Mild Traumatic Brain Injury of Tau.P301L Mice Results in an Impairment of Neural Plasticity

Abstract

Background: Traumatic brain injury (TBI), even single-impact mild TBI (mTBI), is associated with increased risk of neuronal damage and neurodegeneration, leading to dementia, in particular Alzheimer’s disease (AD). The tell-tale histopathological defects of AD, deposits of amyloid and protein tau are observed following TBI. However, little is known about the mechanisms underlying the association, and its impact on synaptic plasticity. Objectives: This study aimed to analyze whether mTBI alters or accelerates relevant changes in synaptic plasticity at early stages of tau pathology in a mouse model. Methods: A total of 24 mice were analyzed in this study, comprising Tau.P301L transgenic mice and age and background matched wild-type mice as controls. Animals received a mild single-dose closed-head impact injury or a sham surgery. We measured ex vivo parameters of basal synaptic excitability, short-term synaptic plasticity and long-term potentiation. Results: While no changes in basal synaptic excitability and presynaptic short-term plasticity were observed, long-term potentiation (LTP) in the CA1 region was severely impaired. This deficit was aggravated in the Tau.P301L mice compared to wild-type control animals. Conclusions: Our data imply a high health risk of even a single mTBI episode. Single-impact mTBI combined with genetic predisposition is proposed to trigger signals implicated in neurodegeneration.