3R tau expression modifies behavior in transgenic mice

Natalia Shiryaev, Yan Jouroukhin, Illana Gozes

Research output: Contribution to journalArticle

Abstract

Tauopathy is a group of disorders characterized by the accumulation of hyperphosphorylated tau protein in the brain, resulting in dementia. Here, tau-related behavior was evaluated in a mouse model with brain overexpression of the shortest human tau isoform (0N3R). Two groups of animals [tau-transgenic (tau-tg) and control littermates] were tested for learning and memory at 1 and 7 months. In the Morris water maze, all mice learned the task at 1 month of age and did not learn at 7 months. In contrast, at 7 months, the tau-tg animals demonstrated better retention of the passive avoidance response compared with their control littermates, which did not learn. In the open field test, no differences were measured between transgenic and nontransgenic young mice, but significantly higher locomotion was observed in the 7-month-old tau-tg mice compared with controls. Behavior during the elevated plus maze test was the same at 1 month, but at 7 months increased entrance to the different arms was observed in the tau-tg group. Tau expression and phosphorylation levels were analyzed at 8 months. In the subcortical brain region associated with passive avoidance behavior, the tau-tg mice demonstrated increased brain tau expression coupled with reduced relative phosphorylation. In contrast, increased tau expression and phosphorylation were measured in the cerebral cortex of the tau-tg mice. In conclusion, 7-8-month-old tau-tg mice overexpressing nonmutated 0N3R human tau isoform demonstrated enhanced behavior in the passive avoidance test, paralleled by relative tau hypophosphorylation in the subcortical brain region.

Original languageEnglish (US)
Pages (from-to)2727-2735
Number of pages9
JournalJournal of neuroscience research
Volume88
Issue number12
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

    Fingerprint

Keywords

  • Learning and memory
  • Open field test (OFT)
  • Passive avoidance test (PAT)
  • Tau hypophosphorylation
  • Tau-transgenic model
  • Three-repeat tau

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this