Analysis of synaptosomes isolated from hippocampus tissue of patients with Mesial Temporal Lobe Epilepsy using proteomics and metabolomics

Abstract

Epilepsy is a chronic neurological disorder characterized by the occurrence of epileptic seizures due to abnormal neuronal discharges. Mesial Temporal Lobe Epilepsy (MTLE) is the most common type of focal epilepsy and present a high proportion of patients who do not respond to treatment with Antiepileptic Drug Treatment (AED). Most of these patients with drug-resistant epilepsy show a type of hippocampal lesion characterized by extensive neuronal damage and atrophy, called Hippocampal Sclerosis (HS). The synapses are electric and chemical communications between the neurons and synaptosomes are membrane vesicles that contain the synaptic components. The study of synaptosomes can give clues about the synaptic transmission and its abnormalities, since they contain all the machinery involved in the release, reuptake and storage of neurotransmitters. In addition, synaptic proteins have been studied as possible therapeutic targets in many neurological diseases. In this context, we propose to analyze the synaptosomes isolated from brain tissue (hippocampus) of patients with MTLE in comparison with normal tissue, using proteomics and metabolomics to evaluate the changes in their molecular content which can be related to epileptogenesis and the mechanisms underlying AED-resistance. This information can also be used subsequently in the identification of new therapeutic targets for patients with drug resistant MTLE. (AU)