The goals of the present project are to evaluate the neurotoxic effect of gut microbiota compound – p-cresol, clarify the role of S1R in p-cresol induced depressive-like behaviour, estimate the therapeutic efficacy and neuroprotective properties of S1R agonists. Using the animal and cell culture models, we will investigate rearrangement and redistribution of S1R-associated complexes in the plasma membrane and mitochondria-associated membrane (MAM); evaluate the activities of S1R-associated signalling pathways (ERK, Akt, BDNF, IP3R, Bip, Rac etc) in different brain structures (hippocampus, nucleus accumbens, prefrontal cortex) and cultured cells under the action of p-cresol, as well as under the actions of sigma ligands.

Principal investigator: Elene Zhuravliova