Cited 3 time in webofscience Cited 3 time in scopus

Region-specific amyloid-β accumulation in the olfactory system influences olfactory sensory neuronal dysfunction in 5xFAD mice

Title
Region-specific amyloid-β accumulation in the olfactory system influences olfactory sensory neuronal dysfunction in 5xFAD mice
Authors
Son, GowoonYoo, Seung JunKang, ShinwooRasheed, Ameer Abu BakrJung, Da HaePark, HyunjunCho, BongkiSteinbusch, Harry W. M.Chang, Keun-ASuh, Yoo-HunMoon, Cheil
DGIST Authors
Cho, Bongki; Moon, Cheil
Issue Date
2021-01
Citation
Alzheimer's Research and Therapy, 13(1), 4
Type
Article
Article Type
Article
Author Keywords
Alzheimer&aposs diseaseOlfactory dysfunctionbeta-amyloid5xFADOlfactory sensory neuronZonal organizationOdor detection testCa2+ imagingTopographic analysisNeuronal turnover
Keywords
ALZHEIMERS-DISEASECOGNITIVE IMPAIRMENTPRECURSOR PROTEINALPHA-SYNUCLEINEXPRESSIONRECEPTORBULBINVOLVEMENTPOPULATIONINNATE
ISSN
1758-9193
Abstract
Background: Hyposmia in Alzheimer’s disease (AD) is a typical early symptom according to numerous previous clinical studies. Although amyloid-β (Aβ), which is one of the toxic factors upregulated early in AD, has been identified in many studies, even in the peripheral areas of the olfactory system, the pathology involving olfactory sensory neurons (OSNs) remains poorly understood. Methods: Here, we focused on peripheral olfactory sensory neurons (OSNs) and delved deeper into the direct relationship between pathophysiological and behavioral results using odorants. We also confirmed histologically the pathological changes in 3-month-old 5xFAD mouse models, which recapitulates AD pathology. We introduced a numeric scale histologically to compare physiological phenomenon and local tissue lesions regardless of the anatomical plane. Results: We observed the odorant group that the 5xFAD mice showed reduced responses to odorants. These also did not physiologically activate OSNs that propagate their axons to the ventral olfactory bulb. Interestingly, the amount of accumulated amyloid-β (Aβ) was high in the OSNs located in the olfactory epithelial ectoturbinate and the ventral olfactory bulb glomeruli. We also observed irreversible damage to the ectoturbinate of the olfactory epithelium by measuring the impaired neuronal turnover ratio from the basal cells to the matured OSNs. Conclusions: Our results showed that partial and asymmetrical accumulation of Aβ coincided with physiologically and structurally damaged areas in the peripheral olfactory system, which evoked hyporeactivity to some odorants. Taken together, partial olfactory dysfunction closely associated with peripheral OSN’s loss could be a leading cause of AD-related hyposmia, a characteristic of early AD. © 2021, The Author(s).
URI
http://hdl.handle.net/20.500.11750/12701
DOI
10.1186/s13195-020-00730-2
Publisher
BioMed Central
Related Researcher
  • Author Moon, Cheil Laboratory of Chemical Senses
  • Research Interests Brain convergent science based on chemical senses; olfaction; 감각신경계 기반 뇌융합과학; 후각 신경계
Files:
Collection:
Division of Biotechnology1. Journal Articles
Department of Brain and Cognitive SciencesLaboratory of Chemical Senses1. Journal Articles


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