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Persistently Upregulated Hippocampal mTOR Signals Mediated by Fecal SCFAs Impair Memory in Male Pups with SMM Exposure in Utero / 生物医学与环境科学(英文)
Biomedical and Environmental Sciences ; (12): 345-356, 2019.
Artículo en Inglés | WPRIM | ID: wpr-773408
ABSTRACT
OBJECTIVE@#To investigate the molecular mechanisms of the adverse effects of exposure to sulfamonomethoxin (SMM) in pregnancy on the neurobehavioral development of male offspring.@*METHODS@#Pregnant mice were randomly divided into four groups control- (normal saline), low- [10 mg/(kg•day)], middle- [50 mg/(kg•day)], and high-dose [200 mg/(kg•day)] groups, which received SMM by gavage daily during gestational days 1-18. We measured the levels of short-chain fatty acids (SCFAs) in feces from dams and male pups. Furthermore, we analyzed the mRNA and protein levels of genes involved in the mammalian target of rapamycin (mTOR) pathway in the hippocampus of male pups by RT-PCR or Western blotting.@*RESULTS@#Fecal SCFA concentrations were significantly decreased in dams. Moreover, the production of individual fecal SCFAs was unbalanced, with a tendency for an increased level of total fecal SCFAs in male pups on postnatal day (PND) 22 and 56. Furthermore, the phosphatidylinositol 3-kinase (PI3k)/protein kinase B (AKT)/mTOR or mTOR/ribosomal protein S6 kinase 1 (S6K1)/4EBP1 signaling pathway was continuously upregulated until PND 56 in male offspring. In addition, the expression of Sepiapterin Reductase (SPR), a potential target of mTOR, was inhibited.@*CONCLUSION@#In utero exposure to SMM, persistent upregulation of the hippocampal mTOR pathway related to dysfunction of the gut (SCFA)-brain axis may contribute to cognitive deficits in male offspring.
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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Efectos Tardíos de la Exposición Prenatal / Sulfamonometoxina / Química / Oxidorreductasas de Alcohol / Toxicidad / Ácidos Grasos Volátiles / Heces / Serina-Treonina Quinasas TOR / Hipocampo / Memoria Límite: Animales / Embarazo Idioma: Inglés Revista: Biomedical and Environmental Sciences Año: 2019 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Efectos Tardíos de la Exposición Prenatal / Sulfamonometoxina / Química / Oxidorreductasas de Alcohol / Toxicidad / Ácidos Grasos Volátiles / Heces / Serina-Treonina Quinasas TOR / Hipocampo / Memoria Límite: Animales / Embarazo Idioma: Inglés Revista: Biomedical and Environmental Sciences Año: 2019 Tipo del documento: Artículo