Can the cellular wiring of the brain shed light on epilepsy?

Abstract

Since Cajal’s and Golgi’s pioneering studies of neuronal morphology, neuroscientists have widely recognized the fundamental importance of the branching structure of brain cells in both physiological function and disease. Epilepsy, a chronic neurological disorder characterized by unprovoked seizures, is associated with abnormal neuronal discharges and hyperexcitability. Despite significant advancements in epilepsy research, the relationship between this pathology and neural morphology remains is not fully understood. NeuroMorpho.Org is an open-access repository containing over 260,000 digital reconstructions of neural morphologies from 94 species collected from nearly 1000 labs worldwide. In this work we downloaded 1,417 reconstructions from 19 NeuroMorpho.Org archives to explore morphological changes of brain cells in hippocampus and neocortex, the main epileptogenic regions.  Even though NeuroMorpho.Org contained reconstructions from patients with epilepsy, the lack of proper controls makes their analysis difficult to interpret. Our preliminary results show that genetic models of epilepsy do not affect the morphology of neurons or glia in either brain region. In contrast, pharmacologically induced epilepsy mainly alters the morphology of microglial cells. Understanding the changes in cellular architecture associated with this pathology can open new opportunities to develop new treatments and improve the life quality of patients.