Celastrol Mediated Regulation of the HnRNPA1-Thyroxine Axis in the Amygdala Alleviates High Fat Diet-Induced Demyelination and Cognitive Deficits in Mice.
Xuemin Yao, Shuangpan Zhang, Guoxin Zhang, Ying Liu, Yongping Zhu, Wenli Wang, Chunyan Zhu, Na Lin
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引用次数: 0
Abstract
High fat diet (HFD) is closely linked to demyelination and cognitive deficiency. Previously, we reported that the covalent binding and downregulation of heterogeneous nuclear ribonucleoprotein A1 (HnRNPA1) were responsible for the effectiveness of celastrol against high fat diet (HFD) induced obesity. However, little is known about cognitive functions. This study aimed to evaluate the effectiveness and mechanism of celastrol on cognitive functions and demyelination in HFD mice. In HFD mice, the anti-cognitive dysfunction and anti-demyelination effects of celastrol and HnRNPA1-shRNA were evaluated by Morris water maze and luxol-fast-blue staining. Then, the common biological pathway of celastrol and HnRNPA1-shRNA was clarified by the transcriptomic and metabolomic analyses of amygdala tissue and verified in the amygdala and in cultured MO3.13 cells. Celastrol and HnRNPA1-shRNA alleviated cognitive impairments and amygdala demyelination in HFD mice. By transcriptome analysis, genes co-regulated by celastrol and HnRNPA1-shRNA were focused on the myelin generating cells-oligodendrocyte. Celastrol and HnRNPA1-shRNA alleviated oligodendrocyte differentiation disorder and myelin loss induced by HFD. Association analysis of metabolome and transcriptome indicated that the enhanced central transport and inhibited inactivation of thyroxine may underlie celastrol and HnRNPA1-shRNA mediated regulation of oligodendrocyte. In MO3.13 cells, celastrol mediated downregulation of HnRNPA1. In addition, the pro-maturation effects of celastrol and HnRNPA1-shRNA were confirmed by the downregulation of Dio3 and O1, as well as the upregulation of MBP. Through HnRNPA1-thyroxine axis, celastrol protects against HFD-induced demyelination and cognitive deficits.
期刊介绍：
Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field.
Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters.
By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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