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
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
načítá se...