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Behavioral analysis of a 3xTg murine model for Alzheimer´s disease: sex-specific differences age-dependent

Gisela Romina Bustos

  • caba,
  • Argentina
  • Gisela Romina Bustos ¹
  • , Maria del Carmen Krawczyk ¹
  • , Julieta Millan ¹
  • , Mariano G Blake ²
  • , Mariano M Boccia ¹
  • 1 Laboratorio de Neurofarmacología de los Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
  • 2 Instituto de Fisiología y Biofísica (IFIBIO UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.

Alzheimer´s disease is a neurodegenerative disorder, characterized by extracellular Amyloid- peptide neuritic plaques and neurofibrillary tangles, composed of filamentous aggregates of hyperphosphorylated tau protein. In 2003, LaFerla and co-workers developed a triple transgenic (3xTg) mouse model harboring PS1M146V, APPSwe, and tauP301L transgenes. In the present work, we carried on two distinct behavioral tasks at different ages (3 to 6 months) to study 3xTg mice performance in order to assess possible cognitive impairment. In addition, we examined potential sex-specific differences on each behavioral task.
In our modify version of the Inhibitory Avoidance Task, 3xTg male mice had significant differences in their latencies to step-trough compare to wild type mice at four and seven months. When studying 3xTg female mice, differences were observed only at four months old. Interestingly, both wild type and 3xTg mice had increased latencies to step-trough when tested 48h post-training. Notwithstanding, wild type performance was significantly better than 3xTg mice suggesting memory impairment by the latter. When studying behavioral performance in the Holeboard task, only females at 3 months old and males at 5 months old showed significant differences when compare to control groups. Taking these results together, we might conclude there are sex- specific differences between 3xTg and wild type mice depending both on the behavioral task and the age of the subjects.