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.

Hippocampal expression of heat shock proteins in mesial temporal lobe epilepsy with psychiatric comorbidities and their relation to seizure outcome

“…We further evaluated HSP70 and HSP90 differences related to clinical variables. Clinical characteristics were homogenously distributed among epileptic groups, except for global IQ and performance in memory tests, on which MTLE patients with psychosis presented with lower scores, in accordance with previous findings in schizophrenic patients and in epileptic patients with interictal psychosis . No information in the literature is available regarding HSP90 levels and memory, but in our series, hippocampal HSP90 expression was positively correlated with verbal and nonverbal neuropsychological scores.…”

Neurotrophin receptors expression in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with seizure type and surgical outcome

“…Our previous studies [7][8][9] together with the present results demonstrate that there is an overall structural abnormality and alterations in expression of NTs and their receptors in the epileptogenic hippocampus, that are differentially modulated in presence of psychiatric comorbidities. The clinical significance of these alterations is yet being established.…”

“…8 ( Figure 4, a-s). In CA3, increased TrkB IR was seen in MTLE + P and controls when compared to MTLE and MTLE + D ( Figure 5, a-d).…”

“…Mesial temporal lobe epilepsy (MTLE), the most common cause of intractable epilepsy in adults, usually shows hippocampal sclerosis (HS), neuronal loss, gliosis and mossy fiber sprouting [3][4][5][6]. We have recently shown neuropathological data suggesting that there is a structural basis for psychiatric symptoms in the hippocampus of MTLE patients [7,8], and altered neurotrophin (NT) expression in presence of psychiatric comorbidities [9].…”

Animal models of epilepsy: use and limitations

“…Neurotrophins are upregulated in the hippocampus of mesial TLE patients,16 as well as in the hippocampus and neocortex of pilocarpine-treated rats 17. Cognitive and memory deficits commonly found in TLE patients18,19 are also present in pilocarpine-injected rats 20,21…”