Journal of Neuroendocrinology最新文献

{"title":"Disruption of circadian rhythms is associated with cognitive impairment during gestation.","authors":"Shan Li, Jialu Xu, Han Yue, Jiaxin Yin, Yuqi Yuan, Sijia Ni, Haifei Wang, Yibin Zhang, Xiaobin Liao, Jing Tao, Yan Yang","doi":"10.1111/jne.70178","DOIUrl":"https://doi.org/10.1111/jne.70178","url":null,"abstract":"<p><p>Disruption of circadian rhythms is increasingly recognized as a contributor to cognitive dysfunction, but its role in gestation-associated cognitive changes remains unexplored. Here we combine human cognitive screening with a comprehensive longitudinal mouse model to investigate whether gestational cognitive impairment and postpartum recovery are coupled with disruption and restoration of hippocampal circadian rhythms. Cognitive function was assessed in pregnant and postpartum women using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). In mice, four reproductive stages were compared: control, gestation, 1 month postpartum, and 3 months postpartum. Serum gonadotropins and sex hormones levels were quantified using ELISA. Home-cage locomotor activity was recorded over 48 h under a 12 h:12 h light-dark cycle. Hippocampal-dependent memory was evaluated using the novel object recognition test and Barnes maze at Zeitgeber times ZT6 (day) and ZT18 (night). Hippocampal amyloid β (Aβ) deposition was visualized via immunofluorescence; protein expression of amyloid precursor protein (APP), β-site amyloid precursor protein cleaving enzyme-1 (BACE1), and phosphorylated tau was measured by Western blots. Hippocampal clock gene expression was quantified by RT-qPCR at six time points; circadian parameters (mesor, amplitude, acrophase) were derived by cosinor analysis and compared between groups. Human cognitive screening confirmed modest gestational decline with postpartum recovery. In mice, gestation disrupted daily locomotor activity rhythms and reduced nocturnal preference; both partially recovered by 1 month and fully by 3 months postpartum. Behaviourally, pregnancy impaired the normal day-night difference and performance in novel object exploration and Barnes maze, which recovered progressively. At the molecular level, gestation increased hippocampal APP and BACE1 expression, elevated Aβ42 deposition, and induced tau hyperphosphorylation at multiple sites-hallmarks of Alzheimer's disease-related pathology. These alterations partially reversed by 1 month postpartum and normalized by 3 months. Hippocampal clock genes maintained 24 h rhythmicity, but gestation induced gene-specific phase shifts, amplitude reductions, and mesor alterations. These parameters showed gradual, gene-dependent normalization postpartum. Gestational cognitive impairment and postpartum recovery are associated with reversible disruption and restoration of both hippocampal circadian rhythms and Alzheimer's disease-related molecular pathology. These findings are correlational in nature and provide a foundation for future causal investigations.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":"e70178"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690683","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":"The pituitary adenylate cyclase-activating polypeptide receptor and its splice variants: Unique roles in affective and motivated behavior.","authors":"Brody A Carpenter, Jessica R Barson","doi":"10.1111/jne.70186","DOIUrl":"10.1111/jne.70186","url":null,"abstract":"<p><p>Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide with established roles in stress, affective behavior, and motivated behavior. Its primary receptor in the brain, the PACAP type I receptor (PAC1), has multiple variants due to alternative splicing of the gene, and these variants have been found to have different relationships with the stress response. In the field of motivated behavior, however, there has been much more limited research on these variants. This review focuses on the PAC1 and its splice variants, to propose that they should be thoroughly characterized in the context of motivated behavior. It develops the hypothesis that, for the motivated behavior of drug use, upregulation of a specific receptor variant during repeated episodes of drug use and withdrawal serves to reverse the early relationship between PACAP and drug use, switching from negative feedback in a non-dependent state to positive feedback in a dependent state. The review will first examine the known brain distribution and receptor dynamics of the PAC1 variants. Next, it will examine the known roles of PACAP and its receptor variants in stress, anxiety, and depression. Then, it will describe the known role of the PACAP system in alcohol use, as an example of drug use. Finally, the review will consider these known relationships in order to advance the proposal about how the PAC1 receptor variants may interact with drug use and dependence. Further research on this relationship could allow for the development of novel and effective medications for the treatment of drug use disorders.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":"e70186"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of LysaKare infusion on serum potassium levels in patients with gastroenteropancreatic neuroendocrine tumours eligible for treatment with [¹⁷⁷Lu]Lu-DOTA-TATE: A post-authorisation safety study.","authors":"Johannes Hofland, Chiara Maria Grana, Martin O Weickert, Andrew R Moore, Tahir Shah, Vineet Prakash, Agnieszka Kolasińska-Ćwikła, Wouter W de Herder, Francesca Spada, Lingfei Xu, Ramon Fite, Yuan Wu, Jarosław B Ćwikła","doi":"10.1111/jne.70172","DOIUrl":"10.1111/jne.70172","url":null,"abstract":"<p><p>A post-authorisation safety study (PASS) was conducted to assess the impact of LysaKare (2.5% Lysine-Arginine solution) on serum potassium concentrations and its safety/tolerability profile in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NET) eligible for ¹⁷⁷Lu-DOTATATE treatment. In a phase IV, multicentre, single-arm, open-label PASS, adults with somatostatin receptor-positive GEP-NET who were eligible for ¹⁷⁷Lu-DOTATATE treatment received 1000 mL of LysaKare (monotherapy) intravenously over 4 h. The primary endpoint was the change in serum potassium levels over the course of 24 h. Secondary endpoints included the incidence of LysaKare-related adverse events (AEs) and changes in laboratory parameters. Forty-one patients were treated (median age, 57 years; 92.7% White and 7.3% Black; 53.7% male) and 40 completed post-treatment follow-up. Mean (standard deviation [SD]) serum potassium was 4.33 (0.397) mmol/L pre-dose, increasing by 0.60 (0.666) mmol/L after 4 h (time to maximum change, range, 2-24 h) before decreasing to around the pre-dose level: the mean (SD) increase after 24 h was 0.07 (0.396) mmol/L. Other electrolytes and blood gas components mostly showed transient changes that lasted ~24 h. A general trend of transient metabolic acidosis was also observed based on laboratory values. Serum potassium grade increased from baseline in 41.5% of patients. By comparison, five patients (12.2%) had a treatment-related AE of hyperkalaemia (grade 3, n = 1); all resolved within 24 h, either without treatment (n = 3) or following intravenous furosemide (n = 2). There were no serious AEs and no AEs leading to treatment discontinuation/interruption. This PASS identified no new safety signals attributable to LysaKare. Trial registration: EudraCT, 2019-004073-76. Registered 20/08/2020.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":"e70172"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiological recording of hypothalamic brain regions in vivo using the transpharyngeal surgical approach in the rat","authors":"Mike Ludwig,&nbsp;Gareth Leng,&nbsp;Colin H. Brown","doi":"10.1111/jne.70177","DOIUrl":"10.1111/jne.70177","url":null,"abstract":"<p>Transpharyngeal (ventral) surgery in urethane-anaesthetised rats allows in vivo electrophysiological recording and/or imaging from superficial hypothalamic brain regions and from the pituitary gland. This surgical approach leaves the whole brain intact, providing a stable platform to study single or multiple identified cells over several hours with all central and peripheral inputs intact and the endocrine system functioning, which allows repeated drug application and stimulation of afferent inputs, as has been done for the arcuate nucleus, organum vasculosum of the lamina terminalis (OVLT) and suprachiasmatic nucleus (SCN) inputs to the supraoptic nucleus (SON). Exposing the ventral surface of the brain also allows simultaneous microdialysis for drug administration directly into the SON and for the collection of dialysate samples for measurement of somatodendritic neuropeptide release without disruption of the brain parenchyma. The most recent development using transpharyngeal surgery is two-photon imaging from the vasculature of the ventral surface of the brain, which has given insight into how SON neuronal activity affects cerebral blood flow and has identified a previously unknown SCN to OVLT portal blood system. Here we provide a brief history of the development of transpharyngeal surgery in the rat, instructions to complete the surgery and suggestions for future studies, extrapolating from the most recent developments in its use.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type III CD38 is present in the membrane of neurosecretory vesicles and has a cytosol-facing catalytic domain in primate oxytocin neurons.","authors":"Tatsuki Miyamoto, Akari Matsushima, Akito Otubo, Chihong Song, Kazuyoshi Murata, Takumi Oti, Hirotaka Sakamoto","doi":"10.1111/jne.70187","DOIUrl":"10.1111/jne.70187","url":null,"abstract":"<p><p>CD38, an ADP-ribosyl cyclase that generates cyclic ADP-ribose (cADPR), is essential for Ca²⁺-dependent oxytocin release. However, its subcellular localisation and membrane topology within oxytocin neurones have remained unclear. We investigated the distribution and orientation of CD38 in oxytocin-producing neurones of Japanese macaques (Macaca fuscata) using immunoelectron microscopy combined with biochemical isolation of neurosecretory vesicles (NSVs). CD38 immunoreactivity was selectively detected on oxytocin-containing NSVs in axon terminals in the posterior pituitary and dendrites of the supraoptic nucleus, whereas vasopressin vesicles and the plasma membrane lacked detectable labelling. Cryo-electron microscopy confirmed the structural integrity of purified NSV fractions, and Western blotting verified the presence of CD38 protein within these fractions. Permeabilisation-dependent immunogold labelling further demonstrated that the NSV membrane localisation of CD38 and that the N-terminal region of CD38 is oriented toward the vesicle lumen, consistent with a type III membrane topology in which the catalytic domain faces the cytosol. This arrangement positions the active site near cytosolic NAD⁺, enabling localised cADPR production adjacent to Ca²⁺-mobilising channels that support regulated exocytosis. These findings identify, in primate oxytocin neurones, a previously unrecognised, vesicle-associated pool of CD38 with a cytosol-facing catalytic domain and provide a structural framework for understanding how intracellular type III CD38 contributes to neuropeptide release.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":"e70187"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The lesser the better? A systematic review and meta-analysis of resection strategy in lung neuroendocrine tumors","authors":"Gal Aviel,&nbsp;Ranin Hojerat,&nbsp;Islam Idais,&nbsp;Bruria Hirsh-Raccah,&nbsp;Simona Grozinsky-Glasberg,&nbsp;Anat Bel Ange,&nbsp;Oz M. Shapira,&nbsp;Amit Korach,&nbsp;Uzi Izhar,&nbsp;Ori Wald","doi":"10.1111/jne.70176","DOIUrl":"10.1111/jne.70176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Lung neuroendocrine tumors (LNETs) are rare, with surgical resection as the mainstay of treatment, although the optimal extent remains uncertain. Herein, we present the first meta-analysis to assess the effect of resection extent (lobar vs. sub-lobar) on overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic review of the literature to identify studies comparing overall survival following lobectomy versus sub-lobar resection in LNETs. An inverse-variance meta-analysis was performed, and a Cox regression model was applied to reconstructed time-to-event data estimated from published Kaplan–Meier curves to generate pooled survival estimates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six studies encompassing 3,700 patients (lobectomy, <i>n</i> = 2,409; sub-lobar resection, <i>n</i> = 1,291) were included in the final analysis. The pooled 5-year overall survival for the entire cohort was 78.8% (95% CI, 76.6–81.1). No statistically significant difference in overall survival was observed between lobectomy and sub-lobar resection (HR = 1.21; 95% CI, 0.80–1.83; <i>I</i>² = 0%). Segmentectomy and lobectomy demonstrated comparable survival (<i>p</i> = 0.38), whereas wedge resection was associated with higher mortality (HR = 2.02; 95% CI, 1.64–2.49; <i>I</i>² = 0%). Sampling of &gt;10 lymph nodes was more frequent in lobectomy than sub-lobar resection (29.1% [95% CI, 0.8–95.3] vs 7.4% [95% CI, 0.01–98], respectively), likely contributing to the higher rate of nodal pathologic upstaging observed in the lobectomy group (6.2% [95% CI, 0.2–64.9] vs 2.2% [95% CI, 0–99]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this first meta-analysis of surgical resection for LNETs, sub-lobar resection and lobectomy showed no clear difference in overall survival. Adequate lymph node assessment remains essential, irrespective of the surgical approach.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testosterone, cortisol, and fNIRS-based cortical activation associated with competitive task persistence and difficulty.","authors":"Kathleen V Casto, Dale J Cohen, Cameron Hicks, Andrew Bowser","doi":"10.1111/jne.70185","DOIUrl":"10.1111/jne.70185","url":null,"abstract":"<p><p>Motivation for social or resource-related rewards is regulated by areas of the brain that control executive functioning and regulate attention, including the prefrontal cortex (PFC) and temporoparietal junction (TPJ). Testosterone and cortisol are two steroid hormones that influence behaviors related to motivation in social competition and are thought to do so via their independent and interactive effects on these same brain networks. Yet there remains relatively limited evidence for functional hormone-brain correspondence during status contests in humans. In ~120-130 participants, we measured frontal-temporal cortical patterns of neural activity via functional near-infrared spectroscopy (fNIRS), salivary testosterone and cortisol, and task performance in a competitive key-pressing contest for rewards in which the cognitive difficulty of the task was varied. Participants completed the task under one of three conditions for incentivizing performance: a cash prize, positive social judgement, or negative social judgement. The competitive task was associated with increased neural activity bilaterally across the PFC and decreased TPJ activity, especially as task difficulty increased. Individuals who performed better showed greater frontal cortical activation overall and were more likely to have increasing testosterone across the task, but only if cortisol levels simultaneously declined. While hormone change across the task had limited direct ties to brain activity, basal testosterone predicted right vlPFC activation, while the interaction of basal testosterone and cortisol predicted activity in the right TPJ depending on task difficulty. Incentive condition had no clear effects on patterns of brain activity or hormone-brain relationships. These findings support an emerging model of testosterone and cortisol's influence on implicit brain processes underlying attention and goal salience when pursuing social goals. More broadly, this research raises new directions for understanding the neuroendocrine mechanisms behind social and reward-seeking behavior.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":"e70185"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemicolectomy or appendectomy for appendiceal neuroendocrine tumours sized 1-2 cm? A retrospective population-based study of 1514 patients.","authors":"Ker Shiong Tan, Aya Abdelhameed, Mohamed Mortagy, Benjamin E White, Dan Burns, John Ramage","doi":"10.1111/jne.70179","DOIUrl":"https://doi.org/10.1111/jne.70179","url":null,"abstract":"<p><p>Management of appendiceal neuroendocrine tumours (aNET) with a size of 1-2 cm is a topic of debate, with the conflict centred on the potential oncological benefits of right hemicolectomy (RHC) versus appendectomy and the impact of RHC on quality of life. A recent study suggested that RHC may not be needed for certain aNET 1-2 cm in size. A total of 1244 adult patients with aNET 1-2 cm (diagnosed 2012-2022) who underwent appendectomy or RHC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Similarly, a total of 270 patients (diagnosed 2012-2021) were extracted from the National Cancer Registration and Analysis Service (NCRAS) database. Kaplan-Meier (KM) plots for overall survival (OS) were generated with log-rank tests (LR). Univariable and multivariable Cox regression for all-cause mortality were performed. In the NCRAS cohort, 159 and 111 patients underwent appendectomy and RHC, respectively. The median age was 41 and 51 years for appendectomy and RHC, respectively. Most patients were female (63.7%) and of white race (86.3%). Patients who underwent RHC had a higher proportion of node-positive disease. In the SEER cohort, 957 and 287 patients underwent appendectomy and RHC, respectively. Median age was 39 and 47 years for appendectomy and RHC, respectively. Most patients were females (65.3%) and of white race (67.7%). Patients who underwent RHC had a higher proportion of node-positive disease and M1 stage. Sex and race distribution were similar for the two procedures in both NCRAS and SEER. The KM plot for OS in NCRAS (p = .061) and SEER (p = .14) showed no statistical difference between appendectomy and RHC. Cox regression for all-cause mortality showed that there is no statistical difference between appendectomy and RHC in both cohorts after adjusting for other factors, including age and N stage. Cox regression for all-cause mortality for both cohorts combined showed the same result. Survival of appendectomy is non-inferior to RHC in the management of aNET 1-2 cm, even in patients with node-positive disease. These study findings address the gap in current clinical practice guidelines.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":"e70179"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690785","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":"Efficacy of FOLFIRINOX in digestive neuroendocrine carcinoma","authors":"B. P. Butt,&nbsp;H. Sorbye,&nbsp;M. Ladekarl,&nbsp;H. L. Stokmo,&nbsp;I. M. B. Lothe,&nbsp;H. Fawad,&nbsp;E. M. Tabaksblat,&nbsp;M. E. Revheim,&nbsp;B. Dybdahl,&nbsp;A. Couvelard,&nbsp;A. Perren,&nbsp;G. O. Hjortland","doi":"10.1111/jne.70168","DOIUrl":"10.1111/jne.70168","url":null,"abstract":"<p>Digestive neuroendocrine carcinomas (NEC) are rare, aggressive, and treatment-resistant malignancies. Platinum and etoposide are recommended as first line treatment; however, with limited benefit in colorectal NEC and in NEC with low Ki67 of 20%–55%. There is no firm evidence for second-line treatment. Being efficient in digestive adenocarcinomas, FOLFIRINOX is sometimes used also in patients with NEC. In this retrospective cohort study, patients with digestive NEC who received FOLFIRINOX and were diagnosed 2014–2021 were retrospectively identified at three Scandinavian centers. Histology was re-evaluated according to the 2019 WHO classification to exclude NET G3 tumors. Patient characteristics, treatment response, and survival outcomes were assessed. Fifty cases were identified; four of these were classified as mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN). The most common primary sites were colon (<i>n</i> = 17) and pancreas (<i>n</i> = 13). FOLFIRINOX was administrated predominantly in later lines (82%). Overall response rate (RR) was 44% (95% confidence interval (CI): 29%–58%) and disease control rate 72% (CI: 57%–83%), while median progression free survival was 5.6 months (CI: 4.3–6.9 months). Twenty-three patients with colorectal primary, 12 patients with Ki67 &lt; 55%, and 33 patients previously exposed to platinum and etoposide as first line; the RR was 52%, 50%, and 39%, respectively. This study suggests a role for FOLFIRINOX in digestive NEC. High efficacy was observed, even in patients with hard-to-treat colorectal primaries, in those with Ki67 &lt; 55%, and in patients previously exposed to platinum and etoposide.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581519","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":"GABA receptor modulation of arcuate kisspeptin neuron bursting and synchronization activity in female mice","authors":"Toby Eddleston,&nbsp;Paul G. Morris,&nbsp;Allan E. Herbison","doi":"10.1111/jne.70170","DOIUrl":"10.1111/jne.70170","url":null,"abstract":"<p>The arcuate nucleus kisspeptin (ARN^KISS) neurons intermittently synchronize their activity to operate as the GnRH pulse generator and drive pulsatile reproductive hormone secretion in mammals. Although ARN^KISS neurons are known to receive various GABAergic inputs, the effects of GABA_A and GABA_B receptor modulation on their ability to synchronize remain unknown. We have used GCaMP6s to monitor the activity of multiple ARN^KISS neurons simultaneously in acute brain slices from diestrous female Kiss1-Cre1,Ai162D mice. The effects of modulating GABA_A and GABA_B receptors on calcium transients exhibited by individual ARN^KISS neurons, reflecting burst firing, and their ability to generate synchronous bursting events were examined. The application of GABA was found to robustly suppress the occurrence of individual calcium transients and population bursting. The GABA_A receptor agonist muscimol had a biphasic effect in which ARN^KISS neurons could initially respond with an increase in baseline calcium but then became inhibited with significantly reduced episodes of individual burst firing and population synchronization events. Baclofen, the GABA_B receptor agonist, also reduced the frequency of ARN^KISS neuron burst firing. The receptor antagonists bicuculline and CGP-35348 had no effects on individual bursting frequency or dynamics, or the synchronous activation of ARN^KISS neurons indicating a lack of ongoing GABA transmission in the acute brain slice. These observations show that while GABAergic activation may initially facilitate excitability through GABA_A receptor-mediated depolarization, sustained GABAergic input to ARN^KISS neurons suppresses their burst firing and ability to synchronize through both GABA_A and GABA_B receptors. As such, GABAergic inputs to ARN^KISS neurons appear to have considerable potential to modulate the frequency of pulse generator activity in female mice.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13035435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}