Imbalanced Tryptophan Metabolism In The Pathogenesis Of PSD Rats

Objective: The imbalance of 5-hydroxytryptamine(5-HT)system caused by abnormal tryptophan(Trp)metabolism is considered to be related to the pathogenesis of clinical depression.However,the underlying mechanism for the development of depression leading to abnormalities in tryptophan after stroke is unclear.Here,we will use a middle cerebral artery occlusion(MCAO)rat model to study the role of tryptophan metabolism imbalance in post-stroke depression and explore the treatment of post-stroke depression in rats.Methods: Healthy Sprague Dawley(SD)rats were randomly divided into 4 groups: sham operation group(Sham),surgical control group(MCAO),1-MT treatment group(MCAO+ 1-MT),and Shuganjieyu capsule group(MCAO+SGJY).The Sham operation group underwent the Sham operation,the other three groups received MCAO surgery.After MCAO,rats in the MCAO+ 1-MT group were given subcutaneous injection of indoleamine 2,3-dioxygenase(IDO)inhibitor 1-methyl-dl-tryptophan(1-MT,60 mg/Kg,daily),rats in the MCAO+SGJY group were given shuganjieyu capsule(SGJY,144mg/Kg)for gavage once a day,and Sham group and MCAO group were given the same volume of saline as those in the treatment group.The Sucrose Preference Test was conducted on the 5th day after the operation,and the Marble-buried test was performed on the 6th day after the operation.The behavioral changes of the rats in each group were observed.The development of depression-like behavior was reflected in a decrease of sucrose preference and an increase in the number of Marble-buried test.On the 7th day after administration,the head was cut off and the brain was taken.The volume of cerebral infarction in rats was determined by TTC staining.After the cerebral infarction area was stained by TTC staining method,the volume of cerebral infarction in rats was measured by Image J software.Rat brain tissue was homogenized,centrifuged and sent to the School of Chemistry and Chemical Engineering,Lanzhou University,for the determination of Trp,5-HT,kynurenine(KYN)and other related tryptophan metabolites.Immunohistochemistry was used to detect the number of 5-HT,IDO,and tryptophan hydroxylase(TPH)positive cells in hippocampus and frontal cortex of rats.Results: After MCAO,compared with the neurological scores measured at 1day,the neurological scores of rats in MCAO + 1-MT group and MCAO + SGJY group were significantly reduced at 6 days after surgery(P <0.01).In behavioral tests,the sucrose preference rate of the MCAO group decreased,and the number of marbles was increased.Compared with the MCAO group,the sucrose preference rate of the MCAO + 1-MT group and MCAO + SGJY group increased after administration(P <0.05),and the number of buried marbles decreased(P <0.05).KYN was not detected in the brain tissue of the Sham group rats.Compared with MCAO group,the KYN concentration in the MCAO+1-MT group was significantly decreased(P <0.05).There was no significant difference in 5-HT content,5-HT /Trp ratio and KYN/Trp ratio among the four groups(P>0.05).In hippocampal,compared with that in MCAO group,the expression number of 5-HT positive cells in Sham group and MCAO+SGJY group increased significantly(P < 0.05).In frontal cortex,compared with the Sham group,the expression number of IDO-positive cells in the MCAO group,MCAO + 1-MT group and the MCAO + SGJY group increased(P<0.05).Compared with the MCAO group,the expression number of IDO-positive cells in MCAO+1-MT group and MCAO+SGJY group was significantly reduced(P <0.001).Conclusion: After stroke,the number of 5-HT neurons in the hippocampus decreases,while KYN synthesis increases,and the expression of IDO in the frontal lobe increases.IDO inhibitor 1-MT reduces the synthesis of KYN in the brain tissue and reduces the expression of IDO in the frontal lobe.ShuganJieyu Capsule can increase 5-HT in hippocampus and reduce the expression of IDO.Both drugs can improve the depression-like performance caused by stroke and promote neurological function recovery.This indicates that the abnormal metabolism of tryptophan plays an important role in the occurrence and development of depression in MCAO rats,and its mechanism may be achieved by up-regulating the expression of IDO.1-MT and ShuganJieyu Capsule may be a drug for PSD.