Mindfulness intervention improves cognitive function in older adults by enhancing the level of miRNA-29c in neuron-derived extracellular vesicles

Akinori Takaoka,Nobuaki Himuro,Shin Hashizume,Masako Nakano,Kenta Kubota,Mineko Fujimiya,Seiichi Sato,Eiji Kobayashi

doi:10.1038/s41598-021-01318-y

Abstract

Although mindfulness-based stress reduction (MBSR) improves cognitive function, the mechanism is not clear. In this study, people aged 65 years and older were recruited from elderly communities in Chitose City, Japan, and assigned to a non-MBSR group or a MBSR group. Before and after the intervention, the Japanese version of the Montreal Cognitive Assessment (MoCA-J) was administered, and blood samples were collected. Then, neuron-derived extracellular vesicles (NDEVs) were isolated from blood samples, and microRNAs, as well as the target mRNAs, were evaluated in NDEVs. A linear mixed model analysis showed significant effects of the MBSR x time interaction on the MoCA-J scores, the expression of miRNA(miR)-29c, DNA methyltransferase 3 alpha (DNMT3A), and DNMT3B in NDEVs. These results indicate that MBSR can improve cognitive function by increasing the expression of miR-29c and decreasing the expression of DNMT3A, as well as DNMT3B, in neurons. It was also found that intracerebroventricular injection of miR-29c mimic into 5xFAD mice prevented cognitive decline, as well as neuronal loss in the subiculum area, by down-regulating Dnmt3a and Dnmt3b in the hippocampus. The present study suggests that MBSR can prevent neuronal loss and cognitive impairment by increasing the neuronal expression of miR-29c.

Highlights

Mindfulness-based stress reduction (MBSR) improves cognitive function, the mechanism is not clear
The linear mixed model showed significant effects of the mindfulness-based stress reduction (MBSR) x time interaction on the expressions of DNA methyltransferase 3 alpha (DNMT3A), DNA methyltransferase 3 beta (DNMT3B), and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) in neuron-derived extracellular vesicles (NDEVs) (Table 3). These results suggested that MBSR decreases the expressions of DNMT3A, DNMT3B, and BACE1 in NDEVs because the mean ΔCT – ΔCT values of these genes were higher in the MBSR group than in the non-MBSR group
To the best of our knowledge, this is the first report to show the mechanism behind the effect of MBSR on cognitive function by focusing on miRNA

Summary

Introduction

Mindfulness-based stress reduction (MBSR) improves cognitive function, the mechanism is not clear. The present study suggests that MBSR can prevent neuronal loss and cognitive impairment by increasing the neuronal expression of miR-29c. In AD patients, NDEVs in the blood contain higher levels of Aβ and tau, and lower levels of miR-212 compared to a control group[9,10]. Whether these dysregulated molecules in NDEVs could be normalized by AD treatment is not known. In AD model mice, voluntary physical exercise can improve cognitive impairment by suppressing the expression of miR-132 in the h ippocampus[15]. A randomized study of 120 AD patients in 2016 confirmed the effectiveness of MBSR for maintaining cognitive function[31]

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