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Published on: May 28, 2017
Motor and cognitive deficits in aged tau knockout mice in two background strains
Peng Lei, Scott Ayton, Steve Moon
1Oxidation Biology Unit, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia. ashley.bush@florey.edu.au.
Background:
We recently reported that Parkinsonian and dementia phenotypes emerge between 7-12 months of age in tau-/- mice on a Bl6/129sv mixed background. These observations were partially replicated by another group using pure Bl6 background tau-/- mice, but notably they did not observe a cognitive phenotype. A third group using Bl6 background tau-/- mice found cognitive impairment at 20-months of age.
Results:
To reconcile the observations, here we considered the genetic, dietary and environmental variables in both studies, and performed an extended set of behavioral studies on 12-month old tau+/+, tau+/-, and tau-/- mice comparing Bl6/129sv to Bl6 backgrounds. We found that tau-/- in both backgrounds exhibited reduced tyrosine hydroxylase-positive nigral neuron and impaired motor function in all assays used, which was ameliorated by oral treatment with L-DOPA, and not confounded by changes in body weight. Tau-/- in the C57BL6/SV129 background exhibited deficits in the Y-maze cognition task, but the mice on the Bl6 background did not.
Conclusions:
These results validate our previous report on the neurodegenerative phenotypes of aged tau-/- mice, and show that genetic background may impact the extent of cognitive impairment in these mice. Therefore excessive lowering of tau should be avoided in therapeutic strategies for AD.
Insights
Genetic background influences cognitive deficits in tau knockout mice, impacting neurodegenerative phenotypes. Further research is needed to understand tau
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Tau knockout (tau-/-) mice exhibit Parkinsonian and dementia phenotypes.
- Conflicting results exist regarding cognitive impairment in tau-/- mice across different genetic backgrounds.
- Previous studies reported cognitive deficits at varying ages and on different mouse strains.
Purpose of the Study:
- To reconcile conflicting findings on cognitive phenotypes in tau-/- mice.
- To investigate the impact of genetic background on neurodegenerative phenotypes.
- To evaluate the effect of L-DOPA treatment on motor function.
Main Methods:
- Comparative behavioral studies on 12-month-old tau+/+, tau+/-, and tau-/- mice.
- Comparison between C57BL/6 (Bl6) and Bl6/129sv mixed backgrounds.
- Assessment of motor function and cognitive tasks (Y-maze).
- Evaluation of L-DOPA treatment efficacy.
Main Results:
- Tau-/- mice in both backgrounds showed reduced nigral neuron count and impaired motor function.
- Motor deficits were ameliorated by L-DOPA treatment.
- Cognitive deficits were observed in tau-/- mice on the Bl6/129sv background but not on the pure Bl6 background.
Conclusions:
- Genetic background significantly influences cognitive impairment in aged tau-/- mice.
- Neurodegenerative phenotypes in tau-/- mice are validated.
- Therapeutic strategies for Alzheimer's disease (AD) should consider the role of tau levels.
