Abstracts

Rationale: Granule cell dispersion (GCD) is a common neuropathological feature of hippocampal sclerosis (HS) in patients with temporal lobe epilepsy (TLE). However, the underlying molecular mechanism of GCD formation remains unclear. The present study aimed to investigate the expressional changes of With No Lysine protein kinase subtype 3 (WNK3), a molecule upstream of cation-chloride cotransporters with reciprocal expression in sclerosed hippocampus of TLE patients. Methods: Human tissues were obtained from 12 patients who underwent epilepsy surgery. We selected 8 patients with history of TLE and histopathological evidence for HS. Although epilepsy was diagnosed with clinical features, 4 patients with no histological pathology were used as normal controls. Using Cresyl violet and immunofluorescence staining, we analyzed WNK3 immunoreactivity in hippocampal specimens from histologically normal controls and TLE patients with HS. Results: Cresyl violet staining revealed remarkable GCD formation in hippocampal tissues from patients with TLE. We found significantly wider GCL width in hippocampal specimens from TLE patients than in those from normal controls (p = 0.004). Double-immunofluorescence staining showed that WNK3 expression was significantly increased in dispersed granule neurons in hippocampal tissues from patients with TLE compared with histologically normal hippocampus. Conclusions: These findings demonstrate a potential association between an increased expression of WNK3 and GCD formation during the chronic phase of epilepsy. Controlling WNK3 expression may thus be a novel therapeutic target in epileptogenesis. Funding: This research was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (2015R1D1A1A01059901).