High-fat diet exacerbates 1-Bromopropane-induced loss of dopaminergic neurons in the substantia nigra of mice through mitochondrial damage associated necroptotic pathway.
Ecotoxicol Environ Saf
; 276: 116280, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38574648
ABSTRACT
In recent years, accumulating evidence supports that occupational exposure to solvents is associated with an increased incidence of Parkinson's disease (PD) among workers. The neurotoxic effects of 1-bromopropane (1-BP), a widely used new-type solvent, are well-established, yet data on its relationship with the etiology of PD remain limited. Simultaneously, high-fat consumption in modern society is recognized as a significant risk factor for PD. However, whether there is a synergistic effect between a high-fat diet and 1-BP exposure remains unclear. In this study, adult C57BL/6 mice were fed either a chow or a high-fat diet for 18 weeks prior to 12-week 1-BP treatment. Subsequent neurobehavioral and neuropathological examinations were conducted to assess the effects of 1-BP exposure on parkinsonian pathology. The results demonstrated that 1-BP exposure produced obvious neurobehavioral abnormalities and dopaminergic degeneration in the nigral region of mice. Importantly, a high-fat diet further exacerbated the impact of 1-BP on motor and cognitive abnormalities in mice. Mechanistic investigation revealed that mitochondrial damage and mtDNA release induced by 1-BP and high-fat diet activate NLRP3 and cGAS-STING pathway- mediated neuroinflammatory response, and ultimately lead to necroptosis of dopaminergic neurons. In summary, our study unveils a potential link between chronic 1-BP exposure and PD-like pathology with motor and no-motor defects in experimental animals, and long-term high-fat diet can further promote 1-BP neurotoxicity, which underscores the pivotal role of environmental factors in the etiology of PD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Substantia Nigra
/
Dopaminergic Neurons
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Diet, High-Fat
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Hydrocarbons, Brominated
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Mice, Inbred C57BL
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Mitochondria
Limits:
Animals
Language:
En
Journal:
Ecotoxicol Environ Saf
Year:
2024
Document type:
Article