Dysregulation of prostaglandine E2 and BDNF signaling mediated by estrogenic dysfunction induces primary hippocampal neuronal cell death after single and repeated paraquat treatment.
Food Chem Toxicol
; 144: 111611, 2020 Oct.
Article
em En
| MEDLINE
| ID: mdl-32738378
ABSTRACT
Paraquat (PQ) produces hippocampal neuronal cell death and cognitive dysfunctions after unique and continued exposure, but the mechanisms are not understood. Primary hippocampal wildtype or ßAPP-Tau silenced cells were co-treated with PQ with or without E2, N-acetylcysteine (NAC), NS-398 (cyclooxygenase-2 inhibitor), MF63 (PGES-1 inhibitor) and/or recombinant brain-derived neurotrophic factor (BDNF) during one- and fourteen-days to studied PQ effect on prostaglandin E2 (PGE2) and BDNF signaling and their involvement in hyperphosphorylated Tau (pTau) and amyloid-beta (Aß) protein formation, and oxidative stress generation, that lead to neuronal cell loss through estrogenic disruption, as a possible mechanism of cognitive dysfunctions produced by PQ. Our results indicate that PQ overexpressed cyclooxygenase-2 that leads to an increase of PGE2 and alters the expression of EP1-3 receptor subtypes. PQ induced also a decrease of proBDNF and mature BDNF levels and altered P75NTR and tropomyosin receptor kinase B (TrkB) expression. PQ induced PGE2 and BDNF signaling dysfunction, mediated through estrogenic disruption, leading to Aß and pTau proteins synthesis, oxidative stress generation and finally to cell death. Our research provides relevant information to explain PQ hippocampal neurotoxic effects, indicating a probable explanation of the cognitive dysfunction observed and suggests new therapeutic strategies to protect against PQ toxic effects.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paraquat
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Dinoprostona
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Transdução de Sinais
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Morte Celular
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Fator Neurotrófico Derivado do Encéfalo
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Estrogênios
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Herbicidas
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Hipocampo
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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