کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11025163 | 1701028 | 2019 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chronic fluoride exposure induces neuronal apoptosis and impairs neurogenesis and synaptic plasticity: Role of GSK-3β/β-catenin pathway
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
شیمی زیست محیطی
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چکیده انگلیسی
Fluoride is becoming an ineluctable environmental pollutant and its longterm exposure would cause fluorosis and irreversible brain damage, but the molecular mechanisms remain far from fully understood. In the present study, we firstly evaluated the glycogen synthase kinase 3β (GSK-3β)/β-catenin pathway in the hippocampus of rats exposed to fluoride, given the well-established role of GSK-3β/β-catenin pathway in neuronal death and survival. Our data showed that sustained exposure to 50â¯mg/L and 100â¯mg/L NaF in drinking water dose-dependently induced neuronal loss and apoptosis in rat hippocampus. Neurogenesis was also weakened by fluoride administration in the hippocampal dentate gyrus region. Additionally, the synaptic markers, synaptophysin (SYP) and post-synaptic density 95 (PSD95) protein levels, were decreased by 100â¯mg/L NaF treatment, whereas 50â¯mg/L NaF only reduced SYP expression, indicating a compromised synaptic function. We further demonstrated that NaF, especially the higher dose, induced GSK-3β activity, with decreased inactive phosphorylated GSK-3β levels and increased GSK-3β, the active form of the kinase. Correspondingly, downstream β-catenin signaling was undermined by NaF treatment as evidenced by the fact that both two doses of NaF decreased nucleus β-catenin status and the higher dose of NaF also reduced cytoplasmic β-catenin protein expression. Taken together, the present study firstly showed the aberrant changes of GSK-3β/β-catenin signaling in the fluoride-exposed brain, highlighting the involvement of GSK-3β/β-catenin signaling in the fluoride-induced neurotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemosphere - Volume 214, January 2019, Pages 430-435
Journal: Chemosphere - Volume 214, January 2019, Pages 430-435
نویسندگان
Pei Jiang, Gongying Li, Xueyuan Zhou, Changshui Wang, Yi Qiao, Dehua Liao, Dongmei Shi,