Localization of the Serotonin Transporter in the Dog Intestine and Comparison to the Rat and Human Intestines

Serotonin is crucial in gastrointestinal functions, including motility, sensitivity, secretion, and the inflammatory response. The serotonin transporter (SERT), responsible for serotonin reuptake and signaling termination, plays a prominent role in gastrointestinal physiology, representing a promising therapeutic target in digestive disorders. Serotonin transporter expression has been poorly investigated in veterinary medicine, under both healthy and pathological conditions, including canine chronic enteropathy, in which the serotonin metabolism seems to be altered. The aim of the present study was to determine the distribution of SERT immunoreactivity (SERT-IR) in the dog intestine and to compare the findings with those obtained in the rat and human intestines. Serotonin transporter-IR was observed in canine enterocytes, enteric neurons, lamina propria cells and the tunica muscularis. Data obtained in dogs were consistent with those obtained in rats and humans. Since the majority of the serotonin produced by the body is synthesized in the gastrointestinal tract, SERT-expressing cells may exert a role in the mechanism of serotonin reuptake.

Effect of adaptation to intermittent hypoxia on serotonin metabolism and oxidative stress in the hippocampus of rats with experimental post-traumatic stress disorder

Введение. Посттравматическое стрессовое расстройство (ПТСР) формируется спустя длительный срок после переживания психической травмы. Имеются данные о низком уровне серотонина у больных ПТСР, который часто сочетается с окислительным стрессом, обусловленным нейровоспалением. Представляется актуальным поиск эффективных средств немедикаментозной коррекции ПТСР. Одним из высокоэффективных и наиболее широко используемых методов является адаптация к периодической гипоксии (АПГ). Цель работы - исследование влияния АПГ на обмен серотонина и показатели окислительного стресса в гиппокампе животных при экспериментальном ПТСР. Методика. Исследование выполнено на 34 половозрелых самцах крыс Вистар, которые были разделены на 4 группы («Контроль», «ПТСР», «АПГ», «ПТСР+АПГ»). В качестве модели экспериментального ПТСР была использована модель хронического предаторного стресса, где животные подвергались «запаху хищника» (кошачьей мочи) по 10 мин в течение 10 сут. После этого крыс адаптировали к периодической гипоксии в гипобарической барокамере в течение 14 сут, начиная с 30 мин в 1-е сут на симулированной высоте 1000 м, с постепенным увеличением «высоты» и времени экспозиции до 4000 м в течение 4 ч на 5-е сут и в последующие дни. Поведенческие реакции животных изучали при помощи теста «приподнятый крестообразный лабиринт» (ПКЛ). Концентрацию серотонина и его метаболита 5-гидроксииндолуксусной кислоты (5-ГИУК) определяли методом высокоэффективной жидкостной хроматографии. Содержание первичных и вторичных продуктов перекисного окисления липидов (ПОЛ) оценивали спектрофотометрически согласно методике И.А. Волчегорского и соавт. Уровень окислительной деструкции белков оценивали по содержанию карбонилированных белков. Результаты. При тестировании в ПКЛ было установлено, что у животных через 14 сут после завершения предаторного стресса по сравнению с контролем наблюдалось усиление тревожности, которое ограничивалось курсом АПГ. Одновременно с этим установлено снижение содержания серотонина и повышение уровня 5-ГИУК, что привело к существенному повышению метаболического индекса серотонина. Курс АПГ не привел к статистически значимым изменениям содержания серотонина и его метаболита по сравнению с контролем. В группе «ПТСР+АПГ» по сравнению с группой «ПТСР» отмечено повышение концентрации серотонина при одновременном снижении 5-ГИУК и метаболического индекса серотонина. Исследование окислительного стресса в гиппокампе животных с ПТСР-подобным состоянием показало повышение базального уровня карбонилированных белков по сравнению с контролем и увеличение содержания вторичных продуктов ПОЛ. Заключение. При экспериментальном ПТСР в гиппокампе снижение содержания серотонина ассоциировано с усилением его метаболизма, что сопровождается усилением окислительного стресса. Нейропротекторное действие АПГ выражается в нивелировании окислительного стресса в гиппокампе. Background. Post-traumatic stress disorder (PTSD) develops long after a mental traumatic event. In patients with PTSD, low serotonin levels often combine with oxidative stress-induced inflammation. Searching for effective non-pharmacological therapies for PTSD is important. Adaptation to intermittent hypoxia (AIH) is one of highly effective and widely used methods. The aim of this study was to elucidate the effect of AIH on serotonin metabolism and oxidative stress in the hippocampus of rats with PTSD. Methods. The study was performed on 34 sexually mature male Wistar rats divided into 4 groups: control, PTSD, AIH, and PTSD+AIH. Experimental PTSD was modeled with chronic predator stress, where animals were exposed to predator smell (cat urine) for 10 days, 10 min daily. Then rats were conditioned in a hypobaric altitude chamber for 14 days at a 1,000-m simulated altitude for 30 min on day 1 with altitude and duration progressively increasing to 4,000 m for 4 h on day 5 and all the remaining days. Behavioral reactions of rats were studied with the elevated plus maze (EPM) test. Concentrations of serotonin and the serotonin metabolite, 5-hydroxy indole acetic acid (5-HIAA), were measured by high-performance liquid chromatography. Contents of primary and secondary lipid peroxidation (LPO) products were measured spectrophotometrically according to the method of I.A. Volchegorskiy et al. The oxidative damage to proteins was assessed by the content of carbonylated proteins. Results. The EPM test showed that 14 days after the predator stress completion, the anxiety level was higher than in control, and this effect was alleviated by AIH. Also, stress-exposed rats had lower serotonin and higher 5-HIAA concentrations, which resulted in a significantly higher serotonin metabolic index compared to the control. The course of AIH did not cause any significant changes in concentrations of serotonin and its metabolite as compared to the control. In the PTSD + AIH group compared to the PTSD group, the serotonin concentration was increased whereas the 5-HIAA concentration and the metabolic serotonin index were decreased. Studying oxidative stress in the hippocampus of rats with the PTSD-like condition showed that both the basal level of carbonylated proteins and the content of LPO secondary products were increased compared to the control group. Conclusions. In experimental PTSD in the hippocampus, the decrease in serotonin content was associated with the increase in its metabolism and with potentiation of oxidative stress. The neuroprotective effect of AIH was evident as alleviation of oxidative stress in the hippocampus.

Effects of oral administration of an aqueous ginger extract on anxiety behavior and tryptophan and serotonin metabolism in the rat

Background: Zingiber officinale (ginger) is used widely as a herb and medicine. It contains among its constituents 6-Gingerol (a phenol) and quercetin (a flavonoid) that possess anxiolytic and antidepressant properties, but the potential biochemical mechanism(s) of these effects has not been assessed, particularly in relation to serotonin synthesis and neurotransmission. Aims and Objectives: We investigated the anxiolytic-like activity of an aqueous ginger extract by evaluating its influence on behavior, and its effects on serotonin metabolism and on metabolism and disposition of the serotonin precursor tryptophan (Trp) in rats. Materials and Methods: An aqueous ginger extract was given orally in a single daily dose equivalent to 500 mg of ginger material per kg body weight for 3 weeks. The elevated plus maze test of anxiety and Trp metabolism and disposition and brain serotonin synthesis and turnover were assessed in Ginger-treated and control rats. Results: When compared with controls, ginger-treated rats showed a significant increase in the time spent in the open arm, indicative of decreased anxiety. However there was no effect on locomotor activity in open field test. The extract caused significant decreases in activities of liver Trp 2,3-dioxygenase and significant increases in concentrations of serum Trp and corticosterone and brain Trp, serotonin and the major serotonin metabolite 5-hydroxyindoleacetic acid. Conclusion: An aqueous ginger extract exerts an anxiolytic effect in a behavioral model of anxiety, which may be caused by increased serotonin synthesis, and influences tryptophan metabolism and disposition in a manner analogous to antidepressant drugs.

Fecal Microbiome Transplantation from Children with Autism Spectrum Disorder Modulates Tryptophan and Serotonergic Synapse Metabolism and Induces Altered Behaviors in Germ-Free Mice

ABSTRACT To determine the relationship of the gut microbiota and its metabolites with autism spectrum disorder (ASD)-like behaviors and preliminarily explore the potential molecular mechanisms, the fecal microbiota from donors with ASD and typically developing (TD) donors were transferred into germ-free (GF) mice to obtain ASD-FMT mice and TD-FMT mice, respectively. Behavioral tests were conducted on these mice after 3 weeks. 16S rRNA gene sequencing of the cecal contents and untargeted metabolomic analysis of the cecum, serum, and prefrontal cortex were performed. Untargeted metabolomics was also used to analyze fecal samples of TD and ASD children. Western blotting detected the protein expression levels of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and serotonin 1A receptor (5-HT1AR) in the colon and TPH2, SERT, and 5-HT1AR in the prefrontal cortex of mice. ASD-FMT mice showed ASD-like behavior and a microbial community structure different from that of TD-FMT mice. Tryptophan and serotonin metabolisms were altered in both ASD and TD children and ASD-FMT and TD-FMT mice. Some microbiota may be related to tryptophan and serotonin metabolism. Compared with TD-FMT mice, ASD-FMT mice showed low SERT and 5-HT1AR and high TPH1 expression levels in the colon. In the prefrontal cortex, the expression levels of TPH2 and SERT were increased in the ASD-FMT group relative to the TD-FMT group. Therefore, the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. These changes may be related to changes in some key proteins involved in the synthesis and transport of serotonin. IMPORTANCE The relationship between the gut microbiota and ASD is not yet fully understood. Numerous studies have focused on the differences in intestinal microbial and metabolism profiles between TD and ASD children. However, it is still not clear if these microbes and metabolites cause the development of ASD symptoms. Here, we collected fecal samples from TD and ASD children, transplanted them into GF mice, and found that the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. We also demonstrated that tryptophan and serotonin metabolism was also altered in ASD and TD children. Together, these findings confirm that the microbiome from children with ASD may lead to ASD-like behavior of GF mice through metabolites, especially tryptophan and serotonin metabolism.

A systematic analysis of vascular paroxysm pathophysiology in perimenopause: methods for nutritional correction

Materials and Methods. A systematic analysis of publications retrieved from PubMed/MEDLINE database as well as in the list of primary sources of the identified scientific papers was carried out by using current methods for large data analysis within the framework of topological and metric approaches applied for data recognition/classification. A map of molecular-pathophysiological processes was compiled followed by performing analysis of metric condensations.Results. Three clusters of terms describing an impact of various biological processes into the pathophysiology of hot flushes were identified: inflammation combined with insulin resistance (cluster 1), the presence of chronic comorbid pathologies in patients (cluster 2), and disorders of serotonin metabolism (cluster 3). The use of menopausal hormone therapy (MHT) is not accepted for all patients. A promising direction in treatment of mild and moderate hot flushes is based on using nutraceuticals: vitamins, trace elements and substances obtained from plant extracts (isoflavones, phytoestrogens, etc.). Here, this set of interactions between pathophysiology of hot flushes and deficiency of certain micronutrients, inflammation, insulin resistance, chronic comorbid pathologies and disorders of serotonin metabolism is described. Replenished deficiency of vitamins C, E, A, B2, PP, B6, B12, and folates aids to reduce chronic inflammation, insulin resistance and normalize functioning of the autonomic nervous system. Natural and synthetic agonists of GABA receptors and tryptophan derivatives are necessary for serotonin biosynthesis and elimination of other neurotransmitter imbalances in order to normalize activity of the hypothalamic thermoregulatory region.Conclusion. Plant isoflavones (including phytoestrogens) together with vitamins and other micronutrients help to overcome estrogen-dependent withdrawal symptoms and eliminate dysfunction of autonomic nervous system