Modulation of DNA methylation and protein expression in the prefrontal cortex by repeated administration of D-lysergic acid diethylamide (LSD): Impact on neurotropic, neurotrophic, and neuroplasticity signaling
Antonio Inserra, Antonella Campanale, David Cheishvili, Sergiy Dymov, Amy H. Y. Wong, Nathalie Marçal, Robert A. Syme, Lorne Taylor, Danilo de Gregorio, Timothy E. Kennedy, Moshe Szyf, Gabriella Gobbi
Progress in Neuro-Psychopharmacology and Biological Psychiatry June 28, 2022 DOI: 10.1016/j.pnpbp.2022.110594 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Lysergic acid diethylamide (LSD) |
| Dose | 30 μg/kg/day |
| Duration | 7 days |
| Topics | Neuroplasticity LSD |
| Keywords | Prefrontal cortex Modulation music Cell biology Neurotrophin Biochemistry Cognition Receptor |
| Citations | 39 |
| Key findings | Repeated LSD administration modulates DNA methylation and protein expression in the mouse prefrontal cortex, affecting genes involved in neuroplasticity and nervous system development. |
Abstract
AimPsychedelic compounds elicit relief from mental disorders. However, the underpinnings of therapeutic improvement remain poorly understood. Here, we investigated the effects of repeated lysergic acid diethylamide (LSD) on whole-genome DNA methylation and protein expression in the mouse prefrontal cortex (PFC).MethodsWhole genome bisulphite sequencing (WGBS) and proteomics profiling of the mouse prefrontal cortex (PFC) were performed to assess DNA methylation and protein expression changes following 7 days of repeated LSD administration (30 μg/kg/day); a treatment we previously found to potentiate excitatory neurotransmission and to increase dendritic spine density in the PFC in mice. qRT-PCR was employed to validate candidate genes detected in both analyses.ResultsLSD significantly modulated DNA methylation in 635 CpG sites of the mouse PFC, and in an independent cohort the expression level of 178 proteins. Gene signaling pathways affected are involved in nervous system development, axon guidance, synaptic plasticity, quantity and cell viability of neurons and protein translation. Four genes and their protein product were detected as differentially methylated and expressed, and their transcription was increased. Specifically, Coronin 7 (Coro7), an axon guidance cue; Penta-EF-Hand Domain Containing 1 (Pef1), an mTORC1 and cell cycle modulator; Ribosomal Protein S24 (Rps24), required for pre-rRNA maturation and biogenesis of proteins involved with cell proliferation and migration, and Abhydrolase Domain Containing 6, Acylglycerol Lipase (Abhd6), a post-synaptic lipase.ConclusionsLSD affects DNA methylation, altering gene expression and protein expression related to neurotropic-, neurotrophic- and neuroplasticity signaling. This could represent a core mechanism mediating the effects of psychedelics.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 32
- Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. Brain Sciences January 25, 2025
- Reports of self-compassion and affect regulation in psilocybin-assisted therapy for alcohol use disorder: An interpretive phenomenological analysis. Psychology of Addictive Behaviors June 5, 2023
- Effects of repeated lysergic acid diethylamide (LSD) on the mouse brain endocannabinoidome and gut microbiome. British Journal of Pharmacology March 1, 2023
- The Effects of Psychedelics on Neuronal Physiology. Annu Rev Physiol November 6, 2023
- Psychedelics in neuroinflammation: Mechanisms and therapeutic potential Progress in Neuro-Psychopharmacology and Biological Psychiatry January 31, 2025
and 27 more in the library
Cites 21
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Proceedings of the National Academy of Sciences April 13, 2021
- Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Journal of Neuroscience October 1, 2003
- Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Experimental Brain Research June 1, 2013
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
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