrane on the entire OHC basolateral surface.展开更多
Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial c...Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial cells of adult rat were cultured. Immunocytochemistry and Bromodeoxyuridine (BrdU)labeling were used to detect properties and mitotic status of cultured cells. Results The cultured auditory epithelial cells showed a large, flat epithelial morphotype and expressed F-actin and cytokeratin, a subset of cells generated from auditory epithelium were labeled by calretinin, a specific marker of early hair cell. Conclusion Adult rat auditory epithelium can be induced to generate hair cell-like cells by nature culture, this phenomenon suggests that progenitor cells may exist in rat cochlea and they may give birth to new hair cells. Whether these progenitor cells are tissue specific stem cells is still need more study.展开更多
Most recent studies on regeneration of inner ear hair cells focus on use of stem cells, gene therapy and neurotrophic factors. Cochlear gene therapy has been successfully used in the treatment of neu- rosensory hearin...Most recent studies on regeneration of inner ear hair cells focus on use of stem cells, gene therapy and neurotrophic factors. Cochlear gene therapy has been successfully used in the treatment of neu- rosensory hearing loss. This suggests that cochlear hair cell regeneration is possible. The objective of this paper is to review research and clinical application of inner near hair cell regeneration.展开更多
The purpose of the present study was to determine protectivie effects of basic fibroblast growth factor (bFGF) on cochlear neurons and hair cells in vitro and in vivo. In experiment I, cultured spiral ganglion neurons...The purpose of the present study was to determine protectivie effects of basic fibroblast growth factor (bFGF) on cochlear neurons and hair cells in vitro and in vivo. In experiment I, cultured spiral ganglion neurons (SGNs) prepared from P3 mice were exposed to 20mM glutamate for 2 hours before the culture medium was replaced with fresh medium containing 0, 25, 50, and 100 ng/ml bFGF, respectively. Fourteen days later, all cultures were fixed with 4% paraformaldehyde, and stained with 1% toluidine blue. The number of surviving SGNs were counted and the length of SGNs neurites were measured. Exposure to 20 mM glutamate for 24 hours resulted in an inhibition on neurite outgrowth of SGNs and elevated cell death. Treatment of the cultures with bFGF led to promotion of neurite outgrowth and elevated number of surviving SGNs. Effects of bFGF were dose dependent with the highest potency at 100 ng/ml. In experiment Ⅱ, in vivo studies were carried out with guinea pigs in which bFGF or artificial perilymph was perfused into the cochlea to assess possible protective effects of bFGF on cochlear hair cells and compound action potentials(CAP). The CAPs were measured before, immediatly and 48 hours after exposure to noise. Significant differences in CAP were observed (p<0. 05 ) among the bFGF perfused group, control group(t =3. 896 ) and artificial perilymph perfused group (t =2. 520) at 48 hours after noise exposure, Cochleae were removed and hair cell Loss was analyzed in surface preparations prepared from all experimental animals. Acoustic trauma caused loss of 651 and 687 inner hair cells in the control and artificial perilymph perfused group, respectively. In sharp contrast, only 31 inner hair cells were lost in the bFGF perfused ears. Similarly, more outer hair cells died in the control and perilymph perfuesed group (41830 and 41968, respectively) than in the group treated with bFGF (34258). Our results demonstrate that bFGF protected SGNs against glutmate neurotoxicity in vitro. In addition, treatment with bFGF also protected hair cells from acoustic trauma.展开更多
The electrically evoked somatic motility of outer hair cells (OHC), briefly termed OHC electromotility, plays a crucial role in cochlear amplification that underlies the remarkably high sensitivity and frequency sel...The electrically evoked somatic motility of outer hair cells (OHC), briefly termed OHC electromotility, plays a crucial role in cochlear amplification that underlies the remarkably high sensitivity and frequency selectivity of the mammalian hearing. Accompanying OHC electromotility is a voltage-dependent gating charge movement within the cell lateral membrane, manifested as a measurable nonlinear capacitance (NLC) in OHCs. The electromotility and NLC of OHCs are highly correlated by sharing a common molecular substrate, the motor protein prestin. In this study, we systematically characterized the quantitative relationship between OHC electromotility and NLC in their voltage dependences for the purpose of further understanding the electromechanical transduction in OHCs. The results demonstrated that the two possess differing voltage dependences with the V^2 of electromotility consistently being -20 mV depolarized in comparison with that of NLC although their slope factors a are statistically identical. Further investigations showed that the initial state of OHCs influences the voltage dependence of electromotility but not that of NLC, indicating that some biophysical factors other than the motor protein per se are involved in the process of OHC length changes. We proposed that the cytoskeletal spectrin-actin framework underneath the OHC plasma membrane and the cell' s turgor are the two most probable factors that cause the voltage-dependence discrepancy between OHC electromotility and NLC.展开更多
Objective To investigate the occurrence and possible mechanisms of apoptosis in cochlear epithelium and spiral ganglion neurons after mefloquine treatment. Methods We used quantitative RT-PCR apoptosis-focused gene ar...Objective To investigate the occurrence and possible mechanisms of apoptosis in cochlear epithelium and spiral ganglion neurons after mefloquine treatment. Methods We used quantitative RT-PCR apoptosis-focused gene arrays (96-well, 84 apoptosis related genes) to assess changes of gene expression in the cochlear basilar membrane (hair cells-supporting cells) and spiral ganglion neurons of rat cochlear organotypic cultures treated with 100 IxM mefloquine for 3 h. Results Significant up-or down-regulation in gene expression was detected in 23 genes in the cochlear basilar membrane, and in 32 genes in the spiral ganglion neurons compared with time-matched controls. The responding genes could be classified as pro-or anti-apoptotic, and were mainly implicated in the Bcl-2, Caspase, Card, IAP, TNF ligand / TNF receptor, Death domain / Death effector domain, DNA damage / p53, and NF-kappa B families. Synthetic analysis suggested that these families could be revised to two major pathways mainly involved in t]he death receptor-mediated signaling pathway and apoptotic mitochondrial pathway. In addition, it was found that numerous anti-apoptotic genes such as Bcl2al, Birclb, Birc3, Birc4, Bnipl, Cflar, II10, Lhx4, Mcll, Nfkbl, Prlr, Prok2, and TNF were greatly up-regulated in the cochlear tissue, which might imply the co-existence of protective response in the ceils at the early stage of mefloquine-induced damage.展开更多
Diabetes mellitus (DM) is a chronic systemic disease characterized by hyperglycemia, with various patho-genic mechanisms. From absolute or relative insulin deficiency, patients with DM often demonstrate vari-ous level...Diabetes mellitus (DM) is a chronic systemic disease characterized by hyperglycemia, with various patho-genic mechanisms. From absolute or relative insulin deficiency, patients with DM often demonstrate vari-ous levels of metabolic disorders. Major clinical manifestations of DM include metabolic disorders, vascu-lar lesions, circulatory disturbances and neurologic complications. Along with advances in DM research, re-ports of DM related tinnitus and hearing impairment have increased continuously. Research on DM related auditory system dysfunction has focused on cochlear microcirculation, cellular homeostasis, genetics and ag-ing. Cochlear microcirculation plays an important role in cochlear physiology and its disorders are associat-ed with many inner ear diseases. Ischemia and subsequent reperfusion seen in cochlear microcirculation dis-orders are important factors in hearing damage. Understanding cochlear microcirculation and structural as well as functional changes in DM patients with hearing loss and their causal factors will help reveal patho-genic mechanisms in diabetic hearing loss and provide new ideas in developing interventions and preventing damages caused by diabetes.展开更多
Lead is a major environmental toxicant throughout the world.Lead can induce severe neurotoxicity including irreversible hearing impairment.Many in vivo studies have shown that lead damages the auditory nervous system,...Lead is a major environmental toxicant throughout the world.Lead can induce severe neurotoxicity including irreversible hearing impairment.Many in vivo studies have shown that lead damages the auditory nervous system,but has little or no effect on cochlear sensory hair cells.To gain insights on lead ototoxic and neurotoxic effects in vitro,lead acetate (LA) was applied to postnatal day 3-4 rat cochlear organotypic cultures for 24 or 72 h with doses of 0.1,0.5,1,2 or 4 mM.After 24 or 72 h treatment with lead acetate,nearly all of cochlear sensory hair cells were intact.However,after 72 h treatment,the peripheral auditory nerve fibers projecting to the hair cells and the spiral ganglion neurons (SGN) were damaged when lead concentration exceeded 2 mM.Our results indicated that 72 h treatment with only the high doses (> 2 mM) of lead actate damaged SGNs and peripheral nerve fibers;hair cells remained structurally intact even after 4 mM treatment.These results show that lead primarily damages cochlear nerve fibers andSGNratherthanhaircells.展开更多
Lentivirus carrying the Atohl gene can infect Corti's organ and express a hair-like cell surface marker in the supporting cell area. However, expression of the gene carried by adenovirus is instantaneous, which undou...Lentivirus carrying the Atohl gene can infect Corti's organ and express a hair-like cell surface marker in the supporting cell area. However, expression of the gene carried by adenovirus is instantaneous, which undoubtedly limits its clinical application. Lentivirus acts as a carrier that can stably and continuously express genes. In this study, the cochlear structure and hearing level were not affected, and Atohl gene carried by lentivirus promoted the production of hair-like cells in the cochlear supporting cell area. This led to expression of the hair-like cell surface marker myosin 7a 30 days after lentivirus carrying Atohl was microinjected into the cochlear round window of rats.展开更多
Alternating currents injected into the cochlea are able to evoke outer hair cell-mediated basilar membrane motion, thus give rise to production of otoacoustic emissions. This electrically evoked otoacoustic emission(E...Alternating currents injected into the cochlea are able to evoke outer hair cell-mediated basilar membrane motion, thus give rise to production of otoacoustic emissions. This electrically evoked otoacoustic emission(EEOAE) provides a useful tool for the research of out hair cell electromotility in vivo. This article reviews the research work on EEOAEs in mammals. Features of the EEOAEs and theories of their generation are introduced. Methods of EEOAE measurement are also described.展开更多
Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals ...Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atohl to regulate hair cell regeneration in the mammalian cochlea.展开更多
基金supported by the National Natural Science Foundation of China,No.81420108010,81271084,81200740,81371093
文摘Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.
文摘The damage to spiral organs related to age and sex in guinea pigs was studied by the surface preparation technique. Hair cell loss of spiral organs of the following four age groups: 8month, 1, 2, and 2.5-year old pigs, was assessed. Each group was divided Into two subgroups according to different sexes. The decrease of hair cell population was linearly related to age, but not related to sex. The damage rate was greater in outer hair cells than in inner hair calls. In all of animals of different ages and both sexes, outer hair cell loss was prominent at the apex of cochlea. Less damage to outer hair cell was found at the base of cochlea. Damage to inner hair cell was also increased with age, but to a lesser extent.
基金supported by NIH (NIDCD DC 05989)NSFC (30600700, 30772413)
文摘Prestin has been identified as a motor protein responsible for outer hair cell (OHC) electromotility and is expressed on the OHC surface. Previous studies revealed that OHC electromotility and its associated nonlinear capacitance were mainly located at the OHC lateral wall and absent at the apical cuticular plate and the basal nucleus region. Immunofluorescent staining for prestin also failed to demonstrate prestin expression at the OHC basal ends in whole-mount preparation of the organ of Corti. However, there lacks a definitive demonstration of the pattern of prestin distribution. The OHC lateral wall has a trilaminate organization and is composed of the plasma membrane, cortical lattice, and subsurface cisternae. In this study, the location of prestin proteins in dissociated OHCs was examined using immunofluorescent staining and confocal microscopy. We found that prestin was uniformly expressed on the basolateral surface, including the basal pole. No staining was seen on the cuticular plate and stereocilia. When co-stained with a membrane marker di-8-ANEPPS, prestin-labeling was found to be in the outer layer of the OHC lateral wall. After separating the plasma membrane from the underlying subsurface cisternae using a hypotonic extracellular solution, prestin-labeling was found to be in the plasma membrane, not the subsurface cisternae. The data show that prestin is expressed in the plasma membrane on the entire OHC basolateral surface.
基金This work was supported by the National Natural Science Foundation Of China (No.39970785) .
文摘Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial cells of adult rat were cultured. Immunocytochemistry and Bromodeoxyuridine (BrdU)labeling were used to detect properties and mitotic status of cultured cells. Results The cultured auditory epithelial cells showed a large, flat epithelial morphotype and expressed F-actin and cytokeratin, a subset of cells generated from auditory epithelium were labeled by calretinin, a specific marker of early hair cell. Conclusion Adult rat auditory epithelium can be induced to generate hair cell-like cells by nature culture, this phenomenon suggests that progenitor cells may exist in rat cochlea and they may give birth to new hair cells. Whether these progenitor cells are tissue specific stem cells is still need more study.
文摘Most recent studies on regeneration of inner ear hair cells focus on use of stem cells, gene therapy and neurotrophic factors. Cochlear gene therapy has been successfully used in the treatment of neu- rosensory hearing loss. This suggests that cochlear hair cell regeneration is possible. The objective of this paper is to review research and clinical application of inner near hair cell regeneration.
文摘The purpose of the present study was to determine protectivie effects of basic fibroblast growth factor (bFGF) on cochlear neurons and hair cells in vitro and in vivo. In experiment I, cultured spiral ganglion neurons (SGNs) prepared from P3 mice were exposed to 20mM glutamate for 2 hours before the culture medium was replaced with fresh medium containing 0, 25, 50, and 100 ng/ml bFGF, respectively. Fourteen days later, all cultures were fixed with 4% paraformaldehyde, and stained with 1% toluidine blue. The number of surviving SGNs were counted and the length of SGNs neurites were measured. Exposure to 20 mM glutamate for 24 hours resulted in an inhibition on neurite outgrowth of SGNs and elevated cell death. Treatment of the cultures with bFGF led to promotion of neurite outgrowth and elevated number of surviving SGNs. Effects of bFGF were dose dependent with the highest potency at 100 ng/ml. In experiment Ⅱ, in vivo studies were carried out with guinea pigs in which bFGF or artificial perilymph was perfused into the cochlea to assess possible protective effects of bFGF on cochlear hair cells and compound action potentials(CAP). The CAPs were measured before, immediatly and 48 hours after exposure to noise. Significant differences in CAP were observed (p<0. 05 ) among the bFGF perfused group, control group(t =3. 896 ) and artificial perilymph perfused group (t =2. 520) at 48 hours after noise exposure, Cochleae were removed and hair cell Loss was analyzed in surface preparations prepared from all experimental animals. Acoustic trauma caused loss of 651 and 687 inner hair cells in the control and artificial perilymph perfused group, respectively. In sharp contrast, only 31 inner hair cells were lost in the bFGF perfused ears. Similarly, more outer hair cells died in the control and perilymph perfuesed group (41830 and 41968, respectively) than in the group treated with bFGF (34258). Our results demonstrate that bFGF protected SGNs against glutmate neurotoxicity in vitro. In addition, treatment with bFGF also protected hair cells from acoustic trauma.
文摘The electrically evoked somatic motility of outer hair cells (OHC), briefly termed OHC electromotility, plays a crucial role in cochlear amplification that underlies the remarkably high sensitivity and frequency selectivity of the mammalian hearing. Accompanying OHC electromotility is a voltage-dependent gating charge movement within the cell lateral membrane, manifested as a measurable nonlinear capacitance (NLC) in OHCs. The electromotility and NLC of OHCs are highly correlated by sharing a common molecular substrate, the motor protein prestin. In this study, we systematically characterized the quantitative relationship between OHC electromotility and NLC in their voltage dependences for the purpose of further understanding the electromechanical transduction in OHCs. The results demonstrated that the two possess differing voltage dependences with the V^2 of electromotility consistently being -20 mV depolarized in comparison with that of NLC although their slope factors a are statistically identical. Further investigations showed that the initial state of OHCs influences the voltage dependence of electromotility but not that of NLC, indicating that some biophysical factors other than the motor protein per se are involved in the process of OHC length changes. We proposed that the cytoskeletal spectrin-actin framework underneath the OHC plasma membrane and the cell' s turgor are the two most probable factors that cause the voltage-dependence discrepancy between OHC electromotility and NLC.
文摘Objective To investigate the occurrence and possible mechanisms of apoptosis in cochlear epithelium and spiral ganglion neurons after mefloquine treatment. Methods We used quantitative RT-PCR apoptosis-focused gene arrays (96-well, 84 apoptosis related genes) to assess changes of gene expression in the cochlear basilar membrane (hair cells-supporting cells) and spiral ganglion neurons of rat cochlear organotypic cultures treated with 100 IxM mefloquine for 3 h. Results Significant up-or down-regulation in gene expression was detected in 23 genes in the cochlear basilar membrane, and in 32 genes in the spiral ganglion neurons compared with time-matched controls. The responding genes could be classified as pro-or anti-apoptotic, and were mainly implicated in the Bcl-2, Caspase, Card, IAP, TNF ligand / TNF receptor, Death domain / Death effector domain, DNA damage / p53, and NF-kappa B families. Synthetic analysis suggested that these families could be revised to two major pathways mainly involved in t]he death receptor-mediated signaling pathway and apoptotic mitochondrial pathway. In addition, it was found that numerous anti-apoptotic genes such as Bcl2al, Birclb, Birc3, Birc4, Bnipl, Cflar, II10, Lhx4, Mcll, Nfkbl, Prlr, Prok2, and TNF were greatly up-regulated in the cochlear tissue, which might imply the co-existence of protective response in the ceils at the early stage of mefloquine-induced damage.
基金Projects of Hebei Provincial Administration of Traditional Chinese Medicine,No.2012068
文摘Diabetes mellitus (DM) is a chronic systemic disease characterized by hyperglycemia, with various patho-genic mechanisms. From absolute or relative insulin deficiency, patients with DM often demonstrate vari-ous levels of metabolic disorders. Major clinical manifestations of DM include metabolic disorders, vascu-lar lesions, circulatory disturbances and neurologic complications. Along with advances in DM research, re-ports of DM related tinnitus and hearing impairment have increased continuously. Research on DM related auditory system dysfunction has focused on cochlear microcirculation, cellular homeostasis, genetics and ag-ing. Cochlear microcirculation plays an important role in cochlear physiology and its disorders are associat-ed with many inner ear diseases. Ischemia and subsequent reperfusion seen in cochlear microcirculation dis-orders are important factors in hearing damage. Understanding cochlear microcirculation and structural as well as functional changes in DM patients with hearing loss and their causal factors will help reveal patho-genic mechanisms in diabetic hearing loss and provide new ideas in developing interventions and preventing damages caused by diabetes.
基金financially supported in part by NIH R01DC006630
文摘Lead is a major environmental toxicant throughout the world.Lead can induce severe neurotoxicity including irreversible hearing impairment.Many in vivo studies have shown that lead damages the auditory nervous system,but has little or no effect on cochlear sensory hair cells.To gain insights on lead ototoxic and neurotoxic effects in vitro,lead acetate (LA) was applied to postnatal day 3-4 rat cochlear organotypic cultures for 24 or 72 h with doses of 0.1,0.5,1,2 or 4 mM.After 24 or 72 h treatment with lead acetate,nearly all of cochlear sensory hair cells were intact.However,after 72 h treatment,the peripheral auditory nerve fibers projecting to the hair cells and the spiral ganglion neurons (SGN) were damaged when lead concentration exceeded 2 mM.Our results indicated that 72 h treatment with only the high doses (> 2 mM) of lead actate damaged SGNs and peripheral nerve fibers;hair cells remained structurally intact even after 4 mM treatment.These results show that lead primarily damages cochlear nerve fibers andSGNratherthanhaircells.
基金supported by grants from the National Basic Research Program of China (973 Program), No. 2012CB967900, 2012CB967904the National Natural Science Foundation of China, No. 81070782+2 种基金the Natural Science Foundation of Zhejiang Province, China, No. 30672308the Qianjiang Talent Project of Science and Technology Ministry in Zhejiang Province, No. 2011R10014the Natural Science Foundation of Ningbo, No. 2011A610042
文摘Lentivirus carrying the Atohl gene can infect Corti's organ and express a hair-like cell surface marker in the supporting cell area. However, expression of the gene carried by adenovirus is instantaneous, which undoubtedly limits its clinical application. Lentivirus acts as a carrier that can stably and continuously express genes. In this study, the cochlear structure and hearing level were not affected, and Atohl gene carried by lentivirus promoted the production of hair-like cells in the cochlear supporting cell area. This led to expression of the hair-like cell surface marker myosin 7a 30 days after lentivirus carrying Atohl was microinjected into the cochlear round window of rats.
文摘Alternating currents injected into the cochlea are able to evoke outer hair cell-mediated basilar membrane motion, thus give rise to production of otoacoustic emissions. This electrically evoked otoacoustic emission(EEOAE) provides a useful tool for the research of out hair cell electromotility in vivo. This article reviews the research work on EEOAEs in mammals. Features of the EEOAEs and theories of their generation are introduced. Methods of EEOAE measurement are also described.
基金This work was supported by grants from the National Basic Research Program of China (973 Program, No. 2015CB965000), the National Natural Science Foundation of China (Nos. 81570911, 81470692, 81470687, 81371094, 81230019, 81500790, 81570921, 31500852, and 31501194), the Jiangsu Province Natural Science Foundation (Nos. BIC20150022, BK20140620, and BK20150598), and the Fundamental Research Funds for the Central Universities (Nos. 2242014R30022, and 021414380037).
文摘Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atohl to regulate hair cell regeneration in the mammalian cochlea.