Search Results (1,208)

Zearalenone (ZEA) is a potent estrogenic mycotoxin known to disrupt reproductive functions, but its precise central neuroendocrine mechanisms remain unclear. This study investigated the effects of ZEA on the hypothalamic-pituitary Kiss1/GPR54 signaling pathway in weaned gilts. A total of 32 gilts were randomly assigned to four dietary treatments contained with 0, 0.15, 1.5, or 3.0 mg/kg ZEA for a 32-day feeding trial. Histopathology, immunohistochemistry, and mRNA/protein expression analyses of GPR30, Kiss1, GPR54, GnRH, and GnRHR in the hypothalamus and pituitary gland were conducted. ZEA exposure induced significant histological damage in both tissues. In the hypothalamus, Kiss1, GPR54, GnRH, and GnRHR exhibited a non-linear response, increasing at moderate doses and decreasing at 3.0 mg/kg ZEA, whereas GPR30 expression was continuously upregulated. In the pituitary gland, GnRHR showed a similar non-linear pattern. Furthermore, high-dose ZEA down-regulated pituitary Kiss1 and GPR54 while up-regulating GnRH and GPR30 expressions. In conclusion, ZEA induces reproductive neuroendocrine toxicity through a complex, dose-dependent modulation of the Kiss1/GPR54 signaling axis. The persistent upregulation of GPR30 suggests it acts as a crucial mediator in disrupting this endocrine feedback loop within the hypothalamus and pituitary gland. Full article

Background: The dorsal raphe nucleus (DRN) produces and distributes serotonin, while the hypothalamus (HYP) uses serotonergic signals to regulate physiological processes in chickens. Coconut oil (COCO), rich in medium-chain fatty acids, is rapidly absorbed without re-esterification. Methods: Day-old broilers (Ross 708 male, n = 160) were distributed into two dietary treatments with five replicates of 16 birds each. The birds were fed a corn–soybean meal (SBM) basal diet supplemented with 3% of poultry fat (CON) or coconut oil (COCO). The body-weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were recorded over a 3-week period, and the data were subjected to a t-test. Untargeted metabolomic analysis by high-performance liquid chromatography (HPLC-MS) was used to evaluate the influence of the type of dietary fat on metabolite profiles in the DRN, HYP, and plasma of broiler chickens. Principal component analysis (PCA) was used to identify unique metabolites, and ANOVA was used to identify the metabolites that were significantly abundant (p < 0.05). The metabolites were then annotated using the KEGG and HMDB databases. Results: Birds in the COCO treatment gained more weight on average (0.8446 kg/bird) than birds in the CON group (0.8132 kg/bird; p = 0.0496). Five metabolites associated with multiple significant cellular processes, such as brain function, energy metabolism, and neurotransmission, showed similar differential expression patterns, while two metabolic pathways (butanoate metabolism and alanine, aspartate and glutamate metabolism) were identified. Conclusions: The dietary inclusion of COCO improves BWG in poultry and enhances their overall well-being by modulating metabolite profiles, supporting neurotransmission, and enriching the metabolic pathways essential for growth and brain function. Full article

As a representative form of extreme weather, typhoons inflict widespread and systemic damage, posing a severe threat to the livestock industry. The stress they induce, typhoon stress (TS), is an unavoidable and complex environmental challenge that severely disrupts the ovarian function of Wenchang chickens. In this preliminary study, we employed a two-group comparison design (n = 6 per group) integrating behavioral observations, serum biochemical assays, histopathological examinations, and molecular analyses (qPCR, 16S rDNA sequencing, and transcriptome sequencing) to explore the role of the microbiota–gut–brain–ovarian axis (MGBOA) in this process. The findings revealed that TS markedly reduced water intake and locomotor activity, while it elevated serum corticosterone (CORT) and oxidative stress markers. It also induced shifts in gut microbiota composition, including a decrease in Bacteroides and an increase in Escherichia–Shigella. Furthermore, TS compromises duodenal intestinal barrier integrity, as evidenced by downregulation of the tight junction proteins TJP1 and CLDN1, structural damage to intestinal villi, and a reduced villus-to-crypt ratio. In the hypothalamus, VIP mRNA expression was upregulated, while GHSR expression was downregulated; the expression of the tight junction protein CLDN5 was also reduced. In the ovary, reproductive potential was suppressed, manifested by a reduction in follicle number and downregulation of STAR expression. Ovarian transcriptome analysis highlighted enrichments in pathways associated with inflammation (e.g., Toll-like receptor signaling) and lipid metabolism (e.g., PPAR signaling). These results support the hypothesis that TS impairs egg production via the MGBOA, providing preliminary mechanistic insights into how environmental stressors might disrupt animal productivity through MGBOA-mediated pathways. Full article

Eating behavior requires a balance between metabolic and hedonic components. Anxiety and dietary type may influence the quantity, patterns, and other aspects of food intake. Modern diets, especially in Western societies, often contain high levels of calories from fat and simple sugars (e.g., cafeteria-style diets). This type of diet may promote overweight and/or obesity in some, although many consumers remain at a normal weight. The mechanisms underlying susceptibility or resistance to weight gain remain unclear. Here, Sprague-Dawley male rats were fed a cafeteria diet for 10 weeks and then classified into quartiles based on body mass. We evaluated locomotor activity and anxiety-like behaviors and analyzed hypothalamic proteomics in overweight (Q4) rats compared with underweight (Q1) rats. Our results showed that locomotor activity and anxiety-like behaviors did not differ across quartiles (p > 0.05). Nevertheless, the expression of several hypothalamic proteins differed between Q4 and Q1 rats. Functional enrichment analysis of these differentially expressed proteins (p ≤ 0.05) revealed changes in cytoskeleton dynamics, synaptic communication, energy production and utilization, biosynthesis of cellular components (including nucleotides and carbohydrates), and regulation of metabolism between Q1 and Q4 rats. Neuro-humoral hypothalamic output regulates metabolism and food intake. Therefore, these functional changes in the hypothalamus may be associated with rats’ susceptibility/resistance to weight gain. Full article

Pluripotent stem cells (PSCs) have proven outstanding potential to revolutionize biomedical research. Specifically, their capacity to form 3D multicellular systems that recapitulate organ development and biology, known as organoids, has transformed basic and translational research. The groundbreaking technology is also being applied to the intricate hypothalamus–pituitary (HP) axes, including the target organs (such as gonads, thyroid and adrenal glands). These HP axes govern critical physiological processes, including reproduction, metabolism and stress. Here, we provide an overview of PSC-derived organoid models that are part of the HP axes, both as individual and multi-organ systems, and evaluate their culturing conditions, phenotypic characteristics, advantages, drawbacks and challenges, as well as their potential for disease modeling and therapeutic discovery. By offering this wide perspective, our review will also serve as a key resource for researchers navigating the evolving landscape of PSC-derived organoid technologies in endocrinology. Full article

Gonadotropin-releasing hormone 1 (GnRH1) and its receptor (GnRHR1) are central neuropeptides on the hypothalamic–hypophysis–gonadal (HHG) axis and play key roles in vertebrate reproduction. Although GnRH1/GnRHR1 signaling has been extensively studied in models such as mouse, rat, zebrafish, and human, knowledge from other species is limited. This work used cloning, Sanger sequencing, and qPCR to highlight the molecular structure, evolutionary history, and sex-differentiated transcription of GnRH1/GnRHR1 signaling from hamster. These findings showed that GnRH1/GnRHR1 hamster proteins exhibit a molecular evolutionary history highly similar for peptides reported in other species and with which they share a high degree of structural homology. Expression profiles indicated a GnRH1 transcript in several tissues with higher expression levels in testes, adrenals, uterus, epididymis, female hypothalamus, and Harderian glands. GnRHR1 expression levels were seen exclusively in male and female hypophysis with higher levels in female hypophysis. Expression levels showed significant differences for GnRH1 in several tissues during estrous; GnRHR1 expression during estrous was detected only in hypophysis with increased expression levels seen during metestrus and diestrus. These results suggest a highly conserved homology of GnRHR1/GnRHR1 signaling, thus highlighting its evolutionary importance. These expression levels underscore the importance of GnRHR1 as a master regulator of reproductive endocrinology and could implicate hamster peptides as potential therapeutic biological models for human endocrine diseases. Full article

Background: Paraneoplastic limbic encephalitis (PLE) with anti-Ma2 antibodies is a rare immune-mediated disorder associated with testicular cancer, particularly in young males. While neurological manifestations are well documented, hypothalamic–pituitary dysfunctions remain underreported. We present a case of anti-Ma2 PLE associated with testicular cancer together with a systematic review of PLE associated with testicular cancer, selectively restricted to anti-Ma2 positive cases and focusing on hypothalamic–endocrine involvement. Case presentation: We describe a 21-year-old male diagnosed with anti-Ma2 PLE and intratubular germ cell neoplasia of the right testis. He underwent orchifunicolectomy and immunosuppressive therapy with neurological improvement. Four years later, he developed new-onset temporal seizures, decreased libido, and a polyuria–polydipsia syndrome. Dynamic endocrine testing, including a water deprivation test and copeptin measurement, supported a diagnosis of partial central diabetes insipidus (CDI). Methods: A systematic literature review was performed in accordance with PRISMA guidelines. PubMed was searched using predefined keywords without time restriction. Studies reporting PLE associated with testicular tumors in humans with confirmed anti-Ma2 antibody positivity were included. Results: Eleven studies were included, reporting a total of 38 patients with anti-Ma2-associated PLE and testicular cancer. Hypothalamic or diencephalic involvement was described in 16 patients (42.0%), while endocrine manifestations were explicitly reported in four cases. Only two previous reports mentioned CDI, without detailed diagnostic evaluation. Conclusions: This study highlights the importance of recognizing hypothalamic-endocrine manifestations in PLE. In patients presenting with polydipsia and polyuria, CDI should be carefully differentiated from primary polydipsia using dynamic testing. Hypothalamic involvement may emerge years after tumor treatment, warranting long-term endocrine surveillance. Full article

Puberty is a neuroendocrine process required for sexual maturity; it is regulated by the hypothalamic–hypophysis–gonadal (HHG) axis. Kisspeptin (KISS1) plays a vital role in activating this axis by stimulating the secretion of gonadotropin-releasing hormone (GnRH). Cadmium (Cd) exposure disrupts KISS1 signaling in female rodents; its effects on hypothalamic gene expression during male puberty remain poorly understood. This study investigated the effects of Cd exposure on hypothalamic Kiss1, Kiss1r, and Gnrh1 expression, preputial separation (PS) as a marker of pubertal onset, testosterone levels, Cd concentration, and total antioxidant capacity (TAC) in the serum and hypothalamus of pubertal male Wistar rats. Animals received once a week intraperitoneal injection of CdCl₂ (1 mg/Kg body weight/100 µL) or saline (100 µL) and were euthanized on postnatal day (PND) 35 or 49. Cd exposure reduced serum testosterone levels and TAC. Also, pubertal onset was delayed. At PND 35, Cd decreased hypothalamic Kiss1 expression, whereas at PND 49, it reduced Kiss1r and Gnrh1 expression. These results suggest that Cd alters hypothalamic gene expression, which may contribute to delayed puberty and impaired sexual maturity. Our findings suggest the vulnerability of puberty to exposure to Cd, acting as an endocrine disruptor and neurotoxicant, with alterations for male reproductive maturity. Full article

Background/Objectives: Non-thyroidal illness syndrome (NTIS) also known as low FT3 syndrome is characterized by altered thyroid hormone levels during severe illness, is common in end-stage renal disease, and reflects metabolic and inflammatory stress. This study evaluated the thyroid hormone profiles of patients undergoing maintenance hemodialysis, assessing relationships between NTIS severity and dialysis adequacy while accounting for mineral and bone metabolism markers, anemia status, duration of dialysis therapy, and their association with the number of deaths during follow-up. Methods: This prospective bi-center study included adults receiving maintenance hemodialysis for at least 3 months. Patients treated for thyroid disease or taking medications affecting the hypothalamus–pituitary–thyroid axis were excluded. Thyroid-stimulating hormone, free triiodothyronine (fT3), and free thyroxine (fT4) levels were measured, and dialysis adequacy was assessed using spKt/V. Patients were classified as euthyroid or having NTIS (stratified by severity), and associations between clinical characteristics and the number of deceased patients during a 6-month observation period were analyzed using receiver operating characteristic (ROC) curves to determine prognostic cut-off values for thyroid hormones. Results: Among 74 patients, 50% had NTIS and exhibited significantly lower dialysis adequacy than euthyroid individuals (median spKt/V 1.0 vs. 1.1; p = 0.03), with spKt/V declining as NTIS severity increased (stages I–III, p = 0.008). NTIS severity correlated with age and pulmonary comorbidities, while mineral and bone metabolism markers were comparable between the groups. During the 6-month follow-up, 23% of the patients died, exhibiting significantly lower fT3 and fT4 levels than survivors. ROC analysis identified clinically relevant fT3 and fT4 cut-off values that were associated with the number of deaths. Conclusions: NTIS in hemodialysis patients correlates with reduced dialysis adequacy and appears to be a prognostic factor for risk of death. NTIS severity correlated with declining spKt/V, potentially reflecting disease burden, and thyroid hormone assessment may provide prognostic information. Full article

The global poultry industry faces escalating challenges in animal welfare and production efficiency in the post-antibiotic era. Feed intake, a crucial determinant of growth, is frequently suppressed under stress, forming a key bottleneck for sustainable production. The microbiota–gut–brain (MGB) axis provides a novel framework to understand this complex regulation. Short-chain fatty acids (SCFAs), produced from dietary fiber by gut microbiota, serve as vital chemical messengers within this axis, modulating hypothalamic feeding centers and systemic metabolism. This review summarizes SCFA biosynthesis and kinetics in poultry and examines their neural, humoral, and immune pathways to the brain. Emphasis is placed on receptor-mediated signaling, epigenetic regulation, energy sensing, and neuroimmune modulation through which SCFAs regulate feeding and reduce inflammation. Practical strategies—such as substrate engineering, microbiota modulation, and exogenous regulators—are discussed to enhance SCFA levels and poultry health. Future directions include multi-omics integration, novel additives, and predictive models to advance antibiotic-free nutrition. Full article

Aggressive behavior in Muscovy ducks (Cairna moschata) has become a predominant concern in intensive farming systems, leading to reduced animal welfare and production losses. To unravel the molecular mechanisms underlying this behavior, transcriptomic profiling was performed on the hypothalamus, a key regulatory hub for aggressive responses. A total of 120 healthy 60-day-old female Muscovy ducks were continuously monitored for 24 h/day over one month using Media Recorder 2.0 software. Based on instantaneous and continuous behavioral observations, the ducks were categorized into three groups: aggressor (Experimental group I, actively attacking conspecifics), victim (Experimental group II, receiving aggression), and non-aggressive (Control group, no aggressive interactions). Hypothalamic tissues were collected from each group (n = 4 per group) for Illumina HiSeq 2000 high-throughput transcriptome sequencing. Functional annotation and enrichment analysis of differentially expressed genes (DEGs) were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, followed by quantitative real-time PCR (qRT-PCR) validation. GO analysis identified 626 DEGs in the aggressor group and 649 DEGs in the victim group compared to the control group, with 26 DEGs directly involved in aggressive behavior regulation. Integration of GO and KEGG annotations revealed 69 candidate genes associated with aggressive behavior, enriched in two GO terms (behavior [GO:0007610] and sensory perception of pain [GO:0019233]) and the ERBB signaling pathway (map04012). qRT-PCR validation of 14 randomly selected candidate genes (e.g., NPY, ERBB4, MAPK9, PRDM12) confirmed that their expression patterns were consistent with transcriptomic data, verifying the reliability of the sequencing results. These findings provide novel insights into the molecular genetic basis of aggressive behavior in Muscovy ducks and lay a foundation for developing targeted strategies to mitigate aggression in intensive farming systems. Full article

Background: Chronic insomnia disorder (CID) frequently coexists with diarrhea-predominant irritable bowel syndrome (IBS-D), a comorbidity characterized by gut–brain axis dysfunction and persistent inflammatory activation. However, the molecular mechanisms underlying this overlap remain incompletely understood, and effective multitarget interventions are lacking. Objectives: This study aimed to identify quercetin as a potential bioactive compound for IBS-D-associated insomnia and to investigate whether its protective effects are associated with modulation of the PI3K/AKT/NF-κB signaling pathway. Methods: CID- and IBS-D-related targets were collected from public databases. Candidate compounds were screened using bioinformatics and network pharmacology analyses, followed by molecular docking. Experimental validation was conducted in 36 male C57BL/6J mice assigned to control, CID+IBS-D model, quercetin-treated, and quercetin-plus-Recilisib-treated groups. Sleep-related behavior, EEG/EMG-derived sleep architecture, intestinal function, inflammatory markers, and pathway-related proteins were assessed. Results: Quercetin was identified as a core candidate compound. Network pharmacology revealed 43 shared targets among CID, IBS-D, and quercetin, with significant enrichment in PI3K/AKT-related signaling. In vivo, quercetin improved sleep-associated phenotypes and intestinal dysfunction; reduced visceral hypersensitivity; restored ZO-1 and Occludin expression; suppressed hypothalamic and colonic inflammatory responses; and was accompanied by reduced phosphorylation of PI3K, AKT, IκB, and NF-κB p65 in the hypothalamus. Quercetin also increased hypothalamic 5-HT1A and GABA_A Rα5 expression. These effects were partially reversed by Recilisib, supporting the involvement of PI3K/AKT-associated signaling in quercetin-mediated protection. Conclusions: Quercetin alleviated key sleep-related and IBS-D-like phenotypes in a composite murine model of gut–sleep comorbidity. The protective effects were associated with reduced inflammatory activation and modulation of PI3K/AKT/NF-κB-related signaling. These findings support quercetin as a promising candidate for gut–brain axis-related comorbid disorders, while further studies are needed to define pathway specificity, tissue exposure, and translational applicability. Full article

The present study investigated the impact of microplastics, specifically polystyrene microparticles (PS-MP), on the hypothalamic-pituitary-gonadal (HPG) neurohormonal axis, which regulates reproductive functions in animals and humans. The primary objective was to examine the effects of PS-MP on the expression of key genes and hormone concentrations within the gonadotropic system of sheep. Two doses of PS-MP—the lower dose (LD; 0.015 mg/kg) and the higher dose (HD; 0.15 mg/kg)—were administered intravenously every three days over two estrous cycles (34 days). Both doses significantly decreased the relative abundance of gonadotropin-releasing hormone (GnRH) transcripts in the mediobasal hypothalamus (MBH), whereas only the HD reduced GnRH mRNA levels in the preoptic area (POA). These transcript-level changes were not accompanied by detectable alterations in GnRH protein concentration. In the MBH, the expression of kisspeptin (KISS-1) and neurokinin B (NKB) genes decreased following exposure to the HD, whereas in the POA, significant decrease in expression were observed only after the LD administration. Changes in prodynorphin (PDYN) gene expression were confined to the MBH and were dose-dependent: the LD increased transcript levels, whereas the HD caused a decrease. The HD of PS-MP also significantly downregulated GnRH receptor (GnRHR) expression in the anterior pituitary (AP). Both PS-MP doses resulted in marked reductions in luteinizing hormone beta (LHβ) and follicle-stimulating hormone beta (FSHβ) subunit gene expression in the AP, without significant changes in hormone protein concentrations. Exposure to PS-MP reduced plasma LH and FSH concentrations: the lower dose reduced both hormones, while the higher dose significantly reduced mainly FSH, showing statistical differences between doses. To summarize, the present study demonstrates that PS-MP exerts a modulatory effect on the secretory activity of the central reproductive system in sheep, at both the hypothalamic and pituitary levels. Consequently, PS-MP has the potential to induce significant disruptions to the reproductive processes of large farm animals. Full article

Background: Obesity is associated with hypothalamic dysfunction characterized by neuroinflammation and altered transcriptional programs. While resveratrol (RSV) has shown beneficial metabolic effects in peripheral tissues, its central effects on hypothalamic gene expression in obesity remain poorly understood. This study provides the first predictive transcriptomic analysis of the hypothalamic response to RSV in a mouse model of diet-induced obesity. C57BL/6 male mice were fed a high-fat diet (HFD) to induce obesity and then subsequently treated with RSV. Methods: Hypothalamic RNA was extracted and analyzed using RNA sequencing. Differentially expressed genes (DEGs) were identified and functionally analyzed through KEGG pathway analysis. Results: Although RSV did not significantly alter body weight, it reversed the expression of several HFD-induced DEGs. Key genes modulated by RSV included Aqp7, Ccl27a, Lta, Rilp, M6pr-ps, C1ra, Snail1, Gbgt1, and Ppargc1b, which are involved in inflammation, lipid metabolism, mitochondrial function, and immune signaling. Pathway enrichment analysis revealed significant modulation of TNF and NF-κB signaling, cytokine–cytokine receptor interactions, glycosphingolipid biosynthesis, and phagosome-related activity. Remarkably, 45% of RSV-responsive transcripts were non-coding RNAs, suggesting epigenetic regulation. Conclusions: RSV reprograms the hypothalamic transcriptome in obesity, targeting both coding and non-coding RNAs associated with inflammation and metabolic regulation, independently of weight loss. These findings identify RSV as a potential central modulator of metabolic dysfunction and highlight the hypothalamus as a promising therapeutic target in obesity-related disease. Full article

Background: Posttraumatic stress disorder (PTSD) is a mental illness in which central stress-regulating regions, including locus coeruleus (LC) and paraventricular nucleus of hypothalamus (PVN), play key roles. Clonidine, a central sympatholytic drug, can inhibit LC activity and reduce PTSD-related symptoms, suggesting noradrenergic involvement. Glia-driven immune mechanisms may link LC activity to PVN responses. Since TRPA1 ion channel is implicated in both neuroinflammation and stress adaptation, we aimed to determine whether its presence modulates the function of brain structures contributing to PTSD-related alteration in central stress adaptation. Methods: Foot shock PTSD model was applied to Trpa1 wild-type (WT) and knockout (KO) mice, and outcomes were assessed four weeks later. Immunohistochemistry was used to evaluate tyrosine hydroxylase (TH) levels in the LC and glial activation in the PVN. Behavioral effects of clonidine and circulating corticosterone levels were also examined. Results: Stress increased LC/TH immunoreactivity and PVN glial activation. Trpa1 deletion exaggerated LC/TH responses but reduced PVN astrocyte activation. Clonidine increased freezing and decreased jumping (a hyperarousal marker). KO mice showed enhanced jumping and did not respond to clonidine. Corticosterone levels remained unchanged. Conclusions: TRPA1 may support stress adaptation in PTSD by regulating LC noradrenergic output and PVN neuroinflammation, independently of α₂-adrenergic signaling. Full article