In vivo functional brain mapping in a conditional mouse model of human tauopathy (tau p301l) reveals reduced neural activity in memory formation structures

Pablo D. Perez; Gabrielle Hall; Tetsuya Kimura; Yan Ren; Rachel M. Bailey; Jada Lewis; Marcelo Febo; Naruhiko Sahara

doi:10.1186/1750-1326-8-9

In vivo functional brain mapping in a conditional mouse model of human tauopathy (tau _p301l) reveals reduced neural activity in memory formation structures

Pablo D. Perez, Gabrielle Hall, Tetsuya Kimura, Yan Ren, Rachel M. Bailey, Jada Lewis, Marcelo Febo, Naruhiko Sahara

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Background: Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age. Previous behavioral and biochemical work has linked the expression and aggregates of mutant tau to functional impairments. The present work used manganese-enhanced magnetic resonance imaging (MEMRI) to investigate basal levels of brain activity in the rTg4510 and control mice. Results: Our results show an unmistakable curtailment of neural activity in the amygdala and hippocampus, two regions known for their role in memory formation, but not the cortex, cerebellum, striatum and hypothalamus in tau expressing mice. Conclusion: Behavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tau_P301L-induced neurodegeneration.

Original language	English (US)
Article number	9
Journal	Molecular neurodegeneration
Volume	8
Issue number	1
DOIs	https://doi.org/10.1186/1750-1326-8-9
State	Published - 2013
Externally published	Yes

Keywords

Alzheimer's disease
Manganese enhanced MRI
Neurodegenerative disease
Tauopathy
rTg4510

ASJC Scopus subject areas

Molecular Biology
Clinical Neurology
Cellular and Molecular Neuroscience

Access to Document

10.1186/1750-1326-8-9

Cite this

@article{fc5ac984cff049a69cb6fd0457feabe2,

title = "In vivo functional brain mapping in a conditional mouse model of human tauopathy (tau p301l) reveals reduced neural activity in memory formation structures",

abstract = "Background: Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age. Previous behavioral and biochemical work has linked the expression and aggregates of mutant tau to functional impairments. The present work used manganese-enhanced magnetic resonance imaging (MEMRI) to investigate basal levels of brain activity in the rTg4510 and control mice. Results: Our results show an unmistakable curtailment of neural activity in the amygdala and hippocampus, two regions known for their role in memory formation, but not the cortex, cerebellum, striatum and hypothalamus in tau expressing mice. Conclusion: Behavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tauP301L-induced neurodegeneration.",

keywords = "Alzheimer's disease, Manganese enhanced MRI, Neurodegenerative disease, Tauopathy, rTg4510",

author = "Perez, {Pablo D.} and Gabrielle Hall and Tetsuya Kimura and Yan Ren and Bailey, {Rachel M.} and Jada Lewis and Marcelo Febo and Naruhiko Sahara",

note = "Funding Information: MF is supported by NIH grant DA019946 and a seed grant from the McKnight Brain Institute. NS is supported by NIH grant NS067127 and Thomas H. Maren Junior Investigator Fund from University of Florida. NS and JL are supported by the Center for Translational Research in Neurodegenerative Disease and the Department of Neuroscience at University of Florida. The authors thank Dr. Stephen J. Blackband for providing the mouse brain atlas. MRI data were obtained at the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) facility in the McKnight Brain Institute of the University of Florida.",

year = "2013",

doi = "10.1186/1750-1326-8-9",

language = "English (US)",

volume = "8",

journal = "Molecular neurodegeneration",

issn = "1750-1326",

publisher = "BioMed Central",

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T1 - In vivo functional brain mapping in a conditional mouse model of human tauopathy (tau p301l) reveals reduced neural activity in memory formation structures

AU - Perez, Pablo D.

AU - Hall, Gabrielle

AU - Kimura, Tetsuya

AU - Ren, Yan

AU - Bailey, Rachel M.

AU - Lewis, Jada

AU - Febo, Marcelo

AU - Sahara, Naruhiko

N1 - Funding Information: MF is supported by NIH grant DA019946 and a seed grant from the McKnight Brain Institute. NS is supported by NIH grant NS067127 and Thomas H. Maren Junior Investigator Fund from University of Florida. NS and JL are supported by the Center for Translational Research in Neurodegenerative Disease and the Department of Neuroscience at University of Florida. The authors thank Dr. Stephen J. Blackband for providing the mouse brain atlas. MRI data were obtained at the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) facility in the McKnight Brain Institute of the University of Florida.

PY - 2013

Y1 - 2013

N2 - Background: Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age. Previous behavioral and biochemical work has linked the expression and aggregates of mutant tau to functional impairments. The present work used manganese-enhanced magnetic resonance imaging (MEMRI) to investigate basal levels of brain activity in the rTg4510 and control mice. Results: Our results show an unmistakable curtailment of neural activity in the amygdala and hippocampus, two regions known for their role in memory formation, but not the cortex, cerebellum, striatum and hypothalamus in tau expressing mice. Conclusion: Behavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tauP301L-induced neurodegeneration.

AB - Background: Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age. Previous behavioral and biochemical work has linked the expression and aggregates of mutant tau to functional impairments. The present work used manganese-enhanced magnetic resonance imaging (MEMRI) to investigate basal levels of brain activity in the rTg4510 and control mice. Results: Our results show an unmistakable curtailment of neural activity in the amygdala and hippocampus, two regions known for their role in memory formation, but not the cortex, cerebellum, striatum and hypothalamus in tau expressing mice. Conclusion: Behavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tauP301L-induced neurodegeneration.

KW - Alzheimer's disease

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KW - Tauopathy

KW - rTg4510

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