Neuroendocrinology最新文献

{"title":"Effect of Thyroid Status Modulation on Pituitary and Peripheral Hormone Concentrations in Healthy Older Subjects.","authors":"Evie van der Spoel, Saskia Cornet, Ana Zutinic, Bart Ballieux, P Eline Slagboom, Hanno Pijl, Diana van Heemst","doi":"10.1159/000542832","DOIUrl":"10.1159/000542832","url":null,"abstract":"<p><strong>Introduction: </strong>Depending on age, sex, and familial longevity, alterations in thyroid status occur frequently and often co-occur with differences in other hormonal axes. However, studies that explore the effects of thyroid status modulation on other hormonal axes remain scarce. We aimed to determine the effects of thyroid status modulation on prolactin, IGF-1, cortisol, LH, testosterone, and SHBG levels. We also explored whether effects differed depending on type of challenge, sex, and familial longevity.</p><p><strong>Methods: </strong>Data were gathered from two single-arm challenge studies comprising an intramuscular injection of 0.1 mg recombinant human TSH (rhTSH, N = 29) or 100 µg T3 orally (N = 27) in healthy older individuals. Changes in hormone concentration profiles relative to baseline were determined for 4 and 5 days, respectively.</p><p><strong>Results: </strong>IGF-1 increased with a maximum of 6.3% (SEM = 1.6%, p = 0.002) in the rhTSH challenge and 8.8% (SEM = 1.6%, p < 0.001) in the T3 challenge, while LH (19.3% [SEM = 6.6%, p = 0.048]), testosterone (13.8% [SEM = 4.7%, p = 0.048]), and SHBG (11.8% [SEM = 3.5%, p = 0.02]) increased significantly in the T3 challenge only. Moreover, prolactin significantly decreased in both rhTSH and T3 challenges (-8.8% [SEM = 3.4%, p = 0.048] and -12.0% [3.3%, p = 0.004], respectively) as did cortisol (-14.8% [SEM = 3.6%, p < 0.001] and -15.6% [SEM = 3.5%, p < 0.001]). There was no significant interaction with type of challenge, sex, or familial longevity, except for prolactin in the rhTSH challenge (p = 0.004) which decreased significantly in men only.</p><p><strong>Conclusions: </strong>Upon modulation of thyroid status, changes were observed in IGF-1, prolactin, and cortisol. In the T3 challenge, LH, testosterone, and SHBG increased in men. Observed changes are hypothesized to be driven by (f)T3.</p><p><strong>Introduction: </strong>Depending on age, sex, and familial longevity, alterations in thyroid status occur frequently and often co-occur with differences in other hormonal axes. However, studies that explore the effects of thyroid status modulation on other hormonal axes remain scarce. We aimed to determine the effects of thyroid status modulation on prolactin, IGF-1, cortisol, LH, testosterone, and SHBG levels. We also explored whether effects differed depending on type of challenge, sex, and familial longevity.</p><p><strong>Methods: </strong>Data were gathered from two single-arm challenge studies comprising an intramuscular injection of 0.1 mg recombinant human TSH (rhTSH, N = 29) or 100 µg T3 orally (N = 27) in healthy older individuals. Changes in hormone concentration profiles relative to baseline were determined for 4 and 5 days, respectively.</p><p><strong>Results: </strong>IGF-1 increased with a maximum of 6.3% (SEM = 1.6%, p = 0.002) in the rhTSH challenge and 8.8% (SEM = 1.6%, p < 0.001) in the T3 challenge, while LH (19.3% [SEM = 6.6%, p = 0.048]), testostero","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770694","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":"Acquiring Social Safety Engages Oxytocin Neurons in the Supraoptic Nucleus: Role of Magel2 Deficiency.","authors":"Prabahan Chakraborty, Hugo Lamat, Emilie M André, Pierre Fontanaud, Freddy Jeanneteau","doi":"10.1159/000538437","DOIUrl":"10.1159/000538437","url":null,"abstract":"<p><strong>Introduction: </strong>Exposure to social trauma may alter engagement with both fear-related and unrelated social stimuli long after. Intriguingly, how simultaneous discrimination of social fear and safety is affected in neurodevelopmental conditions remains underexplored. The role of the neuropeptide oxytocin is established in social behaviors and yet unexplored during such a challenge post-social trauma.</p><p><strong>Methods: </strong>Using Magel2 knockout mice, an animal model of Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS), we tested memory of social fear and safety after a modified social fear conditioning task. Additionally, we tracked the activity of oxytocin neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus by fiber photometry, as animals were simultaneously presented with a choice between fear and safe social cue during recall.</p><p><strong>Results: </strong>Male Magel2 KO mice trained to fear females with electrical footshocks avoided both unfamiliar females and males during recalls, lasting even a week post-conditioning. On the contrary, trained Magel2 WT avoided only females during recalls, lasting days rather than a week post-conditioning. Inability to overcome social fear and avoidance of social safety in Magel2 KO mice were associated with the reduced engagement of oxytocin neurons in the SON but not the PVN.</p><p><strong>Conclusion: </strong>In a preclinical model of PWS/SYS, we demonstrated region-specific deficit in oxytocin neuron activity associated with behavioral generalization of social fear to social safety. Insights from this study add to our understanding of oxytocin action in the brain at the intersection of social trauma and PWS/SYS.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"138-153"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867781","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 French Neuroendocrinology Is Enriched by Its Diversity.","authors":"David Vaudry","doi":"10.1159/000543954","DOIUrl":"10.1159/000543954","url":null,"abstract":"","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"101-102"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189004","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":"The Impact of SGLT2 Inhibitors on Dementia Onset in Patients with Type 2 Diabetes: A Meta-Analysis of Cohort Studies.","authors":"Jiani Pan, Huiping Yang, Jiatong Lu, Ling Chen, Tian Wen, Shijie Zhao, Liye Shi","doi":"10.1159/000543533","DOIUrl":"10.1159/000543533","url":null,"abstract":"<p><strong>Introduction: </strong>Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated neuroprotective effects and hold potential advantages in enhancing cognitive function. This study aimed to clarify the association between SGLT2 inhibitors and the risk of dementia among individuals diagnosed with type 2 diabetes (T2D).</p><p><strong>Methods: </strong>All cohort studies concerning the impact of SGLT2 inhibitors on dementia onset in patients with T2D were identified. The literature search encompassed PubMed, Embase, Cochrane Library, and Web of Science from establishment to March 2024, with no language restriction. The quality of the literature was evaluated using the Newcastle-Ottawa Scale (NOS). Meta-analysis was conducted using RevMan 5.4 software, calculating pooled risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous outcomes.</p><p><strong>Results: </strong>Five cohort studies encompassing a total of 331,908 patients were included in the analysis. The findings showed that individuals receiving SGLT2 inhibitors had a lower risk of dementia (I2 = 42%, p = 0.14; RR: 0.77; 95% CI: 0.71-0.84) compared to the control group. Subgroup analyses confirmed the consistent beneficial effects of SGLT2 inhibitors across different study regions (I2 = 0%, p = 0.60) and genders (I2 = 0%, p = 0.50).</p><p><strong>Conclusions: </strong>SGLT2 inhibitors may reduce the dementia risk in T2D patients. Given the limitations of the study, further investigations were warranted to confirm the benefits.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"351-359"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971687","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":"Cognitive Disorders in Type 1 Diabetes: Role of Brain Glucose Variation, Insulin Activity, and Glucocorticoid Exposure.","authors":"Julie Brossaud, Pascal Barat, Marie-Pierre Moisan","doi":"10.1159/000541989","DOIUrl":"10.1159/000541989","url":null,"abstract":"<p><strong>Background: </strong>The number of patients with type 2 diabetes (T2D) and type 1 diabetes (T1D) is on the rise, partly due to a global increase in new T1D cases among children. Beyond the well-documented microvascular and macrovascular complications, there is now substantial evidence indicating that diabetes also impacts the brain, leading to neuropsychological impairments. The risk of developing neuropsychiatric symptoms is notably higher in childhood due to the ongoing maturation of the brain, which makes it more susceptible to damage. Despite this awareness, the specific effects of diabetes on cognitive function remain poorly understood.</p><p><strong>Summary: </strong>This review synthesizes literature on the impact of diabetes on cognition and its relationship with brain structural changes. It presents data and hypotheses to explain how T1D contributes to cognitive dysfunction, with a particular focus on children and adolescents. The emphasis on the pediatric population is intentional, as young diabetic patients typically have fewer comorbidities, reducing confounding factors and simplifying the investigation of cognitive alterations.</p><p><strong>Key message: </strong>We examine the roles of hypo- and hyperglycemia, as well as the emerging role of glucocorticoids in the development of neuropsychological disorders. When specific mechanisms related to T1D are available, they are highlighted; otherwise, data and hypotheses applicable to both T1D and T2D are discussed.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"211-225"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470842","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":"Obesogens and Energy Homeostasis: Definition, Mechanisms of Action, Exposure, and Adverse Effects on Human Health.","authors":"Bayram Yilmaz, Cihan Suleyman Erdogan, Suleyman Sandal, Fahrettin Kelestimur, David O Carpenter","doi":"10.1159/000542901","DOIUrl":"10.1159/000542901","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a major risk factor for noncommunicable diseases and is associated with a reduced life expectancy of up to 20 years, as well as with other consequences such as unemployment and increased economic burden for society. It is a multifactorial disease, and physiopathology of obesity involves dysregulated calorie utilization and energy balance, disrupted homeostasis of appetite and satiety, lifestyle factors including sedentary lifestyle, lower socioeconomic status, genetic predisposition, epigenetics, and environmental factors. Some endocrine-disrupting chemicals (EDCs) have been proposed as \"obesogens\" that stimulate adipogenesis leading to obesity. In this review, definition of obesogens, their adverse effects, underlying mechanisms, and metabolic implications will be updated and discussed.</p><p><strong>Summary: </strong>Disruption of lipid homeostasis by EDCs involves multiple mechanisms including increase in the number and size of adipocytes, disruption of endocrine-regulated adiposity and metabolism, alteration of hypothalamic regulation of appetite, satiety, food preference and energy balance, and modification of insulin sensitivity in the liver, skeletal muscle, pancreas, gastrointestinal system, and the brain. At a cellular level, obesogens can exert their endocrine disruptive effects by interfering with peroxisome proliferator-activated receptors and steroid receptors. Human exposure to chemical obesogens mainly occurs by ingestion and, to some extent, by inhalation and dermal uptake, usually in an unconscious manner. Persistent pollutants are lipophilic features; thus, they bioaccumulate in adipose tissue.</p><p><strong>Key messages: </strong>Although there are an increasing number of reports studying the effects of obesogens, their mechanisms of action remain to be elucidated. In addition, epidemiological studies are needed in order to evaluate human exposure to obesogens.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"72-100"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770697","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":"Immunohistochemical Identification of Sensory Neuropeptides Calcitonin Gene-Related Peptide, Substance P, and Pituitary Adenylate Cyclase-Activating Polypeptide in Efferent Vestibular Nucleus Neurons.","authors":"David Lorincz, Hannah Rose Drury, Rebecca Lim, Alan Martin Brichta","doi":"10.1159/000542984","DOIUrl":"10.1159/000542984","url":null,"abstract":"<p><strong>Introduction: </strong>The efferent vestibular system (EVS) originates in brainstem efferent vestibular nuclei (EVN) and modifies afferent vestibular signals at their source, in peripheral vestibular organs. Recent evidence suggests that EVS is also involved in the development of motion sickness symptoms, including vertigo and nausea, but the underlying mechanism is unknown. One possible link between EVN and motion sickness symptoms is through the neuropeptide calcitonin gene-related peptide (CGRP). CGRP often co-exists with substance P and pituitary adenylate cyclase-activating polypeptide (PACAP), two neuropeptides with similar vasodilatory effects. Collectively, these sensory neuropeptides have been associated with vestibular migraine pathophysiology and motion sickness. While CGRP and the fast EVS neurotransmitter, acetylcholine (ACh), have previously been identified in EVN neurons and their peripheral terminals, the presence of substance P and PACAP in the EVN has not yet been described.</p><p><strong>Methods: </strong>We used fluorescent immunohistochemistry combined with confocal microscopy to examine the distribution of these three neuropeptides in the mouse EVN. In transgenic choline acetyltransferase (ChAT)-gCaMP6f mice, EVN neurons were positively identified using the fluorescent expression of gCaMP6f. In wild-type C57/BL6 mice, EVN neurons were confirmed using ChAT immunolabelling.</p><p><strong>Results: </strong>Consistent with previous studies, CGRP was labelled in a subset of cholinergic EVN neurons. Additionally, we also show evidence for substance P and PACAP expression in EVN of transgenic and wild-type mice.</p><p><strong>Conclusion: </strong>The presence of CGRP, substance P, and PACAP in EVN neurons suggests a complex peptidergic modulation of cholinergic signalling, whose release into local blood vessels may contribute to motion sickness symptoms.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"269-282"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11991750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813436","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":"Temozolomide Treatment in Refractory Pituitary Adenomas and Pituitary Carcinomas.","authors":"Congcong Deng, Shuangjian Yang, Changqin Pu, Xuexue Bai, Chenxin Tian, Ming Feng","doi":"10.1159/000543427","DOIUrl":"10.1159/000543427","url":null,"abstract":"<p><strong>Background: </strong>Temozolomide (TMZ), a nonclassical alkylating agent, possesses lipophilic properties that allow it to cross the blood-brain barrier, making it active within the central nervous system. Furthermore, the adverse reactions of the TMZ are relatively mild, which is why it is currently recommended as a first-line chemotherapy drug for refractory pituitary adenomas (RPAs) and pituitary carcinomas (PCs).</p><p><strong>Summary: </strong>Systematic evaluations indicate a radiological response rate of 41% and a hormonal response rate of 53%, underscoring TMZ clinical efficacy, particularly when combined with radiotherapy. Functional tumors demonstrate a higher response rate compared to nonfunctional tumors. While the optimal duration of TMZ treatment remains undetermined, studies suggest that longer therapy durations may lead to better prognoses. Additionally, prior to TMZ administration, it is advisable to conduct immunohistochemical analysis of O6-methylguanine-DNA methyltransferase, MSH2, MSH6, MLH1, PMS2, and N-methylpurine DNA glycosylase to assess the potential impact of repair mechanisms such as direct repair, mismatch repair pathway, and base excision repair on TMZ treatment. The efficacy of TMZ analogs, combined TMZ therapies, and TMZ with nanomaterials following TMZ treatment failure remains uncertain.</p><p><strong>Key messages: </strong>The involvement of experienced multidisciplinary pituitary teams in all management decisions for RPAs/PCs patients is essential.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"335-350"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11991747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952345","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":"Gray Matter Reserve Modulates the Association between Glymphatic System Function and Cognition in Patients with Type 2 Diabetes Mellitus.","authors":"Wenqing Xia, Xiao Yin, Yujie Zhang, Shenghui Ge, Yuchen Chen, Jianhua Ma","doi":"10.1159/000542902","DOIUrl":"10.1159/000542902","url":null,"abstract":"<p><strong>Introduction: </strong>The glymphatic system is regarded as a key factor in the pathogenesis of neurodegenerative diseases. Given the heightened risk of cognitive impairment in patients with type 2 diabetes mellitus (T2DM), the possible alterations in the glymphatic system in T2DM patients remain to be explored. Diffusion tensor imaging (DTI) analysis along the perivascular space (ALPS) index can be utilized to model the glymphatic system in humans. Our aim was to explore the relationship between the ALPS index and cognitive function in patients with T2DM and whether this relationship is modulated by gray matter (GM) integrity anchored by the ALPS index.</p><p><strong>Methods: </strong>All participants underwent evaluation using a comprehensive cognitive assessment scale to determine their neurocognitive status. The ALPS index was calculated based on DTI data, and the disparity in ALPS index values between patients with T2DM and healthy controls (HCs) was examined. Furthermore, multiple linear regression analysis was conducted in the T2DM group to identify the GM regions associated with the ALPS index, and the volumes of the GM partitions were extracted. The volume of GM partitions was used as the regulating variable, the ALPS index was used as the independent variable, and cognitive test scores were used as the dependent variable in our analysis.</p><p><strong>Results: </strong>The ALPS index differed significantly between the two groups, and the ALPS index in patients with T2DM was significantly lower than that in HCs. In addition, our analysis revealed a correlation between the ALPS index and GM volume in the insular region, consistent with the observed GM atrophy in the patient cohort. Moreover, a significant negative correlation was observed between the ALPS index in patients and performance on the Trail-Making Test-A (TMT-A), and this relationship was moderated by GM integrity. In patients with more severe GM atrophy, the ALPS index was more strongly correlated with cognitive function.</p><p><strong>Conclusions: </strong>In this study, a decreased ALPS index was found in T2DM patients, indicating impaired glymphatic function in this population. Furthermore, a significant association was detected between the ALPS index and cognitive performance in T2DM patients, and this correlation was influenced by GM integrity. Therefore, the ALPS index has the potential to be used as a biomarker of cognitive impairment in diabetic patients. Further studies are needed to investigate the diagnostic and therapeutic implications of glymphatic dysfunction in T2DM patients with cognitive impairment.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"48-59"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770696","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":"Absence of the Peptide Transporter 1 Induces a Prediabetic and Depressive-Like Phenotype in Mice.","authors":"Justine Vily-Petit, Amelie Taki, Flore Sinet, Maud Soty, Bruno Guiard, Juliane Zemdegs, Gael Malleret, Anne Stefanutti, Gilles Mithieux, Amandine Gautier-Stein","doi":"10.1159/000539499","DOIUrl":"10.1159/000539499","url":null,"abstract":"<p><strong>Introduction: </strong>Protein-enriched diets improve glycemic control in diabetes or emotional behavior in depressive patients. In mice, these benefits depend on intestinal gluconeogenesis activation by di-/tripeptides. Intestinal di-/tripeptides absorption is carried out by the peptide transporter 1, PEPT1. The lack of PEPT1 might thus alter glucose and emotional balance.</p><p><strong>Methods: </strong>To determine the effects of PEPT1 deficiency under standard dietary conditions or during a dietary challenge known to promote both metabolic and cognitive dysfunction, insulin sensitivity, anxiety, and depressive-like traits, hippocampal serotonin (5-HT) and insulin signaling pathway were measured in wild-type (WT) and Pept1-/- mice fed either a chow or a high-fat high-sucrose (HF-HS) diet.</p><p><strong>Results: </strong>Pept1-/- mice exhibited slight defects in insulin sensitivity and emotional behavior, which were aggravated by an HF-HS diet. Pept1-/- mice fed a chow diet had lower hippocampal 5-HT levels and exhibited cerebral insulin resistance under HF-HS diet. These defects were independent of intestinal gluconeogenesis but might be linked to increased plasma amino acids levels.</p><p><strong>Conclusion: </strong>Pept1-/- mice develop prediabetic and depressive-like traits and could thus be used to develop strategies to prevent or cure both diseases.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"226-241"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296418","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}