Neurotransmitter Metabolic Disturbance in Methamphetamine Abusers: Focus on Tryptophan and Tyrosine Metabolic Pathways
Methamphetamine (METH) abuse disrupts the homeostasis of neurotransmitter (NT) metabolism, contributing to a wide range of neurological and psychological disorders. However, the specific effects of METH on NT metabolism, particularly for the tryptophan (TRP) and tyrosine (TYR) metabolic pathways, re...
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2024-12-01
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| author | Xi Wang Weilan Wu Jing Liu Miaoyang Hu Jie Cheng Jianping Xiong Xufeng Chen Rong Gao Jun Wang |
| author_facet | Xi Wang Weilan Wu Jing Liu Miaoyang Hu Jie Cheng Jianping Xiong Xufeng Chen Rong Gao Jun Wang |
| author_sort | Xi Wang |
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| description | Methamphetamine (METH) abuse disrupts the homeostasis of neurotransmitter (NT) metabolism, contributing to a wide range of neurological and psychological disorders. However, the specific effects of METH on NT metabolism, particularly for the tryptophan (TRP) and tyrosine (TYR) metabolic pathways, remain poorly understood. In this study, serum samples from 78 METH abusers and 79 healthy controls were analyzed using Ultra-High-Performance Liquid Chromatography with Tandem Mass Spectrometry (UHPLC-MS/MS). A total of 41 substances, primarily from the TRP and TYR metabolic pathways, were detected and subjected to multivariate analysis. Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) revealed a significant separation of serum metabolites between METH abusers and controls, encompassing the disturbance of serotonergic, kynurenic, and microbial metabolism. In the serotonergic pathway, METH significantly reduced melatonin (MLT) levels and impaired the conversion of serotonin (5-HT) to N-acetylserotonin (NAS), a key precursor of MLT. In the kynurenic pathway, METH promoted a shift to the toxic metabolic pathway, evidenced by elevated levels of 3-hydroxykynurenine (3-HK) and quinolinic acid (QA). Furthermore, microbial metabolic pathway-related indole and its derivatives were markedly suppressed in METH abusers. Gender-specific differences were also observed, with NT metabolism in TRP and TYR pathways showing more pronounced alterations in male or female subgroups. Therefore, the current study provides a comprehensive overview of the disturbance in TRP- and TYR-associated NT metabolism caused by METH abuse and highlights NT metabolism as a promising therapeutic target for METH-induced neural and psychiatric disorders. |
| format | Article |
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| language | English |
| publishDate | 2024-12-01 |
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| series | Toxics |
| spelling | doaj-art-b358f4009db34eaa8d9f4d47cee2570f2024-12-27T14:56:46ZengMDPI AGToxics2305-63042024-12-01121291210.3390/toxics12120912Neurotransmitter Metabolic Disturbance in Methamphetamine Abusers: Focus on Tryptophan and Tyrosine Metabolic PathwaysXi Wang0Weilan Wu1Jing Liu2Miaoyang Hu3Jie Cheng4Jianping Xiong5Xufeng Chen6Rong Gao7Jun Wang8Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, ChinaCenter for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaCenter for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaMethamphetamine (METH) abuse disrupts the homeostasis of neurotransmitter (NT) metabolism, contributing to a wide range of neurological and psychological disorders. However, the specific effects of METH on NT metabolism, particularly for the tryptophan (TRP) and tyrosine (TYR) metabolic pathways, remain poorly understood. In this study, serum samples from 78 METH abusers and 79 healthy controls were analyzed using Ultra-High-Performance Liquid Chromatography with Tandem Mass Spectrometry (UHPLC-MS/MS). A total of 41 substances, primarily from the TRP and TYR metabolic pathways, were detected and subjected to multivariate analysis. Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) revealed a significant separation of serum metabolites between METH abusers and controls, encompassing the disturbance of serotonergic, kynurenic, and microbial metabolism. In the serotonergic pathway, METH significantly reduced melatonin (MLT) levels and impaired the conversion of serotonin (5-HT) to N-acetylserotonin (NAS), a key precursor of MLT. In the kynurenic pathway, METH promoted a shift to the toxic metabolic pathway, evidenced by elevated levels of 3-hydroxykynurenine (3-HK) and quinolinic acid (QA). Furthermore, microbial metabolic pathway-related indole and its derivatives were markedly suppressed in METH abusers. Gender-specific differences were also observed, with NT metabolism in TRP and TYR pathways showing more pronounced alterations in male or female subgroups. Therefore, the current study provides a comprehensive overview of the disturbance in TRP- and TYR-associated NT metabolism caused by METH abuse and highlights NT metabolism as a promising therapeutic target for METH-induced neural and psychiatric disorders.https://www.mdpi.com/2305-6304/12/12/912methamphetamineneurotransmitterstryptophan metabolismtyrosine metabolism |
| spellingShingle | Xi Wang Weilan Wu Jing Liu Miaoyang Hu Jie Cheng Jianping Xiong Xufeng Chen Rong Gao Jun Wang Neurotransmitter Metabolic Disturbance in Methamphetamine Abusers: Focus on Tryptophan and Tyrosine Metabolic Pathways Toxics methamphetamine neurotransmitters tryptophan metabolism tyrosine metabolism |
| title | Neurotransmitter Metabolic Disturbance in Methamphetamine Abusers: Focus on Tryptophan and Tyrosine Metabolic Pathways |
| title_full | Neurotransmitter Metabolic Disturbance in Methamphetamine Abusers: Focus on Tryptophan and Tyrosine Metabolic Pathways |
| title_fullStr | Neurotransmitter Metabolic Disturbance in Methamphetamine Abusers: Focus on Tryptophan and Tyrosine Metabolic Pathways |
| title_full_unstemmed | Neurotransmitter Metabolic Disturbance in Methamphetamine Abusers: Focus on Tryptophan and Tyrosine Metabolic Pathways |
| title_short | Neurotransmitter Metabolic Disturbance in Methamphetamine Abusers: Focus on Tryptophan and Tyrosine Metabolic Pathways |
| title_sort | neurotransmitter metabolic disturbance in methamphetamine abusers focus on tryptophan and tyrosine metabolic pathways |
| topic | methamphetamine neurotransmitters tryptophan metabolism tyrosine metabolism |
| url | https://www.mdpi.com/2305-6304/12/12/912 |
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