Frontiers in Neuroendocrinology最新文献

{"title":"The interplay of insulin signaling and neurotransmitters on sleep in Drosophila.","authors":"Karl Rennick-Zuefle, Aalim M Weljie, Pinky Kain","doi":"10.1016/j.yfrne.2026.101252","DOIUrl":"https://doi.org/10.1016/j.yfrne.2026.101252","url":null,"abstract":"<p><p>Sleep is a fundamental homeostatic process regulated by innate circadian rhythms and conserved across various animal species. While the roles of neurotransmitters in sleep-wake cycles are well-documented, emerging research suggests that the metabolic hormone insulin significantly moderates sleep-associated neurotransmission. Despite these evident biological links, the underlying mechanisms remain poorly understood. Utilizing the fruit fly (Drosophila melanogaster) as a genetic model, this review synthesizes recent findings regarding the interplay between insulin, neurotransmitters, and metabolism in context of sleep. By examining how dietary and metabolic factors influence these pathways, we aim to provide a foundation for developing targeted therapeutic interventions for sleep disorders.</p>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":" ","pages":"101252"},"PeriodicalIF":6.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The skin microbiome and affective symptoms: neuroimmune, neuroendocrine, and sensory pathways linking inflammatory dermatoses to mood and anxiety burden","authors":"Roberto Coccurello","doi":"10.1016/j.yfrne.2026.101251","DOIUrl":"10.1016/j.yfrne.2026.101251","url":null,"abstract":"<div><div>The skin functions as a neuro-immuno-endocrine organ with an extensive microbial interface capable of bidirectional signaling with the central nervous system. While the gut–brain axis is well established, the skin–microbiota–brain (SMB) axis remains underexplored, particularly with respect to affective symptom dimensions (depression, anxiety, stress) that commonly co-occur with chronic inflammatory dermatoses. This review synthesizes evidence across clinical, translational, and experimental studies and organizes it by strength (associational findings, mechanistic plausibility, and limited interventional signals). We outline a systems-level model in which cutaneous microbial dysbiosis is associated with brain-relevant pathways via immune, neuropeptide, and metabolic routes. Candidate mediators include cytokines (IL-6, IL-17, TNF-α), neuropeptides (e.g., substance P, CGRP), and microbial-derived metabolites (e.g., SCFA-like compounds and tryptophan catabolites). These signals are hypothesized to influence neuroimmune tone and neurovascular signaling based largely on broader systemic inflammation and stress biology; direct causal evidence specifically attributing affective outcomes to skin microbiome perturbations in humans remains limited. In parallel, top-down neuroendocrine signaling via hypothalamic–pituitary–adrenal (HPA) axis activation, cortisol-related signaling, and sympathetic outflow can alter skin barrier function, antimicrobial peptide expression, and microbial ecology, potentially contributing to symptom-maintaining loops (e.g., itch–sleep disruption–stress). Importantly, we consider counterarguments (psychosocial burden, reverse causality, treatment effects, and the localized nature of lesions) and identify research priorities required to test causality (longitudinal sampling, mechanistic biomarker panels, and preregistered interventional studies with affective endpoints and mediation analyses). By integrating dermatological, microbiological, and neuroimmunological evidence within a symptom-centered framework, the SMB axis is positioned as a biologically plausible but still evolving model that may help explain affective symptom burden in subsets of patients with inflammatory skin disease and guide mechanism-informed translational research.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"81 ","pages":"Article 101251"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orexin signaling across the female lifespan: developmental, reproductive, and aging perspectives from humans and animal models","authors":"Katarzyna Kirsz,&nbsp;Dorota A. Zięba","doi":"10.1016/j.yfrne.2026.101235","DOIUrl":"10.1016/j.yfrne.2026.101235","url":null,"abstract":"<div><div>Orexin-A and orexin-B are hypothalamic neuropeptides that coordinate arousal, metabolic, and reproductive functions through orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). This review synthesizes evidence from humans, experimental models, and domestic species to examine how orexin signaling modulates female physiology across the lifespan. Perinatally, orexin activation supports neonatal survival by stabilizing respiration, feeding, and sleep–wake organization. During puberty, orexins integrate metabolic and circadian cues to regulate gonadotropin-releasing hormone output and reproductive onset. In pregnancy and lactation, central and peripheral adaptations coordinate maternal metabolism, uteroplacental communication, and prolactin-dependent lactation. In aging, reduced orexin tone contributes to sleep fragmentation, metabolic dysregulation, and cognitive decline. Therapeutically, dual orexin receptor antagonists and intranasal orexin delivery illustrate stage-specific intervention strategies. Evidence across life stages derives from human, rodent, and large-animal models and must be interpreted within species-, sex-, and stage-specific biological constraints. Collectively, orexin signaling represents a conserved integrative network with health relevance.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"81 ","pages":"Article 101235"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional brain connectivity in type 1 diabetes and associations to diabetes complications – a systematic review of fMRI studies","authors":"Janusiya A. Muthulingam ,&nbsp;Jens B. Frøkjær ,&nbsp;Mimoza Gjela ,&nbsp;Niels Ejskjaer ,&nbsp;Asbjørn M. Drewes ,&nbsp;Tine M. Hansen ,&nbsp;Suganthiya S. Croosu","doi":"10.1016/j.yfrne.2026.101249","DOIUrl":"10.1016/j.yfrne.2026.101249","url":null,"abstract":"<div><div>A systematic review was conducted to investigate functional brain changes in type 1 diabetes mellitus (T1DM) assessed with functional magnetic resonance imaging (fMRI) between 2006 and 2025. A total of 27 eligible studies were included, involving 1072 participants with T1DM, with a mean age ranging from 20.4 to 51.5 years. The quality of these studies was evaluated using the NIH Quality Assessment Tool.</div><div>Resting-state fMRI (n = 12) demonstrated 1) altered brain networks, especially in the default mode and salience networks, and 2) changes in subcortical regions and the frontal lobe. Task-based fMRI (n = 15) showed increased activity in the visual, salience, and thalamic networks, and decreased activity in the default mode network. The review highlights the complex relationship between T1DM and brain changes, presenting evidence of deviations from normal brain activity in specific areas involved in sensory-motor, limbic and cognitive regions that may reflect neurophysiological adaptations or consequences related to T1DM.</div><div><strong>Registration</strong>: PROSPERO (International Prospective Register of Systematic Reviews) under ID: CRD42023456789.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"81 ","pages":"Article 101249"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review and meta-analysis of the relationship between midlife physical activity and later-life cognition: Is sex an overlooked factor?","authors":"Joel S. Burma ,&nbsp;Jansie H. Nel ,&nbsp;Hannah Cheung ,&nbsp;Dakota Hofforth ,&nbsp;Devanshi Zala ,&nbsp;K.Alix Hayden ,&nbsp;Paul E. Ronksley ,&nbsp;Cara L. Carty ,&nbsp;Milan Chang ,&nbsp;Alden L. Gross ,&nbsp;Sarah-Naomi James ,&nbsp;Emmanuelle Kesse-Guyot ,&nbsp;Norberto Rodriguez-Espinosa ,&nbsp;Kristine Yaffe ,&nbsp;Cindy K. Barha","doi":"10.1016/j.yfrne.2026.101250","DOIUrl":"10.1016/j.yfrne.2026.101250","url":null,"abstract":"<div><div>Midlife (ages 40–59) may be a critical window to preserve cognitive health; however, the long-term impact of midlife physical activity (PA) on late-life cognition remains unclear. This systematic review synthesized cohort evidence of the relationship between midlife physical activity levels and later-life cognition, while exploring the potential moderating role of biological sex. The Medline, Embase, Web of Science, APA PsycINFO, CINAHL, and SPORTDiscus databases were searched. Cohort studies that assessed midlife physical activity and used standardized neuropsychological tests in cognitively unimpaired adults were included. Risk of bias was completed using the Risk of Bias in Non-randomized Studies–of Exposure tool. Random-effects <em>meta</em>-analyses (Cohen’s <em>d</em>) compared none/low vs. moderate/high PA for global cognition, verbal episodic memory, executive functions, verbal fluency, and processing speed domains. Fifteen studies (n = 33,295; 66.1% female) were included in the qualitative synthesis, with eight used in the <em>meta</em>-analyses. All studies relied on self-reported PA measures, and only one study completed sex-stratified analyses. Higher midlife PA was associated with better later-life global cognition (<em>d</em> = 0.22, 95% CI: 0.06–0.38), verbal episodic memory (<em>d</em> = 0.19, 95% CI: 0.06–0.32), and processing speed (<em>d</em> = 0.20, 95% CI: 0.03–0.36). Heterogeneity was substantial (I² 72.2–84.7%). Pooled effects were not significant for executive functions (<em>d</em> = 0.09, −0.16–0.34) or verbal fluency (<em>d</em> =  − 0.03, 95% CI: −0.21–0.16). Midlife PA showed modest, albeit population-meaningful associations with higher later-life global cognition, episodic memory, and processing speed. Future cohorts should standardize and incorporate objective PA metrics and ensure inclusion of sex-stratified estimates to clarify dose–response and sex-specific effects.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"81 ","pages":"Article 101250"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From significant to meaningful: ATOMizing the study of sex differences and similarities","authors":"Carla Sanchis-Segura ,&nbsp;Cristina Forn ,&nbsp;Rand R Wilcox","doi":"10.1016/j.yfrne.2025.101228","DOIUrl":"10.1016/j.yfrne.2025.101228","url":null,"abstract":"<div><div>The sex differences field often relies on an implicit and flawed heuristic: defining a “difference” by any statistically significant gap between group averages. This practice yields findings that are often not useful, even counterproductive, for understanding sex-related variation and for advancing personalized healthcare.</div><div>Following current statistical consensus, we argue that sex differences should be defined not by significance alone but by context-dependent criteria prioritizing informativeness. Drawing on the American Statistical Association’s ATOM principles (Accept uncertainty, be Thoughtful, be Open, be Modest), we call for explicit, justified definitions and for a shift from group averages to meaningful individual variation.</div><div>To illustrate this methodological and philosophical shift, we introduce Thresholded Probability of Superiority (TPS), a method that treats sex differences as probability distributions rather than overgeneralized, fixed abstractions. Thus, TPS allows for a more nuanced, relevant, and actionable understanding of sex-related variation, with greater potential to inform precision medicine.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"80 ","pages":"Article 101228"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145719038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of ovary-immune interactions in the context of age and disease","authors":"Macy E. Zardeneta,&nbsp;Kaylin A. Pickle,&nbsp;Farida Sohrabji","doi":"10.1016/j.yfrne.2026.101234","DOIUrl":"10.1016/j.yfrne.2026.101234","url":null,"abstract":"<div><div>The ovary, a dynamic endocrine organ, plays a central role in female reproductive function through the secretion of hormones such as 17β-estradiol, progesterone, testosterone, and inhibin. Beyond its endocrine activity, the ovary serves as a critical site of immune modulation, with tissue-resident and circulating immune cells contributing to folliculogenesis, ovulation, implantation, and pregnancy. This review explores the reciprocal interactions between the ovarian and immune systems across health, disease, and aging. We highlight the diverse functions of ovarian immune cell types in maintaining reproductive homeostasis and their dysregulation in conditions such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), ovarian hyperstimulation syndrome, and autoimmune diseases. Additionally, we discuss how ovarian removal or dysfunction influences systemic inflammation and increases susceptibility to cardiovascular and neurologic disorders. Together, these findings underscore the ovary’s dual role as an endocrine and immune organ, highlighting its significance in female health and disease beyond reproduction.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"80 ","pages":"Article 101234"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disproportionate mental health risks in autistic females: A rapid review with quantitative and narrative syntheses","authors":"Adeline Lacroix ,&nbsp;Chih-Chen Tzang ,&nbsp;Jennifer Xiaofan Yu ,&nbsp;Benjamin Koshy Jacob ,&nbsp;Mishel Alexandrovsky ,&nbsp;Anna Winge-Breen ,&nbsp;Terri Rodak ,&nbsp;Meng-Chuan Lai","doi":"10.1016/j.yfrne.2025.101229","DOIUrl":"10.1016/j.yfrne.2025.101229","url":null,"abstract":"<div><div>Mental health conditions are highly prevalent among autistic people, but an updated synthesis of sex-stratified prevalence data, contributing factors, and support strategies is lacking.<!--> <!-->To address this knowledge gap, we conducted a rapid review utilizing PRISMA-ScR guidelines. MEDLINE, CINAHL, and PsycINFO databases were searched for studies (2004–2024) including female participants with a clinical autism diagnosis, and with a focus on mental health. Of 8,420 records screened, 218 met inclusion criteria. An exploratory quantitative synthesis of population-based and registry-based studies revealed higher rates of mental health conditions in autistic females than males for anxiety, mood, eating, obsessive–compulsive, psychotic, and personality disorders. Narrative synthesis identified moderating factors, including sex-related physiology, gendered experiences, age, age at autism diagnosis, autism characteristics, and co-occurring conditions. Biological and social mechanisms likely interact as contributing factors. Severe consequences of poor mental health underscore the need for tailored approaches accounting for the specific profiles of autistic females.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"80 ","pages":"Article 101229"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis and potential therapies for perimenopausal depression: Insights from the estrogen-gut microbiota axis","authors":"Xuli Wang ,&nbsp;Yudong Lin ,&nbsp;Mingmei Zhou","doi":"10.1016/j.yfrne.2026.101233","DOIUrl":"10.1016/j.yfrne.2026.101233","url":null,"abstract":"<div><div>Perimenopause represents a critical phase during which women are particularly susceptible to depression. Although fluctuations in estrogen levels resulting from ovarian aging and imbalances in the gut microbiota have been identified as contributing factors to the onset of depression, the interplay among these elements is frequently overlooked. Fluctuations in estrogen levels can further influence neurogenesis or apoptosis through effects on neurotransmitter balance, neuroinflammation, neuroendocrine regulation, and mitochondrial function. Meanwhile, dramatic shifts in estrogen levels can diminish microbial diversity and stability, thereby disrupting the homeostasis of metabolites and neurotransmitters via the gut-brain axis (GBA). Such disturbances may induce neuroinflammation, potentially leading to or exacerbating depressive symptoms. Additionally, the estrobolome (gut bacterial genes encoding estrogen-metabolizing enzymes) plays a regulatory role in the reabsorption, excretion, and systemic levels of estrogen through the modulation of β-glucuronidase activity, thereby affecting estrogen homeostasis. This review first examines the influence of fluctuations in estrogen levels on the composition and function of the gut microbiota, as well as the role of the gut microbiota in estrogen metabolism. It then discusses how estrogen deficiency and dysbiosis of the gut microbiota contribute to the pathogenesis of perimenopausal depression, discussing the potential for a vicious cycle mediated by the estrogen-gut microbiota axis that increases susceptibility to this condition. Finally, this review presents bioactive compounds derived from dietary sources or medicinal plants that exhibit estrogenic and prebiotic properties, which may offer diverse strategies for the prevention and management of perimenopausal depression through modulation of the estrogen-gut microbiota axis.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"80 ","pages":"Article 101233"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"We must look beyond primary reinforcement to understand nicotine use in women","authors":"Kathleen R. McNealy ,&nbsp;Scott T. Barrett ,&nbsp;Rick A. Bevins","doi":"10.1016/j.yfrne.2026.101231","DOIUrl":"10.1016/j.yfrne.2026.101231","url":null,"abstract":"<div><div>Women exhibit greater nicotine use vulnerability than men. Common cessation treatments are less effective for women, suggesting unique contributors to women’s smoking that are not fully characterized or targeted by available treatments. High estradiol is associated with enhanced smoking and cessation difficulty, whereas high progesterone is associated with reduced smoking and better cessation success. Hormonal contraceptives can produce similar or even outsized alterations in nicotine use outcomes. Despite clear effects of natural and synthetic sex steroid hormones on nicotine intake, the behavioral pathways by which hormones alter nicotine use outcomes remain unmapped. In this review paper, we propose that uncovering such mechanisms requires examining sex steroid hormone modulation of <em>non-primary reinforcement</em> factors in our animal models. Parallel effects of natural and synthetic sex steroid hormones on nicotine self-administration occur in animal models. Further, women’s smoking is more influenced by environmental stimuli, such as the smell, taste, and visual cues associated with nicotine use than by the reinforcing effects of nicotine. In building our case, we first summarize research supporting the import of environmental factors in nicotine intake for women and translation to female rats. We also synthesize findings on how biological sex and sex steroid hormones influence these mechanisms in humans and rats. Lastly, we will detail promising directions for future research.</div></div>","PeriodicalId":12469,"journal":{"name":"Frontiers in Neuroendocrinology","volume":"80 ","pages":"Article 101231"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}