biostudies-literatureUnknown18(2)Ohnishi MIn the chronic phase after intracerebral hemorrhage (ICH), the aftereffect-associated lowering of motivation burdens many patients; however, the pathogenic mechanism is unclear. Here, we revealed for the first time that indoleamine 2, 3-dioxygenase (IDO) expression and enzyme activity are increased in the collagenase-induced murine ICH model. IDO is a rate-limiting enzyme situated at the beginning of the kynurenine pathway and converts tryptophan, a source of serotonin (5-hydroxytryptamine; 5-HT), to kynurenine. In this study, we showed that IDO is localized in 5-HTergic neurons. After ICH, the synaptosomal 5-HT level decreased, but this effect was neutralized by subcutaneous injections of 1-methyl tryptophan (MT), a specific IDO inhibitor. These results suggest that ICH-induced IDO weakenPloS onee0273037https://www.ebi.ac.uk/biostudies/studies/S-EPMC9907831biostudies-literatureIndoleamine 2, 3-dioxygenase is responsible for low stress tolerance after intracerebral hemorrhage.PMC9907831Aokawa HHata TAkagi MOhnishi MInoue AYonemura SYamashita-Ibara MMaehara SYokofujita OKotsuki MfalseIndoleamine 2, 3-dioxygenase is responsible for low stress tolerance after intracerebral hemorrhage.In the chronic phase after intracerebral hemorrhage (ICH), the aftereffect-associated lowering of motivation burdens many patients; however, the pathogenic mechanism is unclear. Here, we revealed for the first time that indoleamine 2, 3-dioxygenase (IDO) expression and enzyme activity are increased in the collagenase-induced murine ICH model. IDO is a rate-limiting enzyme situated at the beginning of the kynurenine pathway and converts tryptophan, a source of serotonin (5-hydroxytryptamine; 5-HT), to kynurenine. In this study, we showed that IDO is localized in 5-HTergic neurons. After ICH, the synaptosomal 5-HT level decreased, but this effect was neutralized by subcutaneous injections of 1-methyl tryptophan (MT), a specific IDO inhibitor. These results suggest that ICH-induced IDO weaken2023-01-01T00:00:00Z20232025-04-04T23:52:44.308Z2025-04-04T23:52:44.308ZS-EPMC99078313675349610.1371/journal.pone.0273037