ArticleCell death discovery2023
Dopaminergic neurodegeneration in the substantia nigra is associated with olfactory dysfunction in mice models of Parkinson's disease.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Engineered extracellular vesicles-mediated curcumin delivery in brain microenvironment modulating lysosomes, mitochondria, and microglia reprogram for parkinson's disease therapy.Journal of nanobiotechnology · 2025Article
- Capsaicin and nicotine alleviate MPTP induced olfactory dysfunction by suppressing cGAS/TBK1/STING and MAPK mediated neuroinflammation.NPJ Parkinson's disease · 2025Article
- Intranasal iron administration induces iron deposition, immunoactivation, and cell-specific vulnerability in the olfactory bulb of C57BL/6 mice.Zoological research · 2025Article
- Role of the Central Cholinergic Nervous System in Motor and Non-Motor Symptoms of Parkinson's Disease.Current neuropharmacology · 2025Review
- Drug discovery and development for Parkinson's disease: are preclinical models good enough?Frontiers in aging neuroscience · 2025Review
- Progressive iron overload in middle-aged mice impairs olfactory function, triggers lipid oxidation and induces apoptosis.Frontiers in pharmacology · 2024Article
- Experimental Animal Models of Prodromal Parkinson's Disease.Journal of Parkinson's disease · 2024Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Olfactory dysfunction represents a prodromal stage in Parkinson's disease (PD). However, the mechanisms underlying hyposmia are not specified yet. In this study, we first observed an early olfactory dysfunction in mice with intragastric rotenone administration, consistent with dopaminergic neurons loss and α-synuclein pathology in the olfactory bulb. However, a much severer olfactory dysfunction was observed without severer pathology in olfactory bulb when the loss of dopaminergic neurons in the substantia nigra occurred. Then, we established the mice models by intrastriatal α-synuclein preformed fibrils injection and demonstrated the performance in the olfactory discrimination test was correlated to the loss of dopaminergic neurons in the substantia nigra, without any changes in the olfactory bulb analyzed by RNA-sequence. In mice with intranasal ferric ammonium citrate administration, we observed olfactory dysfunction when dopaminergic neurodegeneration in substantia nigra occurred and was restored when dopaminergic neurons were rescued. Finally we demonstrated that chemogenetic inhibition of dopaminergic neurons in the substantia nigra was sufficient to cause hyposmia and motor incoordination. Taken together, this study shows a direct relationship between nigral dopaminergic neurodegeneration and olfactory dysfunction in PD models and put forward the understandings that olfactory dysfunction represents the early stage of neurodegeneration in PD progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.