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1.
Braz. j. biol ; 83: e242086, 2023. graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1278530

RESUMO

Abstract The work aims were to describe the histological and histochemical structure of the gastroesophageal tube of Iguana iguana and verify the occurrence and distribution of immunoreactive serotonin (5-HT) and somatostatin (SS) cells. Fragments of the gastrointestinal tract (GIT) of five iguanas were which underwent standard histological and immunohistochemistry technique. Immunoreactive cells for 5-HT and SS were quantified using the STEPanizer. The oesophagus has ciliated columnar pseudostratified epithelium with staining Alcian blue (AB) + and goblet cells highly reactive to periodic acid Schiff (PAS). In the cervical oesophagus, the numerical density of 5-HT cells per unit area (QA [5-HT cells]/µm2) was 4.6x10-2 ± 2.0 and celomatic oesophagus presented QA = 4.0x10-2 ± 1.0. The epithelium of the stomach is simple columnar, PAS and AB +. The cranial and middle regions of the stomach presented (QA [5-HT cells]/µm2) = 6.18x10-2 ± 3.2 and the caudal region, QA = 0.6x10-2 ± 0.2. The SS cells were only observed in the caudal stomach, with numerical density (QA [SS cells]/µm2) = 1.4x10-2 ± 0.9 In I. iguana, variation was observed in terms of the distribution of mucus secretions and the pattern of occurrence of serotonin and somatostatin-secreting enteroendocrine cells in the TGI, which possibly will result in an interspecific adaptive response.


Resumo Os objetivos do trabalho foram descrever a estrutura histológica e histoquímica do tubo gastroesofágico da Iguana iguana e verificar a ocorrência e distribuição de células serotonina (5-HT) e somatostatina (SS) imunorreativas. Fragmentos do trato gastrointestinal (TGI) de cinco iguanas foram submetidos à técnica histológica e imunohistoquímica padrão. As células imunorreativas para 5-HT e SS foram quantificadas usando o STEPanizer. O esôfago apresenta epitélio pseudoestratificado colunar ciliado Alcian blue (AB) positivo, com células caliciformes altamente reativas ao ácido periódico de Schiff (PAS). No esôfago cervical, a densidade numérica de células 5-HT por unidade de área (QA [células 5-HT] / µm2) foi de 4.6x10-2 ± 2.0 e o esôfago celomático apresentou QA = 4.0x10-2 ± 1.0. O epitélio do estômago é colunar simples, PAS e AB positivo. As regiões cranial e média do estômago apresentaram (QA [células 5-HT] / µm2) = 6.18x10-2 ± 3.2 e a região caudal, QA = 0.6x10-2 ± 0.2. As células SS foram observadas apenas no estômago caudal, com densidade numérica (QA [células SS] / µm2) = 1.4x10-2 ± 0.9. Em I. iguana, foi observada variações em termos da distribuição das secreções de muco e padrão de ocorrência das células enteroendócrinas secretoras de serotonina e somatostatina no TGI, o que possivelmente reflete uma resposta adaptativa interespecifica.


Assuntos
Animais , Serotonina , Iguanas , Estômago , Imuno-Histoquímica , Trato Gastrointestinal
2.
Int J Mol Med ; 50(1)2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35543167

RESUMO

The present study aimed to investigate whether prucalopride, as a 5­hydroxytryptamine 4 (5­HT4) receptor agonist, improved intestinal motility by promoting the regeneration of the enteric nervous system (ENS) in rats with diabetes mellitus (DM). A rat model of DM was established using an intraperitoneal injection of streptozotocin. The rats were randomly divided into four groups of 6 rats/group: Control, DM (DM model), DM + A (5 µg/kg prucalopride) and DM + B (10 µg/kg prucalopride). The rats in the Control group were given an equal volume of citric acid solvent. After successful model establishment, high blood glucose levels were maintained for 2 weeks before administration of prucalopride. The colonic transit time was measured using the glass bead discharge method. It was revealed that the colonic transit time of diabetic rats was the longest, and this was significantly shortened in the DM + B group. Subsequently, the colons were collected. The expression levels of Nestin, glial fibrillary acidic protein (GFAP), SOX10, RNA­binding protein human antigen D (HuD) and ubiquitin thiolesterase (PGP9.5) were determined via immunohistochemical analysis. Immunofluorescence double staining of 5­HT4 + Nestin and Ki67 + Nestin was performed. The 5­HT level was measured using ELISA. Compared with that in the control group, Nestin expression was significantly increased in the DM and DM + A groups, and it was concentrated in columnar epithelial cells and the mesenchyme. Furthermore, the expression levels of Nestin in the DM + A group were higher than those in the DM group. No difference was observed in the expression levels of Nestin between the DM + B group and the Control group. The expression levels of 5­HT protein were highest in the Control group; however, the expression levels of 5­HT protein in the DM group, DM + A group and DM + B group exhibited an increasing trend. Similar trends in the expression of 5­HT4 and Nestin were not observed; however, similar trends in the expression of Nestin and Ki67 were observed. The expression levels of GFAP, SOX10, PGP9.5 and Ki67 in the DM + A and DM + B groups were higher compared with those in the DM group. In the DM + A group, HuD expression was decreased compared with that in the Control group but it was markedly higher compared with that in the DM group. In conclusion, prucalopride may improve intestinal motility by promoting ENS regeneration in rats with DM.


Assuntos
Diabetes Mellitus Experimental , Sistema Nervoso Entérico , Animais , Benzofuranos , Diabetes Mellitus Experimental/metabolismo , Sistema Nervoso Entérico/metabolismo , Motilidade Gastrointestinal/fisiologia , Antígeno Ki-67/metabolismo , Nestina/metabolismo , Ratos , Serotonina/metabolismo
3.
Sci Rep ; 12(1): 7605, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534532

RESUMO

The significance of serotonin (5HT) in mental health is underscored by the serotonergic action of many classes of psychiatric medication. 5HT is known to have a significant role in neurodevelopment, thus 5HT disruption during development may have a long term impact on brain structure and circuits. We previously generated a model of 5HT alteration throughout neurodevelopment by maternal administration of the selective serotonin reuptake inhibitor fluoxetine. We found resulting social behavior alterations in the offspring during both postnatal and adult ages. Previous work by others has indicated that early 5HT disruption influences neuronal morphology. Therefore, in the current study we sought to determine if dendritic morphological changes occur in areas involved in the social behavior deficits we previously observed, specifically the primary motor (M1) and medial prefrontal (mPFC) cortices. We quantified dendritic morphology of projection neurons in M1 and mPFC at postnatal day (P)10 and P79 in mice exposed to fluoxetine. Basilar dendritic complexity and spine density were persistently decreased in M1 fluoxetine-exposed neurons while in the mPFC, similar reductions were observed at P79 but were not present at P10. Our findings underscore that the developing brain, specifically the projection cortex, is vulnerable to 5HT system perturbation, which may be related to later behavioral disruptions.


Assuntos
Fluoxetina , Córtex Pré-Frontal , Animais , Fluoxetina/farmacologia , Camundongos , Serotonina , Inibidores de Captação de Serotonina/farmacologia , Comportamento Social
4.
Proc Natl Acad Sci U S A ; 119(21): e2118847119, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35594393

RESUMO

SignificanceTransmembrane signaling through G protein-coupled receptors (GPCRs), originally described as requiring coupling to intracellular G proteins, also uses G protein-independent pathways through ß-arrestin recruitment. Biased ligands, by favoring one of the multiple bioactive conformations of GPCRs, allow selective signaling through either of these pathways. Here, we identified Serodolin as the first ß-arrestin-biased agonist of the serotonin 5-HT7 receptor. This new ligand, while acting as an inverse agonist on Gs signaling, selectively induces ERK activation in a ß-arrestin-dependent way. Importantly, we report that Serodolin decreases pain intensity caused by thermal, mechanical, or inflammatory stimuli. Our findings suggest that targeting the 5-HT7R with ß-arrestin-biased ligand could be a valid alternative strategy to the use of opioids for the relief of pain.


Assuntos
Arrestina , Serotonina , Arrestina/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Humanos , Ligantes , Dor/tratamento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , beta-Arrestina 1/metabolismo , beta-Arrestinas/metabolismo
5.
Comput Math Methods Med ; 2022: 5451277, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35502411

RESUMO

The study was aimed at understanding the brain network and the change rule of brain neurotransmitter 5-hydroxytryptamine (5-HT) in autism children through resting-state electroencephalogram (EEG). 20 autistic children in hospital were selected and defined as the observation group. Meanwhile, 20 healthy children were defined as the control group. EEG signals were collected for the two groups. Fuzzy C-means (FCM) algorithm was used to extract features of EEG signals, and DTF was applied for the causal association between multichannel EEG signals. The two groups were compared for the average function value and regional efficiency of the brain neurotransmitter 5-HT. The results showed that the classification accuracy of frontal F7 channel, left frontal FP1 channel, and temporal T6 channel was 95.2%, 95.3%, and 91.2%, respectively. The average of high beta frequency band, low beta frequency band, theta frequency band, and alpha frequency band in the control group was significantly higher than that in the observation group under the optimal threshold (P < 0.05). Compared with normal subjects (34.27), the average function of 5-HT in the brain was 20.13 in patients with low function and 45.74 in patients with hyperfunction. In conclusion, FCM algorithm can feature extraction of EEG signals, especially in the frontal F7 channel, the left frontal FP1 channel, and the TEMPORAL T6 channel, which has high classification accuracy and can well express the EEG signals of autistic children. The level of 5-HT in autistic children is lower than that in healthy people, and it is closely related to loneliness and depression.


Assuntos
Transtorno Autístico , Serotonina , Encéfalo/diagnóstico por imagem , Criança , Eletroencefalografia/métodos , Humanos , Neurotransmissores
6.
Comput Math Methods Med ; 2022: 8286146, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35502412

RESUMO

Objective: To explore the effect of Shugan Jianpi recipe combined with cross moxibustion on biochemical examination indexes and total score of TCM symptoms in patients with spleen-stomach damp-heat diarrhea irritable bowel syndrome (IBS). Methods: Sixty patients with spleen-stomach damp-heat diarrhea (IBS) treated in our hospital from January 2019 to September 2021 were enrolled. The patients were randomly assigned into the control group and study group. The control group was treated with Chang Shugan Jianpi recipe, and the study group was treated with Shugan Jianpi recipe combined with cross moxibustion. The curative effect, single symptom score, total score of TCM clinical symptoms, plasma gastrointestinal hormone level, IBS-QOL score, and recurrence were compared. Results: First of all, we compared the curative effects. The study group was significantly effective in 24 cases, effective in 5 cases, and ineffective in 1 case, and the effective rate was 96.67%. In the control group, 13 cases were markedly effective, 10 cases were effective, and 7 cases were ineffective, and the effective rate was 76.67%. The effective rate of the study group was higher compared to the control group (P < 0.05). Secondly, the individual symptom scores were compared. Compared between the two groups, the scores of diarrhea times, stool characteristics, abdominal pain, and abdominal distension in the study group were lower compared to the control group (P < 0.05). After treatment, the total score of TCM clinical symptoms decreased. Compared between the two groups, the total score of TCM clinical symptoms in the study group was lower compared to the control group at 1 week, 2 weeks, and 4 weeks after treatment (P < 0.05). After treatment, the levels of 5-HT and VIP decreased. The levels of 5-HT and VIP in the study group were lower compared to the control group (P < 0.05). The scores of anxieties, health worry, behavioral disorder, social reaction, somatic intention, interpersonal relationship, dietary concern, and sexual behavior in the study group were lower compared to the control group. The IBS-QOL scores were significantly lower compared to the control group (P < 0.05). Finally, we compared the recurrence. The recurrence rate in the study group was lower compared to the control group (P < 0.05). Conclusion: The prescription combined with cross moxibustion has the effect of soothing the liver and invigorating the spleen, resolving dampness and stomach, and can reduce the main clinical symptoms of patients with diarrhea IBS of spleen-stomach damp-heat type, and the overall effect is significant. It can also enhance the emotional state of anxiety and depression and achieve the overall psychological and physical balance and health state, and the recurrence rate is low, which can be further applied in clinic.


Assuntos
Síndrome do Intestino Irritável , Moxibustão , Diarreia/tratamento farmacológico , Medicamentos de Ervas Chinesas , Temperatura Alta , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/tratamento farmacológico , Qualidade de Vida , Serotonina/uso terapêutico , Baço , Estômago
7.
Eur Rev Med Pharmacol Sci ; 26(8): 2970-2974, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35503641

RESUMO

OBJECTIVE: Serotonin, which is a vasoactive amine, is an important neurotransmitter and is involved in many behavioral and psychological phenomena, such as pain, appetite, mood, and sleep. The primary purpose of our study was to investigate the effect of high-pressure administration of sterile physiological saline isotonic solution (HpPSIS) into nasal cavity and to determine the expression of the serotonin. PATIENTS AND METHODS:  The study was made in two branches, the previous with 14 volunteers, the subsequent study with 40 patients with mild anxiety disorder. The middle third of the inferior turbinate epithelial cells on the right nostril was scraped using a sterile curette and indicated as (pre), then, a spray of sterilized isotonic solution at high pressure on the left nostril was delivered, and 5 minutes later a similar stimulation was delivered on the same nostril. The stimulation was made with a specific spray dispenser. The middle third of the inferior turbinate epithelial cells on the left nostril was scraped using a sterile curette and indicated as (post). Then, based on the first part of our study, we started the second part and gave a treatment on forty new patients with anxiety disorder. RESULTS:  The results of these studies highlight the possibility of endogenous enhancement of serotonin by stimulation of mast cells. In the first part of the study, Serotonin significantly increased in protein extracts after treatment (64.35±5.33 vs. 10.97±2.17; unpaired two tailed t-test, t=9.8, df=24, p≤0.0001; F=6.035; DFn=12; DFd=12). In the second part of the study, in patients treated with HpPSIS, we observed improvement of mood, after one, two and three months, with a statistically significant reduction of DASS-21, while no reduction was observed in control patients, treated with normal pressure commercial spray. CONCLUSIONS:  This pilot study showed that the topical treatment of HpPHIS increases serotonin levels in nasal cavity. The observation reported in this study opens the way to a new valid strategy to enhance the level of endogenous serotonin. We observed a significant improvement of ASI on patients during HpPHIS therapy.


Assuntos
Cavidade Nasal , Serotonina , Administração Intranasal , Humanos , Soluções Isotônicas/metabolismo , Soluções Isotônicas/farmacologia , Cavidade Nasal/metabolismo , Projetos Piloto , Serotonina/metabolismo
8.
Zhongguo Zhen Jiu ; 42(5): 525-32, 2022 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-35543943

RESUMO

OBJECTIVE: To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism. METHODS: A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR. RESULTS: Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05). CONCLUSION: Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.


Assuntos
Hipotireoidismo , Moxibustão , Pontos de Acupuntura , Animais , Depressão/genética , Depressão/terapia , Hipocampo/metabolismo , Hidrocortisona/metabolismo , Hipotireoidismo/complicações , Hipotireoidismo/metabolismo , Hipotireoidismo/terapia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , Serotonina , Tireotropina/metabolismo , Triticum/metabolismo
9.
Comput Math Methods Med ; 2022: 3398732, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35516456

RESUMO

Objective: To explore the effects of pramipexole combined with nerve growth factor (NGF) on cognitive impairment and urinary Alzheimer-associated neural thread protein (AD7c-NTP) expression in patients with Parkinson's disease (PD). Methods: Fifty patients with PD treated in our hospital from February 2020 to April 2021 were enrolled. The patients were arbitrarily assigned into control group and study group. The former was treated with pramipexole, and the latter was treated with pramipexole combined with NGF. The efficacy, cognitive function, serum inflammatory factors, cortisol levels, serum macrophage migration inhibitory factor (MIF), brain-derived neurotrophic factor (BDNF), urine AD7c-NTP levels, and the incidence of adverse reactions were compared. Results: First of all, the effective rate in the study group was higher compared to the control group (P < 0.05). After treatment, the cognitive function was enhanced, and the scores of Montreal cognitive assessment (MoCA) in the study group were higher compared to the control group (P < 0.05). The levels of serum IL-6, CRP, and TNF-α decreased after treatment, and the levels of serum IL-6, CRP, and TNF-α in the study group were remarkably lower compared to the control group (P < 0.05). In addition, the levels of serum DA, NE, and 5-HT increased after treatment, and the levels of serum DA, NE, and 5-HT in the study group were remarkably higher compared to the control group (P < 0.05). Then, the levels of serum MIF and urine AD7c-NTP decreased and BDNF increased after treatment, and the level of BDNF in the study group was higher compared to the control group, while the levels of serum MIF and urine AD7c-NTP in the study group were lower compared to the control group (P < 0.05). Finally, the adverse reactions were compared. The incidence of adverse reactions in the study group was lower compared to the control group, and the difference exhibited not statistically significant (16.00% vs. 24.00%, P > 0.05). Conclusion: Pramipexole combined with NGF therapy not only can effectively strengthen the cognitive impairment of patients with PD and promote clinical efficacy and high safety but also can inhibit inflammatory state, regulate brain neurotransmitters, and reduce urinary AD7c-NTP levels.


Assuntos
Disfunção Cognitiva , Doença de Parkinson , Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Humanos , Interleucina-6 , Fator de Crescimento Neural , Proteínas do Tecido Nervoso , Doença de Parkinson/tratamento farmacológico , Pramipexol , Serotonina , Fator de Necrose Tumoral alfa
10.
Nat Neurosci ; 25(5): 646-658, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35501380

RESUMO

Midbrain dopamine (DA) and serotonin (5-HT) neurons regulate motivated behaviors, including feeding, but less is known about how these circuits may interact. In this study, we found that DA neurons in the mouse ventral tegmental area bidirectionally regulate the activity of 5-HT neurons in the dorsal raphe nucleus (DRN), with weaker stimulation causing DRD2-dependent inhibition and overeating, while stronger stimulation causing DRD1-dependent activation and anorexia. Furthermore, in the activity-based anorexia (ABA) paradigm, which is a mouse model mimicking some clinical features of human anorexia nervosa (AN), we observed a DRD2 to DRD1 shift of DA neurotransmission on 5-HTDRN neurons, which causes constant activation of these neurons and contributes to AN-like behaviors. Finally, we found that systemic administration of a DRD1 antagonist can prevent anorexia and weight loss in ABA. Our results revealed regulation of feeding behavior by stimulation strength-dependent interactions between DA and 5-HT neurons, which may contribute to the pathophysiology of AN.


Assuntos
Dopamina , Serotonina , Animais , Anorexia , Neurônios Dopaminérgicos , Mesencéfalo , Camundongos , Neurônios/fisiologia
12.
Transl Psychiatry ; 12(1): 187, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523779

RESUMO

Cocaine use disorder (CUD) patients display heterogenous symptoms and unforeseeable responses to available treatment approaches, highlighting the need to identify objective, accessible biobehavioral signatures to predict clinical trial success in this population. In the present experiments, we employed a task-based behavioral and pharmacogenetic-fMRI approach to address this gap. Craving, an intense desire to take cocaine, can be evoked by exposure to cocaine-associated stimuli which can trigger relapse during attempted recovery. Attentional bias towards cocaine-associated words is linked to enhanced effective connectivity (EC) from the anterior cingulate cortex (ACC) to hippocampus in CUD participants, an observation which was replicated in a new cohort of participants in the present studies. Serotonin regulates attentional bias to cocaine and the serotonergic antagonist mirtazapine decreased activated EC associated with attentional bias, with greater effectiveness in those CUD participants carrying the wild-type 5-HT2CR gene relative to a 5-HT2CR single nucleotide polymorphism (rs6318). These data suggest that the wild-type 5-HT2CR is necessary for the efficacy of mirtazapine to decrease activated EC in CUD participants and that mirtazapine may serve as an abstinence enhancer to mitigate brain substrates of craving in response to cocaine-associated stimuli in participants with this pharmacogenetic descriptor. These results are distinctive in outlining a richer "fingerprint" of the complex neurocircuitry, behavior and pharmacogenetics profile of CUD participants which may provide insight into success of future medications development projects.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Transtornos Relacionados ao Uso de Substâncias , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Transtornos Relacionados ao Uso de Cocaína/genética , Giro do Cíngulo , Humanos , Mirtazapina , Serotonina
13.
Lab Anim (NY) ; 51(5): 129, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35505141

Assuntos
Dopamina , Serotonina
14.
Dokl Biochem Biophys ; 503(1): 104-107, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35538288

RESUMO

The effect of mild prenatal stress in mice, leading to an increase in the placental serotonin level, on the formation of adaptive behavior in male offspring at the age of 35 days was studied. It was shown that, in BalbC mice, daily immobilization for 1 h during the period from 11 to 14 days of pregnancy led to an increase in placental and fetal serotonin levels on the 15th day of prenatal development. According to "resident-intruder" behavioral test, the prenatally stressed mice showed more reactive behavior in adulthood and low tendency to defend their territory. Thus, placental serotonin, formed under the stress condition, may act as a mediator between the environment and the fetuses and determine the adaptive behavior of offspring.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Serotonina , Adaptação Psicológica , Adulto , Animais , Comportamento Animal , Feminino , Feto , Humanos , Masculino , Camundongos , Placenta , Gravidez , Serotonina/farmacologia , Estresse Psicológico
15.
Artigo em Inglês | MEDLINE | ID: mdl-35561626

RESUMO

Inborn errors of dopamine and serotonin metabolism are diseases caused by deficiencies in enzymes belonging to metabolic pathways. The specific diagnosis of these inborn illnesses is based on the identification and quantification of biomarkers in cerebrospinal fluid (CSF), especially: 5-hydroxy-tryptophane (5-HTP), 5-hydroxy-indol-acetic acid (5-HIAA), 3-ortho-methyl-DOPA (3-OMD), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). In the present work, we propose a novel ultrahigh performance liquid chromatography (UHPLC) method coupled to fluorescence detection (FD) to quantify simultaneously the five dopamine and serotonin metabolites. This method efficiently separates the five molecules in less than 10 min. A complete validation of the proposed method was performed in terms of accuracy, linearity, precision, and lower limit of quantification (LLOQ). Depending on the compound, the obtained LLOQs are between 1 nM and 5 nM, thus allowing to measure concentrations as low as in CSF samples. We also verified the method applicability by analyzing 10 CSF samples in triplicates. The obtained results showed satisfactory repeatability and an ability of this method to clearly distinguish healthy samples from pathologic samples, hence, demonstrating, the method suitability for diagnosing inborn errors of dopamine and serotonin metabolism. Therefore, the proposed UHPLC-FD method appears as a reliable alternative to the current gold standard for the quantification of these biomarkers, which is based on UHPLC coupled to electrochemical detection (ECD).


Assuntos
Dopamina , Serotonina , Biomarcadores/líquido cefalorraquidiano , Cromatografia Líquida de Alta Pressão/métodos , Ácido Homovanílico/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético , Serotonina/metabolismo
16.
ACS Chem Neurosci ; 13(9): 1456-1466, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35467841

RESUMO

Cellular hypoxia causes numerous pathophysiological conditions associated with the disruption of oxygen homeostasis. Under oxygen-deficient conditions, cells adapt by controlling the cellular functions to facilitate the judicious use of available oxygen, such as cessation of cell growth and proliferation. In higher eukaryotes, the process of cholesterol biosynthesis is intimately coupled to the availability of oxygen, where the synthesis of one molecule of cholesterol requires 11 molecules of O2. Cholesterol is an essential component of higher eukaryotic membranes and is crucial for the physiological functions of several membrane proteins and receptors. The serotonin1A receptor, an important neurotransmitter G protein-coupled receptor associated with cognition and memory, has previously been shown to depend on cholesterol for its signaling and function. In this work, in order to explore the interdependence of oxygen levels, cholesterol biosynthesis, and the function of the serotonin1A receptor, we developed a cellular hypoxia model to explore the function of the human serotonin1A receptor heterologously expressed in Chinese hamster ovary cells. We observed cell cycle arrest at G1/S phase and the accumulation of lanosterol in cell membranes under hypoxic conditions, thereby validating our cellular model. Interestingly, we observed a significant reduction in ligand binding and disruption of downstream cAMP signaling of the serotonin1A receptor under hypoxic conditions. To the best of our knowledge, our results represent the first report linking the function of the serotonin1A receptor with hypoxia. From a broader perspective, these results contribute to our overall understanding of the molecular basis underlying neurological conditions often associated with hypoxia-induced brain dysfunction.


Assuntos
Receptor 5-HT1A de Serotonina/metabolismo , Serotonina , Animais , Células CHO , Hipóxia Celular , Colesterol/metabolismo , Cricetinae , Cricetulus , Humanos , Hipóxia , Oxigênio , Serotonina/metabolismo
17.
Folia Neuropathol ; 60(1): 69-75, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359147

RESUMO

INTRODUCTION: Ethanol dependence and abuse is an important problem of public health worldwide and its withdrawal shows some severe behavioural complication. Management of ethanol withdrawal syndrome (EWS) is still a challenge, thus the presented report postulates the possible mechanism involved in the development of EWS. MATERIAL AND METHODS: EWS was induced by administration of ethanol for 21 days and 5-hydroxytryptamine (5-HT) 1b/1d agonist treated group receives Zolmitriptan (ZMT) at 30 mg/kg i.p. 30 min prior to ethanol withdrawal. The effect of 5-HT 1b/1d receptor agonist on EWS was determined by estimating the change in the behaviour of withdrawal signs that included locomotor hyperactivity, agitation, tremor, tail stiffness, stereotyped behaviour, and wet dog shakes at 1, 2, 4, 6 and 12 h of ethanol withdrawal. Ethanol withdrawal induced anxiety was determined by using the elevated plus maze and levels of neurochemicals such as g-aminobutyric acid (GABA), glutamate and dopamine were determined in the brain of each group of rats. RESULTS: Data of the given report reveal that Zolmitriptan reverses ( p < 0.01) the behavioural changes induced due to EWS and also reduces the anxiety level in EWS rats. Moreover, Zolmitriptan was found to stimulate ( p < 0.01) the level of GABA and ameliorate the level of other neurochemicals in the brain of EWS rats. CONCLUSIONS: In conclusion, data of investigation reveal that 5-HT 1b/1d receptor involved in the EWS and treatment with its agonist prevents the behavioural changes in EWS by regulating the level of different neurochemicals.


Assuntos
Serotonina , Síndrome de Abstinência a Substâncias , Animais , Ansiedade/tratamento farmacológico , Etanol/toxicidade , Ratos , Ratos Wistar , Síndrome de Abstinência a Substâncias/tratamento farmacológico
18.
J Phys Chem Lett ; 13(15): 3325-3331, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35394786

RESUMO

The detection of monoamine neurotransmitters has become a vital research subject due to their high correlations with nervous system diseases, but insufficient detection precisions have obstructed diagnosis of some related diseases. Here, we focus on four monoamine neurotransmitters, dopamine, norepinephrine, epinephrine, and serotonin, to conduct their rapid and ultrasensitive detection. We find that the low-frequency (<200 cm-1) Raman vibrations of these molecules show some sharp peaks, and their intensities are significantly stronger than those of the high-frequency side. Theoretical calculations identify these peaks to be from strong out-of-plane vibrations of the C-C single bonds at the joint point of the ring-like molecule and its side chain. Using our surface enhanced low-frequency Raman scattering substrates, we show that the detection limit of dopamine as an example can reach 10 nM in artificial cerebrospinal fluid. This work provides a useful way for ultrasensitive and rapid detection of some neurotransmitters.


Assuntos
Dopamina , Vibração , Neurotransmissores , Serotonina , Análise Espectral Raman
19.
Trop Anim Health Prod ; 54(3): 164, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35435494

RESUMO

The present study was conducted to investigate the effects of tryptophan (Trp) supplementation on rectal temperature, hormone, and cytokine levels in broilers subjected to acute heat stress. A total of 300 18-day-old female Arbor Acres broilers were randomly allocated to five dietary treatment groups with six replicates per treatment group and ten birds per replicate. Broilers were fed a basal diet and in the thermoneutral conditions (TN, 23 ± 1 °C) was considered as the TN group. Broilers were fed a basal diet and exposed to acute heat stress (HS, 34 ± 1 °C) was regarded as the HS group, and other broilers exposed to acute heat stress (34 ± 1°C) were fed a basal diet supplemented with 0.09%, 0.18%, and 0.27% Trp. Results indicated that acute heat stress increased the rectal temperature (P < 0.05), enhanced the concentrations of corticosterone (CORT), dopamine (DA), adrenaline (Adr), adrenocorticotropic hormone (ACTH), and corticotropin-releasing hormone (CRH) in serum (P < 0.05), and elevated the levels of serum tryptophan hydroxylase (TPH)1, tryptophan 2, 3-dioxygenase (TDO), indoleamine 2, 3-dioxygenase (IDO), and kynurenic acid (P < 0.05), compared with the TN group. Meanwhile, acute heat stress increased the levels of serum Trp, hypothalamic Trp, 5-hydroxytryptophan (5-HT), and interleukin-22 (P < 0.05) relative to the TN group. However, compared with the heat stress group, Trp supplementation decreased the rectal temperature of heat-stressed broilers and dietary 0.09% Trp supplementation decreased the levels of serum CRH and TDO (P < 0.05), increased the levels of serum Trp and IL-22 (P < 0.05) in heat-stressed broilers. In addition, dietary supplemented with 0.18% Trp reduced the levels of serum DA, Adr, noradrenaline (NA), CRH, TDO, IDO, kynurenic acid, IL-1ß, and hypothalamic 5-HIAA/5-HT (P < 0.05), increased the levels of serum Trp, 5-HT, and IL-22, and upregulated the concentrations of hypothalamic Trp and 5-HT in heat-stressed broilers (P < 0.05). Moreover, dietary 0.27% Trp supplementation decreased the levels of serum DA, CRH, TDO, and hypothalamic 5-HIAA/5-HT (P < 0.05), and upregulated the levels of serum Trp, 5-HT, IL-22, hypothalamic Trp and 5-HT in heat-stressed broilers (P < 0.05). Taken together, dietary 0.18% Trp supplementation may be the optimal level for broilers reared under acute heat stress.


Assuntos
Dioxigenases , Transtornos de Estresse por Calor , Ração Animal/análise , Animais , Temperatura Corporal , Galinhas , Citocinas , Dieta/veterinária , Suplementos Nutricionais , Feminino , Transtornos de Estresse por Calor/veterinária , Resposta ao Choque Térmico , Hormônios , Temperatura Alta , Ácido Hidroxi-Indolacético , Ácido Cinurênico , Serotonina , Triptofano
20.
BMC Cancer ; 22(1): 457, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473609

RESUMO

BACKGROUND: Glioma is one of the main causes of cancer-related mortality worldwide and is associated with high heterogeneity. However, the key players determining the fate of glioma remain obscure. In the present study, we shed light on tumor metabolism and aimed to investigate the role of tryptophan hydroxylase 1 (TPH-1) in the advancement of glioma. METHOD: Herein, the levels of TPH-1 expression in glioma tissues were evaluated using The Cancer Genome Atlas (TCGA) database. Further, the proliferative characteristics and migration ability of TPH-1 overexpressing LN229/T98G cells were evaluated. Additionally, we performed a cytotoxicity analysis using temozolomide (TMZ) in these cells. We also examined the tumor growth and survival time in a mouse model of glioma treated with chemotherapeutic agents and a TPH-1 inhibitor. RESULTS: The results of both clinical and experimental data showed that excess TPH-1 expression resulted in sustained glioma progression and a dismal overall survival in these patients. Mechanistically, TPH-1 increased the production of serotonin in glioma cells. The elevated serotonin levels then augmented the NF-κB signaling pathway through the upregulation of the L1-cell adhesion molecule (L1CAM), thereby contributing to cellular proliferation, invasive migration, and drug resistance. In vivo experiments demonstrated potent antitumor effects, which benefited further from the synergistic combination of TMZ and LX-1031. CONCLUSION: Taken together, these data suggested that TPH-1 facilitated cellular proliferation, migration, and chemoresistance in glioma through the serotonin/L1CAM/NF-κB pathway. By demonstrating the link of amino acid metabolic enzymes with tumor development, our findings may provide a potentially viable target for therapeutic manipulation aimed at eradicating glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Molécula L1 de Adesão de Célula Nervosa , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Humanos , Camundongos , NF-kappa B/metabolismo , Serotonina/farmacologia , Transdução de Sinais , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo , Triptofano Hidroxilase/farmacologia
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