Original Research

Cellular and Molecular Neurobiology

, Volume 30, Issue 4, pp 577-590

First online:

Profile for Amyloid-β and Tau Expression in Primary Cortical Cultures from 3xTg-AD Mice

  • Carmen ValeAffiliated withDepartamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela
  • , Eva AlonsoAffiliated withDepartamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela
  • , Juan A. RubioloAffiliated withDepartamento de Fisiología, Facultad de Veterinaria, Universidad de Santiago de Compostela
  • , Mercedes R. VieytesAffiliated withDepartamento de Fisiología, Facultad de Veterinaria, Universidad de Santiago de Compostela
  • , Frank M. LaFerlaAffiliated withDepartment of Neurobiology and Behavior, University of California, Irvine
  • , Lydia Giménez-LlortAffiliated withDepartment of Psychiatry and Forensic Medicine, Institute of Neuroscience, Autonomous University of Barcelona
  • , Luis M. BotanaAffiliated withDepartamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela Email author 

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Abstract

Advances in transgenic technology as well as in the genetics of Alzheimer disease (AD) have allowed the establishment of animal models that reproduce amyloid-beta plaques and neurofibrillary tangles, the main pathological hallmarks of AD. Among these models, 3xTg-AD mice harboring PS1 M146V, APP Swe and tau P301L human transgenes provided the model that most closely mimics human AD features. Although cortical cultures from 3xTg-AD mice have been shown to present disturbances in intracellular [Ca2+] homeostasis, the development of AD pathology in vitro has not been previously evaluated. In the current work, we determined the temporal profile for amyloid precursor protein, amyloid-β and tau expression in primary cortical cultures from 3xTg-AD mice. Immunocytochemistry and Western blot analysis showed an increased expression of these proteins as well as several phosphorylated tau isoforms with time in culture. Alterations in calcium homeostasis and cholinergic and glutamatergic responses were also observed early in vitro. Thus, 3x-TgAD cortical neurons in vitro provide an exceptional tool to investigate pharmacological approaches as well as the cellular basis for AD and related diseases.

Keywords

Amyloid-β Microtubule-associated protein tau Amyloid precursor protein Alzheimer disease Calcium Cortical culture 3xTg-AD mice