Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice
ObjectivesThis study aims to investigate the effects of multiple sevoflurane exposures in neonatal mice on hearing function in the later life and explores the underlying mechanisms and protective strategies.Materials and MethodsNeonatal Kunming mice were exposed to sevoflurane for 3 days. Auditory b...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.945277/full |
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| author | Yufeng Li Huiqian Yu Xuehua Zhou Lin Jin Wen Li Geng-Lin Li Geng-Lin Li Xia Shen |
| author_facet | Yufeng Li Huiqian Yu Xuehua Zhou Lin Jin Wen Li Geng-Lin Li Geng-Lin Li Xia Shen |
| author_sort | Yufeng Li |
| collection | DOAJ |
| description | ObjectivesThis study aims to investigate the effects of multiple sevoflurane exposures in neonatal mice on hearing function in the later life and explores the underlying mechanisms and protective strategies.Materials and MethodsNeonatal Kunming mice were exposed to sevoflurane for 3 days. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests, immunofluorescence, patch-clamp recording, and quantitative real-time PCR were performed to observe hearing function, hair cells, ribbon synapses, nerve fibers, spiral ganglion neurons, and oxidative stress.ResultsCompared to control group, multiple sevoflurane exposures during the neonatal time significantly elevated ABR thresholds at 8 kHz (35.42 ± 1.57 vs. 41.76 ± 1.97 dB, P = 0.0256), 16 kHz (23.33 ± 1.28 vs. 33.53 ± 2.523 dB, P = 0.0012), 24 kHz (30.00 ± 2.04 vs. 46.76 ± 3.93 dB, P = 0.0024), and 32 kHz (41.25 ± 2.31 vs. 54.41 ± 2.94 dB, P = 0.0028) on P30, caused ribbon synapse loss on P15 (13.10 ± 0.43 vs. 10.78 ± 0.52, P = 0.0039) and P30 (11.24 ± 0.56 vs. 8.50 ± 0.84, P = 0.0141), and degenerated spiral ganglion neuron (SGN) nerve fibers on P30 (110.40 ± 16.23 vs. 55.04 ± 8.13, P = 0.0073). In addition, the Vhalf of calcium current become more negative (−21.99 ± 0.70 vs. −27.17 ± 0.60 mV, P < 0.0001), exocytosis was reduced (105.40 ± 19.97 vs. 59.79 ± 10.60 fF, P < 0.0001), and Lpo was upregulated (P = 0.0219) in sevoflurane group than those in control group. N-acetylcysteine (NAC) reversed hearing impairment induced by sevoflurane.ConclusionThe findings suggest that multiple sevoflurane exposures during neonatal time may cause hearing impairment in adult mice. The study also demonstrated that elevated oxidative stress led to ribbon synapses impairment and SGN nerve fibers degeneration, and the interventions of antioxidants alleviated the sevoflurane-induced hearing impairment. |
| first_indexed | 2024-04-12T08:49:29Z |
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| id | doaj.art-982f085d196f4ac292a124a833ad3f96 |
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| language | English |
| last_indexed | 2024-04-12T08:49:29Z |
| publishDate | 2022-07-01 |
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| spelling | doaj.art-982f085d196f4ac292a124a833ad3f962022-12-22T03:39:36ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-07-011610.3389/fnins.2022.945277945277Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult MiceYufeng Li0Huiqian Yu1Xuehua Zhou2Lin Jin3Wen Li4Geng-Lin Li5Geng-Lin Li6Xia Shen7Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, ChinaENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, ChinaDepartment of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, ChinaDepartment of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, ChinaENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, ChinaENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, ChinaDepartment of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, ChinaObjectivesThis study aims to investigate the effects of multiple sevoflurane exposures in neonatal mice on hearing function in the later life and explores the underlying mechanisms and protective strategies.Materials and MethodsNeonatal Kunming mice were exposed to sevoflurane for 3 days. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests, immunofluorescence, patch-clamp recording, and quantitative real-time PCR were performed to observe hearing function, hair cells, ribbon synapses, nerve fibers, spiral ganglion neurons, and oxidative stress.ResultsCompared to control group, multiple sevoflurane exposures during the neonatal time significantly elevated ABR thresholds at 8 kHz (35.42 ± 1.57 vs. 41.76 ± 1.97 dB, P = 0.0256), 16 kHz (23.33 ± 1.28 vs. 33.53 ± 2.523 dB, P = 0.0012), 24 kHz (30.00 ± 2.04 vs. 46.76 ± 3.93 dB, P = 0.0024), and 32 kHz (41.25 ± 2.31 vs. 54.41 ± 2.94 dB, P = 0.0028) on P30, caused ribbon synapse loss on P15 (13.10 ± 0.43 vs. 10.78 ± 0.52, P = 0.0039) and P30 (11.24 ± 0.56 vs. 8.50 ± 0.84, P = 0.0141), and degenerated spiral ganglion neuron (SGN) nerve fibers on P30 (110.40 ± 16.23 vs. 55.04 ± 8.13, P = 0.0073). In addition, the Vhalf of calcium current become more negative (−21.99 ± 0.70 vs. −27.17 ± 0.60 mV, P < 0.0001), exocytosis was reduced (105.40 ± 19.97 vs. 59.79 ± 10.60 fF, P < 0.0001), and Lpo was upregulated (P = 0.0219) in sevoflurane group than those in control group. N-acetylcysteine (NAC) reversed hearing impairment induced by sevoflurane.ConclusionThe findings suggest that multiple sevoflurane exposures during neonatal time may cause hearing impairment in adult mice. The study also demonstrated that elevated oxidative stress led to ribbon synapses impairment and SGN nerve fibers degeneration, and the interventions of antioxidants alleviated the sevoflurane-induced hearing impairment.https://www.frontiersin.org/articles/10.3389/fnins.2022.945277/fullsevofluranehearing impairmenthair cellsribbon synapsespiral ganglion neuron nerve fiberoxidative stress |
| spellingShingle | Yufeng Li Huiqian Yu Xuehua Zhou Lin Jin Wen Li Geng-Lin Li Geng-Lin Li Xia Shen Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice Frontiers in Neuroscience sevoflurane hearing impairment hair cells ribbon synapse spiral ganglion neuron nerve fiber oxidative stress |
| title | Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice |
| title_full | Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice |
| title_fullStr | Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice |
| title_full_unstemmed | Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice |
| title_short | Multiple Sevoflurane Exposures During the Neonatal Period Cause Hearing Impairment and Loss of Hair Cell Ribbon Synapses in Adult Mice |
| title_sort | multiple sevoflurane exposures during the neonatal period cause hearing impairment and loss of hair cell ribbon synapses in adult mice |
| topic | sevoflurane hearing impairment hair cells ribbon synapse spiral ganglion neuron nerve fiber oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.945277/full |
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