Neuropeptides最新文献

{"title":"Neuropeptide Y at the crossroads of neurodegeneration: Mechanistic insights and emerging therapeutic strategies","authors":"Viswanthram Palanivel ,&nbsp;Akanksha Salkar ,&nbsp;Avinash Shenoy ,&nbsp;Taslima Akter Eva ,&nbsp;Rumandee Perera ,&nbsp;Nitin Chitranshi ,&nbsp;Veer Gupta ,&nbsp;Yuyi You ,&nbsp;Mehdi Mirzaei ,&nbsp;Stuart L. Graham ,&nbsp;Vivek Gupta ,&nbsp;Devaraj Basavarajappa","doi":"10.1016/j.npep.2025.102583","DOIUrl":"10.1016/j.npep.2025.102583","url":null,"abstract":"<div><div>Neuropeptide Y (NPY), a widely distributed and highly conserved neuropeptide, plays a central role in the regulation of diverse physiological processes, including stress responses, energy homeostasis, vascular tone, and immune modulation, via activation of its receptor subtypes. Beyond its physiological roles, the dysregulation of NPY expression has been documented in several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Machado-Joseph disease, and retinal disorders such as diabetic retinopathy and glaucoma. These alterations in NPY levels and receptor activity highlight its potential not only as a biomarker for disease progression but also as a promising therapeutic target. Previous evidence revealed that NPY exerts neuroprotection by alleviating excitotoxicity, oxidative stress, mitochondrial dysfunction, and neuroinflammation while concurrently facilitating neurogenesis, synaptic plasticity, and cellular resilience. NPY activates receptor-mediated intracellular signaling cascades like PI3K/Akt, MAPK/ERK, and p38K, that control cellular survival, proteostasis, and inflammation and thereby influence disease trajectories. Understanding NPY operation with these mechanisms can unveil new avenues for targeted therapy. Current insights into the complex roles of NPY in neurodegeneration are discussed in this review, and their implications in diagnostic and treatment strategies are addressed.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"115 ","pages":"Article 102583"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATP drives the leptin inhibition of voltage-gated calcium channels via AMPK in isolated neurons of arcuate nucleus in male rats","authors":"Karina Bermeo,&nbsp;Margarita Jacaranda Rosendo-Pineda,&nbsp;Tamara Arenas,&nbsp;Isabel Arenas,&nbsp;David E. Garcia","doi":"10.1016/j.npep.2025.102582","DOIUrl":"10.1016/j.npep.2025.102582","url":null,"abstract":"<div><div>Energy balance is controlled by multiple structures in the central nervous system. Hypothalamus, particularly arcuate nucleus, is a key region in the neuronal control of energy homeostasis. Leptin, an anorexigenic hormone, inhibits voltage-gated calcium channels via AMPK. However, the fine-tuning regulation of this inhibition is still scarcely known. The purpose of this work was to investigate whether intracellular ATP and extracellular glucose concentrations determine the calcium channel regulation by leptin. By using patch-clamp methods, immunocytochemical reagents and pharmacological manipulations, calcium channel-current inhibited by leptin was recorded in isolated neurons of arcuate nucleus. Consistently, leptin-mediated inhibition of calcium channel-current is occluded by lowering the intracellular ATP concentration. On the other hand, leptin maintains this inhibition independently of the extracellular glucose concentration. Furthermore, AMPK regulates constitutively the calcium channel-current inhibited by leptin. These results support for the first time a key role of ATP in the regulation of calcium channel-current by leptin. Remarkably, leptin inhibits calcium channel-current even under low extracellular glucose concentration supporting a calcium channel regulation hierarchically attained by ATP and leptin. Together, these results shed light to the role of ATP and AMPK in the dynamic regulation of calcium channels as critical components in the neuronal control of energy balance.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"115 ","pages":"Article 102582"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nociceptin-mediated SIRT6 downregulation drives cellular senescence in glioblastoma","authors":"Yankai Xu,&nbsp;Jiesi Zhou,&nbsp;Xiaobin Zhou,&nbsp;Yong Li,&nbsp;Senyuan Yang,&nbsp;Zebin Xue","doi":"10.1016/j.npep.2025.102570","DOIUrl":"10.1016/j.npep.2025.102570","url":null,"abstract":"<div><div>Cellular senescence plays a crucial role in glioblastoma (GBM), influencing tumor progression and therapeutic resistance. Nociceptin (N/OFQ), an endogenous neuropeptide, and its receptor NOPr are implicated in various pathological processes, but their role in GBM remains unclear. This study investigated the effects of N/OFQ-NOPr signaling on cellular senescence in GBM. We found elevated plasma N/OFQ levels and increased NOPr expression in GBM tissues compared to normal controls. In U-251 GBM cells, N/OFQ upregulated NOPr expression, induced oxidative stress, and reduced telomerase activity and telomere length, leading to enhanced cellular senescence. Mechanistically, N/OFQ downregulated SIRT6 but not SIRT1 or HDAC, resulting in increased acetylation of p53, upregulation of p21, and suppression of p-Rb. Overexpression of SIRT6 reversed N/OFQ-induced senescence markers, restoring telomerase activity and reducing senescence-associated β-galactosidase. Notably, administration of the selective NOPr antagonist UFP-101 abolished N/OFQ-induced cellular senescence, indicating that this effect is NOPr-dependent. These findings suggest that N/OFQ-NOPr signaling promotes GBM senescence via SIRT6 downregulation, highlighting a potential therapeutic target for modulating senescence in GBM</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"115 ","pages":"Article 102570"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of small peptides in Alzheimer's disease: Advances in memory restoration and targeted delivery systems","authors":"Poonam Verma ,&nbsp;Rubina Khatun ,&nbsp;Kiran Anjum Jew ,&nbsp;Shakti Ketan Prusty ,&nbsp;Shira Knafo","doi":"10.1016/j.npep.2025.102559","DOIUrl":"10.1016/j.npep.2025.102559","url":null,"abstract":"<div><div>Despite extensive research into Alzheimer's disease (AD), few therapeutic strategies have successfully addressed its core pathology at the synaptic level. Small peptides represent a promising class of therapeutic agents capable of modulating key molecular pathways involved in amyloid toxicity, tau hyperphosphorylation, and synaptic degeneration. Their unique ability to cross biological barriers, interact with intracellular targets, and be modified for enhanced stability positions them as viable candidates for next-generation treatments targeting cognitive decline in AD.Small peptides show strong therapeutic potential yet face challenges in clinical application due to poor bioavailability and rapid enzymatic degradation. To deal with these limitations, various delivery strategies such as intranasal administration, nanoparticle encapsulation, and chemical modification have been developed. When combined with advanced delivery systems, small peptides hold significant promise for mitigating synaptic dysfunction and slowing the progression of Alzheimer's disease. In this review, we examine the mechanisms of action of four small peptides that demonstrate potential in alleviating Alzheimer's-related symptoms. We also evaluate the most effective delivery methods, emphasizing how these approaches enhance the peptides' therapeutic efficacy.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102559"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of salivary neurotensin and oxytocin in emotional responses to stress inoculation","authors":"Matthew Branney ,&nbsp;Madison Propp ,&nbsp;Dalton Jensen ,&nbsp;Anoushka Singh ,&nbsp;Mark Payton ,&nbsp;Rebecca Ryznar","doi":"10.1016/j.npep.2025.102560","DOIUrl":"10.1016/j.npep.2025.102560","url":null,"abstract":"<div><div>Neuropeptides comprise a class of signaling molecules that exert direct effects on target tissues and modulatory influences across multiple physiological systems; however, their roles in mediating stress responses remains incompletely characterized. Previous studies have shown that acute stress alters salivary levels of neuropeptides but the extent to which these alterations are associated with mechanisms of stress inoculation and emotional valence requires exploration. This study aimed to examine the relationship between salivary neuropeptides and emotional valence following acute stress in military medical students. Salivary samples for oxytocin, neurotensin and data from two questionnaires, ACE and SPANE, were collected from participants pre- and post-stress inoculation. Spearman rank correlation analysis revealed positive correlations &gt;0.9 for neurotensin and oxytocin at pre- and post-inoculation. Post-inoculation neurotensin showed an inverse correlation with pre-simulation SPANE-P and SPANE-B scores (<em>p</em> = 0.006 and <em>p</em> = 0.009 respectively) and demonstrated a positive correlation with pre-simulation SPANE-N score (<em>p</em> = 0.043). Post-inoculation oxytocin demonstrated a negative correlation with pre-inoculation SPANE-P and SPANE-B scores (<em>p</em> = 0.007 and p = 0.006 respectively). Cohorts were established of participants whose neuropeptide levels increased or decreased during inoculation. Inverse correlations existed between oxytocin post-simulation and post-SPANE positive emotions in the increased oxytocin group (<em>R</em> = −0.4607), and between pre-simulation oxytocin and pre-SPANE positive emotions in the decreased oxytocin group (<em>R</em> = −0.4005). Individual variability in salivary neuropeptide responses to inoculation was inversely associated with positive affect, suggesting these neuropeptides as modulators of affective stress responsivity. Future studies should explore the mechanism of these associations and evaluate the potential of salivary neuropeptides as biomarkers for emotional and stress adaptation.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102560"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory modulation of gastrointestinal motility in mice by Tyr-c[D-Lys-Gly-p-F-Phe-Asp]-D-Pro-NH2, a novel cyclic hexapeptide with multifunctional opioid agonism","authors":"Weifan Ding,&nbsp;Qinqin Zhang,&nbsp;Mengna Zhang,&nbsp;Ning Li,&nbsp;Biao Xu,&nbsp;Yaqi Song,&nbsp;Quan Fang,&nbsp;Nan Zhang","doi":"10.1016/j.npep.2025.102565","DOIUrl":"10.1016/j.npep.2025.102565","url":null,"abstract":"<div><div>Opioid analgesics are critical for managing moderate-to-severe pain，yet are limited by adverse gastrointestinal (GI) effects, notably constipation. This necessitates developing novel opioid agonists with robust analgesia and reduced GI side effects. The cyclic hexapeptide Tyr-c[<em>D</em>-Lys-Gly-<em>p</em>-F-Phe-Asp]-<em>D</em>-Pro-NH₂ (analog 15), a recently characterized multifunctional agonist of μ-opioid receptor (MOR), κ-opioid receptor (KOR), and δ-opioid receptor (DOR), exhibits potent antinociception following subcutaneous (s.c.) administration with constipation observed only at high doses. To further evaluate its GI impact, we assessed the effects of analog 15 on intestinal motility using in vivo upper GI transit and colonic bead expulsion assays. Our results indicated that fentanyl, analog 15, and its parent peptide analog 0 dose-dependently slowed upper GI transit and colonic expulsion after s.c. administration, with the upper GI tract exhibiting greater sensitivity. Mechanistically, fentanyl inhibited the GI motility via both central and peripheral opioid receptors, whereas analog 15 inhibited upper GI transit exclusively through the peripheral MOR, KOR, and DOR, and suppressed colonic transit via the peripheral MOR and KOR, both effects were independent of the central opioid receptor pathway. In conclusion, we demonstrated that the high doses of analog 15 inhibited GI motility through peripherally restricted activation of multiple opioid receptors. This finding aligns with analog 15's limited blood-brain barrier (BBB) permeability, which explains its reduced constipating effects while preserving potent analgesia, thereby supporting the therapeutic potential of multi-target peripheral opioid agonists.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102565"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of interplay between endocannabinoids and neuropeptides in pathogenesis and therapy of depressive and anxiety disorders","authors":"Miłosz Gołyszny ,&nbsp;Jonasz Dragon ,&nbsp;Ewa Obuchowicz","doi":"10.1016/j.npep.2025.102564","DOIUrl":"10.1016/j.npep.2025.102564","url":null,"abstract":"<div><div>A growing body of evidence suggests the existence of a neurochemical and functional interplay between endocannabinoids and neuropeptides, which are both relevant for the pathomechanism and effects of pharmacotherapy in depressive and anxiety disorders. Here, we review the available data on how endocannabinoids influence the activity of the neuropeptidergic systems and conversely, how neuropeptides affect the endocannabinoid system. The explicit/implicit interactions in the relationship of endocannabinoids-neuropeptides are presented. Our paper focuses on both well-known neuropeptides, i.e., corticotropin-releasing hormone/factor, CRH/CRF; oxytocin, OT; arginine-vasopressin, AVP; neuropeptide Y, NPY; orexins/hypocretins, OXs/HCRTs) and less investigated neuropeptides, i.e., nesfatin-1, NEFA; phoenixin, PNX; spexin, SPX; neuropeptide S, NPS). Of all of the brain regions that have been studied, the direct and indirect bidirectional interactions between endocannabinoids and the neuropeptides has most clearly been established in the hypothalamus. It has been proven that neuropeptides are modulators of the multifaceted effects of the endocannabinoid system, namely, its influence on neuroendocrine (CRH/CRF) and behavioral stress responsivity (CRH/CRF, OXs), sociability (OT), feelings of pleasure (OXs/HCRTs, NPS), appetite control (NPY, OXs/HCRTs, CRH/CRF, NEFA) and nociception (OT). This latter effect has only the desirable support of positive influence of endocannabinoids on emotional homeostasis to some extent. Nowadays, increasing attention is being paid to the interplay between endocannabinoids and the less explored peptides, especially NEFA and NPS. This trend is both desirable and necessary for gaining a better understanding of the neurochemical aspects and for providing new insights into the potential therapeutic implications in the treatment of affective disorders.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102564"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrastructural characterization of neuropeptide Y synapses in the central inferior colliculus of the Fischer Brown Norway rat","authors":"Laila S. Almassri ,&nbsp;Joshua C. Harris ,&nbsp;Kristen M. Crane ,&nbsp;Andrew P. Ohl ,&nbsp;Nick J. Tokar ,&nbsp;Brett R. Schofield ,&nbsp;Jesse W. Young ,&nbsp;Jeffrey G. Mellott","doi":"10.1016/j.npep.2025.102566","DOIUrl":"10.1016/j.npep.2025.102566","url":null,"abstract":"<div><h3>Introduction</h3><div>The central nucleus of the inferior colliculus (ICc) is the primary target for ascending auditory projections from the lower auditory brainstem nuclei and the main source of ascending projections to the auditory thalamus. The ICc has an extensive network of tonotopically organized neurons, whose classification is a subject of broad interest. In order to understand the extensive microcircuitry of the ICc, it is important to ascertain the synaptic arrangements among molecularly identified neuronal populations. The objective of this study was to describe inhibitory Neuropeptide Y (NPY) synapses in the central nucleus of the IC.</div></div><div><h3>Method</h3><div>We used electron microscopy (EM) and post-embedding anti-NPY immunogold histochemistry on tissue from adult Fischer Brown Norway rats. Inhibitory NPY synapses were identified by pleomorphic vesicles, symmetric synaptic junctions, and NPY-immunopositive presynaptic boutons.</div></div><div><h3>Results</h3><div>The data demonstrate that NPY terminals largely (∼75 %) form symmetric synapses with pleomorphic vesicles, mostly target small and medium dendrites, and have larger average bouton areas, active zone lengths, and vesicle pools, as compared to the overall GABAergic population.</div></div><div><h3>Discussion</h3><div>The subset of GABAergic neurons that co-express NPY feature synaptic characteristics suggesting that NPY neuromodulation has a widespread role in regulating excitation in the ICc.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102566"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pituitary adenylate cyclase-activating polypeptide (PACAP) attenuates diabetic cardiomyopathy via Nrf2/HO-1 antioxidant signaling and NF-κB-mediated inflammation suppression in streptozotocin-treated mice","authors":"Dong Yang ,&nbsp;Huozhao Ruan ,&nbsp;Liancai Chen ,&nbsp;Haonan Zhang ,&nbsp;Guiying Liu","doi":"10.1016/j.npep.2025.102568","DOIUrl":"10.1016/j.npep.2025.102568","url":null,"abstract":"<div><div>Diabetic cardiomyopathy (DCM), characterized by oxidative stress, inflammation, and pathological remodeling, is still a primary cause of death in diabetes. This study examines how pituitary adenylate cyclase-activating polypeptide (PACAP) might treat diabetic heart dysfunction caused by streptozotocin (STZ), with an emphasis on modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant axis and NF-κB-mediated inflammatory signaling. STZ treatment reduced PACAP expression in serum and cardiac tissues, associated with impaired ventricular contractility and hypertrophy. PACAP treatment reversed these effects, restoring heart function, as shown by increased ejection fraction and fractional shortening. PACAP also reduced cardiac hypertrophy, indicated by decreased cardiomyocyte cross-sectional area and heart weight-to-tibia length ratios. Serum markers of myocardial damage (CK-MB, AST, LDH) were elevated in STZ-treated mice but decreased by PACAP. PACAP lowered hemodynamic stress, as shown by reduced mean arterial pressure. PACAP reduced oxidative damage by increasing antioxidant enzyme activity (catalase, SOD, and GPx) and lowering lipid peroxidation, while also inhibiting NADPH oxidase activity. PACAP reduced STZ-induced myocardial inflammation by lowering TNF-α, IL-6, and IL-1β levels and increasing IL-10 levels in cardiac tissue and serum, mitigating systemic inflammation. PACAP restored Nrf2/HO-1 expression and maintained IκBα, which inhibited NF-κB signaling. These findings suggest PACAP's potential to combat oxidative stress and inflammation in STZ-induced DCM, warranting further mechanistic and translational studies.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102568"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nesfatin1 attenuates autism-like behavior via antioxidant, anti-inflammatory activities in a prenatal valproic acid-induced rat model of autism","authors":"Mitra Farbin ,&nbsp;Razieh Hajisoltani ,&nbsp;Tourandokht Baluchnejadmojarad ,&nbsp;Anahita Hejazi ,&nbsp;Touqeer Ahmed ,&nbsp;Heshmatollah Parsian ,&nbsp;Soraya Mehrabi","doi":"10.1016/j.npep.2025.102561","DOIUrl":"10.1016/j.npep.2025.102561","url":null,"abstract":"<div><div>Nesfatin1, a multifunctional peptide involved in energy homeostasis and neural regulation, has emerged as a promising candidate for modulating neurodevelopmental disorders. The anti-inflammatory, antioxidant, and neuroprotective properties of Nesfatin1 have been proven in the central nervous system (CNS). Therefore, it has emerged as a candidate for targeted therapy of various neurological condition. Autism Spectrum Disorder (ASD) is a significant neurological disorder. Considering the importance of these mechanisms demonstrated by Nefastine1, The current study aimed to investigate the therapeutic potential and mechanisms of Nesfatin1 in a rat model of autism. This study evaluated the therapeutic potential of Nesfatin1 in a rodent model of autism induced by prenatal exposure to valproic acid (VPA). Pregnant Wistar rats received VPA on embryonic day 12.5, and male offspring were subsequently assessed for autism-like behaviors using a comprehensive battery of tests, including the three-chamber social interaction test, marble burying, shuttle box passive avoidance, and the elevated plus maze. Following behavioral testing, rats were euthanized, and blood samples were collected via transcardial perfusion. Serum oxytocin levels were measured, and hippocampal tissues were analyzed for inflammatory markers (IL-6, TNF-α) using ELISA. Additionally, total antioxidant capacity (TAC) and the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assessed. VPA-exposed rats exhibited significant social deficits, increased repetitive behaviors, and impaired cognitive performance, accompanied by heightened neuroinflammation and oxidative stress. Notably, treatment with Nesfatin1 markedly improved social engagement and preference, reduced anxiety and repetitive behaviors, and restored biochemical parameters toward normal levels. Results showed that possible therapeutic mechanism of Nefastin1 are by decreasing inflammation and reducing markers of oxidative stress, while concurrently elevating levels of oxytocin, in addition to the other unknown mechanisms.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"114 ","pages":"Article 102561"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}