Psychedelics Promote Structural and Functional Neural Plasticity
Summary: Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the disso...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718307551 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Calvin Ly Alexandra C. Greb Lindsay P. Cameron Jonathan M. Wong Eden V. Barragan Paige C. Wilson Kyle F. Burbach Sina Soltanzadeh Zarandi Alexander Sood Michael R. Paddy Whitney C. Duim Megan Y. Dennis A. Kimberley McAllister Kassandra M. Ori-McKenney John A. Gray David E. Olson |
| spellingShingle |
Calvin Ly Alexandra C. Greb Lindsay P. Cameron Jonathan M. Wong Eden V. Barragan Paige C. Wilson Kyle F. Burbach Sina Soltanzadeh Zarandi Alexander Sood Michael R. Paddy Whitney C. Duim Megan Y. Dennis A. Kimberley McAllister Kassandra M. Ori-McKenney John A. Gray David E. Olson Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports |
| author_facet |
Calvin Ly Alexandra C. Greb Lindsay P. Cameron Jonathan M. Wong Eden V. Barragan Paige C. Wilson Kyle F. Burbach Sina Soltanzadeh Zarandi Alexander Sood Michael R. Paddy Whitney C. Duim Megan Y. Dennis A. Kimberley McAllister Kassandra M. Ori-McKenney John A. Gray David E. Olson |
| author_sort |
Calvin Ly |
| title |
Psychedelics Promote Structural and Functional Neural Plasticity |
| title_short |
Psychedelics Promote Structural and Functional Neural Plasticity |
| title_full |
Psychedelics Promote Structural and Functional Neural Plasticity |
| title_fullStr |
Psychedelics Promote Structural and Functional Neural Plasticity |
| title_full_unstemmed |
Psychedelics Promote Structural and Functional Neural Plasticity |
| title_sort |
psychedelics promote structural and functional neural plasticity |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2018-06-01 |
| description |
Summary: Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders. : Ly et al. demonstrate that psychedelic compounds such as LSD, DMT, and DOI increase dendritic arbor complexity, promote dendritic spine growth, and stimulate synapse formation. These cellular effects are similar to those produced by the fast-acting antidepressant ketamine and highlight the potential of psychedelics for treating depression and related disorders. Keywords: neural plasticity, psychedelic, spinogenesis, synaptogenesis, depression, LSD, DMT, ketamine, noribogaine, MDMA |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124718307551 |
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doaj-fab3a30f83314b318faa3be216735c442020-11-25T01:05:48ZengElsevierCell Reports2211-12472018-06-01231131703182Psychedelics Promote Structural and Functional Neural PlasticityCalvin Ly0Alexandra C. Greb1Lindsay P. Cameron2Jonathan M. Wong3Eden V. Barragan4Paige C. Wilson5Kyle F. Burbach6Sina Soltanzadeh Zarandi7Alexander Sood8Michael R. Paddy9Whitney C. Duim10Megan Y. Dennis11A. Kimberley McAllister12Kassandra M. Ori-McKenney13John A. Gray14David E. Olson15Department of Chemistry, University of California, Davis, Davis, CA 95616, USADepartment of Chemistry, University of California, Davis, Davis, CA 95616, USANeuroscience Graduate Program, University of California, Davis, Davis, CA 95618, USANeuroscience Graduate Program, University of California, Davis, Davis, CA 95618, USANeuroscience Graduate Program, University of California, Davis, Davis, CA 95618, USADepartment of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USAGenome Center, University of California, Davis, Davis, CA 95616, USADepartment of Chemistry, University of California, Davis, Davis, CA 95616, USACenter for Neuroscience, University of California, Davis, Davis, CA 95618, USADepartment of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USADepartment of Chemistry, University of California, Davis, Davis, CA 95616, USAGenome Center, University of California, Davis, Davis, CA 95616, USA; Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA; MIND Institute, University of California, Davis, Sacramento, CA 95817, USACenter for Neuroscience, University of California, Davis, Davis, CA 95618, USA; Department of Neurology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA; Department of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, CA 95616, USADepartment of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USACenter for Neuroscience, University of California, Davis, Davis, CA 95618, USA; Department of Neurology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USADepartment of Chemistry, University of California, Davis, Davis, CA 95616, USA; Center for Neuroscience, University of California, Davis, Davis, CA 95618, USA; Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA; Corresponding authorSummary: Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders. : Ly et al. demonstrate that psychedelic compounds such as LSD, DMT, and DOI increase dendritic arbor complexity, promote dendritic spine growth, and stimulate synapse formation. These cellular effects are similar to those produced by the fast-acting antidepressant ketamine and highlight the potential of psychedelics for treating depression and related disorders. Keywords: neural plasticity, psychedelic, spinogenesis, synaptogenesis, depression, LSD, DMT, ketamine, noribogaine, MDMAhttp://www.sciencedirect.com/science/article/pii/S2211124718307551 |