Journal of Neuroendocrinology最新文献

{"title":"A male-dominant cell group expressing calbindin-D28K and androgen receptor in the mouse preoptic area requires postnatal testicular androgens and histone deacetylation.","authors":"Yusa Arai, Shinji Tsukahara","doi":"10.1111/jne.70097","DOIUrl":"https://doi.org/10.1111/jne.70097","url":null,"abstract":"<p><p>The mouse brain is masculinized by postnatal testicular androgens, which are active after conversion to estrogens and modulate gene expression epigenetically, at least in part. The preoptic area contains a sexually dimorphic nucleus (SDN) comprising calbindin D-28K (Calb) neurons with a male-biased sex difference in cell number (Calb-SDN), although the mechanisms responsible for the sex difference are not fully understood. We have previously demonstrated that Calb neurons expressing the androgen receptor (AR) are a male-dominant cell group of the Calb-SDN in pubertal mice, while Calb neurons without AR exist in both sexes with equal cell numbers. In this study, we investigated the mechanisms by which more Calb/AR neurons emerge in the male Calb-SDN than in the female one. Immunohistochemistry for Calb and AR was performed using the brain sections from pubertal male mice subjected to sham surgery or neonatal orchidectomy, from pubertal female mice treated with vehicle, testosterone, or estradiol during the postnatal period, and from pubertal male mice whose brains were treated with trichostatin A, a histone deacetylase inhibitor, during the postnatal period. Immunostained brain sections were analyzed stereologically to determine the numbers of Calb-immunopositive and AR-immunopositive cells (Calb⁺/AR⁺ cells) and Calb-immunopositive and AR-immunonegative cells (Calb⁺/AR^- cells) in the Calb-SDN. The number of Calb⁺/AR⁺ cells in the Calb-SDN during the pubertal period was significantly decreased in neonatally orchidectomized males compared with sham males and increased in testosterone- or estradiol-treated females compared with vehicle-treated females; however, the number of Calb⁺/AR^- cells remained unchanged. Trichostatin A treatment significantly reduced the number of Calb⁺/AR⁺ cells, but not the number of Calb⁺/AR^- cells, in the Calb-SDN of males. These findings suggest that estrogens synthesized from postnatal testicular androgens act selectively on the AR-expressing subpopulation of Calb neurons, contributing to the sex difference in the number of Calb neurons in the mouse Calb-SDN. Epigenetic regulation of gene expression, possibly mediated by histone deacetylation, may be involved in the emergence of the AR-expressing subpopulation of Calb neurons.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70097"},"PeriodicalIF":4.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251298","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}

{"title":"GHSRs in the olfactory bulb suppress food motivation and promote exploration without altering spatial memory in male mice.","authors":"Romana Stark, Jeffrey M Zigman, Zane B Andrews","doi":"10.1111/jne.70096","DOIUrl":"https://doi.org/10.1111/jne.70096","url":null,"abstract":"<p><p>The olfactory bulb (OB) is an emerging neuroendocrine centre regulating appetite, metabolism, and behaviours such as those linked to anxiety, motivation and spatial navigation. These processes are likely mediated by one or more of the many hormone receptors found in the OB. For instance, recent studies show that selective OB deletion of the receptor for ghrelin and LEAP2 (GHSR; growth hormone secretagogue receptor) increases anxiety-like behaviour and impacts peripheral glucose and energy homeostasis. As GHSR function has been linked to motivated behaviours and spatial navigation, we decided to investigate whether OB-selective GHSR (OB^GHSR) deletion affects motivation, using an operant progressive ratio schedule, and/or spatial navigation, using a Y maze and radial arm maze. In contrast to wild-type mice, our study shows that OB^GHSR deletion increased motivated sucrose seeking after a short fast, but not in ad libitum fed mice, and had a mild effect to delay extinction learning. In both Y-maze and radial arm maze studies for spatial navigation, OB^GHSR deletion reduced spatial exploration in terms of distance moved and arm entries. However, the proportion of correct and incorrect arm entries relative to the total number of entries was not affected in either the Y-maze or the radial arm maze, suggesting that spatial memory was not affected. Our study demonstrates that intact OB^GHSRs in male mice normally restrain motivated sucrose seeking in a metabolic state-dependent manner and optimise spatial navigation by increasing exploration, without affecting spatial memory.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70096"},"PeriodicalIF":4.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251376","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}

{"title":"Dopamine and prolactin in migraine: Mechanisms and potential therapeutic targets.","authors":"Astrid Johannesson Hjelholt, Randi Maria Hanghøj Tei, Hans Christoph Diener, Jens Otto Lunde Jørgensen","doi":"10.1111/jne.70098","DOIUrl":"https://doi.org/10.1111/jne.70098","url":null,"abstract":"<p><p>Migraine is a complex neurovascular disorder characterized by activation and sensitization of the trigeminovascular system. Hyperprolactinemia is associated with headache, and improvement following prolactin-lowering therapy has been reported in observational studies. Preclinical evidence indicates that prolactin promotes neuronal excitability and sensitization within trigeminal pathways, particularly in females. Downregulation of the protective long prolactin receptor isoform further increases susceptibility to migraine-relevant triggers. Prolactin secretion is under tonic inhibition by dopamine, a key hypothalamic regulator that also modulates central pain pathways. The role of dopamine in migraine pathophysiology is complex. On one hand, prodromal symptoms such as nausea and yawning are considered dopamine-mediated. On the other hand, experimental studies show that dopamine directly inhibits nociceptive trigeminovascular activity in addition to lowering prolactin. Dopamine receptor agonists are established treatments for hyperprolactinemia and have demonstrated a positive effect on hyperprolactinemia-associated headache. A recent placebo-controlled randomized clinical trial suggests that dopamine agonist treatment can be used as a preventive migraine treatment. In conclusion, prolactin and dopamine may modulate migraine via distinct but converging neuroendocrine pathways, which could represent targets for migraine prevention.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70098"},"PeriodicalIF":4.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238755","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}

{"title":"Mild increase of temperature from the thermoneutral zone inhibits reproductive activation in Syrian hamsters through epigenetic inhibition.","authors":"Lalsiamkima Hnamler, Amit Kumar Trivedi","doi":"10.1111/jne.70095","DOIUrl":"https://doi.org/10.1111/jne.70095","url":null,"abstract":"<p><p>The rapid increase in urbanization is drastically altering the habitat composition of the wild population. Urbanization is predominantly changing the landscape, composition of flora and fauna, availability of night light, and the rise in temperature. In the natural habitat, photoperiod and temperature are inseparable. In the present study, we examined the effect of mild temperature change from the thermoneutral zone of Syrian hamsters on reproduction-linked activities. To investigate the neuroendocrine mechanisms underlying heat stress effects on reproduction in hamsters, two experiments were performed on adult male animals. In experiment one, animals were divided into two groups (n = 5/group) and exposed to a long photoperiod (15L:9D) with either low (LT; 20 ± 2°C) or high temperature (HT; 32 ± 2°C). After 21 days, all animals were sampled. In experiment two, hamsters (n = 20) were divided equally into two groups and were exposed to the first short photoperiod of 8L:16D, but with low temperature (LT; 20 ± 2°C) or high temperature (HT; 32 ± 2°C). After 30 days, all animals were exposed to a long day (15L:9D), but animals from each temperature treatment were divided equally into two groups (n = 5/group). Half of the animals (n = 5) of low temperature remained in low temperature (LL group) while the remaining animals were moved to high temperature (LH group). Similarly, half of the animals (n = 5) of high temperature remained in high temperature (HH group), and the rest of the animals were moved to low temperature (HL group). Body mass and testicular volume were measured at different intervals. After 30 days of long-day treatment, the animals were sampled. Findings suggest that exposure to 3 weeks of high temperature attenuates testicular growth, coupled with low testosterone levels and downregulation of Kiss1, Eya3, Tshβ, GnRh, Tet1, Tet2, and Hat1, while upregulation of Dio3, GnIh, Dnmt1, Dnmt3A, Hdac1, and Hdac5 occurs in HT groups. Results from experiment two suggest that low temperature promotes, while high temperature attenuates reproduction and the linked phenomenon. Together, these findings suggest that high temperature modulates the reproductive responses of Syrian hamsters.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70095"},"PeriodicalIF":4.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206737","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}

{"title":"Telotristat ethyl affects tumour-fibroblast crosstalk in small intestinal neuroendocrine tumours.","authors":"Harry Hodgetts, Maria Castanho Martins, Luohai Chen, Andrew R Hall, Tu Vinh Luong, Dalvinder Mandair, Martyn Caplin, Krista Rombouts","doi":"10.1111/jne.70094","DOIUrl":"https://doi.org/10.1111/jne.70094","url":null,"abstract":"<p><p>Small intestinal neuroendocrine tumours (SI-NETs) are associated with mesenteric fibrosis, which causes significant morbidity and mortality. Telotristat ethyl was developed to treat carcinoid syndrome in SI-NET patients. Recent studies indicated telotristat ethyl could have anti-tumour activity; however, the mechanism remains unclear. This study aimed to investigate the effects of telotristat ethyl on SI-NET-fibroblast crosstalk in tumour progression and mesenteric fibrosis. A co-culture paracrine model with GOT1 (tumour) cells and LX2 (stromal) cells was optimized. Cells were treated with conditioned medium with/without telotristat ethyl followed by RNA sequencing and Gene Set Enrichment Analysis. Quantitative RT-PCR, immunohistochemistry, and Western blot were performed on first and second tier targets in tissue from 34 SI-NET patients grouped into categories of mesenteric fibrosis severity. Telotristat ethyl significantly decreased proliferation and serotonin secretion in a dose-dependent manner in GOT1 cells. GSEA data indicated ECM-related reactomes were downregulated in GOT1 cells grown in conditioned medium of LX2 cells with telotristat ethyl. LAMA5, COL6A2, and COL12A1 expression was significantly increased in mild and severely fibrotic patients. Immunohistochemistry determined the localization of proteins such as COL4A2 in the stroma and ADAM12 in tumour cells. Protein analysis of second tier targets showed differences in expression, including β-catenin, which was significantly upregulated, and pAKT/AKT, which tended to increase in primary tumour compared to normal SI. Telotristat ethyl affects the expression of genes associated with the ECM and interferes with SI-NET-fibroblast crosstalk. Further analysis is required; however, this study represents an important step in understanding the mechanisms of telotristat ethyl when treating SI-NET patients.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70094"},"PeriodicalIF":4.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149349","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}

{"title":"Three-dimensional quantification of oxytocin neurons in the hypothalamic paraventricular nucleus reveals sex- and subregion-specific differences in two genetic mouse models of autism.","authors":"Aishwarya Patwardhan, Siyao Li, Jessica Chen, Katrina Y Choe","doi":"10.1111/jne.70092","DOIUrl":"https://doi.org/10.1111/jne.70092","url":null,"abstract":"<p><p>Oxytocin (OXT), a neuropeptide hormone essential to a wide range of social functions, has drawn increasing attention as a crucial contributor to the neurobiology of autism spectrum disorder (ASD). Central OXT system disruptions have been reported in several genetic mouse models of ASD; however, a detailed and systematic characterization of these phenotypes, and cross-model identification of shared and distinct features, are presently lacking. We integrated whole-brain OXT immunolabeling, SHIELD tissue clearing, light-sheet microscopy, and three-dimensional (3D) machine learning-based cell detection to establish a high-throughput, intact-tissue pipeline and quantified OXT immunopositive (OXT+) neurons across subregions of the paraventricular nucleus of the hypothalamus (PVN) in two genetic mouse models of ASD: Cntnap2 and Fmr1 knockout (KO) mice. We validated this pipeline alongside conventional immunohistochemistry using tissue sections. We show subregion- and sex-specific differences in PVN OXT+ cell counts in the two KO models. Notably, whole-PVN analysis revealed additional subregion- and sex-specific differences that were not evident in section-based quantification. These results identify subregion- and sex-specific differences in PVN OXT+ neuronal distribution as a shared phenotype in two genetic mouse models of ASD. This work highlights the importance of region-specific, high-resolution 3D approaches in intact tissue for quantifying cell populations within anatomically complex brain regions.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70092"},"PeriodicalIF":4.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124772","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}

{"title":"Annual rhythms of thyroid hormone signaling: Environmental influences on thyroid function and disease implications.","authors":"Jiaqi Liu, Zixuan Wang, Hanyu Wang, Lu Yu, Yuxin Yu, Hui Sun","doi":"10.1111/jne.70093","DOIUrl":"https://doi.org/10.1111/jne.70093","url":null,"abstract":"<p><p>Hormones within the hypothalamic-pituitary-thyroid (HPT) axis play a central role in acclimatization, dynamically responding to nutritional, thermal, and photoperiodic cues to coordinate metabolic, thermoregulatory, and reproductive functions. Abundant food elevates thyroid hormone (TH), driving energy storage and foraging behaviors, while scarcity reduces TH levels, inducing energy-saving states like hypometabolism or hibernation, in which TH-leptin crosstalk is important. Cold exposure upregulates TH to enhance mitochondrial thermogenesis, with TH acting as a pivotal mediator in the coordination between the hypothalamic thermoregulatory center and peripheral organs. The photoperiodic response converges evolutionarily on the TSH-DIO2-T3 axis, modulating seasonal GnRH release for seasonal reproductive activity. Humans display an annual rhythm of HPT-axis hormones, characterized by winter TSH elevation with TH variability, which affects thyroid dysfunction diagnosis and necessitates seasonally adjusted therapies. Extreme natural environmental stressors and modern environmental changes can profoundly disrupt this acclimatization to decompensate into a pathophysiological state. Meanwhile, thyroid diseases like hypo- and hyperthyroidism show seasonal patterns of disease onset and exacerbation, indicating that the environment impacts disease progression. Thus, cross-species analysis of seasonal dynamics of TH signaling can enhance our understanding of environmental impacts on thyroid function and inform therapeutic strategies aligned with endogenous annual rhythms to optimize the management of thyroid disorders.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70093"},"PeriodicalIF":4.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069855","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}

{"title":"Controversies in NEN: An ENETS position statement on the management of locally advanced neuroendocrine neoplasia of the small intestine and pancreas without distant metastases.","authors":"M E T Tesselaar, S Partelli, A J A T Braat, A Croitoru, A P Soares Santos, J Schrader, S Welin, E Christ, M Falconi, D K Bartsch","doi":"10.1111/jne.70083","DOIUrl":"https://doi.org/10.1111/jne.70083","url":null,"abstract":"<p><p>Locally advanced neuroendocrine neoplasms (NENs) are defined by extensive local invasion in the absence of distant metastases, although specific definitions may vary among study groups. While most patients with NENs present with localized or metastatic disease, a smaller subset is diagnosed with locally advanced tumors. Management of this subgroup remains particularly challenging, owing to the limited evidence base and lack of consensus regarding optimal therapeutic strategies. This guidance document synthesizes the current evidence and expert knowledge on the management of locally advanced NENs of the small intestine and pancreas, addressing four clinically relevant key questions that aim to inform best practice in these patients.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70083"},"PeriodicalIF":4.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064881","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}

{"title":"Cellular mechanisms of long-term osmoregulation in magnocellular neurons.","authors":"Kirk D Haan, Thomas E Fisher","doi":"10.1111/jne.70090","DOIUrl":"https://doi.org/10.1111/jne.70090","url":null,"abstract":"<p><p>Osmoregulation is an essential homeostatic process that maintains the osmolality of the extracellular fluid (ECF) close to a physiological setpoint. Vasopressin (VP) plays a key role in osmoregulation and is secreted by the magnocellular neurosecretory cells (MNCs) of the hypothalamus. MNC electrical activity and VP release increase with elevations of ECF osmolality. MNC osmosensitivity depends on a mechanosensitive N-terminal variant of the transient receptor potential vanilloid type 1 (ΔN-TRPV1) channel that activates in response to osmotically induced cell shrinkage. ΔN-TRPV1 mechanosensitivity depends on their association with microtubules in the MNC cytoskeleton and is modulated by a dense layer of submembranous actin in MNC somata. MNCs exposed to sustained increases in osmolality, however, undergo marked somatic hypertrophy, which suggests that other mechanisms may be important to maintain VP release. Recent evidence suggests that the translocation of ΔN-TRPV1 (and possibly other channels) to the MNC cell surface could contribute to osmotically induced long-term increases in MNC excitability. Osmotically induced ion channel translocation is dependent on MNC firing, Ca²⁺ influx through L-type Ca²⁺ channels, the activation of phospholipase C δ1 and protein kinase C, and soluble N-ethylmaleimide-sensitive factor attachment protein receptor-dependent exocytotic fusion. Other recent work has explored osmotically induced changes in the MNC cytoskeleton that may be related to hypertrophy and ion channel translocation. MNCs may also be activated by elevations in extracellular Na⁺ through the activation of the Na⁺-sensitive Na⁺ channel, Na_X. This review highlights recent advancements in our understanding of long-term MNC regulation at the cellular level.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70090"},"PeriodicalIF":4.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040508","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}

{"title":"Benzophenones: How ultraviolet filters can interfere with reproduction.","authors":"Juan Manuel Riano Gomez","doi":"10.1111/jne.70088","DOIUrl":"https://doi.org/10.1111/jne.70088","url":null,"abstract":"<p><p>Benzophenones (BPs) are widely used as ultraviolet (UV) filters in personal care products, plastics, and food packaging. Although they serve as effective photoprotective agents, growing evidence suggests that BPs can act as endocrine-disrupting chemicals (EDCs), interfering with hormone regulation and reproductive functions. This review summarizes the current knowledge on BP exposure, metabolism, and their potential effects on reproductive health. We discuss the mechanisms by which BPs interact with hormonal receptors, alter steroid metabolism, and influence the hypothalamic-pituitary-gonadal axis. Special attention is given to BP-2 and BP-3, which have been detected in human biological samples, including urine, blood, and fetal tissues. Additionally, we highlight recent findings from in vitro and in vivo studies demonstrating their estrogenic activity and potential impact on reproduction. The review also addresses regulatory concerns, emphasizing the need for stricter policies to limit human and environmental exposure to BPs. Understanding the effects of these chemicals is essential for assessing their safety and developing alternatives to mitigate potential health risks.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":" ","pages":"e70088"},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033617","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}