85 results on '"5-hydroxytryptamine"'
Search Results
2. Tryptophan Supplementation Increases Reproduction Performance, Milk Yield, and Milk Composition in Lactating Sows and Growth Performance of Their Piglets.
- Author
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Miao J, Adewole D, Liu S, Xi P, Yang C, and Yin Y
- Subjects
- Animal Feed analysis, Animals, Dietary Supplements analysis, Female, Lactation, Male, Milk metabolism, Reproduction, Swine growth & development, Milk chemistry, Swine metabolism, Tryptophan metabolism
- Abstract
Tryptophan (Trp) can produce bioactive compounds for appetite regulation, calcium mobilization, and mammary gland homeostasis via a serotonin pathway. This study evaluated the effects of Trp supplementation on the reproduction performance, milk yield, and composition of lactating sows, growth performance of their piglets, and the secretion function of porcine mammary epithelial cells (PMECs). The infrared emulsion analyzer and ELISA analyses revealed that feeding sows with a 0.12% Trp addition increased ( P < 0.05) sow average daily feed intake, milk yield, milk calcium concentration, average daily gain of piglets, fatty acid synthase (FAS) and lactose synthase (LS), β-casein secretion, intracellular Ca
2+ level, the expression of calcium binding protein CaM, and the activity of CaMKII. In a cellular experiment of PMECs treated with Trp, ELISA and flow cytometry analyses revealed that the pretreatment of a Trp hydroxylase inhibitor reduced ( P < 0.05) FAS and LS synthesis, the intracellular Ca2+ level, and the activity of CaMKII. In conclusion, Trp supplementation at 0.12% increased sows' reproductive performance, milk yield, and calcium concentration and piglets' growth performance. Milk yield increased by Trp was linked to 5-hydroxytryptamine-mediated synthesis of FAS, LS, and β-casein in PMECs, while the increase in calcium concentration was attributed to increasing CaM expression and CAMKII activity.- Published
- 2019
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3. Effect of l-tryptophan and its metabolites on food passage from the crop in chicks.
- Author
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Tachibana T, Kadomoto Y, Khan MSI, Makino R, and Cline MA
- Subjects
- Administration, Oral, Alanine, Animals, Asparagine, Glycine, Kynurenic Acid metabolism, Kynurenic Acid pharmacology, Male, Quinolinic Acid metabolism, Quinolinic Acid pharmacology, Tryptophan administration & dosage, Chickens, Crop, Avian drug effects, Gastrointestinal Motility drug effects, Tryptophan pharmacology
- Abstract
l-tryptophan (l-Trp), an essential amino acid, is well known as a precursor of 5-hydroxytryptamine (5-HT) and melatonin. In mammals, l-Trp itself has been reported to suppress gastric emptying in mammals. In addition, 5-HT and melatonin are found in the gastrointestinal tract and affect food passage from the digestive tract in mammals. While the function of these factors in mammals is documented, there is little knowledge on their function in the digestive tract of birds. Therefore, the purpose of the present study was to determine if l-Trp and its metabolites affect the crop emptying rate in chicks (Gallus gallus). We also investigated the effects of kynurenic acid (KYNA) and quinolinic acid (QA), which are metabolites of the kynurenine pathway for l-Trp. Oral administration of l-Trp significantly reduced the crop emptying rate in chicks. Among the metabolites, intraperitoneal injection of 5-HT and melatonin significantly reduced the crop emptying rate, whereas KYNA and QA had no effect. The present study suggests that l-Trp, 5-HT, and melatonin inhibit the movement of food in the digestive tract and thereby affect the utilization of nutrients in the diet of chicks., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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4. Effects of dietary L-tryptophan supplementation on intestinal response to chronic unpredictable stress in broilers.
- Author
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Yue Y, Guo Y, and Yang Y
- Subjects
- Animals, Avian Proteins metabolism, Cortisone blood, Intestines pathology, Male, Poultry Diseases metabolism, Poultry Diseases pathology, Chickens metabolism, Dietary Supplements, Intestinal Mucosa metabolism, Poultry Diseases drug therapy, Stress, Physiological drug effects, Tryptophan pharmacology
- Abstract
Stress has been recognized as a critical risk factor for gastrointestinal diseases in both humans and animals. However, nutritional strategies to attenuate stress-induced intestinal barrier function and underlying mechanisms remain largely unknown. This study tested the hypothesis that L-tryptophan enhanced intestinal barrier function by regulating mucosal serotonin metabolism in chronic unpredictable stress-exposed broilers. One-day-old male broilers (Arbor Acres) were fed a basal diet supplemented with or without L-tryptophan in the absence or presence of chronic unpredictable stress. Feed intake, body weight gain, plasma corticosterone and 5-hydroxytryptamine (5-HT), intestinal permeability, mucosal secretory IgA (sIgA), and mRNA levels for tryptophan hydroxylase 1 (TPH1), IL-1β, IL-6, TNF-α, IL-10, protein abundance for claudin-1, occludin, and ZO-1 were determined. Stress exposure led to elevated plasma corticosterone (P < 0.05), increased intestinal permeability (P < 0.05), reduced growth performance (P < 0.05), and decreased sIgA secretion compared with the controls. These effects were largely reversed (P < 0.05) by L-tryptophan supplementation. Western blot analysis showed that stress exposure resulted in decreased protein abundance for occludin, claudin-1, and ZO-1, which was attenuated by L-tryptophan. mRNA levels for IL-1β, IL-6, and TNF-α were increased, but those for IL-10 were decreased, in the jejunal tissue of broilers subjected to stress. This effect of stress on cytokine expression was abolished by L-tryptophan treatment. The effects of stress were associated with decreased plasma concentration of 5-HT (P < 0.05), and reduced (P < 0.05) mRNA levels for TPH1. L-Tryptophan supplementation markedly attenuated stress-induced alterations in 5-HT and TPH1 mRNA level in jejunal tissues of broilers. Collectively, these results indicate that L-tryptophan supplementation alleviates chronic unpredictable stress-induced intestinal barrier dysfunction by regulating 5-HT metabolism in broilers.
- Published
- 2017
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5. Deletion of TDO2, IDO-1 and IDO-2 differentially affects mouse behavior and cognitive function.
- Author
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Too LK, Li KM, Suarna C, Maghzal GJ, Stocker R, McGregor IS, and Hunt NH
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- Animals, Brain metabolism, Circadian Rhythm, Dopamine metabolism, Exploratory Behavior, Female, Indoleamine-Pyrrole 2,3,-Dioxygenase genetics, Kynurenine metabolism, Learning physiology, Locomotion, Memory, Short-Term physiology, Mice, Mice, Inbred C57BL, Serotonin metabolism, Tryptophan Oxygenase genetics, Behavior, Animal physiology, Cognition physiology, Indoleamine-Pyrrole 2,3,-Dioxygenase physiology, Tryptophan metabolism, Tryptophan Oxygenase physiology
- Abstract
Tryptophan, an amino acid involved in routine energy metabolism, is a key modulator of sickness behaviors associated with inflammatory states and also plays roles in some psychiatric disorders. Tissue concentrations of tryptophan are regulated primarily by the enzymes indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO, encoded by TDO2). Altered IDO1 and TDO activities have been linked to the perturbed serotonergic neurotransmission that may underlie certain psychopathologies. Here we assessed mice genetically modified to be deficient in IDO1, IDO2 or TDO2 for their behavior and cognitive function using an automated home cage system, the IntelliCage™. A well-established behavioural and cognitive test battery was applied during two periods (Runs 1 and 2, "R1" and "R2") separated by one month. Various tryptophan-related neurochemicals also were measured in brain extracts. IDO1(-/-) mice displayed remarkable reductions of early diurnal exploration in the IntelliCage and this persisted in R2. In contrast, early diurnal hyperactivity was observed in IDO2(-/-) mice in both R1 and R2. TDO2(-/-) mice displayed increased diurnal and nocturnal exploration, but only in R2. Cognitive assessment suggested enhanced reference memory in IDO2(-/-) mice in a complex patrolling task, while TDO deficiency was associated with enhanced performance in complex patrolling and discrimination reversal tasks. Neurochemical measures showed attenuated brain serotonin levels in IDO1(-/-) mice and augmented tryptophan and serotonin levels in TDO2(-/-) animals, respectively. No neurochemical alterations were detected in IDO2(-/-) mice. Taken together, these findings reveal complex and dissimilar patterns of behavioral and cognitive changes induced by knockout of three different tryptophan-metabolizing enzymes., (Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.)
- Published
- 2016
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6. Effects of tryptophan supplementation on growth performance, antioxidative activity, and meat quality of ducks under high stocking density.
- Author
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Liu Y, Yuan JM, Zhang LS, Zhang YR, Cai SM, Yu JH, and Xia ZF
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- Animal Husbandry, Animal Nutritional Physiological Phenomena, Animals, Antioxidants, Dietary Supplements, Ducks growth & development, Ducks metabolism, Hypothalamus chemistry, Hypothalamus metabolism, Male, Oxidative Stress, Serotonin chemistry, Serotonin metabolism, Tryptophan administration & dosage, Animal Feed analysis, Diet veterinary, Meat standards, Tryptophan pharmacology
- Abstract
High stocking density (STD) could affect duck welfare and production. The objective of our study was to investigate whether dietary tryptophan (TRP) supplementation could alleviate the detrimental effects of high STD on ducks. White Pekin ducks at 4 to 6 wk of age were raised at 11 birds/m(2) and fed diets containing 0.18, 0.48, 0.78, or 1.08% TRP for 21 d. Growth performance, concentrations of TRP and metabolites in the blood and hypothalamus, antioxidative activities in serum and tissue, meat quality, serum uric acid, and urea nitrogen were measured. Weight gain and feed efficiency were significantly improved by TRP supplementation at ≥ 0.48 and ≥ 0.78% (P < 0.05 and P < 0.001, respectively). Serum TRP, hypothalamic TRP, 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacitic acid (5-HIAA), and 5-HIAA/5-HT were also increased significantly (P < 0.01). These increases plateaued at 0.48% TRP, and no further improvement was obtained by adding more TRP to the diet. Dietary TRP supplementation significantly increased levels of total antioxidant capacity, glutathione peroxidase (GSH-Px), and catalase (CAT) in serum; GSH-Px in liver; and GSH-Px and CAT in breast muscle (P < 0.05). Malondialdehyde levels in breast muscle decreased (P < 0.001). Drip loss of breast muscle and pH decline at 45 min postmortem were reduced by TRP supplementation (P < 0.01 and P < 0.05, respectively). Meat color was similar among different treatments (P > 0.05). Breast muscle shear force was increased significantly when dietary TRP level increased to 1.08% (P < 0.01). For ducks raised at 11 birds/m², dietary TRP supplementation could alleviate stress and improve growth performance, antioxidative activity, and meat quality., (© 2015 Poultry Science Association Inc.)
- Published
- 2015
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7. Effects of L-tryptophan on L-DOPA-induced dyskinesia in the L-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model of Parkinson's disease.
- Author
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Ko WK, Li Q, and Bezard E
- Subjects
- Animals, Antiparkinson Agents therapeutic use, Corpus Striatum metabolism, Dopamine metabolism, Dyskinesia, Drug-Induced etiology, Dyskinesia, Drug-Induced metabolism, Female, Levodopa therapeutic use, Macaca fascicularis, Motor Activity drug effects, Parkinson Disease etiology, Parkinson Disease physiopathology, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Antiparkinson Agents adverse effects, Dyskinesia, Drug-Induced physiopathology, Levodopa adverse effects, Parkinson Disease drug therapy, Tryptophan pharmacology
- Abstract
In animal models of Parkinson's disease (PD), the serotonergic (5-hydroxytryptamine, 5-HT) system is thought to play an important pathophysiological role in the development and expression of l-3,4-dihydroxyphenylalanine (l-3,4-dihydroxyphenylalanine-DOPA)-induced dyskinesia (LID). These abnormal involuntary movements are associated with the unregulated release of dopamine from 5-HT fibres. Thus, modulating the false neurotransmitter release from 5-HT neurons, via attuning the serotonin tone, may be a potential therapeutic strategy in the treatment of LID. In this study, we investigated the effects of the primary precursor of 5-HT, l-tryptophan, on LID in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques. l-tryptophan treatment (0.5-5.0g) dramatically abolished the expression of LID. However, this effect was associated with worsening of the therapeutic effects of L-DOPA. These behavioural data further support the role of the serotonergic system in expression of LID, highlighting the difficult challenge of targeting 5-HT neurons for alleviating dyskinesia and maintaining the therapeutic response of L-DOPA., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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8. ACBP 和5-羟色胺对蜜蜂上颚腺合成 10-羟基-2-癸烯酸的影响.
- Author
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谢子涵, 张晓静, 夏振宇, 李云畅, 郝 悦, and 彭文君
- Subjects
CARNITINE palmitoyltransferase ,UNSATURATED fatty acids ,AMINO acid metabolism ,GENE expression ,HONEYBEES ,TRYPTOPHAN ,ANIMAL feeding - Abstract
Copyright of Chinese Journal of Applied Entomology is the property of Chinese Journal of Applied Entomology, Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2023
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9. Recent Advances in the Hydroxylation of Amino Acids and Its Derivatives.
- Author
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Wang, Bangxu, Xiao, Shujian, Zhao, Xingtao, Zhao, Liming, Zhang, Yin, Cheng, Jie, and Zhang, Jiamin
- Subjects
AMINO acid derivatives ,HYDROXYLATION ,TRYPTOPHAN hydroxylase ,CHEMICAL synthesis ,AMINO acids ,CORYNEBACTERIUM glutamicum ,ASPARTIC acid ,TRYPTOPHAN - Abstract
Hydroxy amino acids (HAAs) are of unique value in the chemical and pharmaceutical industry with antiviral, antifungal, antibacterial, and anticancer properties. At present, the hydroxylated amino acids most studied are tryptophan, lysine, aspartic acid, leucine, proline, etc., and some of their derivatives. The hydroxylation of amino acids is inextricably linked to the catalysis of various biological enzymes, such as tryptophan hydroxylase, L-pipecolic acid trans-4-hydroxylase, lysine hydroxylase, etc. Hydroxylase conspicuously increases the variety of amino acid derivatives. For the manufacture of HAAs, the high regioselectivity biocatalytic synthesis approach is favored over chemical synthesis. Nowadays, the widely used method is to transcribe the hydroxylation pathway of various amino acids, including various catalytic enzymes, into Corynebacterium glutamicum or Escherichia coli for heterologous expression and then produce hydroxyamino acids. In this paper, we systematically reviewed the biosynthetic hydroxylation of aliphatic, heterocyclic, and aromatic amino acids and introduced the basic research and application of HAAs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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10. A comprehensive study on the relieving effect of Lilium brownii on the intestinal flora and metabolic disorder in p-chlorphenylalanine induced insomnia rats.
- Author
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Yanpo Si, Wenjun Wei, Xiaohui Chen, Xiaolong Xie, Tao Guo, Yohei Sasaki, Youbo Zhang, Lili Wang, Fei Zhang, and Shuying Feng
- Subjects
- *
BOTANY , *METABOLIC disorders , *LILIES , *INSOMNIA , *ARACHIDONIC acid , *METALLOTHIONEIN , *INTESTINES , *TRYPTOPHAN - Abstract
Context: The bulb of Lilium brownii F. E. Brown (Liliaceae) (LB) is a common Chinese medicine to relieve insomnia. Objective: To investigate the molecular mechanism of LB relieving insomnia. Materials and methods: Insomnia model was induced by intraperitoneally injection p-chlorophenylalanine (PCPA) in Wistar rats. Rats were divided into three groups: Control, PCPA (400mg/kg, i.p. 2 days), LB (598.64 mg/kg, oral 7 days). The levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE), melatonin (MT), and the expression of GABAA, 5-HT1A and MT receptors, as well as pathological changes in hypothalamus, were evaluated. 16S rDNA sequencing and UPLC-MS/MS were used to reveal the change of the intestinal flora and metabolic profile. Results: The adverse changes in the abundance and diversity of intestinal flora and faecal metabolic phenotype altered by PCPA in rats were reversed after LB treatment, accompanied by the up-regulated levels of 5-HT as 8.14 ng/mL, MT as 16.16 pg/mL, 5-HT1A R and GABAA R, down-regulated level of NE as 0.47 ng/mL, and the improvement of pathological phenomena of cells in the hypothalamus. And the arachidonic acid metabolism and tryptophan metabolism pathway most significantly altered by PCPA were markedly regulated by LB. Besides, it was also found that LB reduced the levels of kynurenic acid related to psychiatric disorders and trimethylamine-N-oxide associated with cardiovascular disease. Conclusion: The mechanism of LB relieving insomnia involves regulating flora and metabolites to resemble the control group. As a medicinal and edible herb, LB could be considered for development as a health-care food to relieve increasing insomniacs in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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11. A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression.
- Author
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Chengguo Ge, Jiusong Yan, Xiaoyu Yuan, and Guangyong Xu
- Subjects
PROSTATE cancer ,TRYPTOPHAN hydroxylase ,CANCER invasiveness ,PROSTATE cancer prognosis ,TRYPTOPHAN ,ZINC-finger proteins ,TRANSCRIPTION factors ,TUMOR growth - Abstract
Alterations in tryptophan (Trp) metabolism facilitate the continuous modulation of tumor progression, including tumor growth, distant metastasis, and chemoresistance development. Although there is a high correlation between Trp metabolism and tumor progression, it is unknown whether and how Trp metabolism affects the development of prostate cancer. In this study, we reported that the overexpression of Trp hydroxylase 1 (TPH1) caused the upregulation of Trp hydroxylation and mediated the production of 5-hydroxytryptamine (5-HT), contributing to tumor growth and poor prognosis in patients with prostate cancer. An increase in 5-HT levels triggered the activation of the Axin 1/b-catenin signaling pathway, thus enhancing cell proliferation and migration. Consequently, β-catenin cooperated with the Krüppel-type zinc finger family transcription factor ZBP-89 to upregulate TPH1 expression, further promoting Trp hydroxylation and forming the TPH1/5-HT/β-catenin/ZBP-89/THP1 positive feedback signaling loop. Interruption of the signaling loop by the THP1 inhibitor 4-chloro-DL-phenylalanine (PCPA) significantly improved anticancer effects and suppressed lung metastasis in prostate cancer-bearing mice. Our findings revealed a mechanism by which TPH1 promotes prostate cancer growth by inducing Trp hydroxylation and identified a novel THP1 target for an innovative prostate cancer therapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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12. Metabolic Changes in Sugarcane Bud Sprouting Stimulated by Microalga Asterarcys quadricellulare.
- Author
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Mógor, Gilda, Mógor, Átila Francisco, Lima, Giuseppina Pace Pereira, de Oliveira, Ricardo Augusto, and Bespalhok Filho, João Carlos
- Abstract
The use of single-bud sugarcane propagules brings a challenge concerning the initial sprouting, as the physiological ages of buds affect their outgrowth. This work is addressed to stimulate the sugarcane buds sprouting in a nature-friendly way using microalgae biomass. A metabolomics approach, connecting physiological and phenotypic changes, was adopted to identify the microalgae effect on sugarcane sprouting. For that, initially the changes in propagules metabolites according to their size and bud position in culm were determined. Then, single-bud propagules from apical, medial and basal segments of culms from cv. RB036152 were immersed in a solution containing microalgae biomass. Budding percentage, sprouts size and changes in sprouts and propagules metabolites—free amino acids; total soluble, reducing and non-reducing sugars; phenolic compounds; polyamines—putrescine, spermine, spermidine; tryptophan, 5-hydroxytryptamine (serotonin) and tryptamine—were determined. Data indicated that bud outgrowth is accompanied by the increase in its amino acids and non-reducing sugars accumulation at the early stages of budding. The propagules immersion in the suspension of green microalgae Asterarcys quadricellulare (CCAP 294/1) biomass improved bud sprouting percentage and promoted remarkable sprouts growth, increasing spermidine and reducing putrescine content in sprouts, thus indicating the polyamines as the key compounds of nitrogen metabolism related to sugarcane sprouting and sprouts growth, a pathway that was triggered by microalgae biomass. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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13. Shen Yuan extract exerts a hypnotic effect via the tryptophan/5-hydroxytryptamine/melatonin pathway in mice.
- Author
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Xia, Tian-Ji, Jin, Su-Wei, Liu, Yong-Guang, Zhang, Shan-Shan, Wang, Zhi, Liu, Xin-Min, Pan, Rui-Le, Jiang, Ning, Liao, Yong-Hong, Yan, Ming-Zhu, and Chang, Qi
- Subjects
- *
CHINESE medicine , *LIQUID chromatography-mass spectrometry , *SLEEP latency , *HERBAL medicine , *ENZYME-linked immunosorbent assay , *POLYMERASE chain reaction , *MELATONIN , *QUANTITATIVE research , *MICE , *SLEEP duration , *ANIMAL experimentation , *PSYCHOLOGICAL stress , *WESTERN immunoblotting , *TRYPTOPHAN , *SEROTONIN , *DEMENTIA , *STROKE , *TUMORS , *DRUGS , *SLEEP disorders , *MENTAL depression , *NEUROTRANSMITTERS - Abstract
Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown. This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms. The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders. The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders. The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1. [Display omitted] • Shen Yuan extract has hypnotic effects in normal mice. • Shen Yuan extract ameliorates sleep disorders in mice caused by restraint stress. • Shen Yuan extract regulates sleep via the tryptophan/5-HT/melatonin pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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14. The Ultimate Ultram Primer III: Tremor-dol Trigger in Serotonin Syndrome : Fatal Forty DDI: tramadol, paroxetine, CYP2D6, serotonin syndrome
- Author
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Hoelzer, Bryan C., Neuman, Stephanie, Marcucci, Catherine, editor, Hutchens, Michael P., editor, Wittwer, Erica D., editor, Weingarten, Toby N., editor, Sprung, Juraj, editor, Nicholson, Wayne T., editor, Lalwani, Kirk, editor, Metro, David G., editor, Dull, Randal O., editor, Swide, Christopher E., editor, Seagull, F. Jacob, editor, Kirsch, Jeffrey R., editor, and Sandson, Neil B., editor
- Published
- 2015
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15. INCREASE IN HEPATIC QUINOLINIC ACID CONCENTRATIONS IN ALCOHOL WITHDRAWN RATS.
- Author
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Bano, Samina, Ara, Iffat, and Naseem, Warda
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ALCOHOLISM ,TRYPTOPHAN ,ALCOHOL withdrawal syndrome ,QUINOLINIC acid ,ETHANOL - Abstract
Background: Behavioral associated disturbance involves excitotoxic quinolinate in alcohol withdrawal syndrome in man due to increase availability of tryptophan. In present study we investigated alcoholism related clinical features in relation to tryptophan and 5-HT levels in rat’s model. Methods: Locally bred male Wistar rats, weighing 200–250 g were housed separately into 6 animals/group with 12 h light: dark cycle at room temp 22±3 °C. They were given diet ad libitum, for three days then alcohol 8% (v/v) was added into the liquid diet. Matched control rats of each group were given maltose-dextrin as a substitute of alcohol. Alcohol withdrawal syndrome was assessed after 7 hours by replacing the alcohol-containing liquid diet with tap water. Results: Alcohol withdrawal group showed significant increase (p<0.001) in holo, apo, and total tryptophan 2, 3 dioxygenase enzyme activities, no significant change in brain tryptophan and 5HIAA however significant decrease (p<0.001) in brain 5HT was observed when compared with chow controls. Both alcohols administered and withdrawal groups showed significant rise in serum corticosterone by p<0.05 and p<0.001 respectively. Liver quinolinic acid concentrations were increased significantly (p<0.01) with robust increase in alcohol withdrawn rats. Conclusion: We conclude that the excitotoxin tryptophan metabolite quinolinic acid of peripheral origin plays significant role in the behavioral manifestation of the alcohol withdrawal syndrome. Tryptophan metabolites should be targeted to develop new strategies in the progress of pharmacological interventions related to alcoholism. [ABSTRACT FROM AUTHOR]
- Published
- 2019
16. Dip2a regulates stress susceptibility in the basolateral amygdala
- Author
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Jing Li, Zixuan He, Weitai Chai, Meng Tian, Huali Yu, Xiaoxiao He, and Xiaojuan Zhu
- Subjects
5-hydroxytryptamine ,acute restraint stress ,basolateral amygdala ,camkii neurons ,dip2a ,metabolomics ,neurotransmitters ,principal component analysis ,stress susceptibility ,tryptophan ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A (Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.
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- 2025
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17. β-Carbolines: Occurrence, Biosynthesis, and Biodegradation
- Author
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Rommelspacher, Hans, Wernicke, Catrin, Lehmann, Jochen, Antkiewicz-Michaluk, Lucyna, editor, and Rommelspacher, Hans, editor
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- 2012
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18. Serotonin regulation in a rat model of exercise-induced chronic fatigue.
- Author
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Liu, Zhandong, Wu, Yanjue, Liu, Tianhui, Li, Ren, and Xie, Minhao
- Subjects
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SEROTONIN , *LABORATORY rats , *HIGH performance liquid chromatography , *HIPPOCAMPUS (Brain) , *MESSENGER RNA , *ANIMAL models in research - Abstract
This study investigated the mechanisms underlying regulation of the serotonin system in the rat brain during exercise-induced chronic fatigue. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed to measure serum tryptophan of the fatigued rat. HPLC was conducted to measure 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex and hippocampus. In addition, 5-HT 1A receptor and 5-HT transporter (5-HTT) mRNA expressions were measured at the same locations using real-time PCR. The results demonstrated a significant reduction in the serum tryptophan level in rats with exercise-induced chronic fatigue. Moreover, increased 5-HT and decreased 5-HIAA levels were detected in the frontal cortex and hippocampus, and these alterations were significant. Further, 5-HTT expression was significantly increased and 5-HT 1A receptor expression was significantly decreased. These results indicate that the 5-HT system plays an important role in the development of exercise-induced chronic fatigue. The 5-HT levels in different parts of the brain increased simultaneously, especially at synapses, and these alterations were associated with changes in 5-HTT and 5-HT 1A mRNA expressions. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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19. Metabolic Changes in Sugarcane Bud Sprouting Stimulated by Microalga Asterarcys quadricellulare
- Author
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Gilda Mógor, Átila Francisco Mógor, Giuseppina Pace Pereira Lima, Ricardo Augusto de Oliveira, João Carlos Bespalhok Filho, Universidade Federal do Paraná (UFPR), and Universidade Estadual Paulista (UNESP)
- Subjects
Polyamines ,Tryptophan ,Amino acids ,5-Hydroxytryptamine ,Sugars ,Tryptamine ,Agronomy and Crop Science - Abstract
Made available in DSpace on 2022-05-01T15:13:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 The use of single-bud sugarcane propagules brings a challenge concerning the initial sprouting, as the physiological ages of buds affect their outgrowth. This work is addressed to stimulate the sugarcane buds sprouting in a nature-friendly way using microalgae biomass. A metabolomics approach, connecting physiological and phenotypic changes, was adopted to identify the microalgae effect on sugarcane sprouting. For that, initially the changes in propagules metabolites according to their size and bud position in culm were determined. Then, single-bud propagules from apical, medial and basal segments of culms from cv. RB036152 were immersed in a solution containing microalgae biomass. Budding percentage, sprouts size and changes in sprouts and propagules metabolites—free amino acids; total soluble, reducing and non-reducing sugars; phenolic compounds; polyamines—putrescine, spermine, spermidine; tryptophan, 5-hydroxytryptamine (serotonin) and tryptamine—were determined. Data indicated that bud outgrowth is accompanied by the increase in its amino acids and non-reducing sugars accumulation at the early stages of budding. The propagules immersion in the suspension of green microalgae Asterarcys quadricellulare (CCAP 294/1) biomass improved bud sprouting percentage and promoted remarkable sprouts growth, increasing spermidine and reducing putrescine content in sprouts, thus indicating the polyamines as the key compounds of nitrogen metabolism related to sugarcane sprouting and sprouts growth, a pathway that was triggered by microalgae biomass. Departamento de Fitotecnia e Fitossanidade Universidade Federal do Paraná, Paraná Departamento de Química Instituto de Biociências Universidade Estadual Paulista Júlio de Mesquita Filho, São Paulo Departamento de Química Instituto de Biociências Universidade Estadual Paulista Júlio de Mesquita Filho, São Paulo
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- 2022
20. The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine
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IMMUNE-RESPONSES ,GUINEA-PIGS ,MOLECULAR-BIOLOGY ,5-hydroxytryptamine ,serotonin ,TRYPTOPHAN ,secretion ,CHAIN FATTY-ACIDS ,MUCOSAL BICARBONATE SECRETION ,ENTEROCHROMAFFIN CELLS ,SEROTONIN TRANSPORTER ,PERIPHERAL SEROTONIN ,metabolism ,BONE-FORMATION - Abstract
Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans.
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- 2021
21. A facile method to anchor reduced graphene oxide polymer nanocomposite on the glassy carbon surface and its application in the voltammetric estimation of tryptophan in presence of 5-hydroxytryptamine.
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Rosy, null, Raj, Mamta, and Goyal, Rajendra N.
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GRAPHENE oxide , *CARBON electrodes , *ELECTROLYTIC reduction , *NANOCOMPOSITE materials , *POLYMERS , *VOLTAMMETRY , *TRYPTOPHAN , *SEROTONIN - Abstract
A 4-amino-3-hydroxy-1-naphthalenesulfonic acid (AHNSA) and reduced graphene oxide (rGO) based polymer nanocomposite (PNC) has been electrodeposited directly on the surface of glassy carbon electrode (GCE) using cyclic voltammertry. The electrochemical reduction of graphene oxide (GO) to rGO and the synthesis of PNC have been inspected using FE-SEM, TEM and Raman spectroscopy. The modified GCE was further used for the voltammetric quantification of Tryptophan (Trp) in the presence and absence of 5-hydroxytryptamine. The PNC modified sensor exhibited improved sensing and electrocatalytic properties in comparison to unmodified GCE, rGO modified GCE and AHNSA modified GCE. The fabricated sensor showed a linear calibration plot in the range of 0.5–200 μM with sensitivity and limit of detection (L.O.D.) of 0.0451 μA μM −1 and 316 nM (n = 3) respectively in comparison to 0.19 μA μM −1 and 2.54 μM (n = 3) respectively for unmodified GCE. The proposed method was also successfully applied for the determination of Trp in commercially available pharmaceutical formulations, human urine and plasma samples. [ABSTRACT FROM AUTHOR]
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- 2016
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22. The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine
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Yanan Sun, Shiqiang Sun, Qingjuan Hu, Pengjie Wang, Xiaoyu Wang, and Ning Liu
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0301 basic medicine ,Serotonin ,QH301-705.5 ,MOLECULAR-BIOLOGY ,Review ,Gut flora ,Catalysis ,5-hydroxytryptamine ,Proinflammatory cytokine ,Inorganic Chemistry ,03 medical and health sciences ,Paracrine signalling ,0302 clinical medicine ,Immune system ,Enterochromaffin Cells ,Humans ,Secretion ,Physical and Theoretical Chemistry ,Biology (General) ,Intestinal Mucosa ,Molecular Biology ,QD1-999 ,Spectroscopy ,biology ,IMMUNE-RESPONSES ,GUINEA-PIGS ,Organic Chemistry ,General Medicine ,biology.organism_classification ,Computer Science Applications ,Cell biology ,TRYPTOPHAN ,Gastrointestinal Microbiome ,secretion ,Intestines ,Chemistry ,030104 developmental biology ,CHAIN FATTY-ACIDS ,MUCOSAL BICARBONATE SECRETION ,SEROTONIN TRANSPORTER ,Enterochromaffin cell ,Enteric nervous system ,PERIPHERAL SEROTONIN ,metabolism ,030217 neurology & neurosurgery ,BONE-FORMATION - Abstract
Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans.
- Published
- 2021
23. Evidence for serotonin function as a neurochemical difference between fear and anxiety disorders in humans?
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Corchs, Felipe, Nutt, David J., Hince, Dana A., Davies, Simon J. C., Bernik, Marcio, and Hood, Sean D.
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ANXIETY disorders treatment , *SEROTONIN uptake inhibitors , *FEAR , *DISEASE remission , *TRYPTOPHAN , *NEUROCHEMISTRY , *TRYPTOPHAN metabolism , *ANXIETY , *SEROTONIN , *ANXIETY disorders - Abstract
The relationships between serotonin and fear and anxiety disorders have been much studied yet many important questions remain, despite selective serotonin reuptake inhibitors having been the primary treatments for these disorders for some time. In order to explore this issue we performed a pooled analysis of six of our studies in remitted patients with a fear/anxiety disorder who were exposed to syndrome-specific aversive stimulation under acute tryptophan depletion. We based our analysis on the hypothesis that the inconsistencies observed in the studies could be predicted by Deakin and Graeff's theory about the dual role of serotonin in responses to threats, whereby serotonin is critical to prevent fear (panic) but not anxiety. In accordance with this view, our results give support to a dissociation of the disorders traditionally grouped under fear and anxiety-related disorders in terms of different roles of serotonin in modulation of responses to aversive stimulation. Implications for future studies and psychiatric nosology are discussed. [ABSTRACT FROM AUTHOR]
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- 2015
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24. Effects of tryptophan supplementation on growth performance, antioxidative activity, and meat quality of ducks under high stocking density.
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Russo, Elisa, Drigo, Michele, Longoni, Corrado, Pezzotti, Raffaele, Fasoli, Paolo, and Recordati, Camilla
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BROILER chickens , *SLAUGHTERING , *BREAST , *MUSCLE anatomy , *POULTRY farming , *ANATOMY - Abstract
High stocking density (STD) could affect duck welfare and production. The objective of our study was to investigate whether dietary tryptophan (TRP) supplementation could alleviate the detrimental effects of high STD on ducks. White Pekin ducks at 4 to 6 wk of age were raised at 11 birds/m² and fed diets containing 0.18, 0.48, 0.78, or 1.08% TRP for 21 d. Growth performance, concentrations of TRP and metabolites in the blood and hypothalamus, antioxidative activities in serum and tissue, meat quality, serum uric acid, and urea nitrogen were measured. Weight gain and feed efficiency were significantly improved by TRP supplementation at =0.48 and =0.78% (P < 0.05 and P < 0.001, respectively). Serum TRP, hypothalamic TRP, 5- hydroxytryptamine (5-HT), 5-hydroxyindoleacitic acid (5-HIAA), and 5-HIAA/5-HT were also increased significantly (P < 0.01). These increases plateaued at 0.48% TRP, and no further improvement was obtained by adding more TRP to the diet. Dietary TRP supplementation significantly increased levels of total antioxidant capacity, glutathione peroxidase (GSH-Px), and catalase (CAT) in serum; GSH-Px in liver; and GSH-Px and CAT in breast muscle (P < 0.05). Malondialdehyde levels in breast muscle decreased (P < 0.001). Drip loss of breast muscle and pH decline at 45 min postmortem were reduced by TRP supplementation (P < 0.01 and P < 0.05, respectively). Meat color was similar among different treatments (P > 0.05). Breast muscle shear force was increased significantly when dietary TRP level increased to 1.08% (P < 0.01). For ducks raised at 11 birds/m2, dietary TRP supplementation could alleviate stress and improve growth performance, antioxidative activity, and meat quality. [ABSTRACT FROM AUTHOR]
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- 2015
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25. The effects of increasing levels of dietary garlic bulb on growth performance, systolic blood pressure, hematology, and ascites syndrome in broiler chickens.
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Liu, Y., Yuan, J. M., Zhang, L. S., Zhang, Y. R., Cai, S. M., Yu, J. H., and Xia, Z. F.
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DUCK food , *ANIMAL welfare , *SEROTONIN , *MEAT quality , *BIRD growth , *DIETARY supplements - Abstract
The effects of dietary garlic bulb were studied separately on hematological parameters, ascites incidence, and growth performance of an ascites susceptible broiler hybrid under both standard temperature conditions (STC) and cold temperature conditions (CTC). A total of 336 one-day-old male broiler chickens were allocated to 4 experimental groups with 4 replicates of 21 birds each under STC. In addition, the same grouping with another 336 birds was used for CTC. Under CTC, the birds were exposed to cold temperatures for induction of ascites. Experimental groups were defined by the inclusion of 0 (control), 5, 10 or 15 g/kg garlic bulbs in the diets under both STC and CTC. Growth performance, systolic blood pressure (as a measure of systemic arterial blood pressure), physiological and biochemical parameters, as well as ascites indices (right ventricle [RV], total ventricle [TV] weights, and RV/TV) were evaluated. Systolic blood pressure was determined using an indirect method with a sphygmomanometer, a pediatric cuff, and a Doppler device. The final body weight decreased quadratically (P = 0.003), with increasing garlic bulb levels in the diets under STC. The feed conversion ratio showed no significant differences among all groups under both STC and CTC. No significant differences were observed in total mortality and ascites-related mortality in all groups under STC, although total mortality (L: P = 0.01; Q: P = 0.001) and ascites-related mortality (L: P = 0.007; Q: P = 0.001) were significantly different among the diets under CTC. Under STC, the systolic blood pressure, packed cell volume, hemoglobin, RV, TV, and RV/TV did not vary significantly among the diets. However, red blood cell count and erythrocyte osmotic fragility decreased linearly (P < 0.005) with increasing garlic bulb levels in the diets under STC. Under CTC, the systolic blood pressure, packed cell volume, red blood cell count, and erythrocyte osmotic fragility decreased (P < 0.05) with increasing garlic levels. It is concluded that the inclusion of 5 g/kg garlic bulb in susceptible broiler chicken diets has a systemic anti-hypertensive effect and could decrease ascites incidence without impairing broiler chicken performance. [ABSTRACT FROM AUTHOR]
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- 2015
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26. Tryptophan and Kynurenic Acid May Produce an Amplified Effect in Central Fatigue Induced by Chronic Sleep Disorder.
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Masatoshi Yamashita and Takanobu Yamamoto
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TRYPTOPHAN , *SEROTONIN , *SLEEP disorders , *SOCIAL interaction , *PHYSICAL fitness , *FATIGUE (Physiology) - Abstract
Tryptophan (TRP) and its neuroactive metabolite, kynurenic acid (KYNA), are thought to play key roles in central fatigue, but the specifics are still unknown. To clarify their roles in the brain, we developed a rat model of central fatigue induced by chronic sleep disorder (CFSD) by disturbing the sleep-wake cycle. Results showed that while 5-hydroxytryptamine (5-HT) concentration did not differ between control and CFSD groups, levels of TRP and KYNA in the CFSD group were about 2 and 5 times higher in the hypothalamus, and 2 and 3.5 times higher in the hippocampus, respectively. Moreover, CFSD-induced fatigue led to abnormal running performance (via treadmill test) and social interaction (via social-interaction test). These results support a TRP-KYNA hypothesis in central fatigue in which increased TRP concentration in the brain and subsequently synthesized KYNA may produce an amplified effect on central fatigue, with enhanced concentrations being a possible mechanism by which social-interaction deficits are generated. [ABSTRACT FROM AUTHOR]
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- 2014
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27. Serum Serotonin Differentiates Between Disease Activity States in Crohn's Patients
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Christopher R. Manzella, Dulari Jayawardena, Wilfredo Pagani, Waddah A. Alrefai, Barbara Jung, Jessica Bauer, Ravinder K. Gill, Ye Li, and Christopher R. Weber
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Adult ,Male ,medicine.medical_specialty ,Serotonin ,Adolescent ,Colon ,medicine.medical_treatment ,Biopsy ,Enzyme-Linked Immunosorbent Assay ,Disease ,Gastroenterology ,Inflammatory bowel disease ,Severity of Illness Index ,5-hydroxytryptamine ,chemistry.chemical_compound ,Young Adult ,Crohn Disease ,Clinical Research ,Ileum ,Internal medicine ,Immunology and Allergy ,Medicine ,Humans ,Intestinal Mucosa ,Ibdjnl/4 ,Serotonin transporter ,Kynurenine ,AcademicSubjects/MED00260 ,Crohn's disease ,biology ,business.industry ,SERT ,serotonin transporter ,Tryptophan ,Middle Aged ,medicine.disease ,Ulcerative colitis ,Pathophysiology ,Cytokine ,C-Reactive Protein ,chemistry ,biology.protein ,Cytokines ,Colitis, Ulcerative ,Female ,business - Abstract
Background Diagnosis and monitoring of inflammatory bowel diseases (IBDs) utilize invasive methods including endoscopy and tissue biopsy, with blood tests being less specific for IBDs. Substantial evidence has implicated involvement of the neurohormone serotonin (5-hydroxytryptamine, 5-HT) in the pathophysiology of IBDs. The current study investigated whether serum 5-HT is elevated in patients with active ulcerative colitis (UC) or Crohn’s disease (CD). Methods Serum samples were obtained from a German cohort of 96 CD and UC patients with active disease, refractory disease, or remission of disease based upon their disease activity index (DAI) and disease history. High pressure liquid chromatography with tandemmass spectrometry was used to measure 5-HT, tryptophan (TRP), and kynurenine (KYN) levels in the serum samples, and Luminex Multiplex ELISA was used to measure cytokine levels. Intestinal mucosal biopsies were obtained from a separate cohort of healthy and CD patients, and the immunoreactivity of the serotonin transporter (SERT) was determined. Results There was no statistically significant difference in TRP or KYN levels between disease categories in either UC or CD. Interestingly, 5-HT levels were significantly elevated in patients with active CD but not active UC when compared with the levels in remission or refractory disease. Serum 5-HT was superior to C-reactive protein and circulating cytokines in differentiating between disease categories in CD. Additionally, SERT immunoreactivity was decreased in the ileum and colon of patients with CD compared to healthy controls. Conclusion We have shown that the serum 5-HT can differentiate between active disease and refractory disease or remission among CD patients, emphasizing the potential suitability of serum 5-HT as an auxiliary measure in diagnosing active CD., Serum serotonin levels discriminate active disease from refractory disease or disease in remission in Crohn’s disease but not in ulcerative colitis. C-reactive protein, tryptophan, kynurenine, and cytokines poorly discriminate between disease states. Serotonin transporter immunofluorescence was decreased in Crohn’s disease.
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- 2020
28. Lactobacillus johnsonii inhibits indoleamine 2,3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats.
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Valladares, Ricard, Bojilova, Lora, Potts, Anastasia H., Cameron, Evan, Gardner, Christopher, Lorca, Graciela, and Gonzalez, Claudio F.
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LACTOBACILLUS , *INDOLEAMINE 2,3-dioxygenase , *TRYPTOPHAN , *METABOLITES , *LABORATORY rats - Abstract
In our previous work, we found that feeding Lactobacillus johnsonii to BioBreeding diabetes-prone (BBDP) rats decreased the incidence of diabetes development. The aim of this study was to investigate host pathways affected by L. johnsonii, with specific focus on the rate-limiting enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO). Suspensions of L. johnsonii or an equal volume of vehicle were orally administered to BBDP rats. Tissue IDO was investigated using quantitative RT-PCR and Western blot, whereas tryptophan, kynurenine, and 5-hydroxytryptamine (5-HT) concentrations were quantified by HPLC and ELISA. IDO activity was also investigated using L. johnsonii culture cell-free supernatant (CFS) with affinity-purified IDO and HT-29 intestinal epithelial cells. L. johnsonii feeding resulted in a 17% reduction in serum kynurenine compared with that in vehicle-fed controls, correlating with a 1.4-fold elevation in 5-HT levels. H2O2 produced by L. johnsonii abolished IDO activity in vitro, and L. johnsonii feeding resulted in a 3.9-fold increase in ileum lumen H2O2. L. johnsonii CFS significantly reduced IDO activity in HT-29 intestinal epithelial cells (47% reduction) compared with that in vehicle-treated controls, an effect abolished by catalase treatment. These data support the role of H2O2 in commensal bacteria-host interactions and highlight the influence of commensal bacteria-derived H2O2 on host physiology. [ABSTRACT FROM AUTHOR]
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- 2013
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29. Supplemental dietary tryptophan modifies behavior, concentrations of salivary cortisol, plasma epinephrine, norepinephrine and hypothalamic 5-hydroxytryptamine in weaning piglets
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Liu, Hua-Wei, Shi, Bao-Ming, Liu, Da-Sen, and Shan, An-Shan
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ENZYME-linked immunosorbent assay , *DIETARY supplements , *TRYPTOPHAN , *ADRENALINE , *ANIMAL behavior , *ANIMAL weaning , *PIGLETS - Abstract
Abstract: Stress behaviors often result when piglets are abruptly weaned and mixed. Surplus dietary tryptophan (Trp) may reduce stress. In this study, three levels of dietary Trp were used, representing the standard requirement for growth (control), supplemental dietary Trp (1g/kg and 2g/kg of feed). Piglets were fed the diets for 28d, during which observations were divided into three phases: prophase (4–6d), metaphase (15–17d), anaphase (26–28d). Daily behavioral observations were made 14:00–16:00 during each phase afternoon. Saliva was collected from multiple pigs in each pen from 16:00 to 17:00, and body weight of each piglet was individually recorded at d 1 and 28. Aggressive behaviors of piglets were recorded for 8h immediately after remixing, and saliva per pen was collected from 16:00 to 17:00. Subsequently, 2 pigs per pen were sampled for blood via the jugular vein and subsequently killed to obtain hypothalamus. Salivary cortisol, plasma norepinephrine and epinephrine, hypothalamic 5-hydroxytryptamine concentrations were measured using enzyme linked immunosorbent assay (ELISA) kit. High-Trp diet significantly raised hypothalamic 5-hydroxytryptamine concentration (P<0.05), and diminished salivary cortisol, plasma norepinephrine and epinephrine concentrations (P<0.05). High-Trp dietary treatment induced more lying and less standing compared with control (P<0.05) during daily behavioral observations of metaphase and anaphase. After remixing, relative to pigs fed the basal diet, pigs fed the Trp supplemented diets engaged in fewer fights and spent time fighting (P<0.05). There were no differences between dietary treatments for growth performance (ADG, ADFI, F/C) of piglets (P>0.05). Consequently, excessively supplemental Trp may modify the behavior reactivity of piglets during weaning and mixing, increase hypothalamic 5-hydroxytryptamine concentration and diminish salivary cortisol, plasma norepinephrine and epinephrine concentrations. [Copyright &y& Elsevier]
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- 2013
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30. Simultaneous determination of tyrosine, tryptophan and 5-hydroxytryptamine in serum of MDD patients by high performance liquid chromatography with fluorescence detection
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Sa, Mu, Ying, Li, Tang, Ai-Guo, Xiao, Le-Dong, and Ren, Ya-Ping
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TYROSINE , *TRYPTOPHAN , *SEROTONIN , *HIGH performance liquid chromatography , *MENTAL illness treatment , *SERUM - Abstract
Abstract: Background: Tyrosine (Tyr), Tryptophan (Trp) and 5-hydroxytryptamine (5-HT) are important amino acids in vivo and have been hypothesized to be involved in many mental disorders. We developed a rapid and sensitive HPLC method for simultaneous measurement of serum Tyr, Trp and 5-HT and explored the clinical significances of Tyr, Trp and 5-HT and the 5-HT/Trp ratio for patients with major depressive disorder (MDD) disease. Methods: Serum samples were deproteinized by 5% perchloric acid and separated on an Atlantis C18 column (4.6×150mm, 5μm) with the mobile phase consisting of 0.1mol/l KH2PO4 and methanol (85:15, V/V).The eluates were monitored by the fluorescence detection with programmed wavelength. Results: Analysis was achieved in <12.0min. The limits of quantification were 0.014, 0.005, and 0.024μmol/l for Tyr, Trp and 5-HT, respectively. Reproducibility and recovery were satisfactory. Tyr, Trp and 5-HT and the 5-HT/Trp ratio were significantly decreased in patients with MDD. Conclusions: In diseases, like MDD, Tyr, Trp and 5-HT play an important role. This method can potentially be applied as prognostic or diagnostic tool or even to follow the evolution of the illness or of the treatment. [Copyright &y& Elsevier]
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- 2012
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31. The effects of the perinatal treatment with 5-hydroxytryptophan or tranylcypromine on the peripheral and central serotonin homeostasis in adult rats
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Hranilovic, Dubravka, Blazevic, Sofia, Ivica, Nedjeljka, Cicin-Sain, Lipa, and Oreskovic, Darko
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HYDROXYTRYPTOPHAN , *SEROTONIN , *HOMEOSTASIS , *LABORATORY rats , *AUTISM , *TRYPTOPHAN , *MONOAMINE oxidase , *MESENCEPHALON - Abstract
Abstract: Serotonin (5HT) is a biologically active amine present in mammals in the brain and the peripheral tissues. Autism is a neurodevelopmental disorder in which 5HT homeostasis is disturbed both centrally and peripherally, but the relationship between the 5HT disturbances in the two compartments is not understood. In an attempt to explore the relationship between the disturbed peripheral 5HT homeostasis and central 5HT functioning, we exposed the developing rat brain to increased 5HT concentrations, by treatment of rats with subcutaneous injections of the immediate 5HT precursor 5-hydroxy-l-tryptophan (5HTP, 25mg/kg), or the non-selective MAO inhibitor tranylcypromine (TCP, 2mg/kg), during the period of the most intensive development of 5HT neurons – from gestational day 13 to post-natal day 21. The effects of the mentioned treatments on peripheral and central 5HT levels were then studied in adult rats. Platelet and plasma 5HT concentrations (measured by ELISA), as well as cortical and midbrain 5HT, tryptophan and 5-hydroxyindoleacetic acid levels (measured by HPLC) were determined in twelve 5HTP treated and eight TCP treated rats, and compared with the values measured in 10 control, saline treated rats. Treatment with 5HTP significantly raised peripheral but not central 5HT concentrations. At adult age, peripheral 5HT homeostasis was re-established, while modest decrease in 5HT concentration was observed in frontal cortex, presumably due to hyperserotonemia-induced loss of 5HT terminals during brain development. Treatment with TCP induced significant 5HT elevations in both compartments. At adult age, permanent changes in 5HT homeostasis were observed, both peripherally (as hyperserotonemia) and centrally (as altered 5HT metabolism with decreased 5HT concentrations). Further studies are planned in order to explore the nature of the different disturbances of 5HT homeostasis induced by the two compounds, and their results are expected to shed some light on the role of hyperserotonemia in autism. [Copyright &y& Elsevier]
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- 2011
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32. Beneficial estrogen-like effects of ginsenoside Rb1, an active component of Panax ginseng, on neural 5-HT disposition and behavioral tasks in ovariectomized mice
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Hao, Kun, Gong, Ping, Sun, Shi-Qing, Hao, Hai-Ping, Wang, Guang-Ji, Dai, Yue, Liang, Yan, Xie, Lin, and Li, Fei-Yan
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ESTROGEN receptors , *GINSENG , *LABORATORY mice , *SEROTONIN , *BRAIN , *CENTRAL nervous system diseases , *MENOPAUSE , *TRYPTOPHAN - Abstract
Abstract: Decreased 5-hydroxytryptamine (5-HT) concentration in the brain has been linked to central nervous system dysfunctions, especially in menopausal women. Ginsenoside Rb1, a potential phytoestrogen, has been shown to improve central nervous system dysfunctions, comparable to the estrogen treatment. To investigate the estrogen-like effects of ginsenoside Rb1 on neural 5-HT disposition and behavioral tasks, we quantified the concentrations of 5-HT and other related endogenous substances in the frontal cortex and striatum of ovariectomized mice. The activities of tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AAAD) and monoamine oxidase (MAO) were also measured to evaluate the synthesis and metabolism of neural 5-HT. Our work shows that both ginsenoside Rb1 and estradiol increased the neural 5-HT concentration. Ginsenoside Rb1 and estradiol administration resulted in elevated TPH and depressed MAO activities, indicating that modulating the synthesis and metabolism of neural 5-HT successfully elevated 5-HT concentration. Ginsenoside Rb1 and estradiol also improved object recognition and decreased immobility time in the forced swimming test. However, a pretreatment with clomiphene (an estrogen receptor antagonist) blocked the beneficial effects of ginsenoside Rb1 and estradiol, suggesting that the estrogen-like effects of ginsenoside Rb1 were estrogen receptor-dependent. [Copyright &y& Elsevier]
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- 2011
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33. Simultaneous determination of tryptophan, kynurenine and 5-hydroxytryptamine by HPLC: Application in uremic patients undergoing hemodialysis
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Zhen, Qianna, Xu, Biao, Ma, Li, Tian, Gang, Tang, Xiufang, and Ding, Min
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TRYPTOPHAN , *KYNURENINE , *SEROTONIN , *HIGH performance liquid chromatography , *UREMIA , *HEMODIALYSIS , *PATIENTS - Abstract
Abstract: Objectives: To develop a reliable HPLC method for the simultaneous determination of plasma tryptophan, kynurenine and 5-hydroxytryptamine to analyze tryptophan metabolism. Design and methods: Separation was carried out on a C8 column with the mobile phase composed of acetate buffer (pH 4.5) and acetonitrile using theophylline as internal standard. The eluates were monitored by ultraviolet detection with programmed wavelength. Results: Analysis was achieved in less than 8.0min. The limits of quantification were 3.97μmol/L, 4.36nmol/L and 0.421μmol/L for tryptophan, 5-hydroxytryptamine and kynurenine, respectively. Reproducibility and recovery were satisfactory. Twenty healthy adults and 20 uremic patients undergoing hemodialysis were analyzed using the present method. Tryptophan metabolism was found to be disturbed in uremic patients and was improved obviously after hemodialysis. Conclusions: The developed HPLC method is simple, reliable and suitable for monitoring tryptophan metabolism in uremic patients undergoing hemodialysis. [Copyright &y& Elsevier]
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- 2011
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34. Distribution of tryptophan hydroxylase-immunoreactive neurons in the brainstem and diencephalon of the pigeon (Columba livia)
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Meneghelli, Cristiane, Rocha, Nelisa Helena, Mengatto, Vanessa, Hoeller, Alexandre Ademar, Santos, Tiago Souza, Lino-de-Oliveira, Cilene, and Marino-Neto, José
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NEURAL physiology , *TRYPTOPHAN , *BRAIN stem , *DIENCEPHALON , *ROCK pigeon , *IMMUNOHISTOCHEMISTRY , *CHROMOGENIC compounds , *ENZYMES - Abstract
Abstract: The distribution of tryptophan hydroxylase (TPH)-containing perikarya and processes in the brainstem and diencephalon of the pigeon (Columba livia) were investigated using single-labeling chromogenic and double-labeling fluorescence immunohistochemical methods for TPH and 5-HT. TPH-immunoreactive (TPH-ir) perikarya were seen extending from the caudal medulla to mid-hypothalamic levels, located in brainstem regions previously described as containing 5-HT-ir somata. Brainstem TPH-ir cell clusters (the midline raphe, and the dorsolateral and ventrolateral serotonergic cell groups) and the circumventricular cerebrospinal fluid-contacting neurons in the taenia choroidea (in the caudal brainstem), recessus infundibuli and paraventricular organ (in the hypothalamus) were shown to co-express 5-HT immunoreactivity. However, heavily labeled TPH-ir cell clusters were observed in the nucleus premamillaris (PMM), in the stratum cellulare internum (SCI), in the nucleus paraventricularis magnocellularis (PVN) and in the medial border of the nucleus dorsomedialis anterior thalami (DMA). Double-labeling experiments indicated that none of these medial hypothalamic TPH-ir cells were immunoreactive to 5-HT. These cells correspond to dopamine- and melatonin-containing neurons previously found in the avian hypothalamus, and appear to be comparable to the mammalian TPH-ir hypothalamic A11–A13 catecholaminergic somata, suggesting that they may be a conserved attribute in the amniote medial hypothalamus. [Copyright &y& Elsevier]
- Published
- 2009
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35. Serotonin and Sensitivity to Trauma-Related Exposure in Selective Serotonin Reuptake Inhibitors-Recovered Posttraumatic Stress Disorder
- Author
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Corchs, Felipe, Nutt, David J., Hood, Sean, and Bernik, Marcio
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SEROTONIN uptake inhibitors , *ANXIETY sensitivity , *TREATMENT of post-traumatic stress disorder , *TRAUMATISM , *TRYPTOPHAN , *ANXIETY disorders , *BLOOD pressure - Abstract
Background: Selective serotonin reuptake inhibitors (SSRIs) are first-line treatments for posttraumatic stress disorder (PTSD). Serotonergic (5HT) attenuation of stress sensitivity is postulated from SSRIs'' effects in other anxiety disorders, and we studied this in PTSD. Methods: Ten patients with PTSD fully recovered on SSRIs (Clinical Global Impression Scale—I 1 and 2) were enrolled in the study. Patients were tested on two occasions 1 week apart; in each session, they received a drink containing large neutral amino acids (LNAAs) either with (sham tryptophan depletion [STD], control) or without (acute tryptophan depletion [ATD]) tryptophan. At 5.5 hours after the drink, subjects were exposed to a trauma-related exposure challenge. Self-reports of PTSD (visual analogue scales [VAS] and the Davidson Trauma Scale [DTS]), anxiety (Spielberger State Inventory [STAI] Form Y-1), and mood (Profile of Mood States [POMS]) were obtained. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure were also measured. Results: The trauma-related exposure challenge induced anxiety on both days, with more marked responses on the ATD day according to VAS, DTS, POMS, and DBP (p < .05). A trend of significance (.1 > p > .05) was observed for STAI Form Y-1, HR, and SBP. Conclusions: These data demonstrate that ATD accentuates responses to trauma-related stimuli in SSRI-recovered PTSD. They also suggest that SSRI-induced increases in serotonin function restrain PTSD symptoms, especially under provocation, supporting a role for serotonin in mediating stress resilience. [Copyright &y& Elsevier]
- Published
- 2009
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- View/download PDF
36. The existence of a local 5-hydroxytryptaminergic system in peripheral arteries.
- Author
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Ni, W., Geddes, T. J., Priestley, J. R. C., Szasz, T., Kuhn, D. M., and Watts, S. W.
- Subjects
- *
SEROTONIN , *VASCULAR smooth muscle , *TRYPTOPHAN , *MONOAMINE oxidase , *ARTERIES , *VASOCONSTRICTORS , *RNA metabolism , *ANIMAL experimentation , *GENE expression , *IMMUNOHISTOCHEMISTRY , *MEMBRANE proteins , *MESENTERIC artery , *MOLECULAR structure , *MUSCLE contraction , *OXIDOREDUCTASES , *RATS , *RESEARCH funding , *TIME , *WESTERN immunoblotting , *THORACIC aorta - Abstract
Background and purpose:5-HT is a vasoconstrictor exhibiting enhanced effects in systemic arteries from subjects with cardiovascular disease. The effect of endogenous 5-HT on arteries is controversial, because the concentration of free circulating 5-HT is low and a 5-hydroxytryptaminergic system has not been identified in peripheral arteries. We hypothesized that a local 5-hydroxytryptaminergic system (including 5-HT synthesis, metabolism, uptake and release) with physiological function exists in peripheral arteries.Experimental approach:The presence of key components of a 5-hydroxytryptaminergic system in rat aorta and superior mesenteric artery was examined using western blot analyses, immunohistochemistry and immunocytochemistry. The function of the rate-limiting enzyme in 5-HT biosynthesis, tryptophan hydroxylase (TPH), and 5-HT transporter was tested by measuring enzyme activity and 5-HT uptake, respectively. Isometric contraction of arterial strips was used to demonstrate the function of released endogenous 5-HT in arterial tissues.Key results:mRNA for TPH-1 was present in arteries, with low levels of TPH protein and TPH activity. Expression and function of MAO A (5-HT metabolizing enzyme) was supported by immunohistochemistry, western analyses and the elevation of concentrations of 5-hydroxyindoleacetic acid (5-HT metabolite) after exposure to exogenous 5-HT. The 5-HT transporter was localized to the plasma membrane of freshly isolated aortic smooth muscle cells. Peripheral arteries actively took up 5-HT in a time-dependent and 5-HT transporter-dependent manner. The 5-HT transporter substrate, (+)-fenfluramine, released endogenous 5-HT from peripheral arteries, which potentiated noradrenaline-induced arterial contraction.Conclusions and implications:This study revealed the existence of a local 5-hydroxytryptaminergic system in peripheral arteries.British Journal of Pharmacology (2008) 154, 663–674; doi:10.1038/bjp.2008.111; published online 14 April 2008 [ABSTRACT FROM AUTHOR]
- Published
- 2008
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37. Low tryptophan diet increases stress-sensitivity, but does not affect habituation in rats
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Tanke, Marit A.C., Alserda, Edwin, Doornbos, Bennard, van der Most, Peter J., Goeman, Kitty, Postema, Folkert, and Korf, Jakob
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- *
AMINO acids , *SEROTONIN , *NEUROTRANSMITTERS , *AFFECTIVE disorders - Abstract
Abstract: Cerebral dysfunction of 5-HT (serotonin) has been associated with stress response and with affective disorders. Stress alone is insufficient to induce depression, since only a minor proportion of subjects that have experienced stressful life events develop depressive episodes. We investigated whether long-term brain 5-HT depletion induced in rats by a diet with low content of its precursor tryptophan affects stress-responsiveness in rats. Stress-sensitivity was measured through various physiological parameters and by measuring the rats’ response to acoustic stimuli. One group of rats was subjected to daily acoustic stimulus sessions for 5 days. Other groups received both immobilization stress and acoustic stimulus sessions daily for either 9 days (chronic experiment) or 1 day (acute experiment). A low tryptophan diet led to decreases in plasma tryptophan levels, low ratio of tryptophan/large neutral amino acid, whole blood 5-HT, and neuronal 5-HT content in the Dorsal and Median Raphe Nuclei, as well as altered c-fos expression in the brain. Without concomitant immobilization, the diet alone did not affect reactivity and habituation to acoustic stimuli, although plasma corticosterone levels, but not the adrenal weights, were increased on day 5. Low tryptophan and chronic immobilization stress together with the acoustic testing procedure increased adrenal weight, plasma corticosterone levels and reactivity to the acoustic stimuli, but not the rate of habituation to acoustic stimuli. These results show that cerebral dysfunction of serotonin achieved through a low tryptophan diet, increases the sensitivity of rats to external and stressful stimuli, but does not impair the capacity to adapt to these stimuli. Accordingly, brain-serotonin modulates reactivity to stress, but not stress coping. [Copyright &y& Elsevier]
- Published
- 2008
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38. Influence of Rapid Tryptophan Depletion on Laboratory-Provoked Aggression in Children with ADHD.
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Stadler, C., Zepf, F.D., Demisch, L., Schmitt, M., Landgraf, M., and Poustka, F.
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- *
TRYPTOPHAN , *SEROTONIN , *AGGRESSION (Psychology) in children , *RISK factors of attention-deficit hyperactivity disorder , *COMORBIDITY , *THERAPEUTICS - Abstract
Background: The present study investigated the effects of rapid tryptophan depletion (RTD), and the ensuing reduction of central nervous system levels of serotonin (5-HT), upon reactive aggression in patients with attention deficit/hyperactivity disorder (ADHD). Furthermore, it was asked whether the relation between 5-HT function and behavioural aggression in patients is influenced by their age, the intensity of their attention problems or their comorbid symptoms. Methods: The study employed a double-blind, within-subject crossover design. On day 1, 22 male adolescent patients with ADHD were subjected to RTD and the subsequent reduction of central 5-HT levels. On day 2, they received a tryptophan-balanced amino acid mixture (BAL), which acted as a placebo. On both days, 4.5 h after the intake of the RTD/BAL amino acids, reactive aggressive behaviour was provoked using a competitive reaction time game, which consisted of both high and low provocation conditions. Results: The number of aggressive responses was significantly higher after low provocation during acute tryptophan depletion, in comparison to the placebo. Furthermore, this study provides evidence that neither age nor the intensity of attention symptoms in ADHD patients had an impact on the relation between 5-HT and reactive aggression. Conclusion: This study indicates that in children with ADHD, there is an inverse relationship between 5-HT and aggression. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2007
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39. A role for branched-chain amino acids in reducing central fatigue.
- Author
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Blomstrand, Eva
- Subjects
- *
BRANCHED chain amino acids , *FATIGUE (Physiology) , *EXERCISE , *SEROTONIN , *MENTAL fatigue , *BLOOD-brain barrier , *LEUCINE , *VALINE , *TRYPTOPHAN , *FATIGUE prevention , *AMMONIA , *BRAIN , *CELL receptors , *THERAPEUTICS ,BRAIN metabolism - Abstract
Several factors have been identified to cause peripheral fatigue during exercise, whereas the mechanisms behind central fatigue are less well known. Changes in the brain 5-hydroxytryptamine (5-HT) level is one factor that has been suggested to cause fatigue. The rate-limiting step in the synthesis of 5-HT is the transport of tryptophan across the blood-brain barrier. This transport is influenced by the fraction of tryptophan available for transport into the brain and the concentration of the other large neutral amino acids, including the BCAAs (leucine, isoleucine, and valine), which are transported via the same carrier system. Studies in human subjects have shown that the plasma ratio of free tryptophan (unbound to albumin)/BCAAs increases and that tryptophan is taken up by the brain during endurance exercise, suggesting that this may increase the synthesis of 5-HT in the brain. Ingestion of BCAAs increases their concentration in plasma. This may reduce the uptake of tryptophan by the brain and also 5-HT synthesis and thereby delay fatigue. Accordingly, when BCAAs were supplied to human subjects during a standardized cycle ergometer exercise their ratings of perceived exertion and mental fatigue were reduced, and, during a competitive 30-km cross-country race, their performance on different cognitive tests was improved after the race. In some situations the intake of BCAAs also improves physical performance. The results also suggest that ingestion of carbohydrates during exercise delays a possible effect of BCAAs on fatigue since the brain's uptake of tryptophan is reduced. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
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40. Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder
- Author
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Argyropoulos, Spilios V., Hood, Sean D., Adrover, Mariona, Bell, Caroline J., Rich, Ann S., Nash, Jon R., Rich, Neil C., Witchel, Harry J., and Nutt, David J.
- Subjects
- *
TRYPTOPHAN , *ANXIETY , *MENTAL illness treatment , *AMINO acids , *SEROTONIN uptake inhibitors - Abstract
Tryptophan depletion studies have suggested that central serotonin (5-hydroxytryptamine, 5-HT) function mediates the therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) in depression and panic disorder. The present study tested the hypothesis that temporary reduction in central 5-HT transmission, through acute tryptophan depletion, could reverse the therapeutic effect of the SSRIs in social anxiety disorder (SAD) patients.Fourteen patients with SAD who showed sustained clinical improvement with SSRI treatment underwent tryptophan depletion in a double-blind, placebo-controlled, crossover design, over 2 days 1 week apart. At the peak time of depletion, the participants also underwent three behavioral challenges: autobiographical script, verbal task, and neutral script. Psychological outcome was assessed with the Spielberger State Anxiety Inventory (STAI) Form Y-1 and visual analog scales (VAS) measuring anxiety, depression, and somatic symptoms.Anxiety was significantly increased on the depletion day compared with the control day, both on the STAI Form Y-1 and composite VAS score. Furthermore, there was a significant depletion × time interaction, explained mainly by the anxiogenic effect of the autobiographical script. In contrast, the verbal and the neutral tasks failed to differentiate between depletion and placebo.Tryptophan depletion induced significant increase of anxiety in treated SAD patients, which was more prominent during the recital of an autobiographical script. This finding supports the notion that SSRIs improve social anxiety by increasing 5-HT availability. The autobiographical script seems to be a more robust challenge test for SAD than the stressful verbal task. [Copyright &y& Elsevier]
- Published
- 2004
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41. Aroclor 1254 inhibits tryptophan hydroxylase activity in rat brain.
- Author
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Khan, Izhar A. and Thomas, Peter
- Subjects
- *
POLYCHLORINATED biphenyls , *TRYPTOPHAN , *SEROTONIN , *NEUROTOXICOLOGY , *MOLECULAR toxicology , *TOXICOLOGY - Abstract
Previous studies have shown that oral exposure of rats to polychlorinated biphenyls (PCBs) results in reduced 5-hydroxytryptamine (5-HT) concentrations in certain brain regions. In the present study, we investigated whether the PCB mixture Aroclor 1254 (0.33 mg/g body weight as a single oral dose) can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT synthesis, and reduce 5-HT concentrations in selected brain areas. In two separate experiments, Aroclor 1254 exposure consistently reduced TPH activity in the brainstem (7.2 and 8.7%), frontal cortex (17.4 and 14.8%), and hypothalamus (10.7 and 9.4%) without altering the rats’ food intake or growth. Moreover, Aroclor 1254 accumulation in the frontal cortex demonstrated a negative correlation with TPH activity (correlation coefficient -0.82). In addition, 5-HT concentrations decreased in the brainstem and frontal cortex after Aroclor 1254 exposure by 9.1 and 19.7%, respectively. These results suggest that the Aroclor 1254-induced decreases in 5-HT concentrations in certain areas of the rat brain are due to inhibition of TPH activity, similar to our recent observations in Atlantic croaker, and that TPH is one of the targets of PCB neurotoxicity in both fish and mammals. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
42. Acute Antidepressant-Like and Antianxiety-Like Effects of Tryptophan in Mice.
- Author
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Wong, P. T. -H. and Ong, Y. P.
- Subjects
- *
TRYPTOPHAN , *MELATONIN , *ANTIDEPRESSANTS , *SEDATIVES , *TRANQUILIZING drugs , *LABORATORY mice , *THERAPEUTICS - Abstract
The antidepressant-like, antianxiety-like and sedative effects of tryptophan (TRP), in the absence and presence of p-chlorophenylalanine (p-CPA), and melatonin were studied in mice using the forced-swimming test, open-field test and activity cage, respectively. Single-dose TRP caused an antidepressant-like effect dose dependently up to 125 mg/kg. No significant effect was observed, however, when the TRP dose was increased to 250 mg/kg, i.e. a reversal of effect occurred at high dose. With p-CPA pretreatment, the effects observed at 125 and 250 mg/kg TRP were similar to those obtained at 50 and 125 mg/kg without p-CPA pretreatment, respectively. Melatonin also caused an antidepressant-like effect in a similar manner, but appeared to be less potent than TRP. These results strongly indicate that the antidepressant-like effect of TRP was due to its conversion to 5-hydroxytryptamine (5-HT). An antianxiety-like effect was observed for TRP only at 250 mg/kg dose together with p-CPA pretreatment, while no sedative effect was observed at all. In contrast, melatonin did not produce any antianxiety-like effect, but produced sedation at 200 mg/kg dose. It may be concluded that the antianxiety-like effect of TRP is unrelated to 5-HT and melatonin formation, but associated with TRP itself or, perhaps, with other anxiolytic metabolites.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
43. CRISPR/Cas9-mediated tryptophan hydroxylase 1 knockout decreases calcium transportation in goat mammary epithelial cells.
- Author
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Zhang, Zhifei, Tian, Huibin, Chen, Xiaoying, Zhao, Haiying, Du, Wei, Gao, Huijie, Luo, Jun, and Zheng, Huiling
- Subjects
- *
TRYPTOPHAN hydroxylase , *TRYPTOPHAN , *PARATHYROID hormone-related protein , *EPITHELIAL cells , *CRISPRS , *CALCIUM , *CALCIUM metabolism - Abstract
• CRISPR/Cas9 technology was used to knock out tryptophan hydroxylase 1 in goat mammary epithelial cell. • The TPH1 knockout GMEC heterozygous clone with no off-target effects was obtained. • Knockout of TPH1 gene in GMEC revealed the role of serotonin on calcium homeostasis. Calcium is one of the major mineral nutrients in goat milk. Tryptophan hydroxylase 1 (TPH1) is a rate-limiting enzyme catalyzing hydroxylation of l -tryptophan into 5-hydroxytryptamine (5-HT, serotonin) essential for maintaining calcium homeostasis. In this study, the TPH1 knockout goat mammary epithelial cells(GMEC) heterozygous clone with no off-target effects were obtained after transfection of the Cas9/sgRNA expression vector firstly. Then the content of 5-HT, intracellular calcium level, and abundance of essential genes related to calcium transportation was evaluated and compared in wild-type GMEC, TPH1 knockout GMEC, to explore the impact of TPH1 on calcium transportation, respectively. Wild-type GMEC and TPH1 knockout GMEC were further treated with exogenous 5-HTP to confirm the role of TPH1 in regulating calcium homeostasis in GMEC. The 5-HT synthesis and intracellular calcium level decreased in TPH1 gene knockout GMEC. The mRNA abundance of secretory-pathway Ca2+-ATPase1 (SPCA1) and plasma membrane Ca2+-ATPase1 (PMCA1) were up-regulated while the mRNA abundance of secretory-pathway Ca2+-ATPase2 (SPCA2) was down-regulated in TPH1 knockout GMEC. Up-regulation of the parathyroid hormone-related peptide (PTHrP), a key regulator of mammary calcium metabolism, induced by 5-HTP were blocked by TPH1 gene knockout. Results suggested that TPH1 knockout decreased calcium transportation via PTHrP and calcium transportation-related factors in GMEC. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
44. Differential Distribution of Serotonin and Tryptophan Hydroxylase in the Human Gastrointestinal Tract.
- Author
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Meyer, Thomas and Brinck, Ulrich
- Subjects
- *
TRYPTOPHAN , *SEROTONIN , *BIOSYNTHESIS , *INTESTINES , *IMMUNOHISTOCHEMISTRY - Abstract
The distribution of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin, was investigated immunohistochemically in various organs of the gastrointestinal tract and compared with that of neuroendocrine markers. While immunoreactivity for serotonin and chromogranin A was restricted to enterochromaffin cells, positive staining for tryptophan hydroxylase was detected in normal enterocytes lining the epithelium of the small intestine. Tryptophan hydroxylase was localized in the supranuclear cytoplasm of absorptive cells, and was absent from the terminal web. The enterocytes of the exfoliation zone at the tips of the villi demonstrated a strong immunoreactivity similar to those at the slope of the villi. Mucus-containing Goblet cells, Paneth cells and stromal cells of the lamina propria remained unlabelled. The duodenal glands of Brunner revealed only sporadically a weak immunostaining for tryptophan hydroxylase. The monooxygenase was also detected in numerous secretory tubules of the pyloric mucosa, where the proportion of positive cells decreased progressively from the crypts towards the upper parts of the gastric glands. No significant immunoreactivity was demonstrated in colon, adrenal cortex, liver, pancreas, and mesenteric lymph nodes. The demonstration of tryptophan hydroxylase in normal enterocytes suggested that epithelial cells of the small intestine are able to synthesize 5-hydroxytryptophan. [ABSTRACT FROM AUTHOR]
- Published
- 1999
- Full Text
- View/download PDF
45. Elevation and Reduction of Plasma Tryptophan and Their Effects on Aggression and Perceptual Sensitivity in Normal Males.
- Author
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Smith, Scott E., Pihl, Robert O., Young, Simon N., and Ervin, Frank R.
- Subjects
- *
MALES , *AGGRESSION (Psychology) , *BRAIN , *AMINO acids , *TRYPTOPHAN , *MIXTURES - Abstract
Data from experimental animals suggest that 5-hydroxytryptainine (5HT) may have an inhibitory effect on aggression, while clinical studies have found a correlation between pathological aggression and low brain 5HT. To investigate this relationship further we used amino acid mixtures designed to raise or tower the levels of the 5HT precursor, tryptophan. Normal male subjects were given tryptophan-depleted, balanced, or tryptophan-supplemented amino add mixtures and tested for aggression 5 hours later. The balanced amino acid mixture served as a control for the tryptophan depletion and supplementation. Testing for aggression was done using the Buss paradigm in which subjects deliver electric shocks to a (nonexistent) partner in response to stimulus tones. Duration and intensity of shock delivered were the measure of aggression, while responsivity to the stimulus tones was the measure of perceptual sensitivity. Neither tryptophan supplementation nor tryptophan depletion had any effect on these measures of aggression or perceptual sensitivity. We conclude that raising or lowering the synthesis of brain 5HT through alterations in tryptophan availability does not influence aggression in normal males as measured by the Russ task. [ABSTRACT FROM AUTHOR]
- Published
- 1986
- Full Text
- View/download PDF
46. Biochemical aspects of tryptophan depletion in primates.
- Author
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Young, Simon, Ervin, Frank, Pihl, Robert, and Finn, Peter
- Abstract
We studied the degree of plasma tryptophan depletion produced by giving normal human males different amounts of a tryptophan-free (T-) amino acid mixture. From the results of this and other studies we concluded that the maximum degree of tryptophan depletion can be produced by a 31.5 g mixture of seven essential amino acids. Administration of a T−amino acid mixture to vervet monkeys lowered tryptophan and 5-hydroxyindoleacetic acid in the cerebrospinal fluid. Levels of tyrosine and the catecholamine metabolites were unchanged. These data support the idea that the effects of T−mixture on mental function in humans which have been reported previously are due to a decrease in 5-hydroxytryptamine. [ABSTRACT FROM AUTHOR]
- Published
- 1989
- Full Text
- View/download PDF
47. A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males.
- Author
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Smith, S., Pihl, R., Young, S., and Ervin, F.
- Abstract
In a previous study we found that a tryptophan-deficient amino acid mixture, designed to lower tissue tryptophan and thus brain 5-hydroxytryptamine (5HT) levels, caused a rapid (5 h) lowering of mood in normal males. Because of the importance of this evidence indicating a direct causal connection between low 5HT and low mood, we have now investigated other possible explanations for the mood lowering effect. Research strongly supports the involvement of environmental setting and cognition in the production and experience of emotions. Therefore we investigated how these factors might influence the mood-lowering effects of tryptophan depletion. In an instructional manipulation subjects were either supplied or not supplied with information designed to account for any possible peripheral sensations that might be related to depressive affect. In an environmental manipulation subjects were exposed either to a supportive and comfortable atmosphere (positive environment), or an unrewarding and unstimulating environment (negative environment). In the control group, which received a balanced amino acid mixture, the positive and negative environments had the expected effects on the scores of the Multiple Affect Adjective Checklist, thus indicating the effectiveness of these procedures. In the tryptophan depletion group neither the instructional nor the environmental manipulation had any influence on the mood lowering effect. It may be that tryptophan depletion lowers mood in normal males because low 5HT influences mood directly rather than via cognitive processes. Our data strongly support the idea that 5HT exerts an effect on mood and that low 5HT may, in some patients, be an important factor contributing to the etiology of clinical depression. [ABSTRACT FROM AUTHOR]
- Published
- 1987
- Full Text
- View/download PDF
48. Tryptophan depletion causes a rapid lowering of mood in normal males.
- Author
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Young, Simon, Smith, Scott, Pihl, Robert, and Ervin, Frank
- Abstract
Normal male human subjects ingested amino acid mixtures which were tryptophan-free, balanced or contained excess tryptophan. The tryptophan-free mixture causes a marked depletion of plasma tryptophan by 5 h. At this time the subjects in the tryptophan-free group had significantly elevated scores on the depression scale of the Multiple Affect Adjective Checklist. The tryptophan-free group also performed worse than the other two groups in a proofreading task carried out while listening to a tape with themes of hopelessness and helplessness (dysphoric distractor). Cognitive theories of depression predict greater distractability of depressed individuals by dysphoric themes. Thus, both measures indicate a rapid mood lowering effect of tryptophan depletion in normal males. This effect is probably mediated by a lowering of brain 5-hydroxytryptamine. Although the mood-lowering effect was not as great as that seen in depressed patients, our results suggest that low brain 5HT might be one factor precipitating depression in some patients. [ABSTRACT FROM AUTHOR]
- Published
- 1985
- Full Text
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49. Brain tryptophan metabolism in schizophrenia: A post mortem study of metabolites on the serotonin and kynurenine pathways in schizophrenic and control subjects.
- Author
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Joseph, M., Baker, H., Crow, T., Riley, G., and Risby, D.
- Abstract
Serotonin (5HT), its chief metabolite 5-hydroxyindoleacetic acid (5 HIAA), its precursor tryptophan, and kynurenine, another metabolite of tryptophan, have been measured in post mortem human brain samples. Concentrations of these metabolites were not found to be significantly different in putamen, hippocampus or temporal cortex from 23 normal subjects compared with 15 subjects in whom a diagnosis of schizophrenia could be restrospectively confirmed. The results have been analysed with respect to cause of death, medication and post mortem changes. Post mortem increases in tryptophan and kynurenine were observed. Some interrelationships between the variables measured within and between the different areas studied are discussed. It is concluded that there is no evidence for a generalised deficit of 5HT in the brain in schizophrenia, nor for gross changes in turnover along the serotonin or kynurenine pathways of tryptophan metabolism in brain. [ABSTRACT FROM AUTHOR]
- Published
- 1979
- Full Text
- View/download PDF
50. Gut-brain communication in hyperfunction of 5-hydroxytryptamine induced by oral zinc oxide nanoparticles exposure in young mice.
- Author
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Zhang, Shanshan, Cheng, Shuqun, Jiang, Xuejun, Zhang, Jun, Bai, Lulu, Qin, Xia, Zou, Zhen, and Chen, Chengzhi
- Subjects
- *
ZINC oxide , *SEROTONIN receptors , *TRYPTOPHAN hydroxylase , *TUMOR necrosis factors , *NEURAL development , *FOOD additives , *TRYPTOPHAN , *TRIMETHYLAMINE oxide - Abstract
Zinc oxide nanoparticles (ZnONPs) have been widely used in food storage containers and food additives in daily life. However, the impact of oral intake of ZnONPs on nervous system is extremely limited, especially on children and adolescents. In this study, four weeks old mice were treated with either vehicle or ZnONPs suspension solution at 26 mg/kg by intragastric administration for 30 days. Our results demonstrated that oral ZnONPs exposure could induce pathological changes in gut and abnormal excitement of enteric neurons. Interestingly, we found that ZnONPs caused enhancement of 5-hydroxytryptamine (5-HT) in gut by activation of its biosynthesis, transport and receptors, and subsequently resulting in increased level of 5-HT in brain via gut-brain communication by blood. Our data also showed that there were no apparent changes on the expressions of interleukin (Il)-6 , Il-1β , C–C motif chemokine ligand 2 (Ccl2), tumor necrosis factor (Tnf) in gut and zinc chelator Mt2 in gut and cortex. Meanwhile, no significant changes were observed on the expressions of tryptophan hydroxylase type 1, 5-HT receptor 3A (Htr3a) and Htr4 in hippocampus and cortex. Our study indicate that oral ZnONPs exposure causes hyperfunction of 5-HT in gut in young mice which may further spread to brain via gut-brain communication. • ZnONPs caused pathological changes and impaired endothelial tight junctions in gut. • ZnONPs caused abnormal excitement of enteric neurons and enhancement of 5-HT in gut. • ZnONPs caused activation of biosynthesis, transport and receptors of 5-HT in gut. • ZnONPs caused enhancement of 5-HT in brain via gut-brain communication by blood. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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