Rhynchophylline Attenuates Tourette Syndrome via BDNF/NF-κB Pathway In Vivo and In Vitro

Rhynchophylline Attenuates Tourette Syndrome via BDNF/NF-κB Pathway In Vivo and In Vitro
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钩藤碱在体内和体外通过 BDNF/NF-kappa B 通路减轻抽动秽语综合征

DOI:
10.1007/s12640-019-00079-x
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发表时间:
2019-11-01
影响因子:
3.7
通讯作者:
Huang, Yaruo
Huang, Yaruo
中科院分区:
医学3区
文献类型:
--
作者:
Long, Hongyan;Ruan, Jie;Huang, Yaruo

文献摘要

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抽动秽语综合征(Tourette syndrome, TS)是多例儿童慢性神经精神疾病之一,其发病机制此前尚未阐明。本研究旨在探讨蛇柳碱(RH)对大鼠抽动秽语综合征(TS)的影响。采用选择性5-HT2A/2C激动剂1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷(DOI)在大鼠和BV2细胞中建立TS模型。行为评价包括刻板印象记录和自主神经活动测试。检测血清、纹状体和细胞上清中白细胞介素-1 β (IL-1 β)、白细胞介素-6 (IL-6)、肿瘤坏死因子- α (tnf - α)等炎性细胞因子水平。Western blot检测纹状体和BV2细胞中BDNF/ nf - κ B通路的表达水平。测定纹状体多巴胺(DA)和多巴胺受体D2 (D2)水平。Western blot和免疫组化分析结果显示,RH显著降低TS模型血清、纹状体和细胞上清中IL-6、IL-1 β和tnf - α的表达,改变TS大鼠和doi诱导的BV2细胞中p - nf - κ B α、P-I κ B α和BDNF的表达。RH还显著降低纹状体中DA和D2的水平。我们的结果表明,RH对TS模型的影响可能与BDNF/NF-kappa B通路的调控有关。
Tourette syndrome (TS) is characterized by one of the chronic neuropsychiatric disorders in multiple children, and the pathogenesis of Tourette syndrome (TS) has not been previously elucidated. The aim of this study was designed to investigate the effects of rhynchophylline (RH) on Tourette syndrome (TS) in rats. TS model was established in rats and BV2 cells by the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior evaluations including stereotypy recording and autonomic activity test were performed. Inflammatory cytokine levels such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in serum, striatum, and cell supernatant were detected. The expression levels of BDNF/NF-kappa B pathway in striatum and BV2 cells were measured by Western blot. Dopamine (DA) and dopamine receptor D 2 (D2) in striatum were also measured. Data indicated that RH significantly decreased IL-6, IL-1 beta, and TNF-alpha in serum, striatum, and cell supernatant of TS model, with altered expression of P-NF-kappa Bp65, P-I kappa B alpha, and BDNF in TS rats, and DOI-induced BV2 cells, as evidenced by Western blot analysis and immunohistochemistry analysis. RH also significantly reduced the levels of DA and D2 in striatum. Our results shown that the regulation of BDNF/NF-kappa B pathway might be involved in the effects of RH on TS model.