Neuroendocrinology最新文献

{"title":"Factors Influencing Costs of Cancer Care for Patients with Neuroendocrine Neoplasms.","authors":"Martin O Weickert","doi":"10.1159/000544050","DOIUrl":"10.1159/000544050","url":null,"abstract":"<p><strong>Background: </strong>Neuroendocrine neoplasms (NENs) are comparatively rare tumours. However, prevalence is increasing steeply, related to rising incidence, earlier detection, and prolonged survival in many cases of metastatic NENs, with implications on healthcare resources.</p><p><strong>Summary: </strong>This commentary/narrative review extracts the relatively scare, available literature related to costs of NEN cancer care, which is mainly based on studies performed in the USA. Key, now implemented or evolving NEN-related treatment options over the last 15 years, is summarised. The commentary further highlights in part preventable aspects that can further contribute to cost pressure in NEN cancer care, including issues related to inappropriate use of available diagnostic tools, and not considering differential diagnoses when assessing people with suspected carcinoid syndrome - with these risks being minimised with access to centres with multi-speciality expertise in the management of people with NENs. Issues observed in people with exocrine and/or endocrine pancreatic deficiencies caused by a NEN or treatment of the NEN are mentioned, as well as some specific aspects related to diagnostics involving 68Ga PET-CT scans and treatment with Lutetium peptide-receptor radionuclide therapy (Lu-PRRT).</p><p><strong>Key messages: </strong>This commentary summarises factors influencing cost of NEN cancer care, and highlights in part preventable issues mostly related to delayed involvement of a NEN multidisciplinary team, observed in a UK NEN referral centre (ENETS Centre of Excellence certified since 2015) over the last 15 years, resulting in suboptimal management of people with NENs and ultimately adding to cost pressure.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-22"},"PeriodicalIF":3.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Hypothalamus and Pituitary Gland Regulate Reproduction and Are Involved in the Development of Polycystic Ovary Syndrome.","authors":"Bin-Yang Long, Xipeng Liao, Xin Liang","doi":"10.1159/000543877","DOIUrl":"10.1159/000543877","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a complex condition with unclear mechanisms, posing a challenge for prevention and treatment of PCOS. The role of the hypothalamus and pituitary gland in regulating female reproduction is critical. Abnormalities in the hypothalamus and pituitary can impair reproductive function. It is important to study hypothalamic and pituitary changes in patients with PCOS.</p><p><strong>Summary: </strong>This article reviews articles on the hypothalamus and PCOS with the goal of summarizing what abnormalities of the hypothalamic-pituitary-ovarian axis are present in patients with PCOS and to clarify the pathogenesis of PCOS. We find that the mechanisms by which the hypothalamus and pituitary regulate reproduction in girls are complex and are associated with altered sex hormone levels, obesity, and insulin resistance. Different animal models of PCOS are characterized by different alterations in the hypothalamus and pituitary and respond differently to different treatments, which correspond to the complex pathogenesis of patients with PCOS.</p><p><strong>Key messages: </strong>Arcuate nucleus (ARC) is associated with luteinizing hormone (LH) surges. Suprachiasmatic nucleus, ARC, and RP3V are associated with LH surges. Animal models of PCOS have different characteristics.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"315-334"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Diet and Vulnerability to Cognitive Impairment in Adulthood: Possible Link with Alzheimer's Disease?","authors":"Laetitia Merle, Marialetizia Rastelli, Frédérique Datiche, Anne Véjux, Agnès Jacquin-Piques, Sébastien G Bouret, Alexandre Benani","doi":"10.1159/000543499","DOIUrl":"10.1159/000543499","url":null,"abstract":"<p><strong>Background: </strong>Aging is the main risk factor for developing cognitive impairments and associated neurodegenerative diseases. However, environmental factors, including nutritional health, are likely to promote or reduce cognitive impairments and neurodegenerative pathologies. An intricate relationship exists between maternal nutrition and adult eating behavior, metabolic phenotype, and cognitive abilities.</p><p><strong>Summary: </strong>The objective of the present review was to collect available data, suggesting a link between maternal overnutrition and the latter impairment of cognitive functions in the progeny, and to relate this relationship with Alzheimer's disease (AD). Indeed, cognitive impairments are major behavioral signs of AD. We first reviewed studies showing an association between unbalanced maternal diet and cognitive impairments in the progeny in humans and rodent models. Then we looked for cellular and molecular hallmarks which could constitute a breeding ground for AD in those models. With this end, we focused on synaptic dysfunction, altered neurogenesis, neuroinflammation, oxidative stress, and pathological protein aggregation. Finally, we proposed an indirect mechanism linking maternal unbalanced diet and progeny's vulnerability to cognitive impairments and neurodegeneration through promoting metabolic diseases. We also discussed the involvement of progeny's gut microbiota in the maternal diet-induced vulnerability to metabolic and neurodegenerative diseases.</p><p><strong>Key messages: </strong>Further investigations are needed to fully decipher how maternal diet programs the fetus and infant brain. Addressing this knowledge gap would pave the way to precise nutrition and personalized medicine to better handle cognitive impairments in adulthood.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"242-266"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell Signaling in the Circadian Pacemaker: New Insights from in vivo Imaging.","authors":"Xavier Bonnefont","doi":"10.1159/000539344","DOIUrl":"10.1159/000539344","url":null,"abstract":"<p><strong>Background: </strong>\"One for all, and all for one,\" the famous rallying cry of the Three Musketeers, in Alexandre Dumas's popular novel, certainly applies to the 20,000 cells composing the suprachiasmatic nuclei (SCN). These cells work together to form the central clock that coordinates body rhythms in tune with the day-night cycle. Like virtually every body cell, individual SCN cells exhibit autonomous circadian oscillations, but this rhythmicity only reaches a high level of precision and robustness when the cells are coupled with their neighbors. Therefore, understanding the functional network organization of SCN cells beyond their core rhythmicity is an important issue in circadian biology.</p><p><strong>Summary: </strong>The present review summarizes the main results from our recent study demonstrating the feasibility of recording SCN cells in freely moving mice and the significance of variations in intracellular calcium over several timescales.</p><p><strong>Key message: </strong>We discuss how in vivo imaging at the cell level will be pivotal to interrogate the mammalian master clock, in an integrated context that preserves the SCN network organization, with intact inputs and outputs.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"103-110"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Understanding of Gonadotrope Lineage Differentiation in the Developing Pituitary.","authors":"Charles Le Ciclé, Joëlle Cohen-Tannoudji, David L'Hôte","doi":"10.1159/000542513","DOIUrl":"10.1159/000542513","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The pituitary gland is a vital endocrine organ regulating body homoeostasis through six hormone-secreting cell types. Among these, pituitary gonadotrope cells are essential for reproductive function. Throughout pituitary ontogenesis, gonadotrope cells differentiate in a stepwise process, involving both morphogenic cues and transcription factors, which drives specification of progenitor cells into specialised endocrine cells. It is crucial to understand the mechanisms underlying gonadotrope differentiation, as developmental defects and abnormalities in this process can lead to many reproductive pathologies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;This review offers a detailed overview of the latest advances in gonadotrope cell differentiation. We addressed this question with a specific focus on three important aspects of gonadotrope differentiation: the identification of the progenitor population giving rise to gonadotrope cells, the early mechanisms that initiate Nr5a1 expression and thus gonadotrope fate commitment, and finally, the mechanisms driving the formation of physical and functional gonadotrope networks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key messages: &lt;/strong&gt;Overall, this review aimed to provide new insights into three aspects of the gonadotrope differentiation process by reconsidering pioneering studies in the light of data gained from latest technological developments. Firstly, we re-investigated the long debated developmental trajectory of pituitary gonadotrope cells. Secondly, we reported new regulatory mechanisms of Nr5a1 expression, focusing on the involvement of ERα. Finally, we highlighted the molecular and cellular mechanisms driving gonadotrope network formation during embryogenesis, a process that seems essential for regulation of gonadotrope activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The pituitary gland is a vital endocrine organ regulating body homoeostasis through six hormone-secreting cell types. Among these, pituitary gonadotrope cells are essential for reproductive function. Throughout pituitary ontogenesis, gonadotrope cells differentiate in a stepwise process, involving both morphogenic cues and transcription factors, which drives specification of progenitor cells into specialised endocrine cells. It is crucial to understand the mechanisms underlying gonadotrope differentiation, as developmental defects and abnormalities in this process can lead to many reproductive pathologies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;This review offers a detailed overview of the latest advances in gonadotrope cell differentiation. We addressed this question with a specific focus on three important aspects of gonadotrope differentiation: the identification of the progenitor population giving rise to gonadotrope cells, the early mechanisms that initiate Nr5a1 expression and thus gonadotrope fate commitment, and finally, the mechanisms driving the formation of physical and functional gonadotrope networks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key messages: &lt;/s","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"195-210"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Transcriptome Sequencing and Analysis Provide a New Approach for the Treatment of Small Cell Neuroendocrine Carcinoma of the Cervix.","authors":"Lewei He, Yuling Wu, Mingyi Lv, Jiyang Jiang, Yifei Li, Tao Guo, Zhenxin Fan","doi":"10.1159/000542833","DOIUrl":"10.1159/000542833","url":null,"abstract":"<p><strong>Introduction: </strong>Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare gynecologic malignant tumor, which has lack of systematic research. In order to investigate its molecular characteristics, origin, and pathogenesis, single-cell transcriptome sequencing (scRNA-Seq) of SCNECC was performed for the first time, the cellular and molecular landscape was revealed, and the key genes for clinical prognosis were screened.</p><p><strong>Methods: </strong>This article initially performed the scRNA-Seq on a tumor tissue sample from an SCNECC patient, combined with scRNA-Seq data from a healthy cervical tissue sample downloaded from a public database; the single-cell transcriptome landscape was constructed. Then, we investigated the cell types, intratumoral heterogeneity, characteristics of tumor microenvironment, and potential predictive markers of SCNECC.</p><p><strong>Results: </strong>We identified two malignant cell populations, tumor stem cells and malignant carcinoma cells, and revealed two tumor progression pathways of SCNECC. By analyzing gene expression levels in the pathophysiology of SCNECC, we found that the expression levels of ERBB4 and NRG1, as well as the expression profile of mTOR signaling pathway mediated by them, were significantly upregulated in malignant carcinoma cells. In addition, we also found that carcinoma cells were able to stimulate malignant cell proliferation through the FN1 signaling pathway. The immune cells were in a stress state, with T-cell depletion, macrophage polarization, and mast cell glycolysis. These results suggested that carcinoma cells could interfere with immune response and promote tumor escape through MIF, TGFb, and other immunosuppressive-related signaling pathways.</p><p><strong>Conclusion: </strong>This study revealed the mechanism of genesis and progression in SCNECC and the related important signaling pathways, such as mTOR, and provided new insights into the treatment of SCNECC.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"13-33"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Caudal Neurosecretory System: A Still Enigmatic Second Neuroendocrine Complex in Fish.","authors":"Karine Rousseau, Fabrice Girardot, Caroline Parmentier, Hervé Tostivint","doi":"10.1159/000536270","DOIUrl":"10.1159/000536270","url":null,"abstract":"<p><p>The caudal neurosecretory system (CNSS) is a neuroendocrine complex, whose existence is specific to fishes. In teleosts, it consists of neurosecretory cells (Dahlgren cells) whose fibers are associated with a neurohemal terminal tissue (urophysis). In other actinopterygians as well as in chondrichthyes, the system is devoid of urophysis, so that Dahlgren cells end in a diffuse neurohemal region. Structurally, it has many similarities with the hypothalamic-neurohypophysial system. However, it differs regarding its position at the caudal end of the spinal cord and the nature of the hormones it secretes, the most notable ones being urotensins. The CNSS was first described more than 60 years ago, but its embryological origin is still hypothetical, and its role is poorly understood. Observations and experimental data gave some evidences of a possible involvement in osmoregulation, stress, and reproduction. But one may question the benefit for fish to possess this second neurosecretory system, while the central hypothalamic-pituitary complex already controls such functions. As an introduction of our review, a brief report on the discovery of the CNSS is given. A description of its organization follows, and our review then focuses on the neuroendocrinology of the CNSS with the different factors it produces and secretes. The current knowledge on the ontogenesis and developmental origin of the CNSS is also reported, as well as its evolution. A special focus is finally given on what is known on its potential physiological roles.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"154-194"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Optogenetic Activation of the Subfornical Organ Produces Sympathetically Mediated Increases in Blood Pressure.","authors":"Monique L Van Acquoy, Teodora Nedelkoska, Simon McMullan, Peter G R Burke, Cara M Hildreth","doi":"10.1159/000545849","DOIUrl":"10.1159/000545849","url":null,"abstract":"<p><strong>Introduction: </strong>The subfornical organ (SFO) is a vital blood pressure-controlling region that elicits blood pressure changes likely via an excitatory (or glutamatergic) projection to the paraventricular nucleus of the hypothalamus (PVN). However, the role of this SFO-PVN pathway in blood pressure control has been poorly defined in the literature. As such, the present study aimed to examine the functional connectivity between the SFO neurons and the PVN and how they intersect to control blood pressure.</p><p><strong>Methods: </strong>In Lewis rats (n = 10), glutamatergic SFO neurons (SFOglut) were transduced with channelrhodopsin via a CaMKIIa-promotor vector (pAAV9-CaMKIIa-hChR2(H134R)-EYFP). Under urethane anaesthesia, changes in blood pressure and renal and splanchnic nerve activities were recorded in response to photostimulation of SFOglut neurons before and after administration of an intravenous ganglionic blocker and V1a receptor antagonism and inhibition of the PVN via muscimol microinjection. Immunohistochemistry was used to examine the projections between the SFO and PVN.</p><p><strong>Results: </strong>Photostimulation of SFOglut neurons produced a frequency-dependent pressor response that was abolished by sympathetic ganglionic blockade but not by inhibiting the vasoactive hormone vasopressin. This pressor response depends on ongoing neuronal transmission within the PVN as it is abolished by bilateral PVN inhibition. Confirming this, we found dense projections from SFOglut neurons to magnocellular and parvocellular PVN neurons. Finally, photostimulation of SFOglut neurons elicited a peak increase in sympathetic nerve activity that was reversibly abolished by phenylephrine administration and abolished by inhibition of the PVN, suggesting that the neuronal circuitry underpinning this response is barosensitive.</p><p><strong>Conclusion: </strong>The pressor response elicited by SFOglut neurons is largely mediated by barosensitive sympathetic nerve activity and dependent on the PVN.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"564-575"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Levels of Organic Acids Associated with the Gut Microbiome Display Significant Alterations in Neuroendocrine Tumor Patients.","authors":"Silje Udjus Johansen, Rasmus Goll, Anna Nordborg, Kai Vernstad, Einar Paul Helge Jensen, Jon Ragnar Florholmen, Terkel Hansen","doi":"10.1159/000543247","DOIUrl":"10.1159/000543247","url":null,"abstract":"<p><strong>Introduction: </strong>The gut microbiome, allegedly involved in both healthy homeostasis and development of disease, is found to be associated with several types of cancer. Short-chain fatty acids (SCFAs), important metabolites derived from the gut microbiota, are described to carry both protective and promoting features in cancer development. Limited research exists on neuroendocrine tumors (NETs) and their association with microbiota-derived SCFAs. The aim of this study was to investigate possible alterations in plasma SCFAs/organic acids in NET patients compared to healthy controls.</p><p><strong>Methods: </strong>We quantified 11 organic acids, including SCFAs, in plasma from 109 NET patients (49 curatively operated patients and 60 patients with distant metastasis) as well as 20 healthy controls. Acids were quantified using liquid chromatography tandem mass spectrometry.</p><p><strong>Results: </strong>We found that levels of 3OH-propionic acid, 3OH-butyric acid, lactic acid, formic acid, acetic acid, glyoxylic acid, and glycolic acid were significantly altered in NET patients with metastatic disease, as well as curatively operated NET patients, compared to healthy controls (p < 0.05). In addition, a trend displaying increased acid level alterations from healthy controls in curatively operated patients with future recurrence, compared to patients with no documented recurrent disease, was detected.</p><p><strong>Conclusion: </strong>Our results demonstrating significantly altered levels of multiple organic acids in NET patients represents a novel finding implicating further research on their role in NET pathophysiology.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"283-294"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothyroidism Promotes Microglia M1 Polarization by Inhibiting BDNF-Promoted PI3K-Akt Signaling Pathway.","authors":"Yuan Zhan, Lang Lang, Fen Wang, Xian Wu, Haiwang Zhang, Yuelin Dong, Hao Yang, Defa Zhu","doi":"10.1159/000542858","DOIUrl":"10.1159/000542858","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Hypothyroidism and its induced neurological-associated disorders greatly affect the health-related quality of patients' life. Meanwhile, microglia in brain have essential regulatory functions on neurodegeneration, but the underlying link between hypothyroidism and microglia function is largely ambiguous.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We deciphered how hypothyroidism modulates the polarization of microglia by constructing methimazole-induced mice model and checking the expression pattern of biomarkers of microglia M1 polarization. Then, we used lipopolysaccharide (LPS)-treated BV2 cells to explore the effecting factors on microglia M1 polarization. Finally, global transcriptome sequencing (RNA-seq) was utilized to identify the underlying regulatory mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We detected that biomarkers of microglia M1 polarization and pro-inflammatory cytokines were significantly increased in hypothyroidism mice brain; hypothyroidism could also repress the expression of BDNF and TrkB, and the anti-inflammatory cytokine such as IL-10. In BV2 cells, LPS treatment decreased expression of BDNF, IL-10, and Arg1, while BDNF overexpression (BDNF-OE) significantly reversed the inflammation induced by LPS. BDNF-OE significantly repressed expression of iNOS and TNF-α, but increased expression of IL-10 and Arg1. For mechanism, RNA-seq analysis demonstrated that BDNF-OE could globally regulate transcriptome profile by affecting gene expression. In LPS-treated BV2 cells, BDNF-OE significantly altered expression pattern of genes involved in PI3K-Akt signaling pathway, including Thbs3, Myc, Gdnf, Thbs1, and Ccnd1 as upregulated genes, and Gnb4, Fgf22, Pik3r3, Pgf, Cdkn1a, and Pdgfra as downregulated genes. Myc, Gdnf, Thbs1, and Ccnd1 showed much higher expression levels than other genes in PI3K-Akt signaling pathway and could be promising targets of BDNF in reversing microglia M1 polarization.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our study demonstrated a sound conclusion that hypothyroidism promotes microglia M1 polarization by inhibiting BDNF expression in brain; BDNF could inhibit the M1 polarization of microglia by activating PI3K-Akt signaling pathway, which could serve as a promising therapeutic target for microglia-induced neurodegenerative or emotional disorders in future.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Hypothyroidism and its induced neurological-associated disorders greatly affect the health-related quality of patients' life. Meanwhile, microglia in brain have essential regulatory functions on neurodegeneration, but the underlying link between hypothyroidism and microglia function is largely ambiguous.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We deciphered how hypothyroidism modulates the polarization of microglia by constructing methimazole-induced mice model and checking the expression pattern of biomarkers of microglia M1 polarization. Then, we used lipopolysaccharide (LPS)-treated BV2 cells to explore t","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"34-47"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}