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

Lambourne, Sarah L., Humby, Trevor ORCID: https://orcid.org/0000-0002-1840-1799, Isles, Anthony Roger ORCID: https://orcid.org/0000-0002-7587-5712, Emson, Piers C., Spillantini, Maria G. and Wilkinson, Lawrence Stephen ORCID: https://orcid.org/0000-0002-9337-6124 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

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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:	17 Oct 2022 09:31
URI:	https://orca.cardiff.ac.uk/id/eprint/3434

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