期刊
HIPPOCAMPUS
卷 33, 期 2, 页码 96-111出版社
WILEY
DOI: 10.1002/hipo.23491
关键词
d-galactose; memory impairment; microglia; miRNA-124; neuroinflammation
MiRNA-124 plays a significant role in memory formation and neurodegenerative diseases. This study investigated the involvement of miRNA-124 in memory impairment induced by d-galactose and explored the underlying neuroprotective mechanism. The results showed that d-galactose administration caused memory impairments in mice, which were alleviated by miRNA-124 agomir injection in the hippocampus, leading to reduced neural damage and neuroinflammation. Molecular analysis and immunohistochemistry revealed that miRNA-124 reduced neuroinflammation through microglial polarization and downregulation of inflammatory mediators. These findings suggest that miRNA-124 may be a potential target for the pathogenesis of memory impairment and neurodegenerative diseases.
MiRNA-124 has been considered to play a significant role in the formation of memory and a variety of neurodegenerative diseases. In this study, the aim is to verify whether miRNA-124 is involved in memory impairment induced by d-galactose, and explore the underlying neuroprotective mechanism. The results revealed that rapid administration of d-galactose (1000 mg/kg subcutaneously) in mice caused memory impairments, as determined by Novel Object Recognition test, Morris Water Maze test, and histological assessments. MiRNA-124 agomir is stereotactic injected into hippocampus, thus alleviated memory impairment induced by d-galactose and reversed the neural damage and neuroinflammation. Furthermore, the results of molecular biological analysis and immunohistochemistry revealed that miRNA-124 markedly reduced neuroinflammation induced by d-galactose through polarization of microglia as determined by detection of ionized calcium binding adapter molecule 1 (Iba-1), inducible nitric oxide synthase (iNOS) and arginase-1(Arg-1), which also downregulated inflammatory mediators, including interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), and upregulated IL-4 and IL-10. Hence, taken together, the results of the present study suggested that miRNA-124 showed a significant negative correlation with memory impairment and neuroinflammation induced by d-galactose rapidly, possibly via polarization of microglia from M1 to M2. It is possible that miRNA-124 can be used as a new target for the pathogenesis of memory impairment, including age-associated neurodegenerative diseases such as Alzheimer's disease.
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