Primary hippocampal estrogenic dysfunction induces synaptic proteins alteration and neuronal cell death after single and repeated paraquat exposure.
Food Chem Toxicol
; 136: 110961, 2020 Feb.
Article
em En
| MEDLINE
| ID: mdl-31715309
ABSTRACT
The extensively utilized herbicide Paraquat (PQ) was reported to generate cognitive disorders and hippocampal neuronal cell death after unique and extended exposure. Although, most of the mechanisms that mediate these actions remain unknown. We researched whether PQ induces synaptic protein disruption, Tau and amyloid beta protein formation, oxidative stress generation, and hippocampal neuronal cell loss through anti-estrogen action in primary hippocampal neurons, after day and two weeks PQ treatment, as a probable mechanism of such learning and memory impairment. Our results reveal that PQ did not alter estrogen receptors (ERα and ERß) gene expression, yet it decreased ER activation, which led to synaptic proteins disruption and amyloid beta proteins generation and Tau proteins hyperphosphorylation. Estrogenic signaling disruption induced by PQ also downregulated the NRF2 pathway leading to oxidative stress generation. Finally, PQ exposure induced cell death mediated by ER dysfunction partially through oxidative stress and amyloid beta proteins generation and Tau proteins hyperphosphorylation. The results presented provide a therapeutic strategy to protect against PQ toxic effects, possibly giving an explanation for the learning and memory impairment generated following PQ exposure.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paraquat
/
Receptores de Estrogênio
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Morte Celular
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Hipocampo
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Proteínas do Tecido Nervoso
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Neurônios
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Food Chem Toxicol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Espanha