Search Results (323)

Hypothyroidism is associated with metabolic, neurobehavioral, and reproductive alterations that may involve neuroendocrine regulatory peptides. Spexin, a neuropeptide implicated in energy homeostasis, has recently attracted attention for its possible role in thyroid and reproductive axis regulation. Therefore, this study aimed to investigate the effects of spexin on neurobehavioral responses and the tissue-specific expression of irisin and KISS-1 in the cerebral cortex and testis under hypothyroid conditions. Thirty-two male Wistar albino rats were randomly divided into four groups: Control, Hypothyroid (methimazole, 0.03% in drinking water for 35 days), Hypothyroid + Spexin (methimazole plus spexin, 25 µg/kg, intraperitoneally), and Spexin (25 µg/kg, intraperitoneally). Behavioral assessments were performed using the Open Field Test and Forced Swim Test. Serum thyroid hormone levels were analyzed, and brain and testis tissues were evaluated immunohistochemically for irisin and KISS-1 expression. Hypothyroid rats showed increased thyroid-stimulating hormone levels, decreased thyroxine concentrations. Spexin administration significantly reduced TSH levels and increased T4 concentrations. Spexin treatment reduced thigmotaxis compared to controls. No significant differences were found among groups in overall locomotor activity, time spent in the central zone, or FST parameters. Immunohistochemical analyses demonstrated reduced irisin and KISS-1 expression in hypothyroid rats, which was restored following spexin treatment. In conclusion, spexin exerted TSH-suppressive and T4-enhancing effects in experimental hypothyroidism. Its effects on irisin and KISS-1 expression suggest potential involvement in neuroendocrine and reproductive axis regulation. Full article

Adolescence is a developmental stage marked by dynamic interactions between diet, the gut microbiome and endocrine maturation, creating a physiological environment in which early metabolic disturbances can rapidly translate into long-term cardiovascular vulnerability. This narrative review summarises the latest research on the diet–microbiome–hormone axis in adolescents, focusing on the metabolic pathways through which microbial metabolites influence host physiology. Short-chain fatty acids (SCFAs), microbially transformed bile acids and postbiotic signalling molecules regulate enteroendocrine communication, insulin sensitivity, vascular function and inflammatory tone, thereby linking dietary exposures to early cardiometabolic alterations. Dysbiosis, driven by ultra-processed dietary patterns, low fibre intake and reduced microbial diversity, promotes metabolic endotoxemia, neuroendocrine imbalance and endothelial impairment, all of which are recognised as early indicators of cardiovascular disease. A distinctive contribution of this review is the integration of PF into the adolescent cardiometabolic framework. This emerging biotechnological process enables the controlled production of structurally defined bioactive compounds, including angiotensin-converting enzyme (ACE) inhibitory peptides, targeted prebiotic oligosaccharides, fermentable substrates that promote SCFA formation, microbially derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), phytosterols and purified postbiotics. These compounds modulate several regulatory pathways, such as the renin–angiotensin–aldosterone system, lipid and bile acid metabolism, gut barrier stability, inflammatory signalling and endocrine axes involving glucagon-like peptide-1 (GLP-1), peptide YY (PYY), leptin, insulin sensitivity and growth hormone/insulin-like growth factor-1 (GH/IGF-1) dynamics. By situating precision fermentation within the broader context of adolescent metabolic susceptibility, this review highlights its potential to support microbiome resilience, stabilise hormonal regulation and mitigate early cardiovascular risk. However, further adolescent-specific clinical trials and long-term safety assessments are required to translate these advances into effective public health strategies. Full article

Cervical neuroendocrine carcinoma (NECC) is a rare but highly aggressive cervical malignancy, accounting for approximately 1% of invasive cervical cancers. Diagnosis is challenging because NECC overlaps morphologically with other poorly differentiated cervical and metastatic tumors, may show crush artifact in small biopsies, and can display variable expression of conventional neuroendocrine markers. This narrative review provides a practical synthesis of the histopathological, immunohistochemical, molecular, and clinical features of NECC, with emphasis on diagnostic pitfalls and differential diagnosis. Recent English-language literature on cervical neuroendocrine carcinoma was reviewed and qualitatively integrated, focusing on morphology, immunohistochemistry, HPV association, molecular alterations, prognosis, and management-relevant diagnostic issues. Accurate diagnosis requires integration of morphology, epithelial differentiation, neuroendocrine marker expression, HPV-related context, and clinic-radiological correlation. Useful markers include broad-spectrum cytokeratins, synaptophysin, chromogranin A, CD56, INSM1, p16, and Ki-67, with additional markers selected according to the differential diagnosis. Diffuse block-type p16 expression and high-risk HPV detection support a cervical HPV-associated origin but are not specific for neuroendocrine differentiation. Molecular studies show frequent association with HPV18 and recurrent alterations involving PI3K/AKT, RAS/MAPK, and TP53-related pathways, although these findings remain insufficiently validated for routine prognostic or therapeutic stratification. NECC requires early recognition and a multimodal diagnostic approach because of its aggressive behavior and poor prognosis. A practical, stepwise integration of morphology, immunohistochemistry, molecular findings, and clinical–radiological data may improve diagnostic consistency and support multidisciplinary management. Full article

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer (PCa) that emerges under androgen deprivation and is associated with therapeutic resistance. The contribution of volume-regulated anion channels (VRACs) to this process remains poorly understood. This study identified leucine-rich repeat-containing 8 subunit D (LRRC8D), a VRAC subunit, as the only family member consistently downregulated in NEPC and associated with neuroendocrine (NE)-like features. LRRC8D downregulation was accompanied by suppression of swelling-activated VRAC currents, increased synaptophysin (SYP) expression, decreased cisplatin sensitivity, and neurosecretory remodeling. Conversely, LRRC8D overexpression enhanced cisplatin-induced apoptosis, reduced colony formation, and suppressed tumor growth in xenograft models, including under cisplatin treatment. Consistent alterations in LRRC8D and SYP expression were also observed in enzalutamide-resistant patient-derived organoids. Mechanistically, RE1-silencing transcription factor (REST) promoted LRRC8D transcription. Functional analyses further demonstrated that CAV-1 acted upstream of LRRC8D, and LRRC8D negatively regulated STAT3 activation. Together, these findings indicate that LRRC8D influences PCa phenotype and platinum responsiveness, and implicate a regulatory axis involving LRRC8D and CAV-1/STAT3 signaling in NE-associated features of advanced PCa. Functional analyses further showed that CAV-1 acted upstream of LRRC8D, and LRRC8D negatively regulated STAT3 activation. Together, these findings indicate that LRRC8D influences PCa phenotype and platinum responsiveness and implicate a regulatory axis involving LRRC8D and CAV-1/STAT3 signaling in NE-associated features of advanced PCa. Full article

Traumatic brain injury (TBI) induces complex molecular and neuroendocrine alterations that extend beyond the site of injury. The hypothalamic–pituitary–adrenal (HPA) axis, a hierarchically organized neuroendocrine system composed of the hypothalamus, pituitary gland, and adrenal glands, plays a central role in coordinating stress and metabolic homeostasis. Despite its critical importance, the temporal transcriptional mechanisms underlying HPA axis dysregulation following TBI remain poorly understood, particularly in relation to coordinated neuronal injury and regeneration processes. This study aimed to investigate the time-dependent transcriptional dynamics of genes associated with neuronal injury and regeneration within the HPA axis following experimental TBI. Moderate-to-severe TBI was induced in Sprague–Dawley rats using a controlled cortical impact (CCI) model. Animals were allocated into sham, acute (24 h), and chronic (30 days) groups. Transcript profiles of 24 HPA axis- and neuroregeneration-related genes were analyzed in hypothalamic, pituitary, and adrenal tissues using quantitative real-time PCR, with normalization to a housekeeping gene and statistical evaluation of differential expression across time points. TBI induced distinct, tissue-specific, and time-dependent transcriptional alterations across the HPA axis. In the acute phase, stress-response genes showed divergent regulation between central and peripheral tissues, whereas the chronic phase was characterized by transcriptional reorganization involving neurotrophic, metabolic, and neuroendocrine pathways. Key regulators such as Hif1a, Rad18, Avp, Gata3, and OxtR exhibited significant and region-specific expression changes. These findings demonstrate that TBI triggers coordinated yet heterogeneous transcriptional responses within the HPA axis, linking central injury to systemic endocrine adaptation. This study provides novel insight into the molecular basis of neuroendocrine dysfunction and recovery after TBI and identifies candidate targets for future therapeutic strategies. Full article

Background: Functional Neurological Disorder (FND) is a common and disabling condition at the interface of neurology and psychiatry, characterized by motor, sensory, seizure-like, or cognitive symptoms that are incongruent with recognized neurological disease but associated with substantial impairment. Despite its frequency and marked female predominance, FND remains underdiagnosed and often misunderstood. Methods: This narrative review synthesizes evidence from neurobiological, biomarker, and treatment studies, with attention to predictive coding, salience network dysfunction, impaired sense of agency, stress-related mechanisms, and sex- and gender-related vulnerability. Results: Current evidence supports a model of FND as a disorder of distributed brain network dysfunction involving abnormal interactions among salience, limbic, motor, and self-monitoring systems. Predictive coding and impaired agency models provide clinically useful frameworks for understanding symptom generation, although they remain mechanistic hypotheses rather than definitive causal explanations. Candidate biomarkers, including functional connectivity alterations, autonomic dysregulation, and HPA axis measures, offer pathophysiological insight but remain insufficiently validated for routine diagnosis. Female predominance likely reflects interacting biological, psychological, and sociocultural mechanisms rather than a single neuroendocrine pathway. Conclusions: This review contributes an integrated, clinically oriented framework linking neurobiology, biomarkers, sex/gender vulnerability, and treatment in FND. Current evidence supports multidisciplinary care combining diagnostic communication, specialized physiotherapy, psychotherapy, and coordinated follow-up, while future research should prioritize standardized phenotyping, longitudinal designs, and multimodal biomarker validation. Full article

Abdominal obesity (AO), assessed through waist circumference (WC), has become a validated complementary anthropometric marker for cardiometabolic risk assessment. Growing evidence suggests that emotional eating (EE), characterized by food intake in response to emotions rather than physiological hunger cues, may be linked to AO by promoting dysregulated eating patterns rich in palatable and energy-dense foods. This behavior may contribute, directly or indirectly, to excess visceral fat accumulation. An analysis of the current evidence was conducted to examine the psychological, physiological, neuroendocrine, and gut–brain axis mechanisms underlying the association between EE and AO, as well as to explore emerging interventions for its management. A narrative review of studies published between 2015 and 2025 was carried out using PubMed and Google Scholar. Search terms related to EE, AO, physiological mechanisms, hedonic hunger, diet quality, gut microbiota, and mindful eating were employed. The findings indicate that EE is associated with emotional dysregulation, chronic activation of the hypothalamic–pituitary–adrenal (HPA) axis, increased cortisol levels, low-grade inflammation, alterations in neurotransmitters such as dopamine, serotonin, and neuropeptide Y (NPY), as well as intestinal dysbiosis. These mechanisms favor impulsive consumption of palatable foods, visceral fat gain, and metabolic deterioration. Interventions such as mindful eating show positive effects in reducing EE; however, their anthropometric impact still requires further validation. In conclusion, EE represents an important behavioral factor in the development and maintenance of AO. Its management requires a multidimensional approach integrating emotional regulation, dietary modification, and psychobehavioral strategies. Full article

The “experimenter gender effect” is a pervasive confound in rodent behavioral neuroscience: the sex of the human handler alters stress, social, and pharmacological responses via olfactory cues and conserved neural circuits. Whether this effect extends to dog—a species co-domesticated with humans for over 15,000 years—has never been systematically tested. Here, we examined sex-biased social preferences in Beagle dogs during both intra- and cross-species interactions, and asked whether baseline neuroendocrine states predict such preferences. Thirty-four adult Beagles (17 males, 17 females) from a standardized laboratory colony underwent social interaction tests with same and opposite-sex conspecifics and with male and female experimenters. Baseline plasma corticosterone, serotonin (5-HT), and dopamine were measured by ELISA. Results indicated that Beagles did not exhibit significant sex-based preferences for either gender of conspecifics or human experimenters in either dog–dog or human–dog social interaction tests (all p > 0.05). However, males showed markedly higher baseline corticosterone, 5-HT, and dopamine than females (all p < 0.0001), a hormonal dimorphism that did not correlate with any behavioral measure in Spearman correlation analysis (p > 0.05). Nevertheless, this study has several limitations: only baseline hormone levels were measured (not stress-induced responses), behavioral tests involved only low-stakes affiliative interactions, and only one breed was studied under standardized conditions. These results suggest that Beagle dogs may lack experimenter-gender preference in social interactions, exhibiting stable, gender-neutral social behavior despite profound underlying hormonal differences. This decoupling of internal state from behavioral output suggests that domestication may have shaped a social phenotype resistant to the experimenter gender effect, supporting the Beagle as a valuable translational model with a stable baseline and low susceptibility to confounding social cues, making it suitable for research on affective and social-cognitive disorders. Full article

Neuroendocrine tumors (NETs) constitute a heterogeneous and predominantly malignant group of neuroendocrine neoplasms that arise from endocrine cells dispersed throughout the body. Their clinical presentation, biological behavior, prognosis, and therapeutic management vary considerably depending on the primary tumor location and hormonal activity. Despite substantial progress in understanding the biology of NETs, identifying reliable molecular biomarkers for diagnosis, prognosis, and prediction of treatment response remains a major challenge. Increasing attention has therefore been devoted to the molecular characterization of NETs, with particular focus on recurrent genetic alterations that may contribute to tumor initiation and progression. In this review, we summarize current knowledge and recent findings referring to certain genes involved in the tumorigenesis of pancreatic and intestinal neuroendocrine tumors. We chose the genes based on data from the COSMIC (Catalogue of Somatic Mutations in Cancer) database, which compiles somatic mutations identified across numerous human cancers. We outline the biological functions of these changes and discuss their potential prognostic and predictive role as molecular markers. We also discuss their clinical relevance in both sporadic and familial forms of NETs, alongside their implications for future research and personalized management strategies. Full article

Survival rates in pediatric cancer have increased substantially over recent decades. However, children and survivors frequently experience treatment-related alterations in physical function, body composition, bone health, and metabolic regulation. Chemotherapy, glucocorticoid exposure, physical inactivity, nutritional imbalance, and inflammatory and neuroendocrine disturbances may contribute to reduced lean mass, decreased bone mineral density, sarcopenic obesity, and long-term cardiometabolic risk. This narrative review critically summarizes current evidence on multimodal exercise and nutritional interventions in pediatric oncology, with particular attention to their effects on physical function, body composition, nutritional status, and metabolic health. Literature searches were conducted in PubMed, Scopus, and Web of Science up to April 2026, combining contextual evidence with studies evaluating combined exercise and nutritional strategies. Current evidence suggests that structured and supervised exercise, particularly resistance and combined aerobic–resistance training, is feasible and safe, and may improve cardiorespiratory fitness, muscle strength, functional capacity, and body composition. Nutritional care should be individualized, prioritizing adequate protein intake, micronutrient status, periodic reassessment of energy requirements, and body composition rather than relying on BMI alone. Nevertheless, available findings remain limited by small sample sizes, heterogeneous protocols, variable supervision, inconsistent outcome assessment, and limited long-term follow-up. Integrating exercise, nutrition, and regular monitoring into pediatric oncology care may help mitigate treatment-related functional and metabolic complications. Future studies should prioritize adequately powered randomized trials, standardized intervention protocols, objective monitoring of exercise intensity, harmonized body composition and functional outcomes, and longer follow-up to define clinically applicable multimodal care models. Full article

Background: Sjögren’s disease (SjD) is a chronic systemic autoimmune disorder primarily characterized by lymphocytic infiltration of exocrine glands, leading to xerostomia and xerophthalmia. Beyond glandular involvement, the disease frequently presents with a broad spectrum of systemic and neuropsychiatric manifestations that significantly affect patients’ quality of life. Methods: A review of the literature was conducted to identify studies addressing neuropsychological symptoms in patients with SjD. Relevant publications describing cognitive dysfunction, mood disorders, sleep disturbances, fatigue, and sexual dysfunction, as well as potential underlying mechanisms and therapeutic approaches, were included and analyzed. Results: Available evidence indicates that neuropsychological symptoms are common among patients with SjD. Cognitive impairment, often described as “brain fog”, may involve deficits in memory, attention, and executive functioning. Depression and anxiety appear to occur more frequently than in the general population and may interact with chronic fatigue and sleep disturbances, contributing to functional impairment. While somatic causes of sexual dysfunctions such as vaginal dryness are well recognized, psychological and psychosexual aspects, including reduced sexual desire, have received comparatively little attention. The pathogenesis of these manifestations is likely multifactorial and may involve immune-mediated processes, cytokine dysregulation, neuroendocrine alterations, microvascular changes, and psychosocial factors. Conclusions: Neuropsychological manifestations represent a significant component of the overall disease burden in SjD. Increased awareness and multidisciplinary management strategies may help improve symptom recognition, patient care, and quality of life. Full article

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex, multi-system disorder involving interactions among metabolic dysfunction, chronic low-grade inflammation, and neuroendocrine dysregulation, rather than a condition confined to the ovary. While current management strategies primarily target symptomatic manifestations, such as menstrual irregularity, hyperandrogenism, and insulin resistance, they do not directly address the underlying integrative pathways linking the gut microbiome, cellular energy sensing, and hypothalamic reproductive control. This review proposes a mechanistic framework in which algae-derived bioactives modulate a gut–SIRT1–kisspeptin axis, thereby offering a systems-level perspective on PCOS pathophysiology and intervention. Gut dysbiosis in PCOS contributes to altered bile acid signaling, disrupted microbial metabolite profiles, and increased inflammatory tone, all of which may impair both metabolic and reproductive functions. Concurrently, reduced activity of the NAD⁺-dependent deacetylase SIRT1 has been documented across ovarian, endometrial, and metabolic tissues, linking energy imbalance to oxidative stress, inflammation, and impaired steroidogenesis. At the neuroendocrine level, dysregulated kisspeptin signaling contributes to abnormal gonadotropin-releasing hormone pulsatility and luteinizing hormone hypersecretion, key features of PCOS. Algae-derived compounds, including polysaccharides, phlorotannins, fucoidan, fucoxanthin, and microalgae bioactives, exhibit prebiotic, anti-inflammatory, and metabolic regulatory properties that intersect with these pathways, particularly through modulation of gut microbiota and activation of AMPK/SIRT1 signaling. The central proposition of this review is that algae-derived bioactives may act across interconnected biological layers: reshaping gut microbial ecology, restoring SIRT1-mediated metabolic balance, and retuning kisspeptin-driven neuroendocrine activity. While individual components of this axis are supported by substantial evidence, direct experimental validation of the complete pathway remains limited. Therefore, this framework is positioned as a translationally grounded but hypothesis-driven model that integrates currently fragmented findings into a coherent and testable paradigm. Future research should prioritize multi-level experimental and clinical studies that simultaneously assess microbiota composition, metabolic signaling, and reproductive neuroendocrine outcomes to establish the therapeutic potential of algae-based interventions in PCOS. Full article

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that impairs psychological functioning and increases susceptibility to various chronic illnesses, including inflammatory, metabolic, and cognitive disorders. Recent advances in neuroscience and microbiology have identified the brain–gut–microbiota axis as a key mediator of neuroimmune and neuroendocrine regulations, providing new insight into the pathophysiology of PTSD. This review synthesizes current findings from preclinical and clinical studies on gut microbiome alterations in PTSD, highlighting the underlying mechanistic pathways. Dysbiosis in PTSD is associated with immune dysregulation, altered neuroendocrine signaling, and neurotransmitter imbalances. Animal models, particularly those using the single prolonged stress paradigm, have demonstrated behavioral and microbial changes that mirror the characteristics of human PTSD. Human studies have revealed reduced abundance of beneficial bacterial taxa and increased inflammation-associated genera in patients with PTSD. Although emerging evidence supports the role of gut microbiota in PTSD, further research is needed to establish causal relationships and optimize microbiome-targeted therapies. Overall, the gut microbiome offers a novel and potentially modifiable target for the prevention and treatment of PTSD. Full article

Background/Objectives: Copper (Cu²⁺) is an essential trace element that participates as a cofactor in key metabolic enzymes such as cytochrome c oxidase and superoxide dismutase. However, excessive copper exposure can be toxic and disturbances in copper homeostasis have been associated with neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. Despite growing evidence linking copper to neuronal dysfunction, the cellular mechanisms by which Cu²⁺ affects neuronal excitability and neurotransmission remain poorly understood. The aim of this study was to investigate the effects of acute Cu²⁺ exposure on ionic currents involved in cellular excitability and neurotransmitter release in bovine chromaffin cells. Methods: Primary cultures of bovine chromaffin cells were used as a neuroendocrine model to study cellular excitability. Voltage-dependent ionic currents were recorded using the whole-cell patch-clamp technique in voltage-clamp configuration. Catecholamine secretion was monitored by amperometry, and cytosolic Ca²⁺ dynamics were measured in fluo-4-loaded cells during depolarization induced by high K⁺ stimulation. Results: Acute Cu²⁺ exposure produced a concentration-dependent enhancement of depolarization-evoked catecholamine release. In parallel, Cu²⁺ inhibited voltage-dependent calcium (ICa), sodium (INa), potassium (IKv), and calcium/voltage-dependent potassium (IKCa-v) currents in a concentration-dependent and partially reversible manner. In addition, Cu²⁺ increased basal cytosolic Ca²⁺ levels while reducing the amplitude of depolarization-evoked Ca²⁺ transients. Conclusions: Acute Cu²⁺ exposure exerts a dual effect in bovine chromaffin cells, inhibiting the ionic currents that support cellular excitability while potentiating catecholamine secretion. This apparent paradox is consistent with a disruption of intracellular Ca²⁺ homeostasis, in which elevated basal cytosolic Ca²⁺ may facilitate exocytosis despite reduced depolarization-evoked Ca²⁺ entry. These findings provide new insight into the mechanisms by which copper may alter neuronal signaling and contribute to neurotoxicity. Full article

The accumulation of microplastics in aquatic ecosystems poses a significant threat to fish physiology and welfare. This study investigated the impact of exposure to virgin polystyrene microplastics (15 µm) on energy balance and welfare in goldfish (Carassius auratus). Fish were exposed for 14 days, and the effects were assessed through an integrated analysis of behavioral, metabolic, neuroendocrine, and physiological parameters. Microplastic exposure significantly reduces feed intake and feed anticipatory activity, indicating a potent anorexigenic effect. This effect was driven by neuroendocrine disruption, characterized by the downregulation of orexigenic neuropeptides (npy, agrp, hcrt) and the upregulation of anorexigenic signaling (pomca, cartpt, lepa). Simultaneously, exposed fish exhibited increased oxygen consumption, suggesting elevated metabolic demands. These factors converged to impaired growth and reduced hepatosomatic index, suggesting altered energy allocation. Furthermore, microplastic exposure induced anxiety-like responses and increased plasma cortisol levels, confirming the activation of the physiological stress response. Overall, these findings demonstrate that microplastics disrupt energy homeostasis and trigger behavioral shifts that ultimately compromise fish welfare and the biological resilience of aquatic species. Full article