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

被引：19

作者：

Inserra, Antonio ^{[1
]}

Campanale, Antonella ^{[1
]}

Cheishvili, David ^{[2
,3
]}

Dymov, Sergiy ^{[4
]}

Wong, Amy ^{[5
]}

Marcal, Nathalie ^{[6
]}

Syme, Robert Andrew ^{[7
]}

Taylor, Lorne ^{[5
]}

De Gregorio, Danilo ^{[1
,8
]}

Kennedy, Timothy E. ^{[6
]}

Szyf, Moshe ^{[4
]}

Gobbi, Gabriella ^{[1
]}

机构：

[1] McGill Univ, Dept Psychiat, Neurobiol Psychiat Unit, Montreal, PQ, Canada

[2] McGill Univ, Dept Oncol, Montreal, PQ, Canada

[3] HKG Epitherapeut, Hong Kong, Peoples R China

[4] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada

[5] McGill Univ Hlth Ctr, Res Inst, Prote Platform, Montreal, PQ, Canada

[6] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ, Canada

[7] Canadian Ctr Computat Genom, Montreal, PQ, Canada

[8] Univ Vita Salute San Raffaele, Div Neurosci, Milan, Italy

来源：

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY | 2022年 / 119卷

关键词：

GENE; PROLIFERATION; PSYCHEDELICS; LIGASE; RPS24; LINKS;

D O I：

10.1016/j.pnpbp.2022.110594

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 mu g/kg/day); a treatment we previously found to potentiate excitatory neuro-transmission 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.

引用

页数：14