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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Macrophage migration inhibitory factor mediates the antidepressant actions of voluntary exercise
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Macrophage migration inhibitory factor mediates the antidepressant actions of voluntary exercise

机译:Macrophage migration inhibitory factor mediates the antidepressant actions of voluntary exercise

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摘要

Voluntary exercise is known to have an antidepressant effect. However, the underlying mechanism for this antidepressant action of exercise remains unclear, and little progress has been made in identifying genes that are directly involved. We have identified macrophage migration inhibitory factor (MIF) by analyzing existing mRNA microarray data and confirmed the augmented expression of selected genes under two experimental conditions: voluntary exercise and electroconvulsive seizure. A proinflammatory cytokine, MIF is expressed in the central nervous system and involved in innate and adaptive immune responses. A recent study reported that MIF is involved in antidepressant-induced hippocampal neurogenesis, but the mechanism remains elusive. In our data, tryptophan hydroxylase 2 (Tph2) and brain-derived neurotrophic factor (Bdnf) expression were induced after MIF treatment in vitro, as well as during both exercise and electroconvulsive seizure in vivo. This increment of Tph2 was accompanied by increases in the levels of total serotonin in vitro. Moreover, the MIF receptor CD74 and the ERK1/2 pathway mediate the MIF-induced Tph2 and Bdnf gene expression as well as serotonin content. Experiments in Mif~(-/-) mice revealed depression-like behaviors and a blunted antidepressant effect of exercise, as reflected by changes in Tph2 and Bdnf expression in the forced swim test. In addition, administration of recombinant MIF protein produced antidepressant-like behavior in rats in the forced swim test. Taken together, these results suggest a role of MIF in mediating the antidepressant action of exercise, probably by enhancing serotonin neurotransmission and neurotrophic factor-induced neurogenesis in the brain.

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  • 作者单位

    School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, South Korea;

    Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul 110-744, South Korea;

    School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan 689-805, South KoreaDivision of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, South KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-744, South KoreaDepartment of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, South KoreaDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, United StatesDepartment of Neuropsychiatry, Dongguk University International Hospital, Dongguk University Medical School, Gyeonggi-do, 410-773, South Korea;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 英语
  • 中图分类 自然科学总论;
  • 关键词

    Glycosylation-inhibiting factor; Major depressive disorder; Physical activity;

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