Clptm1 Downregulation Exerts Antiepileptic Activity by Regulating GABAAR-mediated Inhibitory Synaptic Transmission in PTZ-induced Epileptic Model

Background: Disruption of GABAAR synaptic clustering and a decrease number in their cell surface are thought to contribute to the alteration in the balance between excitatory and inhibitory neurotransmission, which contributes to seizure induction and propagation. Cleft lip and palate transmembrane protein 1 (Clptm1), a multi-pass transmembrane protein, has been showed that it is an intracellular molecule that controls forward trafficking of GABAAR. Clptm1 downregulating increased miniature inhibitory postsynaptic current (mIPSC) in vivo. Thus, Clptm1 controls phasic and tonic inhibitory transmission in brain. In this study, we hypothesized that Clptm1 may be involved in epileptic seizure by regulating GABAAR-mediated inhibitory synaptic transmission in epileptic model.Methods and Results: In PTZ-induced epileptic model, we found that Clptm1 was increased in temporal lobe epilepsy (TLE) patients as well as in epileptic model. Then, we showed that Clptm1 downregulation exerted antiepileptic activities in epileptic model, which was associated to the increased surface GABAARγ2 expression and mIPSCs amplitudes.Conclusions: Clptm1 downregulation exerted antiepileptic activities in epileptic model, thus, it may be a promising target for antiepileptic treatments.

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