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牛磺酸对六溴环十二烷暴露致仔鼠神经行为及神经发育关键蛋白表达改变的影响

Effects of Taurine on Alterations of Neurobehavior and Neurodevelopment Key Proteins Expression in Infant Rats by Exposure to Hexabromocyclododecane.

机构信息

School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, 264003, Shandong, China.

School of Public Health, Dalian Medical University, No. 9 Western Section of Lushun South Road, Dalian, 116044, Liaoning, China.

出版信息

Adv Exp Med Biol. 2017;975 Pt 1:119-130. doi: 10.1007/978-94-024-1079-2_11.

Abstract

Hexabromocyclododecanes (HBCDs) is a widely used flame retardant. Studies have found that HBCDs has toxic effects on endocrine and neural development, leading to adverse effects on behavior, learning and memory. This study aimed to investigate the protective effects of taurine on cognitive function, neurotrophic factors expression of infant rats exposured to HBCDs. Sprague-Dawley rats of 10-days old were oral gavaged of different doses (0.3, 3 and 30 mg/kg) of HBCDs and 30 mg/kg HBCDs with 300 mg/kg taurine for 60 consecutive days. Rat cognitive function was detected by the method of Morris water maze test. The protein expressions of brain derived neurotrophic factor (BDNF), nerve growth factor (NGF) and fibroblast growth factor (FGF) were assayed by Western-blotting. Results showed that rats exposed to HBCDs significantly declined rats spatial learning and memory ability by increasing the latency time of seeking the platform (P < 0.05), decreasing the numbers that each rat had crossed the non-exits and the time spent in the target quadrant as compared with those in control rats (P < 0.05). Taurine treatment significantly reversed the effects of HBCDs. Western-blotting results showed that expression of BDNF, NGF and FGF proteins in the low dose group were obviously increased compared with those in control rats (P < 0.01), and middle-dose and high dose groups significantly decreased. Taurine treatment increased BDNF and NGF expression as compared with high dose groups while Taurine seemed to have no effects on FGF. These result suggested that higher doses of HBCDs early exposure in the developing rats could decrease neurotrophic factors including BDNF, NGF, FGF, which have an impact on neural development, damage on learning and memory.

摘要

六溴环十二烷(HBCDs)是一种广泛使用的阻燃剂。研究发现,HBCDs 对内分泌和神经发育具有毒性作用,导致行为、学习和记忆出现不良影响。本研究旨在探讨牛磺酸对暴露于 HBCDs 的婴儿大鼠认知功能和神经营养因子表达的保护作用。将 10 天大的 Sprague-Dawley 大鼠分别灌胃不同剂量(0.3、3 和 30mg/kg)的 HBCDs 和 30mg/kg 的 HBCDs 加 300mg/kg 的牛磺酸,连续 60 天。采用 Morris 水迷宫试验检测大鼠认知功能,Western-blotting 法检测脑源性神经营养因子(BDNF)、神经生长因子(NGF)和纤维母细胞生长因子(FGF)的蛋白表达。结果显示,与对照组大鼠相比,暴露于 HBCDs 的大鼠寻找平台的潜伏期时间明显延长(P<0.05),穿越非出口的次数和在目标象限的时间减少(P<0.05),表明大鼠的空间学习和记忆能力下降。牛磺酸处理可显著逆转 HBCDs 的作用。Western-blotting 结果显示,与对照组大鼠相比,低剂量组 BDNF、NGF 和 FGF 蛋白表达明显增加(P<0.01),中剂量和高剂量组则明显降低。与高剂量组相比,牛磺酸处理增加了 BDNF 和 NGF 的表达,而牛磺酸对 FGF 似乎没有影响。这些结果表明,发育中的大鼠早期暴露于较高剂量的 HBCDs 可能会降低神经营养因子(包括 BDNF、NGF、FGF)的表达,从而影响神经发育、损害学习和记忆。

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