Circ-Bptf Ameliorates Learning and Memory Impairments via the miR-138-5p/p62 Axis in APP/PS1 Mice.

IF 4.3 2区 医学 Q1 NEUROSCIENCES Molecular Neurobiology Pub Date : 2024-11-01 Epub Date: 2024-03-25 DOI:10.1007/s12035-024-04066-y
Hong-Fang Wang, Yi-Bo Li, Zi-Yu Liu, Wen-Meng Xie, Qing Liu, Run-Jiao Zhang, Wen-Yu Wang, Jia-Xin Hao, Lei Wang, Dan-Dan Geng
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Abstract

Alzheimer's disease (AD) is a common age-associated progressive neurodegenerative disorder that is implicated in the aberrant regulation of numerous circular RNAs (circRNAs). Here, we reported that circ-Bptf, a conserved circRNA derived from the Bptf gene, showed an age-dependent decrease in the hippocampus of APP/PS1 mice. Overexpression of circ-Bptf significantly reversed dendritic spine loss and learning and memory impairment in APP/PS1 mice. Moreover, we found that circ-Bptf was predominantly localized to the cytoplasm and upregulated p62 expression by binding to miR-138-5p. Furthermore, the miR-138-5p mimics reversed the decreased expression of p62 induced by the silencing of circ-Bptf. Together, our findings suggested that circ-Bptf ameliorated learning and memory impairments via the miR-138-5p/p62 axis in APP/PS1 mice. It may act as a potential player in AD pathogenesis and therapy.

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Circ-Bptf通过miR-138-5p/p62轴改善APP/PS1小鼠的学习和记忆障碍
阿尔茨海默病(AD)是一种常见的与年龄相关的进行性神经退行性疾病,它与许多环状 RNA(circRNA)的异常调控有关。在这里,我们报道了源自 Bptf 基因的保守 circRNA circ-Bptf,在 APP/PS1 小鼠的海马中出现了年龄依赖性下降。过表达circ-Bptf能明显逆转APP/PS1小鼠树突棘的缺失以及学习和记忆障碍。此外,我们还发现 circ-Bptf 主要定位于细胞质,并通过与 miR-138-5p 结合上调 p62 的表达。此外,miR-138-5p模拟物逆转了沉默circ-Bptf引起的p62表达下降。我们的研究结果表明,circ-Bptf通过miR-138-5p/p62轴改善了APP/PS1小鼠的学习和记忆损伤。它可能是AD发病机制和治疗的潜在参与者。
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来源期刊
Molecular Neurobiology
Molecular Neurobiology 医学-神经科学
CiteScore
9.00
自引率
2.00%
发文量
480
审稿时长
1 months
期刊介绍: Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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