کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8553070 | 1562576 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pb inhibits hippocampal synaptic transmission via cyclin-dependent kinase-5 dependent Synapsin 1 phosphorylation
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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![عکس صفحه اول مقاله: Pb inhibits hippocampal synaptic transmission via cyclin-dependent kinase-5 dependent Synapsin 1 phosphorylation Pb inhibits hippocampal synaptic transmission via cyclin-dependent kinase-5 dependent Synapsin 1 phosphorylation](/preview/png/8553070.png)
چکیده انگلیسی
Lead (Pb) exposure impairs the nervous system, of which the injury of cognitive development is obvious. But the mechanism of Pb induced disorders of neuro-transmission remain elusive. In this study, primary hippocampal neurons were exposed to Pb at the dosage of 5âμM from days in vitro (DIV) 3 to DIV14 and the electrophysiological recordings were performed at DIV14. Sprague-Dawley (SD) rat pups were exposed to Pb from parturition to weaning indirectly from their mothers whose drinking water containing 250âppm Pb, then directly exposed to Pb at the dosage of 250âppm from postnatal day (PND) 21 to PND30. The results showed that Pb significantly decreased the frequency of both miniature excitatory postsynaptic current (mEPSC) and miniature inhibitory postsynaptic current (mIPSC) in cultured hippocampal neurons. Paird-pulse facilitation (PPF) recordings showed there was significant increase in Pb-exposed group. The increase of the magnitude of PPF (the ratio of second to first response amplitude) further confirmed that Pb reduced presynaptic neuro-transmission. By transmission electron microscope, it found that Pb disarranged presynaptic vesicles distribution and decreased the density of presynaptic vesicles. Moreover, it was interestingly found that phosphorylation of Synapsin1, which was phosphorylated by CDK5, has been decreased upon Pb exposure. With the treatment of R-Roscovitine (Ro), an inhibitor of CDK5, it was detected that Pb induced mEPSC and mIPSC frequency reduction have been reversed. Together, our results suggested that Pb disrupted the distribution of synaptic vesicles and impaired the neurotransmitter release, which was dependent on the phosphorylation level of Synapsin 1 via CDK5. This study will help for elucidation of environmental Pb-induced neuronal disorders.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 296, 15 October 2018, Pages 125-131
Journal: Toxicology Letters - Volume 296, 15 October 2018, Pages 125-131
نویسندگان
Jin-Jun Ding, Rong-Xin Zou, Hui-Ming He, Zhi-Yi Lou, Yi Xu, Hui-Li Wang,