Extra virgin olive oil improves synaptic activity, short-term plasticity, memory, and neuropathology in a tauopathy model.

Elisabetta Lauretti,Domenico Praticò,Ozlem Dincer,Luigi Iuliano,Miroslav Nenov

doi:10.1111/acel.13076

Elisabetta Lauretti, Domenico Praticò + Show 3 more

Open Access

https://doi.org/10.1111/acel.13076

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Journal: Aging Cell	Publication Date: Nov 24, 2019
Citations: 24	License type: CC BY 4.0

Affiliation: Temple University, Sapienza University of Rome

Abstract

In recent years, increasing evidence has accumulated supporting the health benefits of extra virgin olive oil (EVOO). Previous studies showed that EVOO supplementation improves Alzheimer's disease (AD)‐like amyloidotic phenotype of transgenic mice. However, while much attention has been focused on EVOO‐mediated modulation of Aβ processing, its direct influence on tau metabolism in vivo and synaptic function is still poorly characterized. In this study, we investigated the effect of chronic supplementation of EVOO on the phenotype of a relevant mouse model of tauopathy, human transgenic tau mice (hTau). Starting at 6 months of age, hTau mice were fed chow diet supplemented with EVOO or vehicle for additional 6 months, and then the effect on their phenotype was assessed. At the end of the treatment, compared with control mice receiving EVOO displayed improved memory and cognition which was associated with increased basal synaptic activity and short‐term plasticity. This effect was accompanied by an upregulation of complexin 1, a key presynaptic protein. Moreover, EVOO treatment resulted in a significant reduction of tau oligomers and phosphorylated tau at specific epitopes. Our findings demonstrate that EVOO directly improves synaptic activity, short‐term plasticity, and memory while decreasing tau neuropathology in the hTau mice. These results strengthen the healthy benefits of EVOO and further support the therapeutic potential of this natural product not only for AD but also for primary tauopathies.

Highlights

Alzheimer's disease (AD) and related tauopathies are neurodegenerative disorders characterized by the presence of highly phosphorylated and misfolded forms of the microtubule-associated tau protein, which accumulate as neurofibrillary or gliofibrillary tangles in the human brain (Di Meco, 2019)
We found that right after the LTP induction with high-frequency stimulation (HFS), slices from the controls had a significant failure in post-tetanus potentiation, which is another form of shortterm plasticity, which in contrast was significantly ameliorated in the extra virgin olive oil (EVOO)-treated group (Figure 2c)
The findings presented in this paper show that chronic administration of a diet enriched in EVOO results in a significant improvement of working memory, spatial and learning memory, amelioration of hippocampal basal synaptic activity and short-term plasticity, and a significant reduction in tau neuropathology in a relevant mouse model of human primary tauopathy

Summary

| INTRODUCTION

Alzheimer's disease (AD) and related tauopathies are neurodegenerative disorders characterized by the presence of highly phosphorylated and misfolded forms of the microtubule-associated tau protein, which accumulate as neurofibrillary or gliofibrillary tangles in the human brain (Di Meco, 2019). B, we found that while levels of total soluble tau were significantly increased, tau phosphorylated at Ser202/Thr205, as recognized by the AT8 antibody, was significantly reduced when EVOO-rich diet group was compared to control. Since tau phosphorylation and tau oligomers are known to target synapse, we investigated whether overall synaptic integrity of the hTau mice was affected by the EVOO-rich diet To this end, we assayed the steady-state levels of synaptophysin (SYP) indices of presynaptic integrity and the postsynaptic density protein 95 (PSD95) in cortices of the two groups of mice.

| DISCUSSION

Findings

| EXPERIMENTAL PROCEDURES