Abstract：
Disruption of gamma-amino butyric acid type A receptors (GABAA Rs) synaptic clustering and a decrease in the number of GABAA Rs in the plasma membrane are thought to contribute to alteration of the balance between excitatory and inhibitory neurotransmission, which promotes seizure induction and propagation. The multipass transmembrane protein cleft lip and palate transmembrane protein 1 (Clptm1) controls the forward trafficking of GABAA R, thus decaying miniature inhibitory postsynaptic current (mIPSC) of inhibitory synapses. In this study, using a pentylenetetrazol (PTZ)-induced epilepsy rat model, we found that Clptm1 regulates epileptic seizures by modulating GABAA R-mediated inhibitory synaptic transmission. First, we showed that Clptm1 expression was elevated in the PTZ-induced epileptic rats. Subsequently, we found that downregulation of Clptm1 expression protected against PTZ-induced seizures, which was attributed to an increase in the number of GABAA Rγ2s in the plasma membrane and the amplitude of mIPSC. Taken together, our findings identify a new anti-seizure target that provides a theoretical basis for the development of novel strategies for the prevention and treatment of epilepsy.
摘要：
γ-氨基丁酸A型受体（GABAARs）突触聚集的破坏和质膜中GABAARs数量的减少被认为有助于改变兴奋性和抑制性神经传递之间的平衡，促进癫痫的诱导和传播。多次跨膜蛋白唇腭裂跨膜蛋白1（Clptm1）控制GABAAR的正向运输，从而衰减抑制性突触的微型抑制性突触后电流（mIPSC）。在这项研究中,使用戊四氮（PTZ）诱导的癫痫大鼠模型，我们发现Clptm1通过调节GABAAR介导的抑制性突触传递来调节癫痫发作。首先,我们发现在PTZ诱导的癫痫大鼠中Clptm1表达升高。随后，我们发现Clptm1表达的下调可以保护PTZ诱导的癫痫发作，这归因于质膜中GABAARγ2s的数量增加和mIPSC的幅度。一起来看,我们的研究结果确定了一个新的抗惊厥靶点,为制定预防和治疗癫痫的新策略提供了理论基础.
