Microtubule-Associated Proteins in Mesial Temporal Lobe Epilepsy with and without Psychiatric Comorbidities and Their Relation with Granular Cell Layer Dispersion

Abstract

Background. Despite strong association between epilepsy and psychiatric comorbidities, biological substrates are unknown. We have previously reported decreased mossy fiber sprouting in mesial temporal lobe epilepsy (MTLE) patients with psychosis and increased in those with major depression. Microtubule associated proteins (MAPs) are essentially involved in dendritic and synaptic sprouting. Methods. MTLE hippocampi of subjects without psychiatric history, MTLE + major depression, and MTLE + interictal psychosis derived from epilepsy surgery and control necropsies were investigated for neuronal density, granular layer dispersion, and MAP2 and tau immunohistochemistry. Results. Altered MAP2 and tau expression in MTLE and decreased tau expression in MTLE with psychosis were found. Granular layer dispersion correlated inversely with verbal memory scores, and with MAP2 and tau expression in the entorhinal cortex. Patients taking fluoxetine showed increased neuronal density in the granular layer and those taking haloperidol decreased neuronal density in CA3 and subiculum. Conclusions. Our results indicate relations between MAPs, granular layer dispersion, and memory that have not been previously investigated. Differential MAPs expression in human MTLE hippocampi with and without psychiatric comorbidities suggests that psychopathological states in MTLE rely on differential morphological and possibly neurochemical backgrounds. This clinical study was approved by our institution's Research Ethics Board (HC-FMRP no. 1270/2008) and is registered under the Brazilian National System of Information on Ethics in Human Research (SISNEP) no. 0423.0.004.000-07.