Plic-1, a new target in repressing epileptic seizure by regulation of GABAAR function in patients and a rat model of epilepsy

• DOI: 10.1042/cs20150202
• Publication Date: 2015-09-29T02:08:43Z
• Authors: Yujiao Zhang; Zengyou Li; Juan Gu; Yanke Zhang; Wei Wang; Hui Shen; Guojun Chen; Xuefeng Wang
• Keywords: Pentylenetetrazol; Pilocarpine; Picrotoxin

Dysfunction of γ-aminobutyric acid A (GABAA) receptors (GABAARs) is a prominent factor affecting intractable epilepsy. Plic-1, an ubiquitin-like protein enriched in the inhibitory synapses connecting GABAARs and ubiquitin protease system (UPS), plays key role modification GABAAR functions. However, relationship between Plic-1 epileptogenesis not known. In present study, we aimed to investigate levels patients with temporal lobe epilepsy, as well regulating onset progression epilepsy animal models. We found that expression was significantly decreased pilocarpine- pentylenetetrazol (PTZ)-induced rat epileptic Intrahippocampal injection PePα peptide, which disrupts binding GABAARs, shortened latency seizure onset, increased severity duration these two Overexpressed through lentivirus transfection into PTZ model resulted reduction both generalized tonic-clonic duration. Whole-cell clamp recordings revealed peptide miniature postsynaptic currents (mIPSCs) whereas overexpressed mIPSCs pyramidal neurons hippocampus. These effects can be blocked by picrotoxin, inhibitor. Our results indicate important managing seizures enhancing inhibition regulation at synaptic sites.