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Open Access Methodology

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 Perez1, Gabrielle Hall1, Tetsuya Kimura3, Yan Ren2, Rachel M Bailey2, Jada Lewis2, Marcelo Febo1* and Naruhiko Sahara2*

Author Affiliations

1 Department of Psychiatry, University of Florida McKnight Brain Institute, Gainesville, Florida, 32610, USA

2 Center for Translational Research in Neurodegenerative Disease and Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA

3 Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Obu-shi, Aichi, 474-8511, Japan

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Molecular Neurodegeneration 2013, 8:9  doi:10.1186/1750-1326-8-9

Published: 4 February 2013

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:
Tauopathy; Neurodegenerative disease; Alzheimer’s disease; rTg4510; Manganese enhanced MRI