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分娩过程中催产素介导的 GABA 抑制可减弱啮齿动物后代自闭症的发病机制。

Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring.

机构信息

Mediterranean Institute of Neurobiology (INMED), U901, INSERM, Marseille, France.

出版信息

Science. 2014 Feb 7;343(6171):675-9. doi: 10.1126/science.1247190.

Abstract

We report that the oxytocin-mediated neuroprotective γ-aminobutyric acid (GABA) excitatory-inhibitory shift during delivery is abolished in the valproate and fragile X rodent models of autism. During delivery and subsequently, hippocampal neurons in these models have elevated intracellular chloride levels, increased excitatory GABA, enhanced glutamatergic activity, and elevated gamma oscillations. Maternal pretreatment with bumetanide restored in offspring control electrophysiological and behavioral phenotypes. Conversely, blocking oxytocin signaling in naïve mothers produced offspring having electrophysiological and behavioral autistic-like features. Our results suggest a chronic deficient chloride regulation in these rodent models of autism and stress the importance of oxytocin-mediated GABAergic inhibition during the delivery process. Our data validate the amelioration observed with bumetanide and oxytocin and point to common pathways in a drug-induced and a genetic rodent model of autism.

摘要

我们报告称,在丙戊酸和脆性 X 自闭症啮齿动物模型中,分娩过程中催产素介导的神经保护γ-氨基丁酸(GABA)兴奋-抑制转移被消除。在分娩期间和随后,这些模型中的海马神经元细胞内氯离子水平升高,兴奋性 GABA 增加,谷氨酸能活性增强,γ 振荡增加。母亲预先用布美他尼处理可恢复后代的对照电生理和行为表型。相反,在天真母亲中阻断催产素信号会产生具有电生理和行为自闭症样特征的后代。我们的结果表明,这些自闭症啮齿动物模型中存在慢性氯离子调节不足,并强调分娩过程中催产素介导的 GABA 能抑制的重要性。我们的数据证实了布美他尼和催产素的改善作用,并指出了药物诱导和遗传自闭症啮齿动物模型中的共同途径。

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