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 weeks 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. Further, PoWeR elevated hippocampal Dicer gene expression in 3xTg mice, while altering miRNA expression towards a more wild-type profile. Specifically, miR-29, which is validated to target BACE1, was significantly lower in sedentary 3xTg mice when compared to wild-type, but was elevated following PoWeR. Accordingly, BACE1 gene expression, along with detergent soluble Aβ^1-42, were 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.

中文翻译：

---

运动介导的海马 Dicer mRNA 和 miRNA 改变与雌性 3xTg-AD 小鼠的 BACE1 基因表达和 Aβ1-42 降低有关

脑 miRNA 表达的变化与阿尔茨海默病 (AD) 的进展有关，因为调节参与淀粉样蛋白 β (Aβ) 加工的基因产物（如 BACE1）表达的 miRNA 在患有 AD 的患者中失调。运动训练可提高认知能力并减少 BACE1 和 Aβ 斑块负担；然而，这些机制尚未完全了解。使用我们的渐进式加权轮式跑步 (PoWeR) 运动计划，我们评估了 20 周的运动训练对雌性 3xTg-AD (3xTg) 小鼠海马 miRNA 表达变化的影响。PoWeR 足以促进肌肉肥大和增加肌核丰度。此外，PoWeR 提高了 3xTg 小鼠的海马 Dicer 基因表达，同时将 miRNA 表达改变为更野生型。具体来说，miR-29，经验证以 BACE1 为目标，与野生型相比，久坐不动的 3xTg 小鼠显着降低，但在 Power 后升高。因此，BACE1 基因表达，连同洗涤剂可溶性 Aβ^{1-42 ，在功率训练的3xTg}小鼠中较低。我们的数据表明，Power 训练上调 Dicer 基因表达以改变大脑 miRNA 表达，这可能有助于减少 Aβ 积累并延缓 AD 进展。