Journal of Neuroendocrinology最新文献

The specific human leukocyte antigen (HLA) alleles in individuals with tumors that ectopically express adrenocorticotropic hormone (ACTH), resulting in paraneoplastic isolated ACTH deficiency (IAD), remain elusive, primarily because of the scarcity of reported cases. In this study, we endeavored to elucidate the pathogenic mechanisms underlying paraneoplastic IAD, a novel subtype of autoimmune hypophysitis. We specifically examined the histological characteristics of ACTH-expressing cells in cancer tissues of one patient and investigated the prevalence of shared HLA alleles across three patients diagnosed with paraneoplastic IAD. We analyzed the histological features of prostate-cancer tissues, including ectopic ACTH expression, in a patient with paraneoplastic IAD. In addition, we investigated common HLA alleles and estimated haplotypes among this patient and two others with paraneoplastic IAD on which we previously reported. Immunohistochemical analyses revealed ACTH-positive cells in only one of four tissue samples. Ectopic ACTH expression was limited to areas of relatively high-grade prostate cancer, with cellular cords and cribriform glands that exhibited nuclear hyperchromatism. HLA typing revealed shared class II alleles and haplotypes, including DRB4*01:03, among the three cases. This study provides novel histological insights and highlights the commonality of HLA class II alleles in the diagnosis and pathogenesis of paraneoplastic IAD, potentially aiding the identification of new cases and our understanding of the underlying mechanisms of the disease.

Basic and translational investigations play a crucial role in advancing our understanding of neuroendocrine neoplasms (NENs). In this white paper by the Basic and Translational Research Group of the European Neuroendocrine Tumor Society, we discuss the qualities and drawbacks of current disease models and propose good practices for integrating state-of-the-art technologies including bulk and single-cell genomics, transcriptomics, and proteomics in contemporary NEN research. We also provide insights on how to properly handle tissue samples (particularly when starting material is limited) and discuss technical hints of relevance when planning liquid biopsy or tumor immunology studies. Future translational studies of NENs will benefit from centralized biologic material biobanking, research design planning in the context of multi-expertise committees, as well as experimental protocol optimization and sharing across the NEN scientific community.

The prevalence of eating disorders (ED), such as anorexia, bulimia, and binge-eating disorders, is on the rise, and it is imperative to explore the pathophysiological aspects and associations of these disorders to provide better and precise treatment. Dopamine is an essential hormone and a neurotransmitter involved in an array of processes and pathways. Disruption of any of the dopamine pathways can lead to diseases such as Parkinson's, Huntington's, schizophrenia, or anhedonia. The mesolimbic pathway of dopamine has a special association with the feeding behavior of a person, and disruption of this pathway has been shown to be associated with ED. In this article, we comprehensively assess the relation between dopamine and ED and discuss the clinical implications involving the pharmacological associations of drugs influencing dopamine levels and their impact on the treatment of ED.

There is increasing interest in the role of probiotics in supporting maternal well-being throughout female reproduction. However, it remains largely unknown whether the brain of a female with reproductive experience responds differently to probiotics compared to females without reproductive experience. Reproduction involves remarkable neuroplasticity; therefore, we hypothesized that reproducing females are particularly susceptible to the effects of probiotic treatment. Groups of early pregnant or age-matched virgin female Long–Evans rats were administered the probiotic, Lactocaseibacillus rhamnosus HN001 (HN001), in their drinking water or given untreated water for 30 days. To measure changes in gut microbiota, fecal samples were taken regularly. Brains were analyzed at the end of treatment to quantify hippocampal cells containing the neurogenesis marker doublecortin, the synaptic marker synaptophysin, and the microglial activation marker Iba1. For dams, an offspring retrieval test was performed. Main findings show that HN001 administration lowers Bacteroidota abundance in the gut regardless of reproductive experience. In HN001-treated dams there was an increase in the number of times offspring were carried and this was negatively correlated with Bacteroidota abundance in the dam's gut. HN001-treated dams also had more immature neurons in the hippocampus and more thick-type microglial cells in the dorsal hippocampus compared to control dams. HN001-treated females, regardless of reproductive experience, had lower density of synaptophysin immunoreactivity in the CA1, and more thick-type microglia cells in the ventral hippocampus, compared to control females. These results indicate that the probiotic, HN001, alters female rat maternal behavior, plasticity in the hippocampus, and the gut microbiota abundance, with some effects being influenced by reproductive experience.

In Golden hamsters (Mesocricetus auratus), a two-week exposure to chronic social stress in adolescence causes acceleration of agonistic behavior, enhanced adult aggression, impaired waiting impulsivity, and higher food intake, body fat, and long-term increased body weight. In adult rodents, stress is accompanied by widespread alterations in gene expression in the brain. As stress is a potent modulator of both gene expression and behavior, the present research investigated possible mechanistic-related transcriptomic changes in the lateral, dorsomedial, and arcuate nucleus of the hypothalamus caused by adolescent stress using RNA Tag-sequencing, as these areas are involved in the regulation of metabolic and motivated behaviors. In each region, there were approximately 250 genes with higher expression compared to controls and 250 genes with lower expression. Many of the most significantly affected genes have been associated with metabolism and sex hormone function. For example, in the lateral hypothalamus, melanocortin 3 receptor, growth hormone releasing factor, both involved in metabolic processes, and neuropeptide VF precursor, involved in growth hormone inhibitory hormone production, were among the most increased in expression in stressed subjects. In the dorsomedial hypothalamus, neuropeptide W, involved in feeding cessation, was significantly decreased in expression in stressed animals. Across both regions, G-protein coupled receptor 50, involved in thermoregulation, sleep, and sex-related mood disorders, was significantly altered, but in opposite directions. In the arcuate nucleus, a number of blood brain barrier- and inflammation-related genes were altered as well. Furthermore, there were consistent patterns of genetic ensembles identified through gene ontology analysis and weighted gene correlation network analysis that were altered across each region. Many of these involved roles in RNA processing, DNA methylation, myelination, and synaptic organization. These findings reinforce prior behavioral, hormonal, and metabolic changes observed in this developmental model, and help guide future directions of research related to the negative consequences of early life stress.

Recent studies have shown a link between disrupted circadian rhythms and the development of chronic opioid-induced negative effects. Both animal and human studies show a significant bidirectional relationship between the circadian system and opioid effects. Opioids can perturb circadian rhythms, and perturbation of the circadian rhythms can aggravate opioid-mediated adverse effects. These bidirectional interactions may attenuate the outcomes of long-term opioid therapy when not considered. A better understanding of the potential mechanisms underlying these interactions may be essential for more effective management of opioid-induced adverse effects. This review highlights the association between circadian rhythms and opioid-induced hyperalgesia, dependence, and withdrawal, and the possible role of the dopaminergic, serotoninergic, and noradrenergic systems, redox state, and stress in this association. We also highlight the existence of an interaction between other rhythmic biological processes, including the sleep–wake cycle as well as melatonin and glucocorticoid rhythms on the circadian and opioid systems and their possible effects on opioid-related negative effects.

Endoscopic submucosal dissection (ESD) has been reported as a feasible and effective treatment for Gastric Neuroendocrine Tumors (G-NETs). However, most of the experience comes from retrospective tertiary centers in Eastern Asia. Data coming from western centers are lacking. This is a retrospective study, including patients who underwent endoscopic resection of G-NETs by ESD between 2010 and 2020 in Western Centers. Important clinical variables such as demographic, size, type, presence of lymphovascular invasion or distant metastasis, completeness of the endoscopic resection, recurrence, and procedure-related complications were recorded. Seventy-three ESD procedures on G-NETs from 69 patients from 11 centers were included. Median G-NETs size on endoscopy was 12 mm (IQR 10–15). Case mix accounted for 83.6% type 1, 15.1% type 3, and 1.4% type 2. En-bloc resection was possible in 69 procedure 94.5%, R0 resection rate stood at 79.5%. Five patients (7.2%) were referred for additional surgical intervention. One case of perforation was reported (1.4%), treated endoscopically. Three patients (4.4%) had evidence of recurrence during follow-up. ESD is an effective and safe treatment for G-NETs in western centers.

Neuroendocrine neoplasms (NEN) themselves and also their treatment may cause malnutrition, inducing changes in physiological behaviour and eventually leading to increased rates of morbidity and mortality. Malnutrition is a common, under-recognised and under-treated condition in patients with NEN, and there are limited data available on the role of optimising nutrition in this setting. There are no formal evidence-based European Neuroendocrine Tumor Society (ENETS) guidelines on nutrition evaluation and management in patients with NEN to date. This manuscript was initiated during the 2024 ENETS Advisory Board meeting by using an expert panel consensus methodology and specific structured questions, which were identified and addressed through a structured review of the literature. The manuscript aims to identify the presence of specific nutrient deficits and define unmet needs and controversies regarding nutrition and NEN in a succinct manner, to promote collaborative and multidisciplinary research in the field, and to offer practical guidance in terms of how to assess malnutrition and dietary interventions by means of formulating a structured questionnaire.