microRNA-146a modulates behavioural activity, neuroinflammation, and oxidative stress in adult mice

作者：Wenting Zhao, Jereme G. Spiers, Natasha Vassileff, Arun Khadka, Emily J. Jaehne, Maarten van den Buuse, Andrew F. Hill · 发表于：Molecular and Cellular Neuroscience · 年份：2023 · DOI：10.1016/j.mcn.2023.103820 · 被引用次数：27 · 研究领域：MicroRNA in disease regulation、interferon and immune responses、Immune Response and Inflammation

Small non-coding miRNA act as key regulators of several physiological processes due to their ability to interact with numerous target mRNA within a network. Whilst several miRNA can act in concert to regulate target mRNA expression, miR-146a has emerged as a critical modulator of inflammation by targeting key upstream signalling proteins of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and reductions in this miRNA have been observed in several neurological and neurodegenerative disorders. However, a targeted assessment of behaviour and neural tissues following the loss of miR-146a has not been documented. In this study, we examined the behavioural and neuroinflammatory phenotype of mice lacking miR-146a to determine the role of this miRNA in neurological function. Adult miR-146a−/− mice displayed no overt developmental phenotype with the exception of enlarged spleens. Behavioural testing revealed a mild but significant reduction in exploratory locomotor activity and increase in anxiety-like behaviour, with no changes in short-term spatial memory, fear conditioning, or sensorimotor gating. In the brain, the lack of miR-146a resulted in a significant compensatory miR-155 expression with no significant changes in expression of the target Interleukin 1 Receptor Associated Kinase (Irak) gene family. Despite these effects on upstream NF-κB mediators, downstream expression of cytokine and chemokine messengers was significantly elevated in miR-146...