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首页> 外文期刊>Molecular Neurobiology >Alleviation of N -Methyl- d -Aspartate Receptor-Dependent Long-Term Depression via Regulation of the Glycogen Synthase Kinase-3β Pathway in the Amygdala of a Valproic Acid-Induced Animal Model of Autism
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Alleviation of N -Methyl- d -Aspartate Receptor-Dependent Long-Term Depression via Regulation of the Glycogen Synthase Kinase-3β Pathway in the Amygdala of a Valproic Acid-Induced Animal Model of Autism

机译：通过调节氨基甲酸诱导的自闭症动物模型中糖原合成酶激酶-3β途径的糖原合成酶激酶-3β通路的N-甲基-D-海岸酸盐受体依赖性长期抑郁症

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Abstract The amygdala plays crucial roles in socio-emotional behavior and cognition, both of which are abnormal in autism spectrum disorder (ASD). Valproic acid (VPA)-exposed rat offspring have demonstrated ASD phenotypes and amygdala excitatory/inhibitory imbalance. However, the role of glutamatergic synapses in this imbalance remains unclear. In this study, we used a VPA-induced ASD-like model to assess glutamatergic synapse-dependent long-term depression (LTD) and depotentiation (DPT) in the amygdala. We first confirmed that the VPA-exposed offspring exhibited sociability deficits, anxiety, depression-like behavior, and abnormal nociception thresholds. Then, electrophysiological examination showed a significantly decreased paired-pulse ratio in the amygdala. In addition, both NMDA-dependent LTD and DPT were absent from the amygdala. Furthermore, we found that the levels of glycogen synthase kinase3β (GSK-3β) phosphorylation and β-catenin were significantly higher in the amygdala of the experimental animals than in the controls. Local infusion of phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin into the amygdala reversed the increased phosphorylation level and impaired social behavior. Taken together, the results suggested that NMDA receptor-related synaptic plasticity is dysfunctional in VPA-exposed offspring. In addition, GSK-3β in the amygdala is critical for synaptic plasticity at the glutamatergic synapses and is related to social behavior. Its role in the underlying mechanism of ASD merits further investigation.
机译：摘要Amygdala在社会情绪行为和认知中起着至关重要的作用，这两者都是自闭症谱系障碍（ASD）的异常。羟甲酸（VPA） - 散合的大鼠后代已经证明了ASD表型和Amygdala兴奋/抑制性不平衡。然而，在这种不平衡中的谷氨酸蛋白突触的作用仍然不清楚。在这项研究中，我们使用VPA诱导的ASD样模型来评估谷氨酰胺突触依赖性的长期抑郁（LTD）和杏仁核的沉积（DPT）。我们首先证实，VPA暴露的后代表现出社交缺陷，焦虑，抑郁行为和异常的伤害阈值。然后，电生理学检查显示杏仁醛的配对脉冲比显着降低。此外，氨基达拉没有NMDA依赖性有限公司和DPT。此外，我们发现，实验动物的Amygdala在实验动物的氨基合酶KINASE3β（GSK-3β）磷酸化和β-catenin的水平明显高于对照组。局部输注磷脂酰肌醇3-激酶（PI3K）抑制剂Wortmannin进入Amygdala逆转磷酸化水平增加和社会行为受损。在一起，结果表明，NMDA受体相关的突触可塑性在VPA暴露后代具有功能障碍。此外，Amygdala中的GSK-3β对于谷氨酰胺突变突触处的突触可塑性至关重要，与社会行为有关。它在ASD的潜在机制中的作用进一步调查。

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