Drebrin expression patterns in patients with refractory temporal lobe epilepsy and hippocampal sclerosis

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Dombroski, Thais Caroline Dallabona ^[1] ; Peixoto-Santos, Jose Eduardo ^[2] ; Maciel, Karina ^[3] ; Baqui, Munira Muhammad Abdel ^[4] ; Velasco, Tonicarlo Rodrigues ^[5] ; Sakamoto, Americo Ceiki ^[5] ; Assirati, Joao Alberto ^[6] ; Carlotti, Carlos Gilberto ^[6] ; Machado, Helio Rubens ^[6] ; Sousa, Gleice Kelly de ^[7] ; Hanamura, Kenji ^[8] ; Leite, Joao Pereira ^[9] ; Costa da Costa, Jaderson ^{[10, 11]} ; Palmini, Andre Luiz ^{[10, 11]} ; Paglioli, Eliseu ^[12] ; Neder, Luciano ^[13] ; Spreafico, Roberto ^{[14, 15]} ; Shirao, Tomoaki ^[8] ; Garbelli, Rita ^{[14, 15]} ; Martins, Antonio Roberto ^{[3, 16]}

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^[1] Univ Fed Triangulo Mineiro, Discipline Physiol, Uberaba - Brazil

^[2] Univ Fed Sao Paulo, Paulista Med Sch, Dept Neurol & Neurosurg, Discipline Neurosci, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cellular & Mol Biol & Pathogen Bioagents, Ribeirao Preto - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Ribeirao Preto Epilepsy Surg Ctr, Clin Hosp, Ribeirao Preto - Brazil

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg, Ribeirao Preto - Brazil

^[7] Univ Fed Triangulo Mineiro, Grad Program Hlth Sci, Uberaba - Brazil

^[8] Gunma Univ, Dept Neurobiol & Behav, Grad Sch Med, Maebashi, Gumma - Japan

^[9] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav Sci, Ribeirao Preto - Brazil

^[10] Pontificia Univ Catolica Rio Grande do Sul, Epilepsy Surg Program, Sch Med, Dept Internal Med, Porto Alegre, RS - Brazil

^[11] Pontificia Univ Catolica Rio Grande do Sul, Brain Inst, Porto Alegre, RS - Brazil

^[12] Pontificia Univ Catolica Rio Grande do Sul, Sch Med, Dept Surg, Porto Alegre, RS - Brazil

^[13] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol, Ribeirao Preto - Brazil

^[14] Sci Inst Res, Clin Epileptol & Expt Neurophysiol Unit, Milan - Italy

^[15] Ist Nazl Neurol Carlo Besta, Hlth Care Fdn, Milan - Italy

^[16] Inst Neurosci & Behav, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Epilepsia; v. 61, n. 8 JUL 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 18/03677-5 - Caracterização funcional das proteínas gigantes de tripanossomatídeos e a interação com a célula hospedeira
• Beneficiário: Munira Muhammad Abdel Baqui
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/17882-4 - Epilepsias farmacorresistentes: desafios diagnósticos, estudo das comorbidades associadas e novas abordagens experimentais
• Beneficiário: João Pereira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Temático