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P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

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 tauopa...

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Autores principales: Takeuchi, Hiroki, Iba, Michiyo, Inoue, Haruhisa, Higuchi, Makoto, Takao, Keizo, Tsukita, Kayoko, Karatsu, Yoshiko, Iwamoto, Yumiko, Miyakawa, Tsuyoshi, Suhara, Tetsuya, Trojanowski, John Q., Lee, Virginia M. -Y., Takahashi, Ryosuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115982/
https://www.ncbi.nlm.nih.gov/pubmed/21698260
http://dx.doi.org/10.1371/journal.pone.0021050
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author Takeuchi, Hiroki
Iba, Michiyo
Inoue, Haruhisa
Higuchi, Makoto
Takao, Keizo
Tsukita, Kayoko
Karatsu, Yoshiko
Iwamoto, Yumiko
Miyakawa, Tsuyoshi
Suhara, Tetsuya
Trojanowski, John Q.
Lee, Virginia M. -Y.
Takahashi, Ryosuke
author_facet Takeuchi, Hiroki
Iba, Michiyo
Inoue, Haruhisa
Higuchi, Makoto
Takao, Keizo
Tsukita, Kayoko
Karatsu, Yoshiko
Iwamoto, Yumiko
Miyakawa, Tsuyoshi
Suhara, Tetsuya
Trojanowski, John Q.
Lee, Virginia M. -Y.
Takahashi, Ryosuke
author_sort Takeuchi, Hiroki
collection PubMed
description 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.
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spelling pubmed-31159822011-06-22 P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating Takeuchi, Hiroki Iba, Michiyo Inoue, Haruhisa Higuchi, Makoto Takao, Keizo Tsukita, Kayoko Karatsu, Yoshiko Iwamoto, Yumiko Miyakawa, Tsuyoshi Suhara, Tetsuya Trojanowski, John Q. Lee, Virginia M. -Y. Takahashi, Ryosuke PLoS One Research Article 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. Public Library of Science 2011-06-15 /pmc/articles/PMC3115982/ /pubmed/21698260 http://dx.doi.org/10.1371/journal.pone.0021050 Text en Takeuchi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Takeuchi, Hiroki
Iba, Michiyo
Inoue, Haruhisa
Higuchi, Makoto
Takao, Keizo
Tsukita, Kayoko
Karatsu, Yoshiko
Iwamoto, Yumiko
Miyakawa, Tsuyoshi
Suhara, Tetsuya
Trojanowski, John Q.
Lee, Virginia M. -Y.
Takahashi, Ryosuke
P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating
title P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating
title_full P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating
title_fullStr P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating
title_full_unstemmed P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating
title_short P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating
title_sort p301s mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115982/
https://www.ncbi.nlm.nih.gov/pubmed/21698260
http://dx.doi.org/10.1371/journal.pone.0021050
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