Microtubule-associated proteins in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with granular cell layer dispersion.
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.
Ribeirao Preto Medical School, Department of Neurosciences and Behavior, University of Sao Paulo (USP), Avenida Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brazil ; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, Avenida Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brazil ; National Institute of Science and Technology in Translational Medicine (INCT-TM/CNPq), Avenida Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brazil.
Ludmyla
L
Kandratavicius
Mariana Raquel
MR
Monteiro
Jaime Eduardo
JE
Hallak
Carlos Gilberto
CG
Carlotti
Joao Alberto
JA
Assirati
Joao Pereira
JP
Leite
D000293:Adolescent; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D004833:Epilepsy, Temporal Lobe / Q000151:congenital* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009474:Neurons / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins