Drebrin expression patterns in patients with refractory temporal lobe epilepsy and hippocampal sclerosis
Autor: | Karina Maciel, Carlos Gilberto Carlotti, Tonicarlo Rodrigues Velasco, André Luiz Palmini, Tomoaki Shirao, Gleice Kelly de Sousa, Munira Muhammad Abdel Baqui, Jaderson Costa da Costa, Eliseu Paglioli, João Pereira Leite, Jose Eduardo Peixoto-Santos, Roberto Spreafico, Américo Ceiki Sakamoto, Thaís C. D. Dombroski, Rita Garbelli, Luciano Neder, Antonio Roberto Martins, Kenji Hanamura, João Alberto Assirati, Hélio Rubens Machado |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Drug Resistant Epilepsy Dendritic spine PLASTICIDADE NEURONAL CA2 Region Hippocampal Hippocampal formation Biology Hippocampus Temporal lobe 03 medical and health sciences Epilepsy 0302 clinical medicine medicine Humans CA1 Region Hippocampal Aged Aged 80 and over Hippocampal sclerosis Microscopy Confocal Neuronal Plasticity Sclerosis Glutamate Decarboxylase Dentate gyrus Neuropeptides Dendrites Middle Aged medicine.disease Anterior Temporal Lobectomy CA3 Region Hippocampal Immunohistochemistry 030104 developmental biology medicine.anatomical_structure nervous system Neurology Epilepsy Temporal Lobe Case-Control Studies Synaptic plasticity Dentate Gyrus Vesicular Glutamate Transport Protein 1 Female Neurology (clinical) Neuron Microtubule-Associated Proteins psychological phenomena and processes 030217 neurology & neurosurgery |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
Popis: | Objective Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan-drebrin) isoforms, respectively. Methods Hippocampal sections from drug-resistant TLE patients with hippocampal sclerosis (HS; TLE, n = 33), of whom 31 presented with type 1 HS and two with type 2 HS, and autopsy control cases (n = 20) were assayed by immunohistochemistry and evaluated for neuron density, and drebrin A and pan-drebrin expression. Double-labeling immunofluorescences were performed to localize drebrin A-positive spines in dendrites (MAP2), and to evaluate whether drebrin colocalizes with inhibitory (GAD65) and excitatory (VGlut1) presynaptic markers. Results Compared to controls, TLE patients had increased pan-drebrin in all hippocampal subfields and increased drebrin A-immunopositive area in all hippocampal subfields but CA1. Drebrin-positive spine density followed the same pattern as total drebrin quantification. Confocal microscopy indicated juxtaposition of drebrin-positive spines with VGlut1-positive puncta, but not with GAD65-positive puncta. Drebrin expression in the dentate gyrus of TLE cases was associated negatively with seizure frequency and positively with verbal memory. TLE patients with lower drebrin-immunopositive area in inner molecular layer (IML) than in outer molecular layer (OML) had a lower seizure frequency than those with higher or comparable drebrin-immunopositive area in IML compared with OML. Significance Our results suggest that changes in drebrin-positive spines and drebrin expression in the dentate gyrus of TLE patients are associated with lower seizure frequency, more preserved verbal memory, and a better postsurgical outcome. |
Databáze: | OpenAIRE |
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