Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Transl Psychiatry. 2021 Feb 2;11(1):90. doi: 10.1038/s41398-020-01126-4.
The effects of different forms of monosaccharides on the brain remain unclear, though neuropsychiatric disorders undergo changes in glucose metabolism. This study assessed cell viability responses to five commonly consumed monosaccharides-D-ribose (RIB), D-glucose, D-mannose (MAN), D-xylose and L-arabinose-in cultured neuro-2a cells. Markedly decreased cell viability was observed in cells treated with RIB and MAN. We then showed that high-dose administration of RIB induced depressive- and anxiety-like behavior as well as spatial memory impairment in mice, while high-dose administration of MAN induced anxiety-like behavior and spatial memory impairment only. Moreover, significant pathological changes were observed in the hippocampus of high-dose RIB-treated mice by hematoxylin-eosin staining. Association analysis of the metabolome and transcriptome suggested that the anxiety-like behavior and spatial memory impairment induced by RIB and MAN may be attributed to the changes in four metabolites and 81 genes in the hippocampus, which is involved in amino acid metabolism and serotonin transport. In addition, combined with previous genome-wide association studies on depression, a correlation was found between the levels of Tnni3k and Tbx1 in the hippocampus and RIB induced depressive-like behavior. Finally, metabolite-gene network, qRT-PCR and western blot analysis showed that the insulin-POMC-MEK-TCF7L2 and MAPK-CREB-GRIN2A-CaMKII signaling pathways were respectively associated with RIB and MAN induced depressive/anxiety-like behavior and spatial memory impairment. Our findings clarified our understanding of the biological mechanisms underlying RIB and MAN induced depressive/anxiety-like behavior and spatial memory impairment in mice and highlighted the deleterious effects of high-dose RIB and MAN as long-term energy sources.
不同形式的单糖对大脑的影响尚不清楚，尽管神经精神疾病的葡萄糖代谢会发生变化。本研究评估了五种常见消耗的单糖-D-核糖（RIB）、D-葡萄糖、D-甘露糖（MAN）、D-木糖和 L-阿拉伯糖-在培养的神经-2a 细胞中的细胞活力反应。用 RIB 和 MAN 处理的细胞观察到细胞活力明显下降。然后我们表明，高剂量 RIB 给药可诱导小鼠产生抑郁样和焦虑样行为以及空间记忆障碍，而高剂量 MAN 给药仅诱导焦虑样行为和空间记忆障碍。此外，通过苏木精-伊红染色观察到高剂量 RIB 处理小鼠的海马组织明显病理变化。代谢组学和转录组学的关联分析表明，RIB 和 MAN 诱导的焦虑样行为和空间记忆障碍可能归因于海马中四种代谢物和 81 个基因的变化，这些基因参与氨基酸代谢和 5-羟色胺转运。此外，结合先前关于抑郁症的全基因组关联研究，发现海马中 Tnni3k 和 Tbx1 的水平与 RIB 诱导的抑郁样行为之间存在相关性。最后，代谢物-基因网络、qRT-PCR 和 Western blot 分析表明，胰岛素-POMC-MEK-TCF7L2 和 MAPK-CREB-GRIN2A-CaMKII 信号通路分别与 RIB 和 MAN 诱导的抑郁/焦虑样行为和空间记忆障碍相关。我们的研究结果阐明了我们对 RIB 和 MAN 诱导的小鼠抑郁/焦虑样行为和空间记忆障碍的生物学机制的理解，并强调了高剂量 RIB 和 MAN 作为长期能量来源的有害影响。
