Journal of Neuroendocrinology最新文献

{"title":"The neurosteroid paradigm in perinatal depression: From pathophysiology to precision therapeutics","authors":"Nevena V. Radonjić,&nbsp;Khatiya C. Moon,&nbsp;Kristina M. Deligiannidis","doi":"10.1111/jne.70253","DOIUrl":"10.1111/jne.70253","url":null,"abstract":"<p>Neurosteroids and their role in the pathophysiology of perinatal depression have been in the focus of scientific investigation for several decades. Recently, two synthetic analogs of the neurosteroid allopregnanolone—brexanolone and zuranolone—received approval in the United States for the treatment of postpartum depression (PPD) exhibiting a rapid, long-lasting antidepressant effect through a novel mechanism of action. These developments mark a milestone in psychiatric research and advancement in available treatment options. In this review, we examine the role of neurosteroids in perinatal depression, with particular emphasis on their impact on network states and functional connectivity. We synthesize current clinical experience with brexanolone and zuranolone in the treatment of PPD, highlighting efficacy and practical considerations. Finally, we explore emerging precision medicine approaches that leverage the heterogeneity of clinical presentations and treatment responses in PPD to guide the development of targeted therapeutic strategies for this widely prevalent and debilitating condition.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880949","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":"Grief as a neuroendocrine transition: Insights from perinatal loss","authors":"Clare Killikelly,&nbsp;Eva-Maria Stelzer,&nbsp;Rita T. Amiel Castro","doi":"10.1111/jne.70262","DOIUrl":"10.1111/jne.70262","url":null,"abstract":"<p>Grief is an all-encompassing human experience that reverberates across mind, brain, and body. Historically, the scientific study of grief has been rooted primarily in psychological frameworks. Pioneering work has begun to elucidate how attachment loss is encoded not only psychologically but also biologically, and this may be particularly significant during the perinatal period.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873768","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":"Dlk1-deficient mice achieve puberty despite low body weight and low levels of leptin and kisspeptin","authors":"Delanie B. Macedo,&nbsp;Sidney A. Pereira,&nbsp;Meijiao Wang,&nbsp;Han Kim Kyeol,&nbsp;Rona S. Carroll,&nbsp;Ana Claudia Latronico,&nbsp;Ana Paula Abreu,&nbsp;Ursula B. Kaiser","doi":"10.1111/jne.70248","DOIUrl":"https://doi.org/10.1111/jne.70248","url":null,"abstract":"<p>Loss-of-function mutations in <i>DLK1</i>, encoding Delta Like Non-Canonical Notch Ligand 1, have been linked to central precocious puberty (CPP) and increased body fat in girls, suggesting a role in the connection between metabolism and reproduction. <i>DLK1</i> is located in the imprinted region of human chromosome 14, and mice lacking Dlk1 exhibit growth retardation and metabolic changes, phenotypes that overlap with Temple syndrome, an imprinting disorder associated with precocious puberty. However, the mechanisms by which <i>DLK1</i> influences pubertal timing remain unclear. We investigated pubertal timing in <i>Dlk1</i> knockout (KO) mice with either global or selective central nervous system (CNS) deletion of <i>Dlk1</i>, compared with control mice. Puberty onset and body weight were assessed, along with potential mediators of pubertal timing, including leptin and kisspeptin. <i>Dlk1</i>KO females reached puberty at the same age as controls, despite lower body weight. <i>Dlk1</i>KO males had delayed preputial separation but, like females, reached puberty at significantly lower body weight. Serum leptin and hypothalamic <i>Socs3</i> mRNA, a downstream leptin effector, were lower peri-pubertally in <i>Dlk1</i>KO females than in controls. <i>Kiss1</i> mRNA levels in the mediobasal hypothalamus were significantly lower in <i>Dlk1</i>KO females at puberty onset. Selective <i>Dlk1</i> deletion in neurons and glial cells did not affect pubertal timing. These findings suggest that peripheral sources of Dlk1 contribute to the metabolic and endocrine regulation of pubertal timing. The absence of Dlk1 appears to alter the metabolic milieu in which puberty occurs, allowing activation of the reproductive axis despite low body weight and reduced hypothalamic kisspeptin expression.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860016","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":"Comparative analysis of SCGN expression patterns in the anterior pituitary gland of mouse, pig, and human by single-cell transcriptomics","authors":"Cheng-Cheng Wang,&nbsp;Qi-Lin Zhang,&nbsp;Zhen-Le Zang,&nbsp;Hua-Chun Yin,&nbsp;Yu Pan,&nbsp;Yi-Fei Yu,&nbsp;Yi-Ming Li,&nbsp;Zhao-Yun Zhang,&nbsp;Song Li,&nbsp;Hui Yang","doi":"10.1111/jne.70249","DOIUrl":"10.1111/jne.70249","url":null,"abstract":"<p>Secretagogin (SCGN) is a calcium-binding protein implicated in neuroendocrine secretion. However, its expression profile in the anterior pituitary gland and potential species-specific differences remain poorly characterized. We analyzed scRNA-seq data from the pituitary glands of mice, rats, pigs, and humans, then combined it with validation by immunostaining to systematically elucidate the expression and distribution patterns of SCGN in the anterior pituitary gland. SCGN exhibited distinct species-specific expression patterns. In mice, SCGN transcripts were predominantly enriched in PIT1-lineage lactotropes and SF1-lineage gonadotropes, with immunofluorescence confirming high colocalization with LH, FSH, and PRL. In pigs, SCGN was primarily expressed in TPIT-lineage corticotropes, and immunofluorescence colocalization analysis confirmed the highest colocalization rate with ACTH. In humans, SCGN expression was confirmed in the anterior pituitary gland by immunohistochemistry, while scRNA-seq revealed predominant enrichment of its transcripts in PIT1-lineage lactotropes and somatotropes. Notably, comparative interspecies analysis indicated a high degree of similarity in SCGN enrichment within PIT1-lineage cells (particularly lactotropes) between mice and humans. In contrast, SCGN expression was undetectable in the rat anterior pituitary gland at both transcriptional and protein levels. Together, our findings suggest that SCGN may not be an essential or universal regulator of anterior pituitary hormone secretion. Instead, this study provides an informative negative example that highlights the interspecies divergence of the pituitary secretory machinery among mammals.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808819","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":"Primary functional hypothalamic amenorrhoea in the context of feeding and eating disorders or excessive exercise: Insights from non-athletic and elite athletic populations","authors":"Marianna Minnetti,&nbsp;Chiara Tarantino,&nbsp;Monica D'Amico,&nbsp;Emanuele Filice,&nbsp;Chiara Graziadio,&nbsp;Edoardo Mocini,&nbsp;Giuseppe Tiralongo,&nbsp;Daniele Gianfrilli,&nbsp;Andrea M. Isidori,&nbsp;Lorenzo M. Donini,&nbsp;Eleonora Poggiogalle,&nbsp;Maria Grazia Tarsitano,&nbsp;Talent Group","doi":"10.1111/jne.70242","DOIUrl":"10.1111/jne.70242","url":null,"abstract":"<p>Primary amenorrhoea is defined as the absence of menarche by the expected age, with or without delayed pubertal development in adolescents. It may result from anatomical, genetic, endocrine, and functional causes. Among the latter, we propose the term primary functional hypothalamic amenorrhoea (P-FHA) to describe primary amenorrhoea characterised by hypothalamic–pituitary–ovarian axis suppression in the absence of organic disease. P-FHA is frequently associated with low energy availability (LEA), particularly in individuals with feeding and eating disorders (FEDs) or excessive exercise, often within the spectrum of Relative Energy Deficiency in Sport (REDs). Despite its clinical relevance, P-FHA remains under-recognised, with limited dedicated research. This review aims to synthesise clinical studies addressing P-FHA in the context of FEDs or excessive exercise. A systematic literature search was conducted using PubMed, Web of Science, and Scopus. Studies focusing on P-FHA and its association with FEDs, excessive exercise, and REDs were included. Case reports and aggregated studies combining P-FHA and S-FHA were excluded to ensure specificity. Twenty-four studies addressing patients with P-FHA were identified. Available evidence suggests that the reported frequency of functional hypothalamic causes of primary amenorrhoea may have increased over time, although estimates varied substantially across populations and study designs. In patients with FEDs, the prevalence of PA ranged from 2.4% to 14.8%, while athlete cohorts reported frequencies ranging from 7.3% to 53.8%. FEDs and excessive exercise, including REDs-related conditions, emerged as major clinical settings. Data specifically addressing hormonal profiles or body composition in this context remain limited. P-FHA may represent an early clinical manifestation of chronic LEA occurring during a critical developmental window. Early recognition and multidisciplinary management are essential to minimise potential consequences on growth, skeletal health, reproductive function, body composition, and psychological well-being. Further prospective studies are needed to better define its epidemiology, neuroendocrine mechanisms, and optimal management strategies.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727797","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":"SSTR-PeRForm: A harmonized approach to somatostatin receptor PET response assessment in neuroendocrine tumors","authors":"Hannes Leupe,&nbsp;Christophe M. Deroose,&nbsp;Andreas Kjaer,&nbsp;Vikas Prasad,&nbsp;Valentina Ambrosini","doi":"10.1111/jne.70244","DOIUrl":"https://doi.org/10.1111/jne.70244","url":null,"abstract":"","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753699","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":"NUP153 immunoreactivity in neuroendocrine neoplasms supports the diagnosis of NET versus NEC and is modulated by post-translational modifications","authors":"Sven Mattern,&nbsp;Arslan Ali,&nbsp;Vanessa Hollfoth,&nbsp;Eyyub Bag,&nbsp;Katharina Kluthe,&nbsp;Esther Herpel,&nbsp;Frank Bergmann,&nbsp;Thomas Muley,&nbsp;Michael Meister,&nbsp;Judith Lehmann-Koch,&nbsp;Benjamin Goeppert,&nbsp;Arne Warth,&nbsp;Kai Breuhahn,&nbsp;Irina Bonzheim,&nbsp;Stephan Singer,&nbsp;Kerstin Singer","doi":"10.1111/jne.70240","DOIUrl":"10.1111/jne.70240","url":null,"abstract":"<p>Nucleoporins (NUPs) constitute the nuclear pore complex (NPC) and are essentially involved in nuclear transport, chromatin organization, and context-dependent gene regulation. However, the role of NUPs in neuroendocrine (tumor)biology and related diagnostic potential is poorly defined. In this study, we comparatively analyzed immunohistochemical expression patterns of NUP98 and NUP153 (sharing structural and functional similarities) across a large variety of human tissues and tumors (total <i>N</i> &gt; 600), with a focus on neuroendocrine neoplasms (NENs (<i>n</i> = 361)). While both NUPs showed a nuclear rim accentuated staining pattern, NUP98 exhibited ubiquitous and NUP153 a striking cell- and tissue/tumor-type-dependent immunoreactivity. More specifically, NUP153 immunoreactivity was consistently detectable in neuroendocrine tissues (e.g., pancreatic islets) and retained in neuroendocrine tumors (NETs) of the pancreas, lung, appendix, and small intestine, but almost completely absent in neuroendocrine carcinomas (NECs) and non-neuroendocrine carcinomas. Loss of NUP153 staining correlated with poorer clinical outcomes in pancreatic NETs. Further analyses revealed that NUP153 messenger ribonucleic acid (mRNA) and total protein levels were not significantly different between NETs and non-neuroendocrine carcinomas, as evaluated by quantitative real-time polymerase chain reaction and targeted proteomics. Differential isoform usage was ruled out by polymerase chain reaction and sequencing as another possible explanation for the discriminative immunohistochemical findings. Finally, a high density of post-translational modifications (PTMs) within the antigen sequence could be discovered and indicated PTM-dependent detection as the likely cause of differential staining. Collectively, our findings suggest that NUP153 is a differentiation-dependent and PTM-sensitive immunohistochemical marker in NENs with diagnostic and prognostic potential. It also emphasizes the importance of orthogonal molecular analyses for correct interpretation of IHC stainings.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725357","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":"Procedure-specific morbidity and pathologic assessment after resection of small (≤20 mm) pancreatic neuroendocrine tumors","authors":"Aya Maekawa,&nbsp;Giampaolo Perri,&nbsp;Stefano Partelli,&nbsp;Charles de Ponthaud,&nbsp;Safi Dokmak,&nbsp;Carsten Jäger,&nbsp;Maria Lavinia Luzietti,&nbsp;Alessio Marchetti,&nbsp;Valentina Andreasi,&nbsp;Anna Battistella,&nbsp;Bengi Su Yilmaz,&nbsp;Andrea Sheel,&nbsp;Kunal Rajput,&nbsp;Haiyi Hu,&nbsp;Umberto Cillo,&nbsp;Alain Sauvanet,&nbsp;Helmut Friess,&nbsp;Ryan D. Baron,&nbsp;Sébastien Gaujoux,&nbsp;Massimo Falconi,&nbsp;Giovanni Marchegiani","doi":"10.1111/jne.70243","DOIUrl":"10.1111/jne.70243","url":null,"abstract":"<p>Pancreatic neuroendocrine tumors (PanNETs) are increasingly detected, and the optimal extent of resection remains uncertain because perioperative burden and oncologic assessment may differ by procedure. Enucleation (EN) and central pancreatectomy (CP) are often grouped together as parenchyma-sparing resections (PSRs) despite substantial differences in technical complexity, postoperative risk, and oncologic evaluation.We conducted a multicenter retrospective study of consecutive patients who underwent resection for pathologically confirmed PanNETs ≤20 mm. Procedures were categorized as EN, CP, pancreatoduodenectomy (PD), total pancreatectomy (TP), or distal pancreatectomy (DP). Primary outcomes were clinically relevant postoperative pancreatic fistula (CR-POPF) and major morbidity, defined as Clavien-Dindo grade ≥IIIa. A prespecified pairwise comparison focused on EN and CP, and pathologic assessment patterns were analyzed descriptively across procedures. Of 460 patients, 164 (35.7%) underwent EN, 40 (8.7%) CP, 84 (18.2%) PD/TP, and 172 (37.4%) DP. CR-POPF occurred in 115 patients (25.0%), major morbidity in 68 (14.8%), and 90-day mortality in 4 (0.9%). Among PSRs, CP had higher major morbidity than EN (25.0% vs 10.4%, <i>p</i> =.020), higher CR-POPF (50.0% vs. 24.4%, <i>p</i> =.003), and a longer median hospital stay (19.5 vs. 10.0 days, <i>p</i> &lt;.001). Lymph node (LN) assessment was less frequent after EN than CP (40.4% vs. 87.5%, <i>p</i> &lt;.001). Among assessed cases, LN metastases were identified in 44/320 patients (13.8%). EN and CP are not interchangeable as parenchyma-sparing options for small PanNETs. Among patients selected for resection, procedure selection should consider tumor location, function, technical feasibility, and oncologic requirements rather than size alone.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712916","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":"GLP-1 receptor agonists, metabolic syndrome, and Alzheimer's disease: Lessons and opportunities from the EVOKE trials","authors":"Pragati Gupta,&nbsp;Valeria Pozzilli,&nbsp;Anastasia De Giovanni,&nbsp;Elisabetta Sapio,&nbsp;Francesco Motolese,&nbsp;Fioravante Capone,&nbsp;Paolo Pozzilli","doi":"10.1111/jne.70246","DOIUrl":"10.1111/jne.70246","url":null,"abstract":"<p>Metabolic syndrome and Alzheimer's disease (AD) are increasingly recognised as interconnected, sharing vascular, metabolic and inflammatory pathways that accelerate brain ageing and cognitive decline. This review critically examines the evidence that glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for diabetes and obesity, may influence AD related pathways or reduce AD risk in metabolically vulnerable populations. Metabolic syndrome and AD related cognitive impairment share biological mechanisms including vascular damage, insulin resistance and chronic inflammation, suggesting that therapies targeting metabolic dysfunction could influence neurological outcomes. GLP-1RAs are notable for combining systemic benefits, like weight loss, improved glycaemic control, and reduced cardiovascular risk, with possible but incompletely established central nervous system effects. Experimental studies suggest that some GLP-1RAs may reduce amyloid and tau pathology, support mitochondrial function, and limit neuroinflammation, although recent preclinical studies and limited brain penetrance argue against a direct neuroprotective effect. Observational data suggest lower dementia rates among users compared with other antidiabetic treatments. However, the recent EVOKE and EVOKE + trials showed that oral semaglutide did not slow clinical progression in early symptomatic AD, despite positive biomarker effects. This highlights the challenge of translating biological plausibility into meaningful clinical benefit and refocuses attention on disease stage, target population, and mechanism. Beyond summarising evidence, this review advocates a more cautious and mechanism specific framework: preserving cognitive health may require addressing systemic metabolic dysfunction rather than targeting the brain alone. GLP-1 RAs have failed to show an effect in symptomatic AD, but their effects on metabolism might still be beneficial at earlier stages, such as the preclinical phase of AD. Future studies should determine whether earlier intervention in metabolically enriched groups can alter AD related cognitive, vascular, and biomarker trajectories.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712882","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":"Enduring autism-like phenotypes and deregulated hypothalamic prosocial peptides after early-life exposure to indoor flame retardants in male C57BL/6 mice","authors":"Elena V. Kozlova,&nbsp;Gwendolyn M. Gonzalez,&nbsp;Maximillian E. Denys,&nbsp;Anthony E. Bishay,&nbsp;Roberto Gutierrez,&nbsp;Jack Reid,&nbsp;Julia M. Krum,&nbsp;Gregory Lampel,&nbsp;Naran Luvsanravdan,&nbsp;Kayhon M. Rabbani,&nbsp;Jordan Tu,&nbsp;Luis Campoy,&nbsp;Laura M. Anchondo,&nbsp;Crystal N. Luna,&nbsp;Duraan S. Olomi,&nbsp;Eduardo Monarrez,&nbsp;Valeria Carrillo,&nbsp;Jasmin D. Tran,&nbsp;Damon Platt,&nbsp;Yash Korde,&nbsp;Bhuvaneswari D. Chinthirla,&nbsp;Maher Blaibel,&nbsp;Simon Kim,&nbsp;Gladys Chompre,&nbsp;Allison L. Phillips,&nbsp;Heather M. Stapleton,&nbsp;Bernhard Henkelmann,&nbsp;Karl-Werner Schramm,&nbsp;Margarita C. Curras-Collazo","doi":"10.1111/jne.70237","DOIUrl":"10.1111/jne.70237","url":null,"abstract":"<p>Polybrominated diphenyl ethers (PBDEs) are neuroendocrine-disrupting chemicals that produce adverse neurodevelopmental effects. PBDEs have been implicated as risk factors for autism spectrum disorder (ASD), which is characterized by abnormal psychosocial functioning and is commonly comorbid with cognitive deficits and sensory abnormalities. Here, we used a mouse model with translationally relevant exposure to establish direct causal evidence that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neuroendocrine deficits in male offspring. C57Bl6/N mouse dams were exposed to a commercial PBDE mixture, DE-71, via oral administration of 0 (vehicle control, VEH/CON), 0.1 (L-DE-71), or 0.4 (H-DE-71) mg/kg b.w./day for 10 weeks, spanning from 3 weeks prior to gestation through the end of lactation at postnatal day (PND) 21. Mass spectrometric analysis indicated a dose-dependent transfer of PBDEs (in ppb) to brains of F1 male offspring at PND 30, with reduction in levels by PND 110. DE-71-exposed adult F1 male offspring displayed ASD-relevant abnormal neurobehavioral phenotypes, including impaired social novelty preference (SNP) despite intact general sociability and exaggerated repetitive behavior. There were also milder effects on long-term social recognition memory (SRM). DE-71-exposed mice also displayed altered olfactory discrimination of social odors without altered odor preference for non-social odors, impaired novel object recognition memory, and reduced open field habituation relative to VEH/CON. However, no changes were observed in sensorimotor, anxiety-, or depressive-like behaviors. At the molecular level, DE-71-exposed males displayed deregulated gene markers of prosocial neuropeptides, oxytocin, vasopressin, and PACAP systems in hypothalamic and forebrain regions. <i>Oxt</i> was upregulated in the paraventricular nucleus (PVN); <i>Avp</i> was upregulated in the PVN and bed nucleus of the stria terminalis (BNST) but downregulated in the lateral septum (LS); <i>Avp1ar</i> and <i>Adcyap1</i> were upregulated in the BNST; and <i>Adcyap1r1</i> was upregulated in the PVN, supraoptic nucleus (SON), and BNST. Peripheral OXT was increased in L-DE-71 males, while no changes in plasma AVP were observed. These findings demonstrate that developmental PBDE exposure produces enduring behavioral and neuroendocrine phenotypes that resemble core domains of ASD, which may result from early neurodevelopmental reprogramming within central social and memory networks.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673841","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}