Role of abnormal tryptophan metabolism in post-stroke depression in rats

Abnormal tryptophan (Trp) metabolism disrupts the 5-hydroxytryptamine (5-HT) system, contributing to clinical depression. However, the link between altered Trp metabolism and post-stroke depression remains unclear. This study investigates Trp metabolism in rats exhibiting depression-like behavior after middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were divided into three groups: sham operation (sham), MCAO, and MCAO + 1-methyltryptophan (1-MT) treatment groups. The MCAO + 1-MT group received daily subcutaneous injections of 1-MT (60 mg/Kg/day), an indoleamine 2,3-dioxygenase (IDO) inhibitor. Sucrose preference and marble burying tests assessed depression-like behavior. Brain tissue was analyzed for Trp, 5-HT, kynurenine (KYN), and other metabolites. Immunohistochemistry was used to detect 5-HT, IDO, and tryptophan hydroxylase (TPH) expression in the hippocampus and frontal cortex. MCAO reduced sucrose preference and increased marble burying, indicating depression-like behavior. Treatment with 1-MT improved neurological scores and reversed these behavioral changes. The MCAO group showed elevated KYN levels and KYN/Trp ratios, which decreased with 1-MT treatment. No significant differences were observed in 5-HT levels or 5-HT/Trp ratios across groups. The sham group exhibited more 5-HT-positive cells in the hippocampus than the MCAO group, while IDO-positive cells were higher in the frontal cortex of the MCAO group compared to the MCAO + 1-MT group. These results concluded that subcutaneous 1-MT, an IDO inhibitor, enhances neurological function and reduces depression-like behaviour in rats after ischemic stroke. Clinical trials with bigger samples are required to further validate these findings.