Department of Neurology, Binzhou Medical University Hospital, Binzhou, Shandong, China; Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong, China.
The First Clinical Medical College, Binzhou Medical University, Yantai, Shandong, China.
Brain Res. 2022 Sep 1;1790:147983. doi: 10.1016/j.brainres.2022.147983. Epub 2022 Jun 13.
Alzheimer disease (AD) is a neurodegenerative disorder, which is characterized by progressive impairment of memory and cognition. Early diagnosis and treatment of AD has become a leading topic of research. In this study, we explored the effects of the miR-132-3p/FOXO3a-PPM1F axis on the onset of AD for possible early diagnosis and therapy. We found that miR-132-3p levels in the hippocampus and blood were drastically decreased in APP/PS1 mice from 9 months of age, and bi-directional manipulation of miR-132-3p levels induced magnified effects on learning memory behaviors, and manifestation of AD-related pathological characteristics and inflammatory cytokines in APP/PS1 mice of relevant ages. The hippocampal PPM1F expression levels were significantly elevated in APP/PS1 mice from 3 months of age, which was correlated with miR-132-3p levels at different ages. Overexpression of PPM1F remarkably accelerated the progression of learning memory deficits and associated pathological factors in APP/PS1 mice. Further, we showed that miR-132-3p modulated the expression of PPM1F via FOXO3a in HT22 cells. Finally, using peripheral blood samples of human study participants, we found that the miR-132-3p and PPM1F expression levels in patients with AD were also altered with prominent correlations. In conclusion, miR-132-3p indirectly regulates PPM1F expression by targeting FOXO3a, which could play an extensive role in contributing to the establishment of early diagnosis, treatment, and pathogenesis of AD.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是记忆和认知能力的进行性损害。AD 的早期诊断和治疗已成为研究的主要课题。在这项研究中，我们探讨了 miR-132-3p/FOXO3a-PPM1F 轴对 AD 发病的影响，以期进行早期诊断和治疗。我们发现，9 月龄 APP/PS1 小鼠海马和血液中的 miR-132-3p 水平显著降低，miR-132-3p 水平的双向调控对 APP/PS1 小鼠的学习记忆行为以及相关年龄 AD 相关病理特征和炎症细胞因子的表现产生了放大效应。3 月龄 APP/PS1 小鼠海马 PPM1F 表达水平显著升高，与不同年龄的 miR-132-3p 水平相关。过表达 PPM1F 显著加速了 APP/PS1 小鼠学习记忆缺陷和相关病理因素的进展。此外，我们还表明，miR-132-3p 通过 FOXO3a 调节 HT22 细胞中 PPM1F 的表达。最后，使用人类研究参与者的外周血样本，我们发现 AD 患者的 miR-132-3p 和 PPM1F 表达水平也发生了改变，且具有显著相关性。总之，miR-132-3p 通过靶向 FOXO3a 间接调节 PPM1F 的表达，这可能在 AD 的早期诊断、治疗和发病机制中发挥广泛作用。
