Abstracts

Rationale: Temporal lobe epilepsy (TLE) is one of the most frequent types of intractable epilepsy and it comprises 50% of all partial epilepsies. Hippocampal sclerosis (HS), one of the most common causes of TLE, is characterized by seizure generation from the mesial temporal lobe. Although the etiopathogenesis is unknown, changes in synaptic and axonal reorganization have been reported during the course of HS. Complex alterations leading to hippocampal pathogenesis of mesial temporal lobe epilepsy (MTLE) suggests involvement of various genes and signaling pathways including apoptosis. Our aim was to explore the role of both extrinsic and intrinsic apoptotic pathway genes in the pathogenetic mechanisms of hippocampal sclerosis through evaluation of gene expression in surgically removed human brain tissues. Methods: The patients with a diagnosis of HS by MRI and clinical findings who underwent epilepsy surgery were included after their consent. In this study, we have investigated gene expression levels for both extrinsic and intrinsic apoptotic pathway genes in human hippocampal material of 8 patients and 8 autopsy controls by quantitative real-time polymerase chain reaction with TaqMan hydrolyzis probes. Relative expressions were calculated according to the delta Ct method and the results were compared with Mann Whitney U test.Results: Eight epileptic patients who underwent surgery due to hippocampal sclerosis and 8 autopsy specimens as control tissues were investigated. High expression of extrinsic pathway genes such as TNFR1 and FAS was remarkable. However, FAS (TNF receptor superfamily member 6), TNFR1 (Tumor necrosis factor receptor superfamily member 1a), TP53 (Tumor protein p53), BAX (BCL2 associated X protein), BCL2 (B cell CLL/Lymphoma 2), CASPASE3 (Apoptosis related cysteine peptidase 3) and CASPASE9 (Apoptosis related cysteine peptidase 3) genes expression levels showed no statistically significant differences in HS patients compared with control tissue (p= 0.146, p= 0.062, p= 0.865, p= 0.141, p= 0.865, p= 0.534, p= 0.152 respectively).Conclusions: The significance of our study resides in the fact that it is among the first apoptotis related genes expression analyses in the human brain tissue. Previous immunohistochemistry reports have shown that the levels of the apoptotic proteins in human hippocampal tissue are increased. There is high expression for extrinsic pathway genes such as TNFR1 and FAS, however expression results are statistically not significant differences. In addition we didn t find any significant difference between patients and controls for intrinsic pathway genes expression levels. Our future aims are to work with more HS samples and to expand our tissue bank to enlighten the possible role of apoptosis-related genes in the pathogenesis of MTLE.