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

 DO NOT DO THIS! This is in mice and human testing likely will never occur. I see no proof this actually helped neuroplasticity. Neuroplasticity signaling doesn't mean neuroplasticity actually occurred.

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

Author links open overlay panelAntonioInserra^aAntonellaCampanale^aDavidCheishvili^bcSergiyDymov^dAmyWong^eNathalieMarcal^fRobert AndrewSyme^gLorneTaylor^eDaniloDe Gregorio^a1Timothy E.Kennedy^fMosheSzyf^dGabriellaGobbi^a

https://doi.org/10.1016/j.pnpbp.2022.110594Get rights and content

Highlights

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Repeated LSD administration affects the DNA methylation level of genes involved with neurotropic, neurotrophic, and neuroplasticity signaling.

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Repeated LSD administration affects the protein level of genes involved with neurotropic, neurotrophic, and neuroplasticity signaling.

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Repeated LSD administration increases the transcription level of genes involved with neurotropic, neurotrophic, and neuroplasticity signaling detected as both differentially methylated, and differentially expressed.

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This could represent a core mechanism mediating the effects of psychedelics.

Abstract

Aim

Psychedelic 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).

Methods

Whole 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.

Results

LSD significantly modulated DNA methylation in 635 CpG sites of the mouse PFC, and in an independent cohort the expression level of 181 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.

Conclusions

LSD 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.

Data availability

Data will be made available on request.

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Current address: Vita-Salute San Raffaele University, Division of Neuroscience, Milan, Italy.

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