Changes in cognitive ability and serum microRNA levels during aging in mice
Keisuke Yamamoto1, Kohta Miyano2, Minami Fujita2
1Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan.
Abstract:
Mild cognitive impairment (MCI) is an early stage that can result in dementia. MCI can be reversed, and diagnosis at an early stage is crucial to control the progression to dementia. Dementia is currently diagnosed based on interviews and screening tests; however, novel biomarkers must be identified to allow early MCI detection. Therefore, the present study aimed to identify novel biomarkers in the form of blood microRNAs (miRNAs/miRs) for the diagnosis of MCI or early dementia. Blood samples were collected from C57BL/6NJcl male mice at four time points, including 4-week-old (4W), 8-week-old (8W), 36-week-old (36W) and 58-week-old (58W), and serum was isolated. Body weight and blood total cholesterol levels were increased, and blood alkaline phosphatase was decreased with aging. The 8W mice exhibited the highest cognitive ability in the Morris water maze test, whereas the 58W mice demonstrated decreased cognitive ability. The serum RNA concentrations of the 4W, 8W, 36W and 58W mice demonstrated no significant differences. Furthermore, small RNA levels were detected in the serum of all mice. miRNA microarray analysis revealed a >1.5-fold increase in the serum expression of two miRNAs (miR-21a-5p and miR-92a-3p) and a >1.5-fold decrease in the serum expression of two other miRNAs (miR-6769b-5p and miR-709) in 58W mice compared with those in 8W mice. In the future, we aim to further analyze aged mice to discover novel MCI biomarkers.
Insights
This study identifies potential blood microRNA biomarkers for early dementia detection. Specific microRNAs (miRs) showed altered levels in aged mice with cognitive decline, suggesting their role in mild cognitive impairment.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Aging Research
Background:
- Mild cognitive impairment (MCI) is an early stage of dementia, crucial for early intervention.
- Current dementia diagnosis relies on interviews and screening tests, necessitating novel biomarkers for early detection.
- Blood microRNAs (miRNAs) are emerging as promising biomarkers for various neurological conditions.
Purpose of the Study:
- To identify novel blood microRNA (miRNA) biomarkers for the early diagnosis of MCI or dementia.
- To investigate age-related changes in cognitive function and serum miRNA expression in mice.
- To establish a foundation for developing non-invasive diagnostic tools for cognitive decline.
Main Methods:
- Serum samples were collected from C57BL/6NJcl male mice at four age points (4, 8, 36, and 58 weeks).
- Cognitive ability was assessed using the Morris water maze test.
- Serum miRNA expression profiling was performed using microarray analysis.
Main Results:
- Cognitive ability decreased with aging, with 58-week-old mice showing impaired performance compared to 8-week-old mice.
- miRNA microarray analysis revealed significant changes in serum miRNA levels in aged mice.
- Specifically, miR-21a-5p and miR-92a-3p were upregulated, while miR-6769b-5p and miR-709 were downregulated in 58-week-old mice compared to 8-week-old mice.
Conclusions:
- Specific serum miRNAs (miR-21a-5p, miR-92a-3p, miR-6769b-5p, miR-709) show altered expression patterns with aging and cognitive decline in mice.
- These miRNAs represent potential novel biomarkers for early MCI or dementia detection.
- Further research in aged mice is warranted to validate these findings and explore their diagnostic potential.
