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Neurogenomic evidence for a shared mechanism of the antidepressant effects of exercise and chronic fluoxetine in mice

Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant i...

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Published in:PloS one 2012-04, Vol.7 (4), p.e35901
Main Authors: Huang, Guo-Jen, Ben-David, Eyal, Tort Piella, Agnès, Edwards, Andrew, Flint, Jonathan, Shifman, Sagiv
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Ben-David, Eyal
Tort Piella, Agnès
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description Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug--fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The hippocampi of treated mice were investigated at the molecular and cellular levels. Mice treated with fluoxetine and mice who exercised daily showed, not only similar antidepressant behavior, but also similar changes in gene expression and hippocampal neurons. These changes were not observed in mice with environmental enrichment. An increase in neurogenesis and dendritic spine density was observed following four weeks of fluoxetine treatment and voluntary exercise. A weighted gene co-expression network analysis revealed four different modules of co-expressed genes that were correlated with the antidepressant effect. This network analysis enabled us to identify genes involved in the molecular pathways underlying the effects of fluoxetine and exercise. The existence of both neuronal and gene expression changes common to antidepressant drug and exercise suggests a shared mechanism underlying their effect. Further studies of these findings may be used to uncover the molecular mechanisms of depression, and to identify new avenues of therapy.
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subjects Analysis
Animals
Anopheles
Antidepressants
Antidepressive Agents - pharmacology
Anxiety
Behavior
Bioinformatics
Biology
Brain
Brain-derived neurotrophic factor
Dendritic spines
Depression (Mood disorder)
Depression - genetics
Depression - metabolism
Depression - physiopathology
Depression - therapy
Drugs
Enrichment
Environmental factors
Exercise
Exercise Therapy
Fluoxetine
Fluoxetine - pharmacology
Gene expression
Gene Expression - drug effects
Genes
Genetics
Genomes
Hippocampus
Hippocampus - drug effects
Hippocampus - metabolism
Hippocampus - pathology
House mouse
Humans
Laboratory animals
Life sciences
Male
Medicine
Mental depression
Metabolic Networks and Pathways
Mice
Mice, Inbred BALB C
Molecular modelling
Mood
Network analysis
Neurogenesis
Neurogenesis - drug effects
Neurons
Neurons - drug effects
Neurons - pathology
Neurophysiology
Physical Conditioning, Animal
Physical exercise
Physical fitness
Psychopharmacology
Rodents
Spine
title Neurogenomic evidence for a shared mechanism of the antidepressant effects of exercise and chronic fluoxetine in mice
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