title: Neurogenomic evidence for a shared mechanism of the antidepressant effects of exercise and chronic fluoxetine in mice.
abstract: 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.
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. gjh30@mail.cgu.edu.tw
authors.forename: Guo-Jen
authors.initials: GJ
authors.lastname: Huang
authors.forename: Eyal
authors.initials: E
authors.lastname: Ben-David
authors.forename: Agnès
authors.initials: A
authors.lastname: Tort Piella
authors.forename: Andrew
authors.initials: A
authors.lastname: Edwards
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
authors.forename: Sagiv
authors.initials: S
authors.lastname: Shifman
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003863:Depression / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D005081:Exercise Therapy; D005473:Fluoxetine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008807:Mice, Inbred BALB C; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010805:Physical Conditioning, Animal
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine