Abstract
BackgroundTauopathies 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.ResultsOur 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.ConclusionBehavioral impairments associated with changes in activity in these areas may correspond to age progressive mutant tauP301L-induced neurodegeneration.
Highlights
Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates
Findings of tau mutations in subjects affected by frontotemporal dementia and mutant tau expression systems, which lead to tau-positive inclusions, neuron loss and behavioral abnormalities in various animal models, have established a role of this protein in neurodegeneration [4,5,6,7,8,9,10,11]
Expression of human tau in the rTg4510 mouse is controlled by the tetracycline transactivator transgene under the Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) promoter
Summary
Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. Findings of tau mutations in subjects affected by frontotemporal dementia and mutant tau expression systems, which lead to tau-positive inclusions, neuron loss and behavioral abnormalities in various animal models, have established a role of this protein in neurodegeneration [4,5,6,7,8,9,10,11]. Expression of human tau in the rTg4510 mouse is controlled by the tetracycline transactivator (tTA) transgene under the Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) promoter. This leads to selective tau expression from an otherwise transcriptionally inactive tau transgene [12]. Mice develop robust intracellular deposition of tau protein in cortico-limbic areas, which is physiologically relevant to AD and other tauopathies, and they show age-related forebrain atrophy
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