Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Impairments in impulse control in animal models transgenic for the human FTPD-17 tauV337M mutation are exacerbated by age

Lambourne, Sarah L., Humby, Trevor, Isles, Anthony Roger, Emson, Piers C., Spillantini, Maria G. and Wilkinson, Lawrence Stephen 2007. Impairments in impulse control in animal models transgenic for the human FTPD-17 tauV337M mutation are exacerbated by age. Human Molecular Genetics 16 (14) , pp. 1708-1719. 10.1093/hmg/ddm119

Full text not available from this repository.

Abstract

Abnormalities in microtubule-associated tau protein are a key neuropathological feature of both Alzheimer's disease and many frontotemporal dementias (FTDs), including hereditary FTD with Parkinsonism linked to chromosome 17 (FTDP-17). In these disorders, tau becomes aberrantly phosphorylated, leading to the development of filamentous neurofibrillary tangles in the brain. Here we report, in a longitudinal ageing study, the sensorimotor and cognitive assessment of transgenic mice expressing the human tauV337M (‘Seattle Family A’) FTDP-17 mutation, which we have previously shown to demonstrate abnormalities in brain tau phosphorylation. The data indicated highly specific effects of transgene expression on the ability to withhold responding in a murine version of the 5-choice serial reaction time task, behaviour consistent with deficits in impulse control. Ageing exacerbated these effects. In young tauV337M mice, increased impulsivity was present under task conditions making inhibition of premature responding more difficult (longer inter-trial intervals) but not under baseline conditions. However, when older, the tauV337M mice showed further increases in premature responding, including under baseline conditions. These impulse control deficits were fully dissociable from sensorimotor or motivation effects on performance. The findings recapitulate core abnormalities in impulsive responding observed in both frontal variant FTD and FTDP-17 linked to the tauV337M mutation in humans.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Q Science > QH Natural history > QH426 Genetics
Publisher: Oxford University Press
ISSN: 0964-6906
Last Modified: 03 May 2019 08:04
URI: http://orca.cf.ac.uk/id/eprint/3434

Citation Data

Cited 27 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item