Search Results (321)

This study aimed to evaluate the effects of the standardized ileal digestible tryptophan-to-lysine (SID Trp–Lys) ratio through the supplementation of different levels of L-tryptophan on pig performance and immune response following an LPS challenge. A total of 120 entire male pigs, with an average body weight of 16.5 ± 0.50 kg, were allocated in a randomized block design with four treatments, ten replicates per treatment, and three animals per experimental unit. The experimental treatments consisted of SID Trp–Lys ratios of 16%, 18%, 21%, and 24%, achieved through L-tryptophan supplementation. The evaluated performance parameters included the final body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR). Blood samples were collected on day 21 to determine serum serotonin levels, and on day 26, pigs were inoculated with LPS to induce an immune challenge, followed by blood sampling to assess cytokine responses. The results showed that pigs fed the 16% SID Trp–Lys ratio exhibited a lower FBW (p < 0.05). The SID Trp–Lys ratios influenced performance parameters, with quadratic responses (p < 0.05) observed for the FBW and FCR, where the highest FBW and lowest FCR were recorded at 22.05% and 21% SID Trp–Lys, respectively. A linear increase (p < 0.05) was observed for ADG, with a trend for a linear increase (p = 0.056) in ADFI. No effects (p > 0.10) of the SID Trp–Lys ratios were detected on serum serotonin levels. An increase in cytokine levels (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, and TNF-α) was observed in pigs challenged with LPS (p < 0.10) compared to non-challenged animals. An interaction effect (p < 0.10) was detected for IL-2 and IL-18. SID Trp–Lys ratios between 21% and 24% optimize growth performance in pigs from 16 to 33 kg and modulate the immune response under LPS-induced challenge conditions. Full article

Background and Objectives: Serotonin modulates platelet aggregation and secretion, but its role in hemostasis remains controversial. This study hypothesized that the 5-HT₃ receptor antagonist palonosetron may inhibit platelet function and aimed to evaluate its effects on blood coagulation using thromboelastography (TEG). Materials and Methods: Blood samples from 11 healthy volunteers were treated with palonosetron at concentrations of 25, 250, and 2500 ng/mL. Untreated samples served as controls. Coagulation parameters were assessed using global hemostasis (citrated kaolin, citrated rapid TEG, citrated kaolin with heparinase, and citrated functional fibrinogen) and PlateletMapping (adenosine diphosphate [ADP], arachidonic acid, and others) assays. Results: In the global hemostasis assay, maximum amplitude values, reflecting clot strength, decreased with increasing palonosetron concentrations in all tests, including citrated kaolin (p = 0.031), citrated rapid TEG (p = 0.001), citrated kaolin with heparinase (p = 0.033), and citrated functional fibrinogen (p = 0.011). The PlateletMapping assay showed significant reductions in ADP-induced platelet aggregation (p = 0.001), with the largest inhibition observed at 2500 ng/mL (p = 0.007). Despite these changes, all values remained within normal reference ranges. Conclusions: Palonosetron induces hypocoagulable trends in vitro by inhibiting platelet function and fibrinogen-mediated clot strength. However, these changes are unlikely to result in clinically significant hemostatic impairment when used within therapeutic doses. Further research is warranted to confirm these findings and explore their clinical relevance. Full article

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly impacts learning, daily functioning, and personal development. Astaxanthin (ASTA), a naturally occurring antioxidant, has garnered interest as a potential therapeutic agent for various diseases, particularly in mitigating oxidative stress. This study explores a novel application of ASTA in the context of ADHD, aiming to investigate its therapeutic effects and underlying mechanisms. Spontaneously hypertensive rats (SHRs), widely used ADHD model animals, were treated with ASTA (50/100 mg/kg/day) for three weeks, 5 mg/kg/day atomoxetine (ATO) as the positive, and Wistar Kyoto (WKY) rats as control. Behavioral improvements were assessed using the open field test (OFT) and the Morris water maze (MWM). Biochemical analyses were conducted to evaluate changes in the levels of various neurotrophic factors, while histological examinations were performed to assess neuroprotective effects. Additionally, the role of ASTA in the brain–gut axis was investigated. The behavioral symptoms of hyperactivity, anxiety, and impaired spatial memory in ADHD animals were mitigated by ASTA. This improvement is primarily attributed to the restoration of neurotransmitter levels, particularly dopamine (DA), achieved through the modulation of several critical components within the dopamine system, including dopamine receptor 1 (DR1), dopamine transporter (DAT), tyrosine hydroxylase (TH), and synaptic-associated protein 25 (SNAP-25). Additionally, regulating the serotonin transporter (SERT) and glial cell-derived neurotrophic factor (GDNF) supports the recovery of serotonin levels and facilitates optimal brain development. Furthermore, cerebellar cells were protected, and the structure of the intestinal microbiota was regulated. ASTA can mitigate ADHD symptoms in SHR through the modulation of the dopaminergic system, multiple neurotransmitters, neurotrophic factors, and the neuro-intestinal environment, which establishes ASTA as a promising nutraceutical candidate for adjunctive therapy in pediatric ADHD. Full article

Bioelectric membrane potentials regulate cellular growth, differentiation, and movement. Disruptions in bioelectric signaling are strongly linked to cancer development, as abnormal membrane potentials and ion channel activity can drive tumor progression. In breast cancer, ion channel dysfunction and neuroreceptor-related pathways play significant roles in the cell cycle, epithelial–mesenchymal transition, angiogenesis, inflammation, the tumor microenvironment, and tumor progression. Neuroreceptors are critical not only in initiating and advancing cancer but also in conferring resistance to treatments. Neuroreceptors also play a key role, with dopamine receptor D2 activation reducing breast tumor growth by 40% in preclinical models, while serotonin signaling has been shown to promote epithelial–mesenchymal transition (EMT), increasing invasiveness. Advances in understanding these biological mechanisms could lead to more cost-effective and less invasive therapeutic strategies to treat tumors. This review explores the expanding evidence connecting bioelectric activity to breast cancer, focusing on neuroreceptor pharmacology as a transformative therapeutic approach. Examining the modulation of bioelectricity through neuroreceptor pharmacology to influence breast cancer progression and integrating these insights into therapeutic development offers a promising path for addressing treatment challenges and improving precision in managing aggressive cancer subtypes. Full article

Heat stress is one of the major factors affecting crop growth and yield. However, the molecular mechanisms underlying rice heat stress tolerance remain largely unclear. In this study, we identified and characterized the rice high temperature sensitive 2 (hts2) mutant, which is highly susceptible to heat stress. Map-based cloning revealed that the HTS2 encodes a cytochrome P450 protein (CYP71P1) involved in serotonin biosynthesis. HTS2 is ubiquitously expressed across plant tissues and shows strong upregulation in response to heat stress. The HTS2 mutation significantly impairs basal serotonin synthesis in rice, and the heat-sensitive phenotype of the hts2 mutant is completely rescued by exogenous serotonin supplementation. Compared to the wild type, the hts2 mutant exhibits reduced antioxidant capacity, leading to excessive reactive oxygen species (ROS) accumulation and severe oxidative damage, ultimately reducing heat stress tolerance. Furthermore, disruption of HTS2 significantly affects the rice heat shock response, with the heat-induced expression of HsfA2s and their downstream target genes, such as HSP18.0 (heat shock protein 18.0) and OsAPX2 (ascorbate peroxidase 2), markedly depressed in hts2 mutant. Our results suggest a pivotal role of HTS2 in modulating serotonin metabolism and maintaining ROS homeostasis during heat stress, offering new perspectives on the mechanisms underlying heat tolerance and potential strategies to enhance rice resilience to heat stress. Full article

Background/Objectives: Mental disorders such as anxiety, schizophrenia, and depression are linked to alterations in neuroplasticity and neuroprotection within the central nervous system. While conventional drugs are widely used, medicinal plants are emerging as a promising alternative due to their potential therapeutic effects on neuronal function. This study aimed to explore and analyze the impact of medicinal plants on neuroplasticity and neuroprotection in relation to mental disorders using biomodels. Methods: Data were collected from Scopus, Dimensions, and PubMed by using the search terms “Medicinal plants”, “Neuronal Plasticity”, and “Mental Disorder” in accordance with the guidelines of the PRISMA checklist. Results: A total of twenty-three relevant studies were selected to investigate the association between medicinal plants and mental disorders, focusing on factors such as administered doses and the modulation of neurotransmitters in the context of neuroplasticity and neuroprotection. This review highlights the complexity of study designs, target populations, and methodologies. Of the studies, 86% investigated depression, while 13% focused on anxiety. Regarding neurotransmitter modulation, 47% found that medicinal plants influenced serotonin levels, followed by 27% which found that they affected dopamine; according to the remaining studies, medicinal plants impacted norepinephrine, GABA, and acetylcholine. These findings emphasize the importance of precise dosing and neurotransmitter modulation, suggesting that targeted interactions with neural systems may help clarify the specific effects of these plants on mental health. Conclusions: Research on the effects of medicinal plants on psychiatric disorders in animal models suggests their potential to support neuroplasticity and neuroprotection. Positive impacts on mental health are indicated through the modulation of cytokines, neurotransmitters, and specific signaling pathways. Full article

Lysergic acid diethylamide (LSD) is gaining renewed interest as a potential treatment for anxiety, depression, and alcohol use disorder, with clinical trials reporting significant symptom reductions and long-lasting effects. LSD modulates serotonin (5-HT2A) receptors, which, in turn, influence dysfunctional brain networks involved in emotional processing and cognition. It has also shown promise in psychedelic-assisted psychotherapy, where mystical-type experiences are linked to improved psychological well-being. This review examines LSD’s pharmacokinetics, neurobiological mechanisms, and safety considerations, including cardiovascular risks, emotional vulnerability, and the potential for hallucinogen-persisting perception disorder (HPPD). Challenges such as small sample sizes, variable dosing protocols, and regulatory restrictions limit large-scale trials. Future research should focus on standardization, pharmacogenetic influences, and personalized treatment strategies to ensure its safe and effective integration into clinical practice. Full article

Agmatine is a naturally occurring biogenic amine that acts primarily as an inhibitor of neuronal nitric oxide synthase (nNOS). Previous studies have shown that both acute and chronic agmatine administration induced anxiolytic and antidepressant-like effects in rodents. In the dorsal raphe nucleus (DRN), nitric oxide (NO) donors inhibit serotonergic (5-HT) neuronal activity, with the nNOS-expressing 5-HT neurons showing lower baseline firing rates than the non-nNOS expressing neurons. Our study aimed to test the hypothesis that the psychoactive effects of agmatine are mediated, at least in part, via a mechanism involving the stimulation of the DRN 5-HT neurons, as well as to assess the molecular pathway allowing agmatine to modulate the excitability of 5-HT neurons. Using extracellular in vivo electrophysiology, we demonstrated that both acute (1–3 mg/kg, i.v.) and chronic (40 mg/kg/day, i.p., 14 days) agmatine administration significantly increased the firing rate of DRN 5-HT neurons. Quantitative PCR (qPCR) analysis revealed that chronic agmatine treatment selectively upregulated the expression of serotonin-1B (5-HT_1B) and serotonin-2A (5-HT_2A) receptor mRNA in the DRN. Previous studies have shown that DRN 5-HT_2A receptor activation stimulates 5-HT neurons and produces antidepressant-like effects; our findings suggest that agmatine’s excitatory effect on DRN 5-HT neurons may be partially 5-HT_2A receptor-dependent. Given that modulation of the 5-HT neuronal firing activity is critical for the proper antidepressant efficacy, nNOS inhibitors can be potential antidepressants by their own and/or effective adjuncts to other antidepressant drugs. Full article

Serotonin (5-HT), dopamine (DA), and norepinephrine (NE) are key monoamine neurotransmitters regulating behaviors, mood, and cognition. 5-HT affects early brain development, and its dysfunction induces brain vulnerability to stress, raising the risk of depression, anxiety, and autism in adulthood. These neurotransmitters are synthesized from tryptophan and tyrosine via hydroxylation and decarboxylation, and are metabolized by monoamine oxidase (MAO). This review aims to summarize the current findings on the role of dietary phytochemicals in modulating monoamine neurotransmitter biosynthesis, metabolism, and function, with an emphasis on their potential therapeutic applications in neuropsychiatric disorders. Phytochemicals exert antioxidant, neurotrophic, and neurohormonal activities, regulate gene expression, and induce epigenetic modifications. Phytoestrogens activate the estrogen receptors or estrogen-responsive elements of the promoter of target genes, enhance transcription of tryptophan hydroxylase and tyrosine hydroxylase, while inhibiting that of MAO. These compounds also influence the interaction between genetic and environmental factors, potentially reversing dysregulated neurotransmission and the brain architecture associated with neuropsychiatric conditions. Despite promising preclinical findings, clinical applications of phytochemicals remain challenging. Advances in nanotechnology and targeted delivery systems offer potential solutions to enhance clinical efficacy. This review discusses mechanisms, challenges, and strategies, underscoring the need for further research to advance phytochemical-based interventions for neuropsychiatric diseases. Full article

The brain serotonin (5-HT) system modulates glutamatergic and GABAergic transmission in almost every brain area, crucially regulating mood, food intake, body temperature, pain, hormone secretion, learning and memory. Previous studies suggest a disruption of the brain 5-HT system in Fragile X Syndrome, with abnormal activity of the 5-HT transporter leading to altered 5-HT brain levels. We provide an update on therapeutic effects exerted by drugs modulating serotonergic transmission on Fragile X patients and animal models. The enhancement of serotonergic transmission using Selective Serotonin Reuptake Inhibitors (SSRIs) corrected mood disorders and language deficits in Fragile X patients. In Fmr1 KO mice, a model of Fragile X Syndrome, selective 5-HT₇ receptor agonists rescued synaptic plasticity, memory and stereotyped behavior. In addition, drugs specifically acting on 5-HT_1A, 5-HT₂ and 5-HT₅ receptor subtypes were able to correct, respectively, epilepsy, learning deficits and hyperactivity in different Fragile X animal models. In conclusion, the SSRI treatment of Fragile X patients improves mood and language; in parallel, studies on animal models suggest that compounds selectively acting on distinct 5-HT receptor subtypes might provide a targeted correction of other Fragile X phenotypes, and thus should be further tested in clinical trials for future therapy. Full article

The aim of this work is to introduce a computer science solution to manage emotions and affections and connect them to the causes as in humans. The scientific foundation of this work lies in the ability to model the affective and emotional states of an individual or artificial intelligence (AI). Then, in this study, we go a step further by exploring how to extend this capability by linking it to the underlying causes—specifically, by establishing a connection between emotions, affective states, and neurotransmitter activities. The methods used in this study pertain to decision support systems based on complexity theory. Specifically, for the training of the platform to study the link between emotions/affections and neurotransmitters, an electroencephalogram (EEG) acquisition module is integrated into the platform. As a result, this solution provides the bedrock for next-generation AI, i.e., artificial rational–emotive decision-makers. In addition, this research studies the connection of EEG data with neurotransmitters’ activity, opening pathways to applications such as emotional monitoring, mental health, and brain–computer interfaces, adding to cognitively and emotionally enriched AI. The main result of this study is a platform able to manage artificial neurotransmitters such as adrenaline, GABA, dopamine, serotonin, oxytocin, endorphins, and the hormone cortisol for emulating and motivating emotive and affective states. In conclusion, this study highlights the following: (i) the possibility of conducting indirect measurements of emotional states based on EEG data, (ii) the development of a framework capable of generating a wide spectrum of emotional states by modulating neurotransmitter levels within a defined discrete range, and (iii) the ability to establish a connection between neurotransmitters (causes) and emotional states (effects). Full article

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder marked by abdominal pain and irregular bowel habits. Recently, more and more evidence supports gut microbiota imbalance in IBS and highlights the potential of probiotics in restoring gut health and reducing symptoms. In this study, we explored the effects of Lactococcus cremoris PS133 (PS133) on an IBS-like condition in rats triggered by 5-hydroxytryptophan (5-HTP), a serotonin precursor. Eight-week-old Sprague Dawley rats received either PS133 or saline for 14 days, followed by 5-HTP to induce IBS-like symptoms. Colorectal distension tests showed that PS133 reduced visceral hypersensitivity. PS133 also protected intestinal mucin against 5-HTP-induced degradation, as seen in alcian blue staining, and increased the levels of tight junction proteins (occludin and zonula occludens-1) in the colon, indicating improved gut barrier integrity. Additionally, PS133 normalized the levels of substance P (a neuropeptide) in the spinal cord and altered 5-hydroxyindoleacetic acid (a serotonin metabolite) in the brain. Gut microbiota analysis revealed PS133 regulated specific bacterial groups, including [Eubacterium]_coprostanoligenes_group and Lactococcus. Overall, PS133 improved gut function, reduced IBS-like symptoms, and modulated gut microbiota, neurotransmitters, and intestinal barrier health in this IBS model. Full article

Monoamine neurotransmitters play a critical role in the development and function of the nervous system. In this study, we investigated the impact of parental serotonin (5-HT) modulation on the monoamine balance in the identified apical neurons of Lymnaea stagnalis embryos and its influence on embryonic locomotor activity. Using immunocytochemical and pharmacological approaches, we detected serotonin in the apical neurons of veliger-stage embryos, observing that the relative 5-HT level within these neurons varied with seasonal conditions. Pharmacological elevation of parental 5-HT levels significantly increased the relative 5-HT level in the oocytes and subsequently in the apical neurons of their offspring. Notably, while the relative dopamine (DA) levels in these neurons remained stable, the increase in the relative 5-HT level significantly enhanced the embryos’ rotational locomotion. The expression of tryptophan hydroxylase (TPH), a key enzyme in serotonin synthesis, is a prerequisite for the elevation of the relative 5-HT level in apical neurons and is detected as early as the gastrula stage. Importantly, neither a reduction of 5-HT in the maternal organism by chlorpromazine application nor its pharmacological elevation via serotonin precursor (5-HTP) application at the cleavage stage affected the monoamine balance in apical neurons. These findings provide novel insights into how the parental 5-HT level selectively alters the monoamine phenotype of the identified neurons, offering a model for studying environmentally induced neural plasticity in early development. Full article

The crisis of metabolic and mental disorders continues to escalate worldwide. A growing body of research highlights the influence of tryptophan and its metabolites, such as serotonin, beyond their traditional roles in neural signaling. Serotonin acts as a key neurotransmitter within the brain–gut–microbiome axis, a critical bidirectional communication network affecting both metabolism and behavior. Emerging evidence suggests that the gut microbiome regulates brain function and behavior, particularly through microbial influences on tryptophan metabolism and the serotonergic system, both of which are essential for normal functioning. Additionally, sex differences exist in multiple aspects of serotonin-mediated modulation within the brain–gut–microbiome axis, affecting feeding and affective behaviors. This review summarizes the current knowledge from human and animal studies on the influence of tryptophan and its metabolite serotonin on metabolic and behavioral regulation involving the brain and gut microbiome, with a focus on sex differences and the role of sex hormones. We speculate that gut-derived tryptophan and serotonin play essential roles in the pathophysiology that modifies neural circuits, potentially contributing to eating and affective disorders. We propose the gut microbiome as an appealing therapeutic target for metabolic and affective disorders, emphasizing the importance of understanding sex differences in metabolic and behavioral regulation influenced by the brain–gut–microbiome axis. The therapeutic targeting of the gut microbiota and its metabolites may offer a viable strategy for treating serotonin-related disorders, such as eating and affective disorders, with potential differences in treatment efficacy between men and women. This review would promote research on sex differences in metabolic and behavioral regulation impacted by the brain–gut–microbiome axis. Full article

Emerging evidence links depressive disorders to the gut microbiota via the gut–brain axis. Probiotics, which are microorganisms that modulate the gut microbiota, have shown promising results in alleviating depression and are increasingly recognized as functional food components with potential health benefits. This study examines the effects of Lactiplantibacillus plantarum GOLDGUT-HNU082 (Lp082), a probiotic strain with potential applications in functional foods, on chronic unpredictable mild stress (CUMS)-induced depression in mice. Behavioral tests, measurements of the neurotransmitters and inflammatory cytokines in the serum and colon tissue, and the metagenomic sequencing of the gut microbiota were used to investigate potential mechanisms. The results demonstrated that Lp082 significantly alleviated depressive-like behaviors in CUMS mice, restored the balance of key neurotransmitters like serotonin (5-HT), reduced the levels of inflammatory cytokines like TNF-α, and enhanced brain neuroplasticity by promoting hippocampal neurogenesis. Additionally, Lp082 altered the composition of the gut microbiota in CUMS mice and promoted the growth of Bifidobacterium, improving metabolic pathways related to neurotransmitter synthesis. These findings indicate that Lp082, as a potential functional food ingredient, alleviates depressive-like behaviors in mice by reshaping the gut microbiota, offering new insights into the use of probiotics in functional foods for mental health management. Full article