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Hippocampal BMP signaling as a common pathway for antidepressant action.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2021 Dec 22; Vol. 79 (1), pp. 31. Date of Electronic Publication: 2021 Dec 22. - Publication Year :
- 2021
-
Abstract
- The benefits of current treatments for depression are limited by low response rates, delayed therapeutic effects, and multiple side effects. Antidepressants affect a variety of neurotransmitter systems in different areas of the brain, and the mechanisms underlying their convergent effects on behavior have been unclear. Here we identify hippocampal bone morphogenetic protein (BMP) signaling as a common downstream pathway that mediates the behavioral effects of five different antidepressant classes (fluoxetine, bupropion, duloxetine, vilazodone, trazodone) and of electroconvulsive therapy. All of these therapies decrease BMP signaling and enhance neurogenesis in the hippocampus. Preventing the decrease in BMP signaling blocks the effect of antidepressant treatment on behavioral phenotypes. Further, inhibition of BMP signaling in hippocampal newborn neurons is sufficient to produce an antidepressant effect, while chemogenetic silencing of newborn neurons prevents the antidepressant effect. Thus, inhibition of hippocampal BMP signaling is both necessary and sufficient to mediate the effects of multiple classes of antidepressants.<br /> (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Subjects :
- Aging pathology
Animals
Anti-Anxiety Agents pharmacology
Behavior, Animal drug effects
Dentate Gyrus drug effects
Dentate Gyrus metabolism
Duloxetine Hydrochloride pharmacology
Electroconvulsive Therapy
Fluoxetine pharmacology
Ganglia, Spinal drug effects
Ganglia, Spinal pathology
Hippocampus drug effects
Mice, Inbred C57BL
Mice, Transgenic
Neurogenesis drug effects
Stress, Psychological complications
Trazodone pharmacology
Vilazodone Hydrochloride pharmacology
Mice
Antidepressive Agents pharmacology
Bone Morphogenetic Proteins metabolism
Hippocampus metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 79
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 34936033
- Full Text :
- https://doi.org/10.1007/s00018-021-04026-y