Intranasal Rotenone Induces Alpha-Synuclein Accumulation, Neuroinflammation and Dopaminergic Neurodegeneration in Middle-Aged Mice
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F23%3A00079714" target="_blank" >RIV/00159816:_____/23:00079714 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s11064-022-03847-y" target="_blank" >https://link.springer.com/article/10.1007/s11064-022-03847-y</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s11064-022-03847-y" target="_blank" >10.1007/s11064-022-03847-y</a>
Alternative languages
Result language
angličtina
Original language name
Intranasal Rotenone Induces Alpha-Synuclein Accumulation, Neuroinflammation and Dopaminergic Neurodegeneration in Middle-Aged Mice
Original language description
Accumulation of alpha-synuclein (alpha-syn) is central to the pathogenesis of Parkinson's disease (PD). Previous studies suggest that alpha-syn pathology may originate from the olfactory bulb (OB) or gut in response to an unknown pathogen and later progress to the different brain regions. Aging is viewed as the utmost threat to PD development. Therefore, studies depicting the role of age in alpha-syn accumulation and its progression in PD are important. In the present study, we gave intranasal rotenone microemulsion for 6 weeks in 12-month-old female BALB/c mice and found olfactory dysfunction after 4 and 6 weeks of rotenone administration. Interestingly, motor impairment was observed only after 6 weeks. The animals were sacrificed after 6 weeks to perform western blotting and immunohistochemical studies to detect alpha-syn pathology, neuroinflammation and neurodegeneration. We found alpha-syn accumulation in OB, striatum, substantia nigra (SN) and cortex. Importantly, we found significant glial cell activation and neurodegeneration in all the analysed regions which were absent in our previous published studies with 3 months old mice even after they were exposed to rotenone for 9 weeks indicating age is a crucial factor for alpha-syn induced neuroinflammation and neurodegeneration. We also observed increased iron accumulation in SN of rotenone-exposed aged mice. Moreover, inflammaging was observed in OB and striatum of 12-month-old BALB/c mice as compared to 3-month-old BALB/c mice. In conclusion, there is a difference in sensitivity between adult and aged mice in the development and progression of alpha-syn pathology and subsequent neurodegeneration, for which inflammaging might be the crucial probable mechanism.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LX22NPO5107" target="_blank" >LX22NPO5107: National institute for Neurological Research</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
NEUROCHEMICAL RESEARCH
ISSN
0364-3190
e-ISSN
1573-6903
Volume of the periodical
48
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
1543-1560
UT code for WoS article
000904018500001
EID of the result in the Scopus database
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