{"title":"酪氨酸:选择性血清素再摄取抑制剂治疗慢性约束应激诱导肠道先天淋巴样细胞3型细胞减少的关键神经递质。","authors":"Yilin Wu, Chujun Duan, Niqi Shan, Yuling Wang, Shanshou Liu, Linxiao Wang, Yangmengjie Jing, Hanyin Fan, Jinyue Yang, Yuan Zhang, Lin Liu, Ran Zhuang","doi":"10.1021/acschemneuro.5c00271","DOIUrl":null,"url":null,"abstract":"<p><p>Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants. Given the prevalence of depression and its associated immune dysregulation, understanding the role of SSRIs in these processes is crucial. This study aims to explore the effects of SSRIs on chronic restraint stress (CRS)-induced depressive-like behaviors and immune functions. Mice subjected to CRS were administered citalopram (CITA) during the modeling period, followed by behavioral assessments. Histological examination and flow cytometry were used to analyze the immune status and cells of the spleen and intestine. Cellular experiments were performed for verification. We found that CITA treatment significantly alleviated weight loss and depression-like behaviors in CRS mice. Moreover, CITA ameliorated CRS-induced immune dysregulation in the spleen and reversed the decreased villus/crypt ratio in the ileum. Although CITA had minimal impact on restoring intraepithelial lymphocytes after CRS, it significantly reversed the reduction in innate lymphoid cell type 3 (ILC3) levels. Notably, although levels of the serotonin precursor 5-hydroxytryptophan remained unchanged in the ileum, tyrosine levels significantly increased after CRS and were further reduced by CITA treatment. Treatment of primary ILC3s with 4-ethylphenol, a tyrosine metabolite, decreased ILC3 cells and their related IL-7 levels, suggesting that tyrosine may be a key neurotransmitter regulating ILC3 levels through CITA. Hence, CITA effectively ameliorates CRS-induced depressive-like behaviors and immune dysfunctions in the spleen and intestine. Tyrosine is a crucial neurotransmitter in CITA treatment for regulating depression-related intestinal immune disorders.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"2312-2321"},"PeriodicalIF":3.9000,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tyrosine: A Key Neurotransmitter in Selective Serotonin Reuptake Inhibitor Treatment for Chronic Restraint Stress-Induced Reduction of Intestinal Innate Lymphoid Cell Type 3 Cells.\",\"authors\":\"Yilin Wu, Chujun Duan, Niqi Shan, Yuling Wang, Shanshou Liu, Linxiao Wang, Yangmengjie Jing, Hanyin Fan, Jinyue Yang, Yuan Zhang, Lin Liu, Ran Zhuang\",\"doi\":\"10.1021/acschemneuro.5c00271\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants. Given the prevalence of depression and its associated immune dysregulation, understanding the role of SSRIs in these processes is crucial. This study aims to explore the effects of SSRIs on chronic restraint stress (CRS)-induced depressive-like behaviors and immune functions. Mice subjected to CRS were administered citalopram (CITA) during the modeling period, followed by behavioral assessments. Histological examination and flow cytometry were used to analyze the immune status and cells of the spleen and intestine. Cellular experiments were performed for verification. We found that CITA treatment significantly alleviated weight loss and depression-like behaviors in CRS mice. Moreover, CITA ameliorated CRS-induced immune dysregulation in the spleen and reversed the decreased villus/crypt ratio in the ileum. Although CITA had minimal impact on restoring intraepithelial lymphocytes after CRS, it significantly reversed the reduction in innate lymphoid cell type 3 (ILC3) levels. Notably, although levels of the serotonin precursor 5-hydroxytryptophan remained unchanged in the ileum, tyrosine levels significantly increased after CRS and were further reduced by CITA treatment. Treatment of primary ILC3s with 4-ethylphenol, a tyrosine metabolite, decreased ILC3 cells and their related IL-7 levels, suggesting that tyrosine may be a key neurotransmitter regulating ILC3 levels through CITA. Hence, CITA effectively ameliorates CRS-induced depressive-like behaviors and immune dysfunctions in the spleen and intestine. Tyrosine is a crucial neurotransmitter in CITA treatment for regulating depression-related intestinal immune disorders.</p>\",\"PeriodicalId\":13,\"journal\":{\"name\":\"ACS Chemical Neuroscience\",\"volume\":\" \",\"pages\":\"2312-2321\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-06-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Chemical Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acschemneuro.5c00271\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/4 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acschemneuro.5c00271","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/4 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Tyrosine: A Key Neurotransmitter in Selective Serotonin Reuptake Inhibitor Treatment for Chronic Restraint Stress-Induced Reduction of Intestinal Innate Lymphoid Cell Type 3 Cells.
Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants. Given the prevalence of depression and its associated immune dysregulation, understanding the role of SSRIs in these processes is crucial. This study aims to explore the effects of SSRIs on chronic restraint stress (CRS)-induced depressive-like behaviors and immune functions. Mice subjected to CRS were administered citalopram (CITA) during the modeling period, followed by behavioral assessments. Histological examination and flow cytometry were used to analyze the immune status and cells of the spleen and intestine. Cellular experiments were performed for verification. We found that CITA treatment significantly alleviated weight loss and depression-like behaviors in CRS mice. Moreover, CITA ameliorated CRS-induced immune dysregulation in the spleen and reversed the decreased villus/crypt ratio in the ileum. Although CITA had minimal impact on restoring intraepithelial lymphocytes after CRS, it significantly reversed the reduction in innate lymphoid cell type 3 (ILC3) levels. Notably, although levels of the serotonin precursor 5-hydroxytryptophan remained unchanged in the ileum, tyrosine levels significantly increased after CRS and were further reduced by CITA treatment. Treatment of primary ILC3s with 4-ethylphenol, a tyrosine metabolite, decreased ILC3 cells and their related IL-7 levels, suggesting that tyrosine may be a key neurotransmitter regulating ILC3 levels through CITA. Hence, CITA effectively ameliorates CRS-induced depressive-like behaviors and immune dysfunctions in the spleen and intestine. Tyrosine is a crucial neurotransmitter in CITA treatment for regulating depression-related intestinal immune disorders.
期刊介绍:
ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following:
Neurotransmitters and receptors
Neuropharmaceuticals and therapeutics
Neural development—Plasticity, and degeneration
Chemical, physical, and computational methods in neuroscience
Neuronal diseases—basis, detection, and treatment
Mechanism of aging, learning, memory and behavior
Pain and sensory processing
Neurotoxins
Neuroscience-inspired bioengineering
Development of methods in chemical neurobiology
Neuroimaging agents and technologies
Animal models for central nervous system diseases
Behavioral research