Neuroendocrinology最新文献

{"title":"Impact of Indoleamine 2,3-Dioxygenase Enzyme Activity in Neuroendocrine Tumors.","authors":"Camilla Mancini, Giulia Pecora, Gerardo Salerno, Luana Lionetto, Donatella De Bernardini, Giuseppe Costanzi, Saverio Gabrielli, Domenico Veroli, Vincenzo Visco, Maurizio Simmaco, Virginia Zamponi, Rossella Mazzilli, Antongiulio Faggiano","doi":"10.1159/000543658","DOIUrl":"10.1159/000543658","url":null,"abstract":"<p><strong>Introduction: </strong>Indoleamine 2,3-dioxygenase (IDO) converts L-tryptophan (T) to L-kynurenine (K) resulting in an immunosuppressive microenvironment. The aim of the current study was to evaluate in patients with neuroendocrine tumor (NET) (1) T and K concentrations; (2) correlation with clinical outcome; (3) relationship between IDO activity and inflammatory cytokines.</p><p><strong>Methods: </strong>A cross-sectional study was performed to investigate the IDO pathway in patients in follow-up for NET. Clinicopathological features, serum levels of K and T through liquid chromatography, and serum assay of cytokines (IL-6, IL-10, IL-17A, IL-22, IL-23, TNF-α) through MAGPIX were evaluated.</p><p><strong>Results: </strong>Seventy-eight NET patients were enrolled (66 lung, 12 pancreatic): 69.2% were in postoperative remission, 14.1% in stable disease, and 16.7% in disease progression. T was significantly lower in patients older than 65 years (p = 0.003). K and T were significantly lower in patients with progression (p = 0.03, p = 0.004, respectively). T was an independent predictor factor of progression in multivariable analysis (p = 0.041). A cutoff of 7.74 μg/mL significantly differentiates patients with progression and those with stable disease. IL-6 and IL-10 were significantly associated with tumor progression in univariate analysis (p = 0.005, p = 0.001, respectively) but not in the multivariable analysis. A statistically significant negative correlation was found between T and IL-10 (r = -0.366, p value = 0.04).</p><p><strong>Conclusion: </strong>The K/T pathway may play a role as a potential predictor of tumor progression in NET. These findings need to be validated in large prospective studies investigating its metabolites as both prognostic and predictive factors for treatment response.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"411-421"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007830","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":2.8,"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":"Involvement of the AVP/OT System and Lateral Septum in the Modulation of Anxiety/Depression Caused by 14-Week and 20-Week Social Isolation.","authors":"Jing Liu, Weizheng Zhang, Yuting Bai, Rui Fu, Miao Lin, Jialong Li, Liangteng Nie, Xiaohui Dang, Qiao Wang, Yunmeng Zhu, Lu Li, Xing Guo, Lizi Zhang, Yishan Qu, Kaizhe Huang, Xiao Han, Shufeng Shang, Jiayu Xiao, Yin Li, Caihong Huang, Rui Jia, Zhixiong He, Fadao Tai","doi":"10.1159/000544839","DOIUrl":"10.1159/000544839","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic social isolation (CSI) stress leads to numerous maladaptive changes in physiology and psychology, however, very little is known about the effects of longer time-scale CSI and there are divergent views regarding the underlying mechanisms. This study aimed to elucidate the common neuroendocrine mechanisms underlying the maladaptive changes caused by 14-week (14wk) and 20-week (20wk) CSI.</p><p><strong>Methods: </strong>We investigated the impacts of 14wk and 20wk CSI on anxiety-/depression-like behaviors in male C57BL/6N mice with classical behavioral tests, and the immunofluorescence (IF) method was used for quantification of the arginine vasopressin (AVP)/oxytocin (OT) positive neurons in the PVN and screening out the differential activation brain regions (DABrs) on exposure of tail suspension. The expression of Avpr1a and Oxtr in the lateral septum (LS) was assessed by quantitative RT-PCR (qPCR), and the function of LSD Avpr1a+/+ neurons in emotion regulation was verified with pharmacological approaches. The concentration of AVP/OT in plasma was examined with the enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>14wk and 20wk CSI increased anxiety-/depression-like behaviors and altered levels of exploratory locomotion in opposite directions, which are likely due to an imbalance of the AVP/OT system within the PVN and peripheral plasma, differential activation of LSD and thalamic brain regions, and abnormal expression of Avpr1a in LS. Pharmacological results demonstrated that Avpr1a+/+ neurons in the LSD were involved in emotion regulation.</p><p><strong>Conclusion: </strong>This study suggests that the imbalance of the AVP/OT system and the dysfunction of Avpr1a+/+ neurons in the LSD were engaged in common neuroendocrinology mechanisms for anxiety/depression induced by long-term CSI.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"493-519"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502867","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":"A New Bihormonal Model for the Brain Regulation of Gonadotropins in Teleosts.","authors":"Chinelo Nnenna Uju, Umar Farouk Mustapha, Suraj Unniappan","doi":"10.1159/000546403","DOIUrl":"10.1159/000546403","url":null,"abstract":"<p><strong>Background: </strong>The brain-pituitary-gonadal tissues play a key role in the neuroendocrine regulation of reproduction in vertebrates. Brain hormones, especially gonadotropin-releasing hormone (GnRH) is considered an important stimulant of gonadotropins (luteinizing hormone and follicle-stimulating hormone) released from the anterior pituitary. The current concept proposes a single brain hormone (GnRH) stimulating the release of both gonadotropins in fish and mammals. However, two articles published in 2024 proposed a dual-hormone concept in the brain regulation of gonadotropins in female medaka and zebrafish.</p><p><strong>Summary: </strong>The emerging concept proposes GnRH as the LH releasing hormone (LH-RH), and a second hormone, cholecystokinin (Cck), as the FSH-releasing hormone (FSH-RH) in these species. The two studies discussed here found that Cck is a potent FSH-RH. The line of evidence from the first study to support this notion includes the abundance of Cck receptors in the anterior pituitary Fsh-producing gonadotrophs, and severe reproductive defects in female medaka that genetically lacks Cck receptor 2. The second study used zebrafish, and found hypothalamic expression of Cck, anterior pituitary abundance of Cck receptors, and an all-male phenotype when Cck receptor 2 was knocked out. In both studies, Cck was found to be a more potent stimulant of intracellular Ca2+, when compared to GnRH effects.</p><p><strong>Key messages: </strong>These evidence from two independent studies indicate that Cck is a potent FSH-RH, and GnRH is the LH-RH, and supports a bihormonal model for the regulation of gonadotropin secretion from teleost pituitary. However, whether Cck elicits FSH-RH effects in other fish species remains unknown. In addition, the role of other hormones in the diverse endocrine milieu that regulate reproduction in modulating the phenotype seen in Cck receptor deficient fish warrants further consideration.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"648-656"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120305","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":"Doppler Assessment of the Uterine Arteries Is a Valuable Adjunct Tool for the Evaluation of Efficacy of Gonadotropin-Releasing Hormone Agonist Therapy in Girls with Central Precocious Puberty.","authors":"Amanda Veiga Cheuiche, Letícia Guimarães da Silveira, Iara Regina Siqueira Lucena, Márcia Puñales, Fabiola Costenaro, Cristiane Kopacek, Gustavo Monteiro Escott, Sandra Pinho Silveiro, Leila Cristina Pedroso de Paula","doi":"10.1159/000544985","DOIUrl":"10.1159/000544985","url":null,"abstract":"<p><strong>Introduction: </strong>Pelvic ultrasound has been studied for the follow-up of girls with precocious puberty during gonadotropin-releasing hormone agonists (GnRHa) therapy. The addition of Doppler evaluation of uterine arteries needs to be further investigated. We aimed to evaluate the accuracy of the uterine artery pulsatility index (PI) for monitoring GnRHa therapy in girls with precocious puberty.</p><p><strong>Methods: </strong>This is a retrospective cohort study of girls with central precocious puberty (CPP) and early and fast puberty (EFP) treated with GnRHa. We included girls who underwent pelvic ultrasound and Doppler imaging of the uterine arteries before and during therapy. Analyses included uterine artery PI and uterine, endometrial, and ovarian measurements. Receiver operating characteristic (ROC) curves with cutoffs determined by the Youden index were used for data analysis.</p><p><strong>Results: </strong>In total, 28 pairs of PI measurements (54% of girls with CPP, 46% with EFP) before and during GnRHa therapy were included in the paired-sample analysis. The median duration of treatment at the time of ultrasound was 11.5 (7; 19) months. The mean PI was significantly higher during GnRHa therapy than at baseline (6.5 ± 1.8 vs. 4.0 ± 1.6, respectively, p < 0.001). A total of three girls met clinical and laboratory criteria for treatment failure. ROC curve analysis showed that the PI was able to identify an effective GnRHa therapy with a mean area under the curve of 0.967 ± 0.04 (p < 0.001), and the PI cutoff point of 5.4 held a sensitivity of 84%, specificity of 100%, and accuracy of 86%.</p><p><strong>Conclusion: </strong>We found a significant increase in the PI during GnRHa therapy, which reflects higher resistance in the blood flow to the uterus, indicating effective pubertal hormone suppression.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"520-529"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542631","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":"Neurotrophic Effects of GH and GnRH in a Full Sciatic Nerve Transection Model in Male Rats.","authors":"Jorge J A Baca-Alonso, Denisse Calderón-Vallejo, Irma Hernández-Jasso, David Epardo, Jerusa E Balderas-Márquez, Maricela Luna, Carlos Arámburo, J Luis Quintanar, Carlos G Martínez-Moreno","doi":"10.1159/000545129","DOIUrl":"10.1159/000545129","url":null,"abstract":"<p><strong>Introduction: </strong>Peripheral nerve injuries, such as sciatic nerve transection (SNT), are often associated with significant sensory and motor deficits. Growth hormone (GH) and gonadotropin-releasing hormone (GnRH) have been shown to exert neurotrophic effects that can promote nerve regeneration and functional reinnervation. However, the combined impact of these hormones on peripheral nerve repair remains poorly understood.</p><p><strong>Methods: </strong>This study aimed to analyze the individual and combined effects of GH and GnRH in a rat model of SNT, using orchiectomized male rats to prevent steroid-mediated neuroregeneration and neuroprotection. Treatments included GH, GnRH, or a combination of both, with subsequent assessments of motor and sensory function, as well as histological and molecular analyses of the nerve tissue and associated muscles.</p><p><strong>Results: </strong>The results revealed that both GH and GnRH significantly enhanced nerve regeneration and neural function when administered individually. Treated animals exhibited improved axonal growth, myelination, and sensory and motor functional recovery. In addition, GH and GnRH reduced neuroinflammation/reactive gliosis, as evidenced by the downregulation of TNFα, IL-1β, Iba-1, and GFAP, which are typically elevated following nerve injury. These findings indicate that each hormone independently supports critical aspects of nerve repair and functional restoration after injury. Surprisingly, when GH and GnRH were administered together, their beneficial effects were not additive. Instead, the combination of the two treatments led to diminished outcomes in comparison to either treatment alone. Specifically, animals receiving the combined therapy showed reduced axonal organization, impaired myelination, and less functional improvement.</p><p><strong>Conclusion: </strong>GH and GnRH demonstrate considerable potential as individual therapeutic agents for promoting peripheral nerve regeneration, each providing significant benefits in terms of axonal growth, functional recovery, and reduction of neuroinflammation.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"530-552"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657871","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":"Ectopic Corticotropin-Releasing Hormone/Adrenocorticotropic Hormone-Co-Secreting Neuroendocrine Tumors Leading to Cushing's Disease: A Case Presentation and Literature Review.","authors":"Jasmin Ewert, Maximilian Seidl, Jann Achim Hommen, Matthias Schott, Norbert Gattermann","doi":"10.1159/000544727","DOIUrl":"10.1159/000544727","url":null,"abstract":"<p><strong>Background: </strong>Adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) are essential regulators of cortisol production within the hypothalamic-pituitary-adrenal (HPA) axis. Elevated cortisol levels, resulting from excessive ACTH, can lead to Cushing's syndrome, a condition associated with significant morbidity. Neuroendocrine tumors (NETs) can ectopically produce both ACTH and CRH, a rare phenomenon that further contributes to this syndrome.</p><p><strong>Summary: </strong>This review discusses the pathophysiology, types, clinical presentation, diagnosis, and management of NETs that ectopically secrete CRH and ACTH. Particular emphasis is placed on the importance of identifying dual CRH/ACTH secretion, which complicates diagnosis and treatment. Furthermore, the review highlights the prognosis, common complications, and future directions for research in this area. We further report the case of a 53-year-old female patient who presented with severe Cushing's syndrome and was diagnosed with ectopic ACTH syndrome. Despite initial findings suggesting pituitary-dependent hypercortisolism, further investigations revealed the presence of a highly differentiated, atypically located tumor in the lung. Immunohistochemistry of the tumor tissue demonstrated not only ACTH but also CRH and CRH-R1 expression. The simultaneous expression of these molecules supports the hypothesis of a positive endocrine feedback loop within the NET, in which the release of CRH stimulates ACTH expression via binding to CRH-R1.</p><p><strong>Key messages: </strong>This case report highlights the challenges in diagnosing and managing ectopic ACTH syndrome, emphasizing the importance of a comprehensive diagnostic approach to identify secondary factors influencing cortisol production, such as CRH secretion and other contributing neuroendocrine mechanisms. Recognizing the dual secretion of CRH and ACTH in NETs is crucial for accurate diagnosis and optimizing patient management.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"576-588"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433554","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":2.8,"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":"Subject Index.","authors":"","doi":"10.1159/000546687","DOIUrl":"https://doi.org/10.1159/000546687","url":null,"abstract":"","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":"115 5","pages":"481-482"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485189","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":2.8,"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}