Intranasal Rotenone Induces Alpha-Synuclein Accumulation, Neuroinflammation and Dopaminergic Neurodegeneration in Middle-Aged Mice

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Intranasal Rotenone Induces Alpha-Synuclein Accumulation, Neuroinflammation and Dopaminergic Neurodegeneration in Middle-Aged Mice

Popis výsledku v původním jazyce

Accumulation of alpha-synuclein (alpha-syn) is central to the pathogenesis of Parkinson&apos;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.

Název v anglickém jazyce

Intranasal Rotenone Induces Alpha-Synuclein Accumulation, Neuroinflammation and Dopaminergic Neurodegeneration in Middle-Aged Mice

Popis výsledku anglicky

Accumulation of alpha-synuclein (alpha-syn) is central to the pathogenesis of Parkinson&apos;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LX22NPO5107" target="_blank" >LX22NPO5107: Národní ústav pro neurologický výzkum</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

NEUROCHEMICAL RESEARCH

ISSN

0364-3190

e-ISSN

1573-6903

Svazek periodika

48

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

1543-1560

Kód UT WoS článku

000904018500001

EID výsledku v databázi Scopus

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