title: Impulsivity, decreased social exploration, and executive dysfunction in a mouse model of frontotemporal dementia.
abstract: Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder, a major subset of which is characterized by the accumulation of abnormal forms of the protein tau, leading to impairments in motor functions as well as language and behavioral alterations. Tau58-2/B mice express human tau with the P301S mutation found in familial forms of FTLD in neurons. By assessing three age cohorts of Tau58-2/B mice in a comprehensive behavioral test battery, we found that the tauopathy animals showed age-dependent signs of impulsivity, decreased social exploration and executive dysfunction. The deficit in executive function was first limited to decreased spatial working memory, but with aging this was extended to impaired instrumental short-term memory. Tau pathology was prominent in brain regions underlying these behaviors. Thus, Tau-58-2/B mice recapitulate neurological deficits of the behavioral variant of frontotemporal dementia (bvFTD), presenting them as a suitable model to test therapeutic interventions for the amelioration of this variant.
authors.affiliation: Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), University of Queensland, St Lucia Campus, Brisbane, QLD 4072, Australia; Laboratory of Biological Psychology, Brain and Cognition, University of Leuven, 3000 Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Van der Jeugd
authors.affiliation: Laboratory of Biological Psychology, Brain and Cognition, University of Leuven, 3000 Leuven, Belgium.
authors.forename: Ben
authors.initials: B
authors.lastname: Vermaercke
authors.affiliation: Neuroscience Research Australia, Barker Street, Randwick, NSW 2031, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: German Centre for Neurodegenerative Diseases (DZNE), Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.affiliation: Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), University of Queensland, St Lucia Campus, Brisbane, QLD 4072, Australia. Electronic address: j.goetz@uq.edu.au.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002540:Cerebral Cortex / Q000473:pathology; D004195:Disease Models, Animal; D056344:Executive Function / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology*; D057180:Frontotemporal Dementia / Q000235:genetics / Q000473:pathology / Q000523:psychology*; D006624:Hippocampus / Q000473:pathology; D007175:Impulsive Behavior / Q000502:physiology*; D051379:Mice; D009154:Mutation; D012919:Social Behavior; D016875:tau Proteins / Q000235:genetics
chemical_list: D016875:tau Proteins
keywords: Behavior; Executive function; Frontotemporal dementia; Frontotemporal lobar degeneration; Social exploration; Tau