Your browser doesn't support javascript.
loading
A Genetic Model of Epilepsy with a Partial Alzheimer's Disease-Like Phenotype and Central Insulin Resistance.
Alves, Suélen Santos; da Silva Junior, Rui Milton Patrício; Delfino-Pereira, Polianna; Pereira, Marilia Gabriella Alves Goulart; Vasconcelos, Israel; Schwaemmle, Hanna; Mazzei, Rodrigo Focosi; Carlos, Maiko Luiz; Espreafico, Enilza Maria; Tedesco, Antônio Claudio; Sebollela, Adriano; Almeida, Sebastião Sousa; de Oliveira, José Antônio Cortes; Garcia-Cairasco, Norberto.
Afiliación
  • Alves SS; Department of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirao Preto, Brazil.
  • da Silva Junior RMP; Department of Internal Medicine, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirao Preto, Brazil.
  • Delfino-Pereira P; Department of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirao Preto, Brazil.
  • Pereira MGAG; Department of Biochemistry, Biomedical Sciences Institute - Federal University of Alfenas, (UNIFAL), Alfenas, Brazil.
  • Vasconcelos I; Department of Biochemistry and Immunology, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirao Preto, Brazil.
  • Schwaemmle H; Department of Biochemistry and Immunology, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirao Preto, Brazil.
  • Mazzei RF; Department of Psychology, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo (FFCLRP-USP), Ribeirao Preto, Brazil.
  • Carlos ML; Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo (FFCLRP-USP), Ribeirao Preto, Brazil.
  • Espreafico EM; Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirao Preto, Brazil.
  • Tedesco AC; Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo (FFCLRP-USP), Ribeirao Preto, Brazil.
  • Sebollela A; Department of Biochemistry and Immunology, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirao Preto, Brazil.
  • Almeida SS; Department of Psychology, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo (FFCLRP-USP), Ribeirao Preto, Brazil.
  • de Oliveira JAC; Department of Physiology, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Av. Dos Bandeirantes 3900, Ribeirao Preto, SP, 14049-900, Brazil.
  • Garcia-Cairasco N; Department of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirao Preto, Brazil. ngcairas@usp.br.
Mol Neurobiol ; 59(6): 3721-3737, 2022 Jun.
Article en En | MEDLINE | ID: mdl-35378696
Studies have suggested an important connection between epilepsy and Alzheimer's disease (AD), mostly due to the high number of patients diagnosed with AD who develop epileptic seizures later on. However, this link is not well understood. Previous studies from our group have identified memory impairment and metabolic abnormalities in the Wistar audiogenic rat (WAR) strain, a genetic model of epilepsy. Our goal was to investigate AD behavioral and molecular alterations, including brain insulin resistance, in naïve (seizure-free) animals of the WAR strain. We used the Morris water maze (MWM) test to evaluate spatial learning and memory performance and hippocampal tissue to verify possible molecular and immunohistochemical alterations. WARs presented worse performance in the MWM test (p < 0.0001), higher levels of hyperphosphorylated tau (S396) (p < 0.0001) and phosphorylated glycogen synthase kinase 3 (S21/9) (p < 0.05), and lower insulin receptor levels (p < 0.05). Conversely, WARs and Wistar controls present progressive increase in amyloid fibrils (p < 0.0001) and low levels of soluble amyloid-ß. Interestingly, the detected alterations were age-dependent, reaching larger differences in aged than in young adult animals. In summary, the present study provides evidence of a partial AD-like phenotype, including altered regulation of insulin signaling, in a genetic model of epilepsy. Together, these data contribute to the understanding of the connection between epilepsy and AD as comorbidities. Moreover, since both tau hyperphosphorylation and altered insulin signaling have already been reported in epilepsy and AD, these two events should be considered as important components in the interconnection between epilepsy and AD pathogenesis and, therefore, potential therapeutic targets in this field.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Epilepsia / Enfermedad de Alzheimer Límite: Aged / Animals / Humans Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Brasil

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Epilepsia / Enfermedad de Alzheimer Límite: Aged / Animals / Humans Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Brasil