嗅觉障碍小鼠和大鼠模型的研究进展

Research progress of animal models of olfactory disorders

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doi:10.6040/j.issn.1673-3770.0.2023.299

Abstract: Olfactory disorders have a complex aetiology and a prolonged course. Animal models are essential for the further study of the pathophysiology of olfactory disorders, the mechanism of therapeutic response and drug development. However, a systematic and comprehensive review of olfactory modelling methods is lacking. Currently, the most commonly used animal models include mouse and rat models. This review will start with the aetiology. The animal model of olfactory dysfunction was divided into the model of olfactory dysfunction associated with exposure to toxins/drugs, the model of olfactory dysfunction secondary to nasal and sinus diseases, the model of olfactory dysfunction after infection, the model of olfactory dysfunction associated with congenital olfactory dysfunction and normal ageing, the model of olfactory dysfunction after trauma, and the model of olfactory dysfunction associated with the nervous system. This paper summarises the construction methods and pathological changes of these models to provide a reference for the selection of modelling methods for animal models of olfactory dysfunction.

Key words: Olfactory disorder, Animal model, Molding method, Literature review, Etiological classification

CLC Number:

R765.6

LI Zhicheng, YAN Ya, DAI Liangping, YING Junjie, WANG Renzhong. Research progress of animal models of olfactory disorders[J].Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(2): 158-167.

[1] Whitcroft KL, Altundag A, Balungwe P, et al. Position paper on olfactory dysfunction: 2023[J]. Rhinology, 2023. doi:10.4193/Rhin22.483
[2] Whitcroft KL, Altundag A, Balungwe P, et al. Position paper on olfactory dysfunction: 2023[J]. Rhinology, 2023, 61(33): 1-108. doi: 10.4193/Rhin22.483
[3] 邢栋, 魏宏权. 使用3-甲基吲哚制作嗅觉障碍模型的研究进展[J]. 中国中西医结合耳鼻咽喉科杂志, 2020, 28(3): 226-229. doi:10.16542/j.cnki.issn.1007-4856.2020.03.016 XING Dong, WEI Hongquan. Research Progress in the use of 3-methylindole as a moder of oltactory dysfunction[J]. Chinese Journal of Otorhinolaryngology in Integrative Medicine, 2020, 28(3): 226-229. doi:10.16542/j.cnki.issn.1007-4856.2020.03.016
[4] Kim BY, Park J, Kim E, et al. Olfactory ensheathing cells mediate neuroplastic mechanisms after olfactory training in mouse model[J]. Am J Rhinol Allergy, 2020, 34(2): 217-229. doi:10.1177/1945892419885036
[5] Miller MA, O'Bryan MA. Ultrastructural changes and olfactory deficits during 3-methylindole-induced olfactory mucosal necrosis and repair in mice[J]. Ultrastruct Pathol, 2003, 27(1): 13-21. doi:10.1080/01913120309944
[6] Dibattista M, Al Koborssy D, Genovese F, et al. The functional relevance of olfactory marker protein in the vertebrate olfactory system: a never-ending story[J]. Cell Tissue Res, 2021, 383(1): 409-427. doi:10.1007/s00441-020-03349-9
[7] Kim JW, Hong SL, Lee CH, et al. Relationship between olfactory function and olfactory neuronal population in C57BL6 mice injected intraperitoneally with 3-methylindole[J]. Otolaryngol Head Neck Surg, 2010, 143(6): 837-842. doi:10.1016/j.otohns.2010.08.016
[8] Bergström U, Giovanetti A, Piras E, et al. Methimazole-induced damage in the olfactory mucosa: effects on ultrastructure and glutathione levels[J]. Toxicol Pathol, 2003, 31(4): 379-387. doi:10.1080/01926230390201101
[9] Ueha R, Ueha S, Sakamoto T, et al. Cigarette smoke delays regeneration of the olfactory epithelium in mice[J]. Neurotox Res, 2016, 30(2): 213-224. doi:10.1007/s12640-016-9617-5
[10] Baba M, Itaka K, Kondo K, et al. Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles[J]. J Control Release, 2015, 201: 41-48. doi:10.1016/j.jconrel.2015.01.017
[11] Goldstein BJ, Choi R, Goss GM. Multiple polycomb epigenetic regulatory proteins are active in normal and regenerating adult olfactory epithelium[J]. Laryngoscope Investig Otolaryngol, 2018, 3(5): 337-344. doi:10.1002/lio2.180
[12] Bergman U, Ostergren A, Gustafson AL, et al. Differential effects of olfactory toxicants on olfactory regeneration[J]. Arch Toxicol, 2002, 76(2): 104-112. doi:10.1007/s00204-002-0321-2
[13] Ahn S, Choi M, Kim H, et al. Transient anosmia induces depressive-like and anxiolytic-like behavior and reduces amygdalar corticotropin-releasing hormone in a ZnSO4-induced mouse model[J]. Chem Senses, 2018, 43(4): 213-221. doi:10.1093/chemse/bjy008
[14] Takahashi K, Tsuji M, Nakagawasai O, et al. Donepezil prevents olfactory dysfunction and α-synuclein aggregation in the olfactory bulb by enhancing autophagy in zinc sulfate-treated mice[J]. Behav Brain Res, 2023, 438: 114175. doi:10.1016/j.bbr.2022.114175
[15] McBride K, Slotnick B, Margolis FL. Does intranasal application of zinc sulfate produce anosmia in the mouse An olfactometric and anatomical study[J]. Chem Senses, 2003, 28(8): 659-670. doi:10.1093/chemse/bjg053
[16] Hsieh H, Horwath MC, Genter MB. Zinc gluconate toxicity in wild-type vs. MT1/2-deficient mice[J]. Neurotoxicology, 2017, 58: 130-136. doi:10.1016/j.neuro.2016.12.003
[17] Ueha R, Ueha S, Kondo K, et al. Damage to olfactory progenitor cells is involved in cigarette smoke-induced olfactory dysfunction in mice[J]. Am J Pathol, 2016, 186(3): 579-586. doi:10.1016/j.ajpath.2015.11.009
[18] Sahin E, Ortug G, Ortug A. Does cigarette smoke exposure lead to histopathological alterations in the olfactory epithelium An electron microscopic study on a rat model[J]. Ultrastruct Pathol, 2018, 42(5): 440-447. doi:10.1080/01913123.2018.1499685
[19] Ngwa HA, Kanthasamy A, Jin HJ, et al. Vanadium exposure induces olfactory dysfunction in an animal model of metal neurotoxicity[J]. Neurotoxicology, 2014, 43: 73-81. doi:10.1016/j.neuro.2013.12.004
[20] Hsia AY, Vincent JD, Lledo PM. Dopamine depresses synaptic inputs into the olfactory bulb[J]. J Neurophysiol, 1999, 82(2): 1082-1085. doi:10.1152/jn.1999.82.2.1082
[21] Colín-Barenque L, Bizarro-Nevares P, González Villalva A, et al. Neuroprotective effect of carnosine in the olfactory bulb after vanadium inhalation in a mouse model[J]. Int J Exp Pathol, 2018, 99(4): 180-188. doi:10.1111/iep.12285
[22] Foster ML, Rao DB, Francher T, et al. Olfactory toxicity in rats following manganese chloride nasal instillation: a pilot study[J]. Neurotoxicology, 2018, 64: 284-290. doi:10.1016/j.neuro.2017.09.004
[23] Liang CQ, Yang ZX, Zou QY, et al. Construction of an irreversible allergic rhinitis-induced olfactory loss mouse model[J]. Biochem Biophys Res Commun, 2019, 513(3): 635-641. doi:10.1016/j.bbrc.2019.03.110
[24] Steiner UC, Bischoff S, Valaperti A, et al. Endotypes of chronic rhinosinusitis with nasal polyps with and without NSAID â"intolerance[J]. Rhinology, 2020, 58(6): 544-549. doi:10.4193/Rhin19.423
[25] Sedger LM, McDermott MF. TNF and TNF-receptors: from mediators of cell death and inflammation to therapeutic giants-past, present and future[J]. Cytokine Growth Factor Rev, 2014, 25(4): 453-472. doi:10.1016/j.cytogfr.2014.07.016
[26] Sultan B, May LA, Lane AP. The role of TNF-α in inflammatory olfactory loss[J]. Laryngoscope, 2011, 121(11): 2481-2486. doi:10.1002/lary.22190
[27] Turner JH, May L, Reed RR, et al. Reversible loss of neuronal marker protein expression in a transgenic mouse model for sinusitis-associated olfactory dysfunction[J]. Am J Rhinol Allergy, 2010, 24(3): 192-196. doi:10.2500/ajra.2010.24.3460
[28] Jornot L, Cordey S, Caruso A, et al. T lymphocytes promote the antiviral and inflammatory responses of airway epithelial cells[J]. PLoS One, 2011, 6(10): e26293. doi:10.1371/journal.pone.0026293
[29] Pozharskaya T, Lane AP. Interferon gamma causes olfactory dysfunction without concomitant neuroepithelial damage[J]. Int Forum Allergy Rhinol, 2013, 3(11): 861-865. doi:10.1002/alr.21226
[30] Ye J, He JP, Liu ZJ. Olfactory mucosal microstructural changes in a rat model of acute rhinosinusitis with dysosmia[J]. Genet Mol Res, 2014, 13(2): 3859-3868. doi:10.4238/2014.May.16.11
[31] Kanaya K, Kondo K, Suzukawa K, et al. Innate immune responses and neuroepithelial degeneration and regeneration in the mouse olfactory mucosa induced by intranasal administration of Poly(I: C)[J]. Cell Tissue Res, 2014, 357(1): 279-299. doi:10.1007/s00441-014-1848-2
[32] Tian J, Pinto JM, Cui XL, et al. Sendai virus induces persistent olfactory dysfunction in a murine model of PVOD via effects on apoptosis, cell proliferation, and response to odorants[J]. PLoS One, 2016, 11(7): e0159033. doi:10.1371/journal.pone.0159033
[33] Ye Q, Zhou J, He Q, et al. SARS-CoV-2 infection in the mouse olfactory system[J]. Cell Discov, 2021, 7(1): 49. doi:10.1038/s41421-021-00290-1
[34] Xie C, Habif JC, Ukhanov K, et al. Reversal of ciliary mechanisms of disassembly rescues olfactory dysfunction in ciliopathies[J]. JCI Insight, 2022, 7(15): e158736. doi:10.1172/jci.insight.158736
[35] Zhang C, Wang X. Initiation of the age-related decline of odor identification in humans: A meta-analysis[J]. Ageing Research Reviews, 2017, 40: 45-50. doi:10.1016/j.arr.2017.08.004
[36] Seo Y, Ahn JS, Shin YY, et al. Mesenchymal stem cells target microglia via galectin-1 production to rescue aged mice from olfactory dysfunction[J]. Biomedecine Pharmacother, 2022, 153: 113347. doi:10.1016/j.biopha.2022.113347
[37] 刘一帆, 姚淋尹, 郭怡辰, 等. 外伤性嗅觉障碍患者的临床特点及随访研究[J]. 临床耳鼻咽喉头颈外科杂志, 2017, 31(22): 1726-1731. doi:10.13201/j.issn.1001-1781.2017.22.006 LIU Yifan, YAO Linyin, GUO Yichen, et al. Differences in clinical features of post-traumatic olfactory dysfunction and non-post-traumatic olfactory dysfunction: a follow-up study[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2017, 31(22): 1726-1731. doi:10.13201/j.issn.1001-1781.2017.22.006
[38] Siopi E, Calabria S, Plotkine M, et al. Minocycline restores olfactory bulb volume and olfactory behavior after traumatic brain injury in mice[J]. J Neurotrauma, 2012, 29(2): 354-361. doi:10.1089/neu.2011.2055
[39] 王嘉玲, 徐岩, 曹学兵. 帕金森病中嗅觉障碍机制的研究进展[J]. 临床内科杂志, 2022, 39(4): 283-285. doi:10.3969/j.issn.1001-9057.2022.04.020 WANG Jialing, XU Yan, CAO Xuebing. Research progress on the mechanism of olfactory dysfunction in Parkinson's disease[J]. Journal of Clinical Internal Medicine, 2022, 39(4): 283-285. doi:10.3969/j.issn.1001-9057.2022.04.020
[40] Ilkiw JL, Kmita LC, Targa ADS, et al. Dopaminergic lesion in the olfactory bulb restores olfaction and induces depressive-like behaviors in a 6-OHDA model of Parkinson's disease[J]. Mol Neurobiol, 2019, 56(2): 1082-1095. doi:10.1007/s12035-018-1134-5
[41] 祝娃娃, 王健达, 张险峰, 等. MPTP致帕金森病小鼠嗅觉障碍的机制研究[J]. 中风与神经疾病杂志, 2020, 37(10): 904-907. doi:10.19845/j.cnki.zfysjjbzz.2020.0481 ZHU Wawa, WANG Jianda, ZHANG Xianfeng, et al. The mechanism of olfactory impairment in MPTP-induced mouse model of Parkinson's disease[J]. Journal of Apoplexy and Nervous Diseases, 2020, 37(10): 904-907. doi:10.19845/j.cnki.zfysjjbzz.2020.0481
[42] Chen Y, Zhang QS, Shao QH, et al. NLRP3 inflammasome pathway is involved in olfactory bulb pathological alteration induced by MPTP[J]. Acta Pharmacol Sin, 2019, 40(8): 991-998. doi:10.1038/s41401-018-0209-1
[43] Sasajima H, Miyazono S, Noguchi T, et al. Intranasal administration of rotenone to mice induces dopaminergic neurite degeneration of dopaminergic neurons in the substantia nigra[J]. Biol Pharm Bull, 2017, 40(1): 108-112. doi:10.1248/bpb.b16-00654
[44] 章素芳, 李丽喜, 倪俊, 等. 模拟帕金森病的表达人α-synucleinA53T转基因小鼠的早期嗅觉功能观察[J]. 上海交通大学学报(医学版), 2012, 32(8): 1043-1049. doi:10.3969/j.issn.1674-8115.2012.08.018 ZHANG Sufang, LI Lixi, NI Jun, et al. Olfactory dysfunction of human α-synucleinA53T transgenic mice in simulation of early symptoms of Parkinson's disease[J]. Journal of Shanghai Jiao Tong University(Medical Science), 2012, 32(8): 1043-1049. doi:10.3969/j.issn.1674-8115.2012.08.018
[45] 路书彦, 黄汉昌, 姜招峰. 嗅觉障碍与阿尔茨海默病的关系[J]. 中国老年学杂志, 2015, 35(8): 2288-2290. doi:10.3969/j.issn.1005-9202.2015.08.133 LU Shuyan, HUANG Hanchang, JIANG Zhaofeng. Relationship between olfactory dysfunction and Alzheimer's disease[J]. Chinese Journal of Gerontology, 2015, 35(8): 2288-2290. doi:10.3969/j.issn.1005-9202.2015.08.133
[46] 林丽珍, 范杰诚, 郭培武, 等. 神经退行性疾病动物模型嗅觉障碍的研究进展[J]. 中国实验动物学报, 2021, 29(2): 268-274. doi:10.3969/j.issn.1005-4847.2021.02.019 LIN Lizhen, FAN Jiecheng, GUO Peiwu, et al. Research progress in animal models of olfactory dysfunction in neurodegenerative diseases[J]. Acta Laboratorium Animalis Scientia Sinica, 2021, 29(2): 268-274. doi:10.3969/j.issn.1005-4847.2021.02.019
[47] Wesson DW, Levy E, Nixon RA, et al. Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model[J]. J Neurosci, 2010, 30(2): 505-514. doi:10.1523/JNEUROSCI.4622-09.2010
[48] Hu B, Geng C, Guo F, et al. GABAA receptor agonist muscimol rescues inhibitory microcircuit defects in the olfactory bulb and improves olfactory function in APP/PS1 transgenic mice[J]. Neurobiol Aging, 2021, 108: 47-57. doi:10.1016/j.neurobiolaging.2021.08.003
[49] Lachén-Montes M, González-Morales A, de Morentin XM, et al. An early dysregulation of FAK and MEK/ERK signaling pathways precedes the β-amyloid deposition in the olfactory bulb of APP/PS1 mouse model of Alzheimer's disease[J]. J Proteomics, 2016, 148: 149-158. doi:10.1016/j.jprot.2016.07.032
[50] Cassano T, Romano A, Macheda T, et al. Olfactory memory is impaired in a triple transgenic model of Alzheimer disease[J]. Behav Brain Res, 2011, 224(2): 408-412. doi:10.1016/j.bbr.2011.06.029
[51] Hu Y, Ding WT, Zhu XN, et al. Olfactory dysfunctions and decreased nitric oxide production in the brain of human P301L tau transgenic mice[J]. Neurochem Res, 2016, 41(4): 722-730. doi:10.1007/s11064-015-1741-8
[52] 陈晓程, 梁胜祥, 林冰冰, 等. P301L-Tau模型小鼠内嗅皮层-海马神经纤维变化与记忆功能障碍的相关性及其分子机制研究[J]. 康复学报, 2023, 33(2): 136-141. doi:10.3724/SP.J.1329.2023.02007 CHEN Xiaocheng, LIANG Shengxiang, LIN Bingbing, et al. Correlation analysis of the entorhinal cortex-hippocampus nerve fiber changes and memory dysfunction in P301L-tau mouse model and molecular mechanism[J]. Rehabilitation Medicine, 2023, 33(2): 136-141. doi:10.3724/SP.J.1329.2023.02007
[53] Alvarado-Martínez R, Salgado-Puga K, Pe a-Ortega F. Amyloid beta inhibits olfactory bulb activity and the ability to smell[J]. PLoS One, 2013, 8(9): e75745. doi:10.1371/journal.pone.0075745
[54] Coppola DM, Parrish Waters R. The olfactory bulbectomy disease model: a re-evaluation[J]. Physiol Behav, 2021, 240: 113548. doi:10.1016/j.physbeh.2021.113548

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