Hippocampal CA3 Transcriptional Modules Associated with Granule Cell Alterations and Cognitive Impairment in Refractory Mesial Temporal Lobe Epilepsy Patients

In about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological and transcriptomic data trough weighted gene co-expression network analysis, we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. A systems biology approach, integrating clinical, histopathological, and transcriptomic data - through WGCNA - to identify transcriptional modules highly correlated with clinical and histopathological traits, in refractory mesial temporal lobe epilepsy patients.