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Updated: May 14, 2026
An In Vitro Model for Studying Tau Aggregation Using Lentiviral-mediated Transduction of Human Neurons
Published on: May 23, 2019
In vivo functional brain mapping in a conditional mouse model of human tauopathy (tauP301L) reveals reduced neural
Pablo D Perez1, Gabrielle Hall, Tetsuya Kimura
1Department of Psychiatry, University of Florida McKnight Brain Institute, Gainesville, Florida 32610, USA.
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.
Insights
This study reveals reduced brain activity in memory regions of mice with mutant tau protein. These findings link tau pathology to neurodegeneration and cognitive deficits in tauopathies.
Area of Science:
- Neuroscience
- Neurodegenerative Diseases
- Molecular Biology
Background:
- Tauopathies involve intracellular tau protein aggregation.
- The rTg4510 mouse model expresses mutant human tau, developing neurofibrillary tangles, neuronal loss, and cognitive deficits.
- Previous studies linked mutant tau expression to functional impairments.
Purpose of the Study:
- To investigate basal brain activity levels in rTg4510 mice using manganese-enhanced magnetic resonance imaging (MEMRI).
- To correlate neuroimaging findings with known behavioral and biochemical deficits in this tauopathy model.
Main Methods:
- Utilized manganese-enhanced magnetic resonance imaging (MEMRI) to assess neural activity.
- Compared brain activity in rTg4510 (mutant tau) mice with control mice.
- Focused on specific brain regions including the amygdala, hippocampus, cortex, cerebellum, striatum, and hypothalamus.
Main Results:
- Demonstrated a significant reduction in neural activity within the amygdala and hippocampus of tau-expressing mice.
- Observed no significant changes in neural activity in the cortex, cerebellum, striatum, and hypothalamus.
- Highlighted regional differences in the impact of mutant tau on brain function.
Conclusions:
- Reduced neural activity in memory-associated areas (amygdala, hippocampus) correlates with behavioral impairments.
- These findings suggest a link between age-progressive mutant tau (P301L) and neurodegeneration.
- MEMRI provides a valuable tool for assessing functional deficits in tauopathy models.
