Exercise-mediated alteration of hippocampal Dicer mRNA and miRNAs is associated with lower BACE1 gene expression and Aβ1-42 in female 3xTg-AD mice

Cory M. Dungan, Taylor Valentino, Ivan J. Vechetti, Christopher J. Zdunek, Michael P. Murphy, Ai Ling Lin, John J. McCarthy, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Changes to cerebral miRNA expression have been implicated in the progression of Alzheimer's disease (AD), as miRNAs that regulate the expression of gene products involved in amyloid beta (Aβ) processing, such as BACE1, are dysregulated in those that suffer from AD. Exercise training improves cognition and reduces BACE1 and Aβ-plaque burden; however, the mechanisms are not fully understood. Using our progressive weighted wheel running (PoWeR) exercise program, we assessed the effect of 20 wk of exercise training on changes in hippocampal miRNA expression in female 3xTg-AD (3xTg) mice. PoWeR was sufficient to promote muscle hypertrophy and increase myonuclear abundance. Furthermore, PoWeR elevated hippocampal Dicer gene expression in 3xTg mice, while altering miRNA expression toward a more wild-type profile. Specifically, miR-29, which is validated to target BACE1, was significantly lower in sedentary 3xTg mice when compared with wild-type but was elevated following PoWeR. Accordingly, BACE1 gene expression, along with detergent-soluble Aβ1-42, was lower in PoWeR-trained 3xTg mice. Our data suggest that PoWeR training upregulates Dicer gene expression to alter cerebral miRNA expression, which may contribute to reduced Aβ accumulation and delay AD progression.

Original languageEnglish
Pages (from-to)1571-1577
Number of pages7
JournalJournal of Neurophysiology
Volume124
Issue number6
DOIs
StatePublished - Nov 30 2020

Bibliographical note

Publisher Copyright:
Copyright © 2020 the American Physiological Society

Keywords

  • 3xTg
  • Alzheimer's disease
  • Dicer
  • Exercise
  • MiRNA

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology

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