Altered expression of activating transcription factor 3 in the hippocampus of patients with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS)

Abstract

Aim of the study: Activating Transforming factor 3 (ATF3) is a stress induced gene and closely associated with neuro-inflammation while Transforming growth Factor Beta (TGFβ) signalling is also reported to be involved in neuro-inflammation and hyper-excitability associated with drug resistant epilepsy. Animal model studies indicate the involvement of ATF3 and TGFβ receptors to promote epileptogenesis. Human studies also show that TGFβ signalling is activated in MTLE-HS. However, lack of studies on ATF3 and TGFβRI expression in MTLE-HS patients exists. We hypothesize that ATF3 and TGFβRI might be expressed in hippocampi of patients with MTLE-HS and playing role in epileptogenesis. Materials & methods: Protein expression of ATF3 and TGFβRI was performed by western blotting. Localisation of ATF3 was performed by immunohistochemistry and immunoflorescence. Results: Protein expression of ATF3 and TGFβRI was significantly up-regulated in hippocampi of patients as compared to controls. Also ATF3 IR was significantly expressed in hippocampi of patients and ATF3 was expressed predominantly in cytoplasm as compared to nucleus. No correlation was found between ATF3 expression and epilepsy duration and seizure frequency. Conclusions: ATF3 and TGFβRI are both important players in neuro-inflammation and might potentiate epileptogenesis in these patients.