Disinhibition-like behavior in a P301S mutant tau transgenic mouse model of frontotemporal dementia

Magdalena Przybyla; Claire H Stevens; Julia van der Hoven; Anne Harasta; Mian Bi; Arne Ittner; Annika van Hummel; John R Hodges; Olivier Piguet; Tim Karl; Michael Kassiou; Gary D Housley; Yazi D Ke; Lars M Ittner; Janet van Eersel

doi:10.1016/j.neulet.2016.08.007

Disinhibition-like behavior in a P301S mutant tau transgenic mouse model of frontotemporal dementia

Neurosci Lett. 2016 Sep 19:631:24-29. doi: 10.1016/j.neulet.2016.08.007. Epub 2016 Aug 10.

Authors

Affiliations

¹ Dementia Research Unit, Department of Anatomy, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
² Neuroscience Research Australia, Sydney, NSW, Australia.
³ Neuroscience Research Australia, Sydney, NSW, Australia; ARC Centre of Excellence in Cognition and its Disorders, Sydney, NSW, Australia.
⁴ Neuroscience Research Australia, Sydney, NSW, Australia; School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
⁵ School of Chemistry and Faculty of health Sciences, University of Sydney, Sydney, NSW, Australia.
⁶ Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
⁷ Motor Neuron Disease Unit, Department of Anatomy, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
⁸ Dementia Research Unit, Department of Anatomy, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia; Transgenic Animal Unit, Mark Wainright Analytical Centre, University of New South Wales, Sydney, NSW, Australia. Electronic address: l.ittner@unsw.edu.au.

PMID: 27521751
DOI: 10.1016/j.neulet.2016.08.007

Abstract

Frontotemporal dementia (FTD) presents clinically with behavioral changes including disinhibition. Mutations in the tau-encoding MAPT gene identified in familial cases of FTD have been used to generate transgenic mouse models of the human condition. Here, we report behavioral changes in a recently developed P301S mutant tau transgenic mouse, including disinhibition-like behavior in the elevated plus maze and hyperactivity in the open field arena. Furthermore, histological analysis revealed the amygdala as a primary and early site of pathological tau deposition in these mice. Taken together, neuropathological and behavioral changes in P301S tau transgenic mice resemble features of human FTD.

Keywords: Behavior; Frontotemporal dementia; Tau; Transgenic mouse model.

MeSH terms

Amygdala / metabolism
Animals
Anxiety / genetics
Behavior, Animal / physiology*
Disease Models, Animal
Frontotemporal Dementia / genetics*
Frontotemporal Dementia / psychology*
Humans
Hyperkinesis / genetics
Male
Mice
Mice, Transgenic
Motor Activity
Mutation
tau Proteins / genetics*
tau Proteins / metabolism

Substances

MAPT protein, human
tau Proteins