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首页> 外文期刊>The European Journal of Neuroscience >Prenatal exposure to polybrominated diphenylether 99 enhances the function of the glutamate-nitric oxide-cGMP pathway in brain in vivo and in cultured neurons.
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Prenatal exposure to polybrominated diphenylether 99 enhances the function of the glutamate-nitric oxide-cGMP pathway in brain in vivo and in cultured neurons.

机译:产前暴露于多溴二苯醚99可以增强体内和培养的神经元中谷氨酸一氧化氮cGMP通路的功能。

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摘要

Polybrominated diphenylethers (PBDEs) are widely used as flame retardants. Significant amounts of PBDEs are present in the milk of lactating women. The possible neurotoxic effects of PBDEs are not well known. Perinatal exposure to PBDEs affects both motor and cognitive functions by mechanisms that remain unclear. Some types of learning depend on N-methyl-d-aspartate receptor activation, which increases intracellular calcium that binds to calmodulin and activates nitric oxide synthase, increasing nitric oxide formation that activates guanylate cyclase, increasing cGMP formation. Part of this cGMP is released to the extracellular fluid. We studied whether prenatal exposure of rats to PBDE99 alters the function of this glutamate-nitric oxide-cGMP pathway in rat brain in vivo. At 10 weeks of age, rats treated with PBDE99 showed increased function of the glutamate-nitric oxide-cGMP pathway in brain in vivo, as assessed by microdialysis in freely moving rats. The increased function of the pathway was reproduced in primary cultures of cerebellar neurons prepared from rats prenatally exposed to PBDE99 as well as in neurons cultured from normal rats and treated in vitro with PBDE99. Increased calmodulin content and activation of soluble guanylate cyclase by nitric oxide contributed to the increased function of the pathway.
机译:多溴二苯醚(PBDEs)被广泛用作阻燃剂。哺乳期妇女的牛奶中存在大量的多溴二苯醚。 PBDEs可能产生的神经毒性作用尚不清楚。围产期多溴二苯醚的暴露通过尚不清楚的机制影响运动和认知功能。某些类型的学习取决于N-甲基-d-天冬氨酸受体的激活,该激活会增加与钙调蛋白结合的细胞内钙并激活一氧化氮合酶,增加一氧化氮的形成,从而激活鸟苷酸环化酶,增加cGMP的形成。此cGMP的一部分释放到细胞外液中。我们研究了大鼠的产前暴露于PBDE99是否会改变体内谷氨酸-一氧化氮-cGMP通路的功能。在10周龄时,用PBDE99治疗的大鼠体内的谷氨酸一氧化氮cGMP通路的功能增强,这在自由运动大鼠中通过微透析进行了评估。在从产前暴露于PBDE99的大鼠制备的小脑神经元的原代培养物中,以及从正常大鼠培养并经PBDE99体外处理的神经元中,均可以再现该途径的功能增强。钙调蛋白含量的增加和一氧化氮对可溶性鸟苷酸环化酶的激活有助于增加该途径的功能。

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