5th Edition of International Neurology Conference 2026

Abstract

Long non-coding RNAs (lncRNAs) play significant roles in neurological diseases, including epilepsy. Our previous study identified lncRNA-GPHN as downregulated explicitly in a rat model of status epilepticus (SE). Investigate the role and regulatory mechanism of lncRNA-GPHN in the pathogenesis of epilepsy. SE rat and in vitro cell models were used to analyse expression dynamics, cellular localisation, and effects of lncRNA-GPHN on epileptic seizures, followed by HE staining, Nissl staining, and TUNEL staining. Luciferase Reporter assay, ChIRP assay, real-time quantitative PCR, and Western blotting, accompanied by TUNEL assay and whole-cell patch-clamp techniques, were employed to determine the molecular mechanism of lncRNA GPHN in regulating epilepsy in neurons. Post-seizure, lncRNA-GPHN in SE rats' hippocampus was markedly downregulated, hitting a nadir at 24h. FISH and qPCR confirmed its cytoplasmic localization in neurons. EEG showed that lncRNA-GPHN overexpression significantly curtailed seizure frequency and intensity, elevating the threshold, while MWM results pointed to enhanced cognition in SE rats. Histological staining revealed less neuronal damage and better cellular integrity in overexpressing rats, accompanied by a reduction in neuronal apoptosis. In vitro, lncRNA-GPHN reduced neuronal excitability and epileptic potentials dose-dependently. Q-PCR and ChIRP showed lncRNA-GPHN upregulates YWHAH by sequestering miR-320. Dual-luciferase and Western blot validated miR-320's direct suppression of YWHAH and lncRNA-GPHN's counteracting effect. TUNEL staining confirmed that miR-320 overexpression increased apoptosis, which was mitigated by lncRNA-GPHN overexpression and further reduced with combined overexpression. lncRNA-GPHN ameliorates epilepsy by inhibiting apoptosis via the miR-320/ YWHAH axis, providing insights into epilepsy pathogenesis and potential targeted therapeutic strategies.