Journal of Neuroendocrinology最新文献

{"title":"Can acromegaly be controlled in all cases?","authors":"Sabrina Chiloiro,&nbsp;Francesco Padovano Sorrentino,&nbsp;Alessandra Vicari,&nbsp;Antonella Giampietro,&nbsp;Pier Paolo Mattogno,&nbsp;Quintino Giorgio D'Alessandris,&nbsp;Rosalinda Calandrelli,&nbsp;Tommaso Tartaglione,&nbsp;Marco Gessi,&nbsp;Simona Gaudino,&nbsp;Laura De Marinis,&nbsp;Guido Rindi,&nbsp;Francesco Doglietto,&nbsp;Antonio Bianchi,&nbsp;Alfredo Pontecorvi","doi":"10.1111/jne.70241","DOIUrl":"10.1111/jne.70241","url":null,"abstract":"<p>Acromegaly is a rare disease, due in most of the cases to a growth hormone (GH)-secreting pituitary adenoma (PA), namely neuroendocrine tumour (PitNET). The treatment of patients with acromegaly is multimodal and multi-step, including surgery, medical therapies, and radiotherapy. In the last 30 years, the therapeutic armamentarium for the treatment of acromegaly has progressively increased, and the therapeutic algorithm has been significantly modified through the identification of clinical, biochemical, and molecular biomarkers of treatment outcome. The personalization of acromegaly treatment has shifted the paradigm from a ‘trial-and-error’ to a ‘target-to-treat’ treatment approach to achieve early disease control and to reduce the risk of disease-related comorbidities that may lead to an increased mortality. Nevertheless, despite the numerous improvements in the treatment of patients with acromegaly, disease control is not achieved in all patients, according to the results of randomized clinical trials, interventional studies, and prospective and retrospective observational studies. In parallel, the normalization of GH and IGF-I levels may not be sufficient to control acromegaly related symptoms and prevent disease-related comorbidities. In this review, we will report on the most recent aims of treatment and cure in patients with acromegaly, on the efficacy and predictors of response to conventional treatments (such as first- and second-generation somatostatin receptor ligands and growth hormone receptor antagonist). A specific section will focus on the rarer aggressive disease pictures and on the treatment with systemic therapies (such as temozolomide and capecitabine) and on target therapies (such as neo-angiogenesis and immune checkpoint inhibitors).</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/PMC13442985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678338","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":"Rolf Christian Gaillard (1944-2011): A builder of modern European endocrinology and neuroendocrinology.","authors":"Philippe Chanson, Eduardo Spinedi, François Pralong","doi":"10.1111/jne.70245","DOIUrl":"10.1111/jne.70245","url":null,"abstract":"<p><p>Rolf Christian Gaillard was a Swiss physician, scientist, and academic leader whose career contributed significantly to the development of modern European endocrinology and neuroendocrinology. Among his most remarkable qualities was an exceptional talent for organisation and institution-building. Together with his collaborators, Gaillard became internationally recognised for his work on regulation of the hypothalamic-pituitary-adrenal axis. His research demonstrated how immune mediators influence endocrine regulation during infection, inflammation, trauma, and chronic stress. His scientific interests extended beyond neuroendocrinology and included leptin physiology, obesity, appetite regulation, adrenal disorders, adult growth hormone deficiency, metabolic diseases, reproductive endocrinology, and neuroendocrine adaptation. A founding member of European Neuroendocrine Association (ENEA), he subsequently served as its Treasurer and then as its President and largely contributed the success of the ENEA Congresses and Workshops.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":"e70245"},"PeriodicalIF":5.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712914","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":"Correction to “Controversies in NEN: An ENETS position statement on the interchangeability of somatostatin receptor PET tracers”","authors":"","doi":"10.1111/jne.70239","DOIUrl":"https://doi.org/10.1111/jne.70239","url":null,"abstract":"<p>\u0000 <span>Deroose, CM</span>, <span>Ambrosini, V</span>, <span>Hofland, J</span>, et al. <span>Controversies in NEN: an ENETS position statement on the interchangeability of somatostatin receptor PET tracers</span>. <i>J Neuroendocrinol</i>. <span>2026</span>; <span>38</span>(<span>7</span>):e70220. doi:10.1111/jne.70220\u0000 </p><p>We apologize for these errors.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616842","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":"Hyponatremia correction is associated with increased brain-derived neurotrophic factor levels: A pilot secondary analysis of a randomized, double-blind, placebo-controlled, crossover trial","authors":"Eszter Kustos-Tóth,&nbsp;Julia Beck,&nbsp;Lucia Seeger,&nbsp;Sophie Monnerat,&nbsp;Cemile Bathelt,&nbsp;Julie Refardt,&nbsp;Mirjam Christ-Crain","doi":"10.1111/jne.70238","DOIUrl":"10.1111/jne.70238","url":null,"abstract":"<p>Chronic hyponatremia is associated with cognitive deficits, yet the underlying mechanisms remain elusive. A cerebral growth factor which is crucial for cognition and memory is brain-derived neurotrophic factor (BDNF), but its role in hyponatremia has never been investigated. We here examined the influence of hyponatremia correction on serum BDNF levels. This study represents a secondary post hoc analysis of a prospective randomized, double-blind, crossover, placebo-controlled trial. Nine patients with syndrome of inappropriate antidiuresis (SIAD) completed 4 weeks treatments with empagliflozin 25 mg/day versus placebo. Serum sodium, BDNF levels, and Montreal Cognitive Assessment (MoCA) were assessed at baseline and after treatment cycles. Median baseline sodium was 131 mmol/L [130–133], which increased to 134 mmol/L ([131–136], <i>p</i> = .04) after empagliflozin treatment and remained stable after placebo phase (130 mmol/L [126–132], <i>p</i> = .9). Sodium increase was significantly associated with BDNF increase, also after adjusting for treatment arm, sex, age, baseline sodium, and antidepressant treatment (per 1 mmol/L sodium increase: estimate = 0.70 ng/mL, <i>p</i> = .048). This association was stronger upon empagliflozin treatment as shown by the interaction analysis (<i>p</i> = .03). In a subgroup of patients reaching normonatremia after empagliflozin treatment, BDNF increase was slightly higher compared to patients with persistent hyponatremia. MoCA scores did not differ between empagliflozin and placebo phase. Sodium increase was significantly associated with an increase in neurocognitive biomarker BDNF. Further research is needed to clarify BDNF's role in cognitive impairment in hyponatremia and its response to different treatment approaches.</p><p>Trial registration: ClinicalTrials.gov (NCT03202667).</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603817","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":"Transcriptomic changes in the jerboa supraoptic nucleus during osmotic stress: PCSK1 and PTPRN changes are conserved across desert and mesic species","authors":"Benjamin T. Gillard,&nbsp;Nabil Amor,&nbsp;Michael P. Greenwood,&nbsp;Abdulaziz N. Alagaili,&nbsp;David Murphy","doi":"10.1111/jne.70233","DOIUrl":"10.1111/jne.70233","url":null,"abstract":"<p>The supraoptic nucleus (SON) is a hypothalamic region essential for the orchestration of osmoregulation in mammals. We sought to understand how gene expression in the SON is orchestrated in a rodent species adapted for survival in arid desert conditions. After an acclimatisation period, we compared the male and female trancriptomes of the Lesser Egyptian jerboa (<i>Jaculus jaculus</i>) SON under euhydrated, dehydrated, and rehydrated conditions. Gene expression in the jerboa SON was remarkably stable across the conditions with only 46 differentially expressed genes (DEGs) after dehydration and 4 DEGs after rehydration compared to controls; far fewer than previously shown to respond in the jerboa kidney and in the SON of mesic species. When comparing across species (jerboa, camel, and rat), the genes PCSK1 and PTPRN were consistently regulated under conditions of osmotic stress suggesting they have important conserved functions. The dehydration response in jerboa SON is tightly regulated. PCSK1 and PTPRN are identified as conserved components of the response, indicating their importance.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592262","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":"Scanning for representation: A scoping review of racial and ethnic diversity in MRI studies of the maternal brain","authors":"Edwina R. Orchard,&nbsp;Clíona L. Murray,&nbsp;Kathryn M. Wall,&nbsp;Josephine C. P. Levy,&nbsp;Jin Young Shin,&nbsp;Claudia G. Gaebler,&nbsp;Victoria R. Hart-Derrick,&nbsp;Kathy Ayala,&nbsp;Amorine Adodo,&nbsp;Michèle J. Day,&nbsp;Melissa C. Funaro,&nbsp;Kathleen Guan,&nbsp;Termara C. Parker,&nbsp;Jocelyn A. Ricard,&nbsp;Francesca Penner,&nbsp;Tal Yatziv,&nbsp;Helena J. V. Rutherford","doi":"10.1111/jne.70232","DOIUrl":"https://doi.org/10.1111/jne.70232","url":null,"abstract":"<p>A growing number of magnetic resonance imaging (MRI) studies are examining brain changes across pregnancy and early motherhood, gaining fundamental insight into the neural adaptations of motherhood, with critical clinical and policy implications for supporting mother, child, and family unit. As the field takes off, now is the time to take stock of the current literature and neuroscience practices, to ensure that the field is based on studies that are robust, representative, and transparent. Here, we conducted a scoping review to understand the racial and ethnic diversity of participants reported in MRI studies of the maternal brain, guided by the Joanna Briggs Institute methodology. Our findings highlight three key issues in the 203 identified studies of the maternal brain using MRI: (1) the widespread underreporting of participant racial and ethnic data, with only 38.92% of studies reporting race and/or ethnicity demographics; (2) the overrepresentation of white participants, with 48.23% of the samples that report race and/or ethnicity identifying as white/Caucasian; and (3) the disproportionate geographical locations of studies, with 69.95% of studies from North America or Europe and Central Asia. These findings raise concerns about the generalizability of existing research beyond WEIRD (western, educated, industrialized, rich and democratic) populations, and underscore the urgent need for concerted structural change in neuroscience research practices. While identifying a lack of diversity is only the first step, this scoping review serves as a call to action for greater representation in future research, for our own research group as well as others.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 8","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148553349","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":"Effects of cannabidiol in comparison to hormonal therapy on estrogen decline-induced memory impairments and endocannabinoid system in rats","authors":"Fernanda Borsatto Caruso,&nbsp;Maria Paula Arakaki Severo,&nbsp;Anna Clara Machado Colucci,&nbsp;Beatriz Cristina Weidle Vuaden,&nbsp;Layza Kowalski,&nbsp;Patrícia Schonhofen,&nbsp;Felipe Schroeder Franke,&nbsp;Fernanda Bastos de Mello,&nbsp;Fernanda da Silva Rodrigues,&nbsp;Renata Padilha Guedes,&nbsp;Maria Noêmia Martins de Lima,&nbsp;Jaime E. C. Hallak,&nbsp;Antônio Waldo Zuardi,&nbsp;José Alexandre S. Crippa,&nbsp;Nadja Schröder","doi":"10.1111/jne.70234","DOIUrl":"10.1111/jne.70234","url":null,"abstract":"<p>The aim of this study was to investigate the effects of cannabidiol (CBD) on memory deficits induced by ovariectomy and to directly compare its effects with those of hormone therapy, in order to better understand potential shared mechanisms related to menopause-associated cognitive decline, with a particular focus on the endocannabinoid system. Three-month-old female Wistar rats were randomly assigned to four experimental groups: SHAM-Veh (Vehicle), OVX-Veh, OVX-E2 (estradiol), and OVX-CBD. Animals underwent either bilateral ovariectomy or sham surgery. Following a three-week recovery period, rats received daily subcutaneous injections of CBD (10 mg/kg), estradiol (10 μg/kg), or vehicle for 21 consecutive days. Behavioral assessments included object recognition and fear-motivated memory tests. Twenty-four hours after the final treatment, animals were euthanized for neurochemical and molecular analyses. Levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured using high-performance liquid chromatography. Gene expression of cannabinoid receptors CB1 and CB2, as well as enzymes involved in the synthesis and degradation of endocannabinoids (NAPE-PLD, DAGL-A, FAAH, and MGLL), was evaluated in the hippocampus by RT-qPCR. The results demonstrated that CBD treatment produced memory improvements in the object recognition task comparable to those observed with estradiol. Ovariectomy-induced impairments in fear-motivated memory were completely reversed by both CBD and estradiol treatments. Additionally, CBD reduced the expression of FAAH and MGLL, resulting in increased hippocampal levels of AEA and 2-AG, effects similar to those observed with hormone therapy. Estradiol also increased NAPE-PLD expression, contributing to elevated AEA levels. Overall, the findings suggest that CBD exerts a protective effect on memory comparable to standard estrogen therapy, supporting its therapeutic potential for menopause-related cognitive impairments.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 7","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536040","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":"Plasticity of subfornical organ astrocyte structure and supraoptic nucleus hormone expression following extreme dehydration in the desert rodent Gerbillus tarabuli","authors":"Nadir Benhafri,&nbsp;Soumia Remana,&nbsp;Amina Derbouz Rouibate,&nbsp;Zahra Simone Thirouin,&nbsp;Aicha Dekar-Madoui,&nbsp;Charles W. Bourque,&nbsp;Saliha Ouali-Hassenaoui","doi":"10.1111/jne.70236","DOIUrl":"10.1111/jne.70236","url":null,"abstract":"<p>The central nervous system plays a pivotal role in the regulation of water and electrolyte balance, largely via the circumventricular organs (CVOs) and the hypothalamo-neurohypophysial system. <i>Gerbillus tarabuli</i>, a desert-dwelling rodent capable of surviving in arid environments, remains poorly characterized with respect to the neuroendocrine mechanisms underlying its hydromineral adaptation In the present study, we examined the effects of long-term dehydration (4 weeks) in <i>G. tarabuli</i>. We focused on glial fibrillary acidic protein (GFAP) expression in the subfornical organ (SFO), as well as vasopressin (VP) and oxytocin (OT) expression in magnocellular neurons (MCNs) of the supraoptic nucleus (SON) using immunohistochemistry. Physiological parameters, including body mass, plasma osmolality, sodium concentration, hematocrit, and glycemia, were also assessed. In dehydrated gerbils, the observed changes in body mass, plasma osmolality, natremia, and glycemia were not significantly different from those of euhydrated gerbils. In contrast, hematocrit was significantly increased (5.53%), corresponding to a 15.97% reduction in plasma volume. Long-term dehydration induced a marked increase in GFAP immunoreactivity within the SFO, concomitant with a significant increase in VP and OT immunoreactivity and enlargement of magnocellular soma size in the SON. Additionally, the SON of <i>G. tarabuli</i> showed a mediolateral extension in the dorsolateral region of the optic chiasm (OC). Together, these findings identify <i>G. tarabuli</i> as a valuable model for investigating the neuroendocrine mechanisms underlying hydromineral homeostasis and the central adaptations supporting survival in arid environments.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 7","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520676","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":"Right-lateralized maladaptive topological reorganization in hyperthyroidism","authors":"Priyanka Chakraborty,&nbsp;Neeraj Upadhyay,&nbsp;Pawan Kumar,&nbsp;Poonam Rana,&nbsp;Suman Saha,&nbsp;Maria D'souza,&nbsp;Tarun Sekhri,&nbsp;Subash Khushu,&nbsp;Mukesh Kumar","doi":"10.1111/jne.70235","DOIUrl":"https://doi.org/10.1111/jne.70235","url":null,"abstract":"<p>Hyperthyroidism is associated with cognitive impairment and neuropsychiatric symptoms, yet its effects on white matter architecture and neuromolecular organization remain poorly understood. We examined how hyperthyroidism alters white matter wiring architecture and the neuromodulatory systems underlying these disturbances. Diffusion MRI-derived structural connectomes were analyzed in 30 patients with hyperthyroidism (HT) and 28 matched healthy controls (HC). Structural connections were classified into short-, medium-, and long-range pathways, and global and nodal network topology was quantified using graph theoretical analysis. Molecular associations were examined using nine PET-derived neurotransmitter receptor density maps through spatial correlation, multiple regression, and dominance analysis. Associations with thyroid hormone levels, clinical measures, and cognitive scores were evaluated using permutation-based statistical testing. Neurotransmitter-weighted network measures were computed by linking normative neurotransmitter density with graph theoretical metrics. Spatial autocorrelation was controlled using spin permutation testing, with results additionally corrected for multiple comparisons using false discovery rate (FDR) correction. Hyperthyroid patients exhibited significantly increased medium-range (<i>p</i> = .002) and long-range connectivity (<i>p</i> = .02), reduced modularity (<i>p</i> = .009), and increased characteristic path length (<i>p</i> = .032) as compared to controls, indicating disrupted segregation and efficiency. Nodal alterations were predominantly right-lateralized, involving cortical, subcortical, and cerebellar regions. Clinically, BMI predicted modularity (<i>p</i> = .01), while free thyroxine levels predicted characteristic path length (<i>p</i> = .04) and long-range connectivity strength (<i>p</i> = .03). The Nahor–Benson score was associated with increased medium-range connectivity (<i>p</i> = .02) and nodal degree (<i>p</i> = .03) in right cerebellar lobule IV–V. Neurotransmitter receptor distributions explained substantial variance in network topology (adjusted <i>R</i>² = 0.45 in controls; 0.38 in hyperthyroidism), with dominant contributions from 5-HT_1A (33%) and dopamine transporter (17%). Furthermore, 5-HTT-weighted within module degree z-score predicted thyroid-stimulating hormone (TSH) levels in hyperthyroidism (<i>p</i> = .03), linking hormonal dysregulation to molecular connectomic reorganization. Our findings suggest that excess thyroid hormone drives right-lateralized connectomic reorganization and increased metabolic demand, mediated by serotonergic and dopaminergic receptor architecture, linking endocrine dysfunction to large-scale brain network vulnerability. These insights inform mechanistic models and biomarkers for clinical translation.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 7","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467614","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":"Prenatal stress alters offspring neurovascular, autonomic, and immune development in animal models of neuropsychiatric and cardiometabolic disorders","authors":"Monique Martinez,&nbsp;Emily A. Castellanos,&nbsp;Julietta A. Sheng,&nbsp;Taben M. Hale,&nbsp;Stuart A. Tobet","doi":"10.1111/jne.70231","DOIUrl":"https://doi.org/10.1111/jne.70231","url":null,"abstract":"<p>Developmental programming, a permanent adaptation of the fetus/neonate to maternal environmental signals, underlies many adult physiological and psychiatric disorders. Prenatal stress induced by the synthetic glucocorticoid dexamethasone has been shown to increase anxiety- and depressive-like behaviors and lead to hyperreactive neuroendocrine and autonomic nervous system (ANS) responses to stress in adult female offspring. Prenatal stressors can also cause maternal immune activation (MIA), impact mood/stress circuitry, and program neural development. One way to engage molecular immune signals is to activate toll-like receptors (TLRs). Developmental changes have been seen following gestational exposure to lipopolysaccharide (LPS; TLR4), poly I:C (TLR3), and, most recently, TLR7 agonists resiquimod (RQ) or imiquimod (IMQ). Studies have identified changes in ANS function that may be tied to blood–brain barrier (BBB) changes in the paraventricular nucleus of the hypothalamus (PVN) that coincide with anxiety- /depressive-like behaviors that manifest after fetal programming. These adult dysfunctions are a consequence of prenatal stressors and may have a common underlying mechanism related to the dysregulation of communication between the PVN and critical ANS centers in the brainstem. Studies in humans indicate that brainstem loci may be important centers of ANS regulation that can be targeted to attenuate major depressive disorder (MDD) symptoms in adults. Furthermore, data suggest that select immune and BBB characteristics in PVN and autonomic nuclei in the brainstem are critical targets for future studies, aligning with the hypothesis that immune signaling plays a major role in the development and expression of psychiatric disorders. The overarching goal of this review is to outline the cellular and physiological pathways by which prenatal stressors, mainly synthetic glucocorticoid exposure and MIA, produce long-term, sex-biased programming of adult behavior and ANS function relevant to physiological and psychiatric disorders.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 7","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467615","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}