Document Detail

Macrophage migration inhibitory factor mediates the antidepressant actions of voluntary exercise.
MedLine Citation:
PMID:  22826223     Owner:  NLM     Status:  MEDLINE    
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.
Hyo Youl Moon; Se Hyun Kim; Yong Ryoul Yang; Parkyong Song; Hyun Sook Yu; Hong Geun Park; Onyou Hwang; Whaseon Lee-Kwon; Jeong Kon Seo; Daehee Hwang; Jang Hyun Choi; Richard Bucala; Sung Ho Ryu; Yong Sik Kim; Pann-Ghill Suh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-23
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-08     Completed Date:  2012-10-15     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13094-9     Citation Subset:  IM    
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 790-784, Korea.
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MeSH Terms
Analysis of Variance
Blotting, Western
Brain-Derived Neurotrophic Factor / metabolism
Cells, Cultured
DNA Primers / genetics
Depression / therapy*
Electroshock / methods*
Infusions, Intraventricular
Intramolecular Oxidoreductases / administration & dosage,  genetics,  pharmacology*
Macrophage Migration-Inhibitory Factors / administration & dosage,  genetics,  pharmacology*
Mice, Inbred C57BL
Mice, Knockout
Motor Activity / drug effects,  physiology*
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Recombinant Proteins / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Serotonin / metabolism
Tryptophan Hydroxylase / metabolism
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 0/DNA Primers; 0/Macrophage Migration-Inhibitory Factors; 0/Recombinant Proteins; 50-67-9/Serotonin; EC Hydroxylase; EC protein, rat; EC 5.3.-/Intramolecular Oxidoreductases; EC protein, mouse
Comment In:
Nat Rev Neurosci. 2012 Sep;13(9):602   [PMID:  22895476 ]

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