Abstract
Tau plays a pivotal role in the pathogenesis of neurodegenerative disorders: mutations in the gene encoding for tau (MAPT) are linked to Fronto-temporal Dementia (FTD) and hyper-phosphorylated aggregates of tau forming neurofibrillary tangles (NFTs) that constitute a pathological hallmark of Alzheimer disease (AD) and FTD. Accordingly, tau is a favored therapeutic target for the treatment of these diseases. Given the criticality of tau to dementia’s pathogenesis and therapy, it is important to understand the physiological function of tau in the central nervous system. Analysis of Mapt knock out (Mapt−/−) mice has yielded inconsistent results. Some studies have shown that tau deletion does not alter memory while others have described synaptic plasticity and memory alterations in Mapt−/− mice. To help clarifying these contrasting results, we analyzed a distinct Mapt−/− model on a B6129PF3/J genetic background. We found that tau deletion leads to aging-dependent short-term memory deficits, hyperactivity and synaptic plasticity defects. In contrast, Mapt+/− mice only showed a mild short memory deficit in the novel object recognition task. Thus, while tau is important for normal neuronal functions underlying learning and memory, partial reduction of tau expression may have fractional deleterious effects.
Highlights
Tau plays a pivotal role in the pathogenesis of neurodegenerative disorders: mutations in the gene encoding for tau (MAPT) are linked to Fronto-temporal Dementia (FTD) and hyper-phosphorylated aggregates of tau forming neurofibrillary tangles (NFTs) that constitute a pathological hallmark of Alzheimer disease (AD) and FTD
We have analyzed the Mapt−/− model developed by Tucker48 and we have tested Mapt+/−, Mapt−/− and WT littermates on a hybrid B6129PF3/J genetic background
To determine the impact of Mapt deletion on anxiety-like behavior, locomotor activity and short-term memory, six-seven month-old WT, Mapt+/− and Mapt−/− B6129PF3/J mice were subjected to the following behavioral tasks: 1) the elevated zero maze, which tests anxiety-like behavior; 2) the two-trial Y maze, to analyze locomotor activity and short-term spatial recognition memory; 3) open field, a test to determine locomotion, exploratory activities, and anxiety; 4) novel object recognition, a short-term memory test
Summary
Tau plays a pivotal role in the pathogenesis of neurodegenerative disorders: mutations in the gene encoding for tau (MAPT) are linked to Fronto-temporal Dementia (FTD) and hyper-phosphorylated aggregates of tau forming neurofibrillary tangles (NFTs) that constitute a pathological hallmark of Alzheimer disease (AD) and FTD. Some studies have shown that tau deletion does not alter memory while others have described synaptic plasticity and memory alterations in Mapt−/− mice. To help clarifying these contrasting results, we analyzed a distinct Mapt−/− model on a B6129PF3/J genetic background. FAD APP mutant mice develop cognitive and synaptic plasticity deficits These deficits can be prevented through the ablation of tau expression, leading to the hypothesis that tau is required for Aβ-induced synaptic dysfunction and memory deficits. Mapt−/− mice display compromised synaptic function, evidenced by impaired long-term potentiation (LTP)39 -a long term synaptic plasticity mechanism thought to underlie memory- and long-term depression (LTD)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
