MicroRNA-139 modulates Alzheimer's-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2
1Department of Geriatric, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu, China.
Abstract:
Alzheimer's disease (AD) is a neurodegenerative disorder, and is the most common type of dementia in the elderly population. Growing evidence indicates that microRNAs (miRNAs) play a crucial role in neuroinflammation associated with AD progression. In this study, we analyzed the expression of microRNA-139 (miR-139) as well as the learning and memory function in AD. We observed that the miR-139 expression was significantly higher in the hippocampus of aged senescence accelerated mouse prone 8 (SAMP8) mice (2.92 ± 0.13) than in the control mice (1.49 ± 0.08). Likewise, the overexpression of miR-139 by means of hippocampal injection impaired the hippocampus-dependent learning and memory formation. In contrast, the downregulation of miR-139 in mice improved learning and memory function in the mice. The level of cannabinoid receptor type 2 (CB2), a potential target gene of miR-139, was inversely correlated with the miR-139 expression in primary hippocampal cells. Furthermore, we demonstrated that miR-139 inversely modulated the responses to proinflammatory stimuli. Together, our findings demonstrate that miR-139 exerts a pathogenic effect in AD by modulating CB2-meditated neuroinflammatory processes.
Insights
Elevated microRNA-139 (miR-139) levels worsen Alzheimer's disease (AD) by increasing neuroinflammation. Reducing miR-139 in mice improved cognitive function, suggesting a therapeutic target for AD.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) is a leading cause of dementia in older adults.
- MicroRNAs (miRNAs) are implicated in the neuroinflammation characteristic of AD progression.
Purpose of the Study:
- To investigate the role of microRNA-139 (miR-139) in Alzheimer's disease (AD).
- To analyze the relationship between miR-139 expression, cognitive function, and neuroinflammation in an AD mouse model.
Main Methods:
- Expression analysis of miR-139 in the hippocampus of senescence accelerated mouse prone 8 (SAMP8) mice and control mice.
- Assessment of learning and memory functions following miR-139 manipulation (overexpression and downregulation) in the hippocampus.
- Correlation analysis between miR-139 levels and cannabinoid receptor type 2 (CB2) expression in primary hippocampal cells.
- Evaluation of miR-139's effect on neuroinflammatory responses.
Main Results:
- miR-139 expression was significantly higher in the hippocampus of aged SAMP8 mice compared to controls.
- Overexpression of miR-139 impaired hippocampus-dependent learning and memory.
- Downregulation of miR-139 improved learning and memory function.
- CB2 receptor levels were inversely correlated with miR-139 expression.
- miR-139 modulated responses to proinflammatory stimuli.
Conclusions:
- miR-139 plays a pathogenic role in Alzheimer's disease.
- miR-139 exacerbates AD by modulating CB2-mediated neuroinflammatory pathways.
- Targeting miR-139 may offer a therapeutic strategy for AD treatment.
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