Effects of serotonergic psychedelics on synaptogenesis and immediate early genes expression - comparison with ketamine, fluoxetine and lithium

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F25%3A43921541" target="_blank" >RIV/00023752:_____/25:43921541 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/25:43928550 RIV/00216208:11310/25:10498635 RIV/60461373:22310/25:43932759 RIV/60461373:22330/25:43932759

Výsledek na webu

<a href="https://journals.sagepub.com/doi/10.1177/02698811251338232" target="_blank" >https://journals.sagepub.com/doi/10.1177/02698811251338232</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/02698811251338232" target="_blank" >10.1177/02698811251338232</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effects of serotonergic psychedelics on synaptogenesis and immediate early genes expression - comparison with ketamine, fluoxetine and lithium

Popis výsledku v původním jazyce

Background: Recent evidence suggests that psychedelics can induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although the exact underlying molecular mechanisms remain unclear.Aims: This study investigates the effects of psilocin, lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT) on synaptogenesis and immediate early genes (IEGs) expression in direct comparison with ketamine, fluoxetine and lithium after acute (1 h) and/or prolonged (24 h) treatment in vitro.Methods: Rat primary cortical cultures were treated with 10 µM psilocin, 1 µM LSD, 90 µM DMT, 1 µM ketamine, 10 µM fluoxetine and 5 mM lithium. Analysis of synaptic puncta was performed; puncta of presynaptic marker synapsin I/II, postsynaptic density protein 95 (PSD-95) and their co-localization (established synapse) were assessed 24 h after drug treatment. Next, expressions of IEGs encoding activity-regulated cytoskeleton-associated protein (Arc), early growth response 1 (Egr1), and neuronal PAS (Per-Arnt-Sim) domain protein 4 (Npas4) were analysed 1 and 24 h after drug treatments.Results: Psilocin increased synaptic puncta count and induced Arc expression. The effect to promote synaptogenesis was comparable to ketamine and lithium; ketamine additionally increased PSD-95 puncta count. LSD and DMT did not induce any significant effects. Interestingly, fluoxetine had no effect on synaptic puncta count, but upregulated Egr1 and Npas4.Conclusions: Psilocin demonstrated synaptogenic effects comparable to those of ketamine and lithium, and acutely upregulated IEG Arc expression, adding another piece of evidence to its profile as a promising therapeutic agent.

Název v anglickém jazyce

Effects of serotonergic psychedelics on synaptogenesis and immediate early genes expression - comparison with ketamine, fluoxetine and lithium

Popis výsledku anglicky

Background: Recent evidence suggests that psychedelics can induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although the exact underlying molecular mechanisms remain unclear.Aims: This study investigates the effects of psilocin, lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT) on synaptogenesis and immediate early genes (IEGs) expression in direct comparison with ketamine, fluoxetine and lithium after acute (1 h) and/or prolonged (24 h) treatment in vitro.Methods: Rat primary cortical cultures were treated with 10 µM psilocin, 1 µM LSD, 90 µM DMT, 1 µM ketamine, 10 µM fluoxetine and 5 mM lithium. Analysis of synaptic puncta was performed; puncta of presynaptic marker synapsin I/II, postsynaptic density protein 95 (PSD-95) and their co-localization (established synapse) were assessed 24 h after drug treatment. Next, expressions of IEGs encoding activity-regulated cytoskeleton-associated protein (Arc), early growth response 1 (Egr1), and neuronal PAS (Per-Arnt-Sim) domain protein 4 (Npas4) were analysed 1 and 24 h after drug treatments.Results: Psilocin increased synaptic puncta count and induced Arc expression. The effect to promote synaptogenesis was comparable to ketamine and lithium; ketamine additionally increased PSD-95 puncta count. LSD and DMT did not induce any significant effects. Interestingly, fluoxetine had no effect on synaptic puncta count, but upregulated Egr1 and Npas4.Conclusions: Psilocin demonstrated synaptogenic effects comparable to those of ketamine and lithium, and acutely upregulated IEG Arc expression, adding another piece of evidence to its profile as a promising therapeutic agent.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Psychopharmacology

ISSN

0269-8811

e-ISSN

1461-7285

Svazek periodika

39

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

1023-1030

Kód UT WoS článku

001498644800001

EID výsledku v databázi Scopus

2-s2.0-105006982706