{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:02:15Z","timestamp":1768345335629,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2018R1A6A1A03025523"],"award-info":[{"award-number":["2018R1A6A1A03025523"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gravitational changes have been shown to cause significant abnormalities in various body systems, including the cardiovascular, immune, vestibular, and musculoskeletal systems. While numerous studies have examined the response of the vestibular system to gravitational stimulation, research on functional changes in the peripheral inner ear remains limited. The inner ear comprises two closely related structures: the vestibule and cochlea. These components share similar structures and neural functions, highlighting the importance of investigating changes in auditory nerve cells in response to gravitational alterations. To address this gap, we studied the functional and structural changes in the inner ear following exposure to hypergravity stimuli. Our findings demonstrate changes in auditory brainstem responses (ABRs) in the cochlea. ABR recordings were used to analyze click thresholds, as well as the amplitude and latency of tone bursts. The click thresholds at all frequencies increased in the group exposed to hypergravity in the long term. Additionally, tone burst results revealed significantly reduced amplitudes at high frequencies and delayed latencies in the hypergravity models. Notably, greater hair cell loss was observed in the middle and basal turns of the cochlea, indicating that mid and high-frequency regions are more vulnerable to hypergravity stimulation. Furthermore, nerve damage on the cochlear surface was evident in subjects exposed to 4G stimulation for 4 weeks. These findings suggest that the inner ear and its neural activity can be functionally and structurally affected by prolonged exposure to hypergravity.<\/jats:p>","DOI":"10.3390\/ijms26020758","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T03:33:02Z","timestamp":1737084782000},"page":"758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Functional and Structural Changes in the Inner Ear and Cochlear Hair Cell Loss Induced by Hypergravity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0427-3263","authenticated-orcid":false,"given":"Jin Sil","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Inha University, Incheon 22332, Republic of Korea"},{"name":"Inha Research Institute for Aerospace Medicine, College of Medicine, Inha University, Incheon 22332, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5650-3526","authenticated-orcid":false,"given":"Kyu-Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Inha University, Incheon 22332, Republic of Korea"},{"name":"Inha Research Institute for Aerospace Medicine, College of Medicine, Inha University, Incheon 22332, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-2001","authenticated-orcid":false,"given":"Hyun Ji","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Inha University, Incheon 22332, Republic of Korea"},{"name":"Inha Research Institute for Aerospace Medicine, College of Medicine, Inha University, Incheon 22332, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Adamopoulos, K., Koutsouris, D., Zaravinos, A., and Lambrou, G.I. (2021). Gravitational Influence on Human Living Systems and the Evolution of Species on Earth. Molecules, 26.","DOI":"10.3390\/molecules26092784"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jamon, M. (2014). The development of vestibular system and related functions in mammals: Impact of gravity. Front. Integr. Neurosci., 8.","DOI":"10.3389\/fnint.2014.00011"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12576-020-00744-3","article-title":"Understanding vestibular-related physiological functions could provide clues on adapting to a new gravitational environment","volume":"70","author":"Morita","year":"2020","journal-title":"J. Physiol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Carriot, J., Mackrous, I., and Cullen, K.E. (2021). Challenges to the Vestibular System in Space: How the Brain Responds and Adapts to Microgravity. Front. Neural Circuits, 15.","DOI":"10.3389\/fncir.2021.760313"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0165-3806(01)00146-8","article-title":"Development of the rat efferent vestibular system on the ground and in microgravity","volume":"128","author":"Dememes","year":"2001","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1152\/jn.00240.2016","article-title":"Spaceflight-induced synaptic modifications within hair cells of the mammalian utricle","volume":"117","author":"Sultemeier","year":"2017","journal-title":"J. Neurophysiol."},{"key":"ref_7","first-page":"562","article-title":"Changes in the central nervous system and their clinical correlates during long-term spaceflight","volume":"65","author":"Newberg","year":"1994","journal-title":"Aviat. Space Env. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mas\u00e8, M., Viziano, A., Strapazzon, G., Alessandrini, M., and Micarelli, A. (2023). Auditory function in humans at high altitude. A scoping review. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0291919"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1172\/JCI61167","article-title":"Perception of sound and gravity by TMC1 and TMC2","volume":"121","author":"Lin","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cophys.2020.09.004","article-title":"Vascular pathology and hearing disorders","volume":"18","author":"Neng","year":"2020","journal-title":"Curr. Opin. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.cger.2019.11.002","article-title":"Hearing Loss: The Silent Risk for Psychiatric Disorders in Late Life","volume":"36","author":"Blazer","year":"2020","journal-title":"Clin. Geriatr. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107S","DOI":"10.1097\/AUD.0000000000000929","article-title":"The effects of hearing loss on balance: A critical review","volume":"41","author":"Carpenter","year":"2020","journal-title":"Ear Hear."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1097\/AUD.0000000000001474","article-title":"Association Between Hearing Loss, Asymmetric Hearing, and Postural Instability","volume":"45","author":"Wang","year":"2024","journal-title":"Ear Hear."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10162-010-0244-1","article-title":"Sox2 up-regulation and glial cell proliferation following degeneration of spiral ganglion neurons in the adult mouse inner ear","volume":"12","author":"Lang","year":"2011","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1523\/JNEUROSCI.3389-10.2011","article-title":"Opposing gradients of ribbon size and AMPA receptor expression underlie sensitivity differences among cochlear-nerve\/hair-cell synapses","volume":"31","author":"Liberman","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.heares.2006.05.013","article-title":"Afferent synapses are present in utricular hair cells from otoconia-deficient mice","volume":"222","author":"Hoffman","year":"2006","journal-title":"Hear. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.autneu.2006.07.019","article-title":"Motion sickness susceptibility","volume":"129","author":"Golding","year":"2006","journal-title":"Auton. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00221-006-0697-y","article-title":"Space motion sickness","volume":"175","author":"Lackner","year":"2006","journal-title":"Exp. Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"i143","DOI":"10.1093\/bja\/aex336","article-title":"An overview of space medicine","volume":"119","author":"Hodkinson","year":"2017","journal-title":"BJA Br. J. Anaesth."},{"key":"ref_20","first-page":"2","article-title":"Ergonomic challenges for astronauts during space travel and the need for space medicine","volume":"7","author":"Braddock","year":"2017","journal-title":"J. Ergon."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1134\/S0362119717050085","article-title":"Vestibular function and space motion sickness","volume":"43","author":"Kornilova","year":"2017","journal-title":"Hum. Physiol."},{"key":"ref_22","first-page":"31","article-title":"The etiology of spaceflight-associated hearing loss","volume":"87","author":"Kadem","year":"2018","journal-title":"Univ. West. Ont. Med. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1007\/s00405-021-06847-w","article-title":"A review of the impact of hearing interventions on social isolation and loneliness in older people with hearing loss","volume":"278","author":"Ellis","year":"2021","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Podury, A., Jiam, N.T., Kim, M., Donnenfield, J.I., and Dhand, A. (2023). Hearing and sociality: The implications of hearing loss on social life. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1245434"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1007\/s13770-023-00547-8","article-title":"D-Galactose and Hypoxia Induce the Early Onset of Age-Related Hearing Loss Deterioration in a Mouse Model","volume":"20","author":"Batsaikhan","year":"2023","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wang, J., and Puel, J.L. (2020). Presbycusis: An Update on Cochlear Mechanisms and Therapies. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010218"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yang, W., Zhao, X., Chai, R., and Fan, J. (2023). Progress on mechanisms of age-related hearing loss. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1253574"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"582849","DOI":"10.1155\/2014\/582849","article-title":"Oxidative stresses and mitochondrial dysfunction in age-related hearing loss","volume":"2014","author":"Fujimoto","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Teraoka, M., Hato, N., Inufusa, H., and You, F. (2024). Role of Oxidative Stress in Sensorineural Hearing Loss. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084146"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Li, P., Li, S., Wang, L., Li, H., Wang, Y., Liu, H., Wang, X., Zhu, X., Liu, Z., and Ye, F. (2023). Mitochondrial dysfunction in hearing loss: Oxidative stress, autophagy and NLRP3 inflammasome. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1119773"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S0006-3495(03)74893-0","article-title":"Limiting frequency of the cochlear amplifier based on electromotility of outer hair cells","volume":"84","author":"Ospeck","year":"2003","journal-title":"Biophys. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"459","DOI":"10.14336\/AD.2023.0718","article-title":"The Role of Glial Cells in Synaptic Dysfunction: Insights into Alzheimer\u2019s Disease Mechanisms","volume":"15","author":"Yu","year":"2024","journal-title":"Aging Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Clemente-Suarez, V.J., Beltran-Velasco, A.I., Redondo-Florez, L., Martin-Rodriguez, A., Yanez-Sepulveda, R., and Tornero-Aguilera, J.F. (2023). Neuro-Vulnerability in Energy Metabolism Regulation: A Comprehensive Narrative Review. Nutrients, 15.","DOI":"10.3390\/nu15143106"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Teleanu, R.I., Niculescu, A.G., Roza, E., Vladacenco, O., Grumezescu, A.M., and Teleanu, D.M. (2022). Neurotransmitters-Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115954"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/syn.21547","article-title":"Role of perisynaptic parameters in neurotransmitter homeostasis--computational study of a general synapse","volume":"66","author":"Pendyam","year":"2012","journal-title":"Synapse"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1162\/NECO_a_00101","article-title":"Molecular diffusion model of neurotransmitter homeostasis around synapses supporting gradients","volume":"23","author":"Mohan","year":"2011","journal-title":"Neural Comput."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev-physiol-021014-071740","article-title":"Homeostatic control of presynaptic neurotransmitter release","volume":"77","author":"Davis","year":"2015","journal-title":"Annu. Rev. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s10827-013-0462-8","article-title":"Compensating for synaptic loss in Alzheimer\u2019s disease","volume":"36","author":"Abuhassan","year":"2014","journal-title":"J. Comput. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/dneu.22780","article-title":"Axon growth and synaptic function: A balancing act for axonal regeneration and neuronal circuit formation in CNS trauma and disease","volume":"80","author":"Kiyoshi","year":"2020","journal-title":"Dev. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chung, W.S., Baldwin, K.T., and Allen, N.J. (2024). Astrocyte Regulation of Synapse Formation, Maturation, and Elimination. Cold Spring Harb. Perspect. Biol., 16.","DOI":"10.1101\/cshperspect.a041352"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4103\/1673-5374.286952","article-title":"Mechanisms of neuroplasticity and brain degeneration: Strategies for protection during the aging process","volume":"16","author":"Toricelli","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1152\/japplphysiol.00364.2015","article-title":"Effects of chronic hypergravity: From adaptive to deleterious responses in growing mouse skeleton","volume":"119","author":"Gnyubkin","year":"2015","journal-title":"J. Appl. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Desai, R.I., Limoli, C.L., Stark, C.E.L., and Stark, S.M. (2022). Impact of spaceflight stressors on behavior and cognition: A molecular, neurochemical, and neurobiological perspective. Neurosci. Biobehav. Rev., 138.","DOI":"10.1016\/j.neubiorev.2022.104676"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/758\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:30:24Z","timestamp":1759919424000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26020758"],"URL":"https:\/\/doi.org\/10.3390\/ijms26020758","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]}}}