MicroRNAs underlying the antidepressant effect of psilocybin – Establishing an nCounter pipeline for microRNA-quantification in the pig brain
Erik Kaadt, Rolf Søkilde, Hanne D. Hansen, Nakul Ravi Raval, Lene Lundgaard, Jesper Just, Gitte M. Knudsen, Betina Elfving
Research Square January 12, 2024 preprint DOI: 10.21203/rs.3.rs-3787179/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study |
|---|---|
| Population | Pigs |
| Intervention | Psilocybin |
| Dose | a single dose |
| Duration | 1 day and 1 week after a single dose |
| Topics | Psilocybin |
| Keywords | Microrna Antidepressant Pipeline software |
| Key points | Psilocybin administration acutely dysregulated 12 miRNAs in the prefrontal cortex and 2 in the hippocampus of pigs, with sustained changes in 4 hippocampal miRNAs after one week, suggesting miRNA regulation as a mechanism for psilocybin's effects. |
Abstract
Abstract Novel treatment strategies are needed to overcome some of the current challenges related to treatment resistance and treatment latency within the psychiatric field. Recently, psilocybin has shown promise as a novel treatment of major depressive disorder. A single dose of psilocybin is associated with lasting changes in personality and mood. In parallel, various studies have indicated that microRNAs (miRNAs) are regulated after antidepressive interventions. Here, pigs were used to study the transcriptional profiles of miRNAs in the prefrontal cortex (PFC) and hippocampus (HIP), 1 day and 1 week after a single dose of psilocybin. A streamlined process was developed to adapt the Nanostring nCounter technology, specifically the Human v3b miRNA Assay panel, for compatibility with pig tissue samples. The mirmachine tool was used to select miRNAs with complete human-pig sequence conservation to make a conservative reannotation of pig microRNAs. Furthermore, different normalization strategies were employed. Utilizing this pipeline, dysregulation of 12 miRNAs in the PFC and 2 miRNAs in the HIP was ∂identified 1 day after psilocybin administration. Seven days after psilocybin administration, only 4 dysregulated miRNAs were observed in the HIP. Among the 18 identified miRNAs, 9 have previously been linked to depression. Notably, miR-212-3p and miR-107 displayed robust acute regulation across all four normalization strategies in the PFC. The two miRNAs are known to exert anti-inflammatory effects, mirroring previously reported effects of psilocybin. These results suggest that psilocybin may exert its acute and sustained molecular effects through the regulation of specific miRNAs in core brain areas of depression.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cites 12
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
and 7 more in the library