Inhibition of circ_0004381 improves cognitive function via miR-647/PSEN1 axis in an Alzheimer disease mouse model

Abstract Circ_0004381 promotes neuronal damage in Parkinson disease, but its role in Alzheimer disease (AD) is unreported. The goal of this study was to investigate the role and potential mechanisms of circ_0004381 effects in AD models. Primary hippocampal neurons were treated with amyloid-β (Aβ1–42...

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Published in:Journal of neuropathology and experimental neurology 2023-01, Vol.82 (1), p.84-92
Main Authors: Li, Nini, Zhang, Dongdong, Guo, Hena, Yang, Qian, Li, Peng, He, Yifan
Format: Article
Language:English
Subjects:
Alzheimer Disease
Alzheimer's disease
Animals
Apoptosis
Care and treatment
Cognition
Cognitive ability
Disease Models, Animal
Gene expression
Genetic aspects
Health aspects
Male
Mice
Mice, Transgenic
MicroRNA
MicroRNAs - genetics
Neurological research
Presenilin-1 - genetics
RNA, Circular - genetics
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Summary:Abstract Circ_0004381 promotes neuronal damage in Parkinson disease, but its role in Alzheimer disease (AD) is unreported. The goal of this study was to investigate the role and potential mechanisms of circ_0004381 effects in AD models. Primary hippocampal neurons were treated with amyloid-β (Aβ1–42) to construct AD cell models. We found that circ_0004381 was upregulated in Aβ1–42-treated hippocampal neurons. Knockdown of circ_0004381 attenuated Aβ1–42-induced apoptosis, oxidative stress, and mitochondrial dysfunction in hippocampal neurons. Next, we induced microglia activation with lipopolysaccharide (LPS). The results of flow cytometry experiments showed that knockdown of circ_0004381 promoted microglial M2-type polarization and knockdown of circ_0004381 inhibited the production of inflammatory factors by microglia. Furthermore, knockdown of circ_0004381 improved cognitive function of male APPswe/PS1dE9 transgenic mice. Mechanistically, circ_0004381 regulated presenilin-1 (PSEN1) expression by absorbing miR-647. MiR-647 inhibition attenuated the effects of circ_0004381 knockdown. In conclusion, knockdown of circ_0004381 attenuated hippocampal neuronal damage and promoted microglia M2-type polarization through the miR-647/PSEN1 axis, ultimately improving cognitive function in AD model mice.
ISSN:0022-3069
1554-6578
DOI:10.1093/jnen/nlac108