Tauroursodeoxycholic acid alleviates depression-like behavior induced by chronic unpredictable mild stress through amelioration of catecholamine imbalance.

Abstract

Depression is thought to emerge as a result of monoamine neuromodulators' deficiency in a specific central nervous system site. Tauroursodeoxycholic acid (TUDCA) has been found to have a protective role against diseases affecting the central nervous system. The potential effects of TUDCA on brain monoamine neurotransmitters in a stress-induced depression model have not been reported. We investigated the effects of TUCDA treatment on serotonin, norepinephrine and dopamine, catecholamine biosynthesis enzyme tyrosine hydroxylase (TH) and degrading enzyme monoamine oxidase A (MAO-A), NLRP3 and pro-inflammatory IL-1β in the hippocampus and mPFC of male rats subjected to chronic unpredictable mild stress (CUMS). Behavioral results demonstrated that TUDCA exhibits antidepressant and anxiolytic properties. TUDCA treatment markedly reduced the stress-increased the levels of IL-1β and NLRP3 in the hippocampus and mPFC of CUMS rats. Results showed that TUDCA treatment failed to alter serotonin levels in the hippocampus and mPFC, whereas it restored reduced dopamine and norepinephrine in the hippocampus and ameliorated dopamine imbalance in the mPFC of stressed rats. Further analysis showed that TUDCA treatment increases TH expression in the hippocampus and reduces the increased the protein levels of MAO-A in both brain areas. Our research suggests that TUDCA mitigated depressive-like behavior, and the mechanism appeared to be related to the regulation of catecholamine levels and their synthetic and degrading enzymes in both brain areas.