{"title":"Sexually dimorphic distribution of Kiss1 neurons in the bed nucleus of the stria terminalis.","authors":"Samuel T Zdon, Mauro S B Silva, Victor M Navarro","doi":"10.1111/jne.70049","DOIUrl":"https://doi.org/10.1111/jne.70049","url":null,"abstract":"<p><p>Kiss1 neurons play a crucial role in reproductive function and are found in distinct brain regions, including the bed nucleus of the stria terminalis (BNST). However, the sexual dimorphism of Kiss1 neurons in the BNST and their projections has not been fully characterized. This study examined the distribution and projections of Kiss1 neurons in the anterior (aBNST) and principal (prBNST) regions of the BNST in male and female Kiss1-Cre and Kiss1-Cre; tdTomato<sup>loxP/+</sup> mice. Neuroanatomical analysis and tracing experiments were conducted to quantify Kiss1 neurons and map their projections. Males had approximately a threefold higher number of Kiss1 neurons in the prBNST than females, while no significant sex difference was observed in the aBNST. Viral tracing experiments revealed sexually dimorphic projections of Kiss1<sup>adBNST</sup> neurons, with females displaying more diverse projections to various brain regions involved in reproduction and social behaviors. Kiss1<sup>prBNST</sup> neurons project exclusively to the zona incerta and adBNST in both sexes, while females exhibited additional projections to the RP3V and PVH. The sexually dimorphic distribution and projections of Kiss1<sup>BNST</sup> neurons suggest their potential role in modulating sex-specific behaviors and neuroendocrine functions. This neuroanatomical sexual dimorphism may contribute to sex differences in social and reproductive behaviors associated with BNST function, providing new insights into the neural basis of sex-specific behaviors and reproductive regulation.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70049"},"PeriodicalIF":3.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shel-Hwa Yeo, Zulfiye Gul, Ziyue Zhou, Leila Muresan, Ellen G Wall, Allan E Herbison
{"title":"Dynamic changes in Ccn3 expression across the limbic forebrain through the mouse estrous cycle and during lactation.","authors":"Shel-Hwa Yeo, Zulfiye Gul, Ziyue Zhou, Leila Muresan, Ellen G Wall, Allan E Herbison","doi":"10.1111/jne.70050","DOIUrl":"https://doi.org/10.1111/jne.70050","url":null,"abstract":"<p><p>Cellular communication network factor 3 (CCN3), also known as nephroblastoma overexpressed (NOV), is an adipocytokine that has recently been suggested to be secreted selectively by hypothalamic arcuate nucleus kisspeptin (ARN<sup>KISS</sup>) neurons to protect bone density during lactation. Using RNAscope hybridization, we have examined the expression of Ccn3 transcripts in the forebrain of male mice and female mice across the estrous cycle and during lactation. Transcripts for Ccn3 are highly expressed in the cerebral cortex, hippocampus, subthalamic nucleus, and amygdala in both sexes. Lower levels of Ccn3 mRNA were detected within the hypothalamus of females but not males. During lactation (day 11), a substantial 6-fold increase in the numbers of cells expressing Ccn3 mRNA was found in the arcuate and dorsomedial nuclei of the hypothalamus as well as the posterodorsal division of the medial amygdala. Approximately 50% of cells expressing Ccn3 in the ARN during lactation also contained Kiss1 transcripts. An increase in Ccn3 mRNA expression in ARN<sup>KISS</sup> neurons also occurred during proestrus. These observations demonstrate that multiple limbic brain regions and cell types coordinately up-regulate their expression of Ccn3 during lactation in the mouse.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70050"},"PeriodicalIF":3.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinonso A Nwoguh, Marieline El Asmar, Mohamad Mortagy, Rajaventhan Srirajaskanthan, Beth Russell, Benjamin E White, Kandiah Chandrakumaran, John K Ramage
{"title":"The geographical distribution of neuroendocrine neoplasms in England (2012-2018).","authors":"Chinonso A Nwoguh, Marieline El Asmar, Mohamad Mortagy, Rajaventhan Srirajaskanthan, Beth Russell, Benjamin E White, Kandiah Chandrakumaran, John K Ramage","doi":"10.1111/jne.70038","DOIUrl":"https://doi.org/10.1111/jne.70038","url":null,"abstract":"<p><p>Neuroendocrine Neoplasms (NEN) are increasing in incidence in England over the past two decades. Geographic and socio-economic disparities influence both incidence and survival rates. This study explores the relationship between environmental factors, access to specialised care in Centres of Excellence (CoE), and survival outcomes for NEN patients across England using Geographical Information Systems (GIS) to visualise disease distribution. Data on 19,958 NEN cases diagnosed between 2012 and 2018 were retrieved from the National Cancer Registry and Analysis Service (NCRAS) in England. GIS was used to analyse patient data, including spatial units, environmental factors, and travel times to CoE. Statistical analyses, including age-standardised rates, spatial autocorrelation, and survival analyses, were performed using QGIS, SPSS, R, and Stata software. Regional distribution showed the highest age-standardised rates (ASR) in the North-East, with lung NEN demonstrating significant spatial clustering. Environmental exposures, such as PM2.5 pollution, did not show a strong correlation with NEN distribution. Longer travel times to specialised centres were associated with worse overall survival, particularly in rural areas and among patients with higher socio-economic deprivation. Minor variations in survival rates were observed across different geographical regions when compared to London. This study highlights the uneven burden of disease across different regions in England. We have demonstrated variation in the country relating to anatomical sites and significant differences within rural or urban environments. Proximity to specialist centres was associated with better overall survival, highlighting the need for improved access to care.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70038"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kahyee Hor, Laura Dearden, Emily Herzstein, Susan Ozanne, Giles Hardingham, Amanda J Drake
{"title":"Maternal high fat and high sugar diet impacts on key DNA methylation enzymes in offspring brain in a sex-specific manner.","authors":"Kahyee Hor, Laura Dearden, Emily Herzstein, Susan Ozanne, Giles Hardingham, Amanda J Drake","doi":"10.1111/jne.70046","DOIUrl":"https://doi.org/10.1111/jne.70046","url":null,"abstract":"<p><p>Maternal obesity associates with an increased risk of offspring neurodevelopmental disorders. Although the underlying mechanism(s) remain unclear, evidence suggests a role for altered DNA methylation. We utilized a murine model of diet-induced obesity to investigate the impact of maternal obesity on the offspring brain transcriptome and DNA methylation. C57Bl/6 dams were fed high-fat high-sugar (HFD, n = 7) or control (CON, n = 7) diets. Maternal obesity/hyperglycemia associated with offspring growth restriction, with brain-sparing specifically in females. Postnatal hypoglycemia was seen in HFD males, but not females. The 3' RNA-sequencing revealed perturbations in metabolic and cell differentiation pathways in neonatal male and female offspring frontal cortex and cerebellum. Compared with controls, HFD males, but not females, had lower cortical and cerebellar DNMT gene and protein expression, and reduced cerebellar TET enzyme mRNA. Whilst female offspring had lower cerebellar 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) than males, there were no effects of HFD on 5mC/5hmC in cortex or cerebellum in either sex. Our data suggest that maternal obesity has sex-specific effects on fetal neurodevelopment, including enzymes involved in DNA methylation/demethylation. These mechanisms may play a role in the increased risk of neurodevelopmental disorders following obese/diabetic pregnancies, including increased male susceptibility to these disorders.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70046"},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ammir Y Helou, Camila de Carvalho, Larissa A do Carmo, Jackson C Bittencourt
{"title":"Litter sex composition influences plasma prolactin levels but not the melanin-concentrating hormone immunoreactive neurons in the medial preoptic area of late lactating Long-Evans rats.","authors":"Ammir Y Helou, Camila de Carvalho, Larissa A do Carmo, Jackson C Bittencourt","doi":"10.1111/jne.70043","DOIUrl":"https://doi.org/10.1111/jne.70043","url":null,"abstract":"<p><p>This study examines the influence of litter sex composition on melanin-concentrating hormone immunoreactive (MCH-ir) neurons in the ventromedial medial preoptic area (vmMPOA) and on plasma prolactin levels in lactating rats. MCH is a critical regulator of maternal behavior and displays sexual dimorphism within the MPOA, making it an important target for understanding neuroendocrine adaptations in lactation. Prolactin, a pivotal hormone in lactation and maternal care, was also assessed to elucidate its interaction with litter sex composition. Thirty lactating female rats were divided into five experimental groups based on litter sex composition: all-male (10 male pups), all-female (10 female pups), balanced control (five male and five female pups), predominantly male (seven male and three female pups), and predominantly female (three male and seven female pups). On post-partum day 19 (PPD19), the dams were euthanized for biological analysis. Blood samples were collected for plasma prolactin quantification, and the brains were processed to analyze MCH-ir neurons in the vmMPOA. Results showed no significant differences in food and water intake or the number of MCH-ir neurons in the vmMPOA among experimental groups. However, significant variation in prolactin levels was observed, with the all-male offspring group exhibiting the highest levels (mean prolactin level 23.9 ng/mL, p < .001), followed by the all-female group (20.3 ng/mL, p < .01), compared to the control group (14.3 ng/mL). Additionally, the all-male group showed a reduction in body weight gain. These results suggest that although litter sex composition does not alter the number of MCH-ir neurons in the vmMPOA, it significantly impacts maternal prolactin levels. This differential prolactin regulation may reflect distinct physiological demands or caregiving behaviors imposed by homogeneous litters, which could, in turn, influence maternal energy balance, lactation efficiency, and adaptive maternal responses. Understanding these sex-specific influences on maternal neuroendocrine function has important implications for comprehending maternal care dynamics and energy allocation during lactation.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70043"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shumin Wang, Shuting Ren, Siting Lv, Yuankun Liu, Keke Xing, Ting Zhang, Xiaohang Jin, Juan Shi
{"title":"The Analgesic and Antidepressant Role of Oxytocin-Containing Neurons in the Hypothalamic Paraventricular Nucleus in Mice With Spared Nerve Injury.","authors":"Shumin Wang, Shuting Ren, Siting Lv, Yuankun Liu, Keke Xing, Ting Zhang, Xiaohang Jin, Juan Shi","doi":"10.1111/jne.70045","DOIUrl":"https://doi.org/10.1111/jne.70045","url":null,"abstract":"<p><p>Neuropathic pain is the debilitating chronic pain frequently comorbid with anxiety and depression. The mechanism and treatment strategy of neuropathic pain are to be elucidated. Oxytocin (OXT)-containing neurons (simplified as OXT neurons) in the hypothalamic paraventricular nucleus (PVN) have been highlighted recently in the field of pain regulation and social function. But so far, the adaptive change and endogenous function of the neurons in neuropathic pain remain unclear. By immunofluorescent staining, we investigated the changes in FOSB expression in OXT neurons in the PVN with the development of neuropathic pain induced by spared nerve injury (SNI). The effect of neuronal activation on pain, as well as comorbid anxiety and depression, was subsequently assessed by chemogenetic manipulation. FOSB expression in the OXT neurons was significantly increased at 1 day and then gradually decreased at 7, 28, and 49 days after SNI. Activation of OXT neurons in the PVN by the OXT promoter-directed hM3Dq virus or by the Cre-loxP system in OXT-Cre mice significantly improved the mechanical pain, cold pain, and depressive-like behaviors in male and female mice, but exerted weak anxiolytic effects in female mice. These results demonstrate the altered activational status and the analgesic/antidepressant role of the OXT neurons in the PVN, thus providing a cellular-based strategy for the comprehensive treatment of neuropathic pain.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70045"},"PeriodicalIF":3.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vanlal Rempuia, Guruswami Gurusubramanian, Vikas Kumar Roy
{"title":"Exogenous visfatin suppresses pituitary gonadotrophins and stimulates testosterone secretion in a male mouse.","authors":"Vanlal Rempuia, Guruswami Gurusubramanian, Vikas Kumar Roy","doi":"10.1111/jne.70044","DOIUrl":"https://doi.org/10.1111/jne.70044","url":null,"abstract":"<p><p>Visfatin expression has been shown in the testis and pituitary. However, the role of visfatin in the pituitary and testis axis is fragmentary. Furthermore, no study has shown the effects of visfatin on the pituitary gonadotrophins and testicular steroid hormonal secretions in a male mouse. The present study has investigated the effects of exogenous visfatin (most likely a state of hypervisfatinemia) on the gonadotrophins, testosterone, estradiol, androstenedione, and progesterone in a male mouse. The exogenous visfatin was given for 35 days, which covers one spermatogenic cycle. The circulating testosterone was elevated after visfatin treatment, along with down-regulation of AR and steroidogenic markers in the testis. However, the expression of CYP17 was up-regulated in visfatin-treated testis. Visfatin treatment also elevated apoptosis in the different germ cells of the testis. The levels of circulating LH and FSH were also suppressed after visfatin treatment. The immunolocalization of AR exhibited decreased abundance in the pituitary of visfatin-treated mice; thus, it can be suggested that pituitary gonadotrophins secretion might be suppressed by direct action of visfatin rather than via elevated testosterone. In conclusion, our results showed that exogenous visfatin suppresses gonadotrophins and stimulates testicular testosterone secretions in a differential manner. Visfatin has inhibitory effects on pituitary gonadotrophins secretion and stimulatory effects on testosterone secretion from the testis. Thus, conditions similar to hypervisfatinemia likely impair the release of hormones from the pituitary and testis.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70044"},"PeriodicalIF":3.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katharina Karges, Marina Kunstreich, Ulrich-Frank Pape, Jörg Fuchs, Christian Vokuhl, Michael Abele, Dominik T Schneider, Ines B Brecht, Constantin Lapa, Michael C Frühwald, Peter Vorwerk, Antje Redlich, Michaela Kuhlen
{"title":"Pancreatic neuroendocrine tumors in children and adolescents-Data from the German MET studies (1997-2023).","authors":"Katharina Karges, Marina Kunstreich, Ulrich-Frank Pape, Jörg Fuchs, Christian Vokuhl, Michael Abele, Dominik T Schneider, Ines B Brecht, Constantin Lapa, Michael C Frühwald, Peter Vorwerk, Antje Redlich, Michaela Kuhlen","doi":"10.1111/jne.70039","DOIUrl":"https://doi.org/10.1111/jne.70039","url":null,"abstract":"<p><p>Pancreatic neuroendocrine tumors (panNETs) are rare pediatric malignancies with age-specific clinical and biological features. Data on their presentation, management, and outcomes remain limited. This retrospective study analyzed 28 pediatric panNET cases from the German Malignant Endocrine Tumor (MET) Registry enrolled between 1997 and 2024. Clinical presentation, diagnostics, and treatment were evaluated to identify prognostic factors and outcomes. The cohort included 18 females (64.3%) and 10 males (35.7%), with a median age at diagnosis of 14.7 years. Nonfunctional tumors predominated (75%). Genetic syndromes were identified in 17.9% of patients. Localized disease showed a 3-year overall survival (OS) of 100%, while metastatic disease had a 3-year OS of 50.9%. Event-free survival was significantly associated with the presence of distant metastases (M0 vs. M1, p = .0082) and complete surgical resection (R<sub>0</sub> vs. R<sub>1/2</sub> vs. no resection, p = .0077) but not with lymph node involvement (N0 vs. N1, p = .12), tumor localization within the pancreas (head vs. body vs. tail, p = .86), the extent of the primary tumor (pT1-2 vs. pT3-4, p = 1.0), pathological grade (G1 vs. G2-3, p = .28), or proliferation index (Ki67 ≤ 10% vs. >10%, p = .11). This study underscores the importance of disease stage and surgical resection as key prognostic factors in pediatric panNETs. It highlights the need for pediatric-specific management guidelines, integration of genetic screening, and expanded molecular profiling to optimize outcomes for children and adolescents with panNETs.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70039"},"PeriodicalIF":3.3,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}