id_1008. PSILOCIN MODULATE THE MICROGLIA ACTIVITY IN EXPERIMENTAL MODEL OF NEUROINFLAMMATION EVOKED BY LIPOPOLYSACCHARIDE TREATMENT
Kinga Kaim1, Monika Leskiewicz2, Magdalena Regulska2, Ewa Trojan2, Krystyna Gołembiowska1
1 Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, 12 Smętna, 31-343 Kraków, Poland
2 2Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Experimental Neuroendocrinology, 12 Smętna, 31-343 Kraków, Poland
INTRODUCTION: Microglia are the primary resident immune cells of the central nervous system that are responsible for the maintenance of brain homeostasis. Among others they are capable, for nitric oxide (NO) synthesis and various cytokines release. A plethora of evidence suggest that microglia display distinct phenotypes that are associated with the alteration of cell activation under varying environmental cues. Psilocin is the bioactive metabolite of the naturally occurring indole tryptamine – psilocybin, which beneficial effects for some brain disorders treatment was reported. However the precise mechanisms underlying therapeutic effects remain only partially understood.
AIM(S): The objective of this study was to assess the effect of psilocin on the chosen parameters of microglial activity in basal conditions and after lipopolysaccharide (LPS) stimulation.
METHOD(S): Primary microglia cultures were prepared from cortices of 1-2-day-old offspring. Psilocin (10 μM) was added for 1 hour, then microglia were exposed to lipopolysaccharide (LPS, 100 ng/ml) for 24 hours. Cell death was determined by the LDH test. Nitric oxide (NO) synthesis was assessed by the Griess reaction. Protein levels of various cytokines release, A20 ( a negative regulator of NF-kB) and the phosphorylation level of the p65 NF-κB subunit were measured using ELISA kits
RESULTS: Administration of psilocin resulted in a decrease in NO production and mortality of the LPS-stimulated microglia cells. Moreover, psilocin diminished evoked by LPS pro-inflammatory cytokines (IL-1b, TNF-a, IL-6) release. This mechanism was related with decrease in the phospho-p65/total p65 ratio and normalization of the LPS-induced decrease in A20 levels
CONCLUSIONS: The results indicate that psilocin may have an important influence on microglia cell activation. The intricate mechanisms by which psychedelics modulate neuroinflammation underscores their potential as innovative therapeutic agents for treating inflammatory-related brain disorders.
FINANCIAL SUPPORT: This work was supported by statutory funds of the Department of Experimental Neuroendocrinology PAS and National Science Centre grant no. 2020/37/B/NZ7/03753.