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Microtubule-associated proteins in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their
Ludmyla Kandratavicius1, Mariana Raquel Monteiro, Jaime Eduardo Hallak
1Ribeirao 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.
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.
Insights
Investigating microtubule associated proteins (MAPs) in mesial temporal lobe epilepsy (MTLE) reveals differences in patients with psychosis or depression. These findings suggest distinct brain changes underlie psychiatric conditions in MTLE.
Area of Science:
- Neuroscience
- Epilepsy Research
- Psychiatry
Background:
- Epilepsy and psychiatric comorbidities have a strong association, but their biological underpinnings remain unclear.
- Previous research indicated altered mossy fiber sprouting in mesial temporal lobe epilepsy (MTLE) patients with psychosis and major depression.
- Microtubule associated proteins (MAPs) play a crucial role in neuronal sprouting and synaptic plasticity.
Purpose of the Study:
- To investigate the expression of MAPs and their relationship with neuronal morphology and psychiatric comorbidities in MTLE.
- To explore the correlation between granular layer dispersion, memory function, and MAPs expression in the hippocampus.
- To examine the impact of psychotropic medications on neuronal density in MTLE.
Main Methods:
- Hippocampal tissues from MTLE patients (with and without psychiatric history) and controls were analyzed.
- Neuronal density, granular layer dispersion, and immunohistochemistry for MAP2 and tau were assessed.
- Correlations between clinical data, medication use, and neuropathological findings were examined.
Main Results:
- Differential expression of MAP2 and tau was observed in MTLE hippocampi.
- Decreased tau expression was found in MTLE patients with psychosis.
- Granular layer dispersion inversely correlated with verbal memory and MAPs expression; fluoxetine and haloperidol showed differential effects on neuronal density.
Conclusions:
- MAPs, granular layer dispersion, and memory are interconnected in MTLE, representing a novel area of investigation.
- Differential MAPs expression in MTLE hippocampi suggests distinct morphological and neurochemical bases for psychiatric comorbidities.
- These findings highlight the complex interplay between epilepsy, brain structure, and mental health in MTLE.
