title: P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating.
abstract: Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Michiyo
authors.initials: M
authors.lastname: Iba
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Inoue
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tsukita
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Karatsu
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D003704:Dementia / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D055139:Sensory Gating; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016875:tau Proteins