Neuropeptides最新文献

{"title":"Catestatin-like immunoreactivity in the skin and related sensory ganglia","authors":"Victoria Stöckl ,&nbsp;Georgios Blatsios ,&nbsp;Christian Humpel ,&nbsp;Zenon Pidsudko ,&nbsp;Vincenzo Provitera ,&nbsp;Germar-Michael Pinggera ,&nbsp;Teresa Rauchegger ,&nbsp;Josef Troger","doi":"10.1016/j.npep.2025.102520","DOIUrl":"10.1016/j.npep.2025.102520","url":null,"abstract":"<div><h3>Aim</h3><div>The chromogranin A-derived peptide catestatin has previously been shown to be a constituent of the sensory innervation of the eye and dental pulp. The antibody used in these studies not only recognizes authentic catestatin but also larger molecules containing the sequence of catestatin. Therefore, the authors now aimed to explore whether there are additional molecular forms present in the rat skin, rat trigeminal ganglion and rat dorsal root ganglia apart from free catestatin.</div></div><div><h3>Methods</h3><div>Western blot analysis was performed in these tissues and and double immunofluorescence techniques in rat dorsal root ganglia.</div></div><div><h3>Results</h3><div>A very prominent band was found at approximately 50 kDa in the skin representing a middle-sized fragment containing the sequence of this peptide. Recently, the same result has been obtained in the dental pulp indicating that this fragment might represent a main molecular form in various other tissues of the body. It is likely of sensory nature since the band was also present of weaker intensity both in the trigeminal ganglion and dorsal root ganglia and since abundant cells expressed catestatin-like immunoreactivity in rat dorsal root ganglia. Another small sized fragment of weaker intensity was found in these tissues as well. No band was observed in the position of intact chromogranin A in the Western blot.</div></div><div><h3>Conclusion</h3><div>Chromogranin A is proteolytically processed in sensory ganglia to at least two fragments containing the sequence of catestatin which are then anterogradely transported to the skin and the 50 kDa fragment obviously becomes aggregated there in nerve endings.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102520"},"PeriodicalIF":2.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte Glucose-6-phosphorylase-Beta regulates ventromedial hypothalamic nucleus glucose counterregulatory neurotransmission and systemic hormone profiles","authors":"Karen P. Briski,&nbsp;Sushma Katakam,&nbsp;Subash Sapkota,&nbsp;Madhu Babu Pasula,&nbsp;Rami Shrestha,&nbsp;Rajesh Vadav","doi":"10.1016/j.npep.2025.102519","DOIUrl":"10.1016/j.npep.2025.102519","url":null,"abstract":"<div><div>Brain astrocytes generate free glucose at the conclusion of glycogenolysis or gluconeogenesis by glucose-6-phosphatase-beta (Glc-6-Pase-<em>β</em>) hydrolytic action. Astrocytes shape ventromedial hypothalamic nucleus (VMN) control of glucose counterregulation via lactate provision, yet possible effects of astrocyte endogenous glucose production are unknown. Current research investigated eu- and hypoglycemic patterns of VMN neuron counterregulatory neurotransmitter marker protein expression and counterregulatory hormone secretion following in vivo VMN astrocyte Glc-6-Pase-<em>β</em> gene-knockdown. Gene-silencing caused reductions in VMN astrocyte Glc-6-Pase-<em>β</em> protein expression and tissue glycogen and glucose content. Hypoglycemic suppression (dorsomedial VMN; VMNdm) or augmentation (ventrolateral VMN; VMNvl) of glycogen involves Glc-6-Pase-<em>β</em> –independent versus -dependent mechanisms, respectively. siRNA pretreatment reversed hypoglycemic down-regulation of VMNdm glucose levels and intensified up-regulated VMNvl glucose accumulation. Glc-6-Pase-<em>β</em> gene-knockdown correspondingly suppressed or enhanced baseline expression of glutamate decarboxylase_65/67 (GAD) and neuronal nitric oxide synthase (nNOS), protein markers for the counterregulation-inhibiting or -enhancing neurochemicals γ-aminobutyric acid and nitric oxide. Glc-6-Pase-<em>β</em> siRNA pretreatment did not alter hypoglycemic suppression of VMN GAD protein but reversed (VMNdm) or amplified (VMNvl) nNOS up-regulation. VMN Glc-6-Pase-<em>β</em> gene-silencing attenuated hypoglycemic patterns of corticosterone and growth hormone secretion and enhanced glucagon release. In summary, data provide unique evidence that VMN Glc-6-Pase-<em>β</em> activity affects glucose counterregulation. Outcomes document astrocyte Glc-6-Pase-<em>β</em> control of VMN glucose and glycogen accumulation as well as VMN neuron counterregulatory neurotransmission. Further research is warranted to identify Glc-6-Pase-<em>β</em> – mediated adjustments in astrocyte glucose metabolism that affect VMN GABAergic and/or nitrergic signaling within the brain glucostatic circuitry.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102519"},"PeriodicalIF":2.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679826","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":"Profile of cocaine and amphetamine regulated transcript peptide (CARTp) and Corticotropin-releasing factor (CRF) in the brain of Euphlyctis cyanophlyctis during puddle desiccation","authors":"Swapnil A. Shewale ,&nbsp;Sunil J. Koli ,&nbsp;Sneha Sagarkar ,&nbsp;Ameeta Ravikumar ,&nbsp;Shobha Bhargava","doi":"10.1016/j.npep.2025.102518","DOIUrl":"10.1016/j.npep.2025.102518","url":null,"abstract":"<div><div>During the post breeding season, anuran tadpoles are subjected to a wide range of environmental variables due to intermittent dry spells leading to pond desiccation. To avoid these harsh conditions, anurans accelerate rate of metamorphosis. In anurans, hypothalamic corticotropin-releasing factor (CRF) senses stress and activates metamorphosis via hypothamalo-pituitary- interenal/thyroid axis. Cocaine and amphetamine regulated transcript peptide (CARTp) is widely reported in the brains of vertebrates except reptiles. Role of CARTp along with CRF in mitigating the physiological effects of stress in mammals is well established. Therefore, we investigated effect of puddle desiccation on the CARTp and CRF peptide immunoreactivity in the brain of prometamorphic tadpoles of <em>Euphlyctis cyanophlyctis.</em> Animals in the naturally occurring desiccating puddle were fixed on field and the expression of CARTp and CRF were studied using immunohistochemistry. CARTp-immunoreactivity in entopeduncular nucleus (AEN and PEN), nucleus medialis septi (NMS) and hypothalamus (dHy and vHy) significantly increased in the prometamorphic tadpoles exposed to puddle desiccation as compared to controls. In preoptic area (POA) and Edinger Westphal nucleus (EW) significant increase in CARTp as well as CRF immunoreactive cells were observed in puddle desiccation group. Strong CRF immunoreactivity was observed in median eminence of stressed group. Puddle desiccation induced increase in the expression of CARTp and CRF peptide in the neuroendocrine axis may suggest their involvement in environmental stress induced accelerated metamorphosis. Moreover, elevated expression of CARTp but not CRF peptide in regions regulating energy homeostasis may indicate starvation due to scarcity of food or stress induced appetite suppression.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102518"},"PeriodicalIF":2.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670409","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":"Factors affecting the physical stability of peptide self-assembly in neurodegenerative disorders","authors":"Jahnu Saikia ,&nbsp;Mouli Sarkar ,&nbsp;Vibin Ramakrishnan","doi":"10.1016/j.npep.2025.102517","DOIUrl":"10.1016/j.npep.2025.102517","url":null,"abstract":"<div><div>Biological systems comprise of diverse biomolecules, including proteins, nucleic acids, lipids, and carbohydrates. Peptides, which are short chains of amino acids, exhibit unique properties when assembled to nano-level architectures. Self-assembling peptides possess a remarkable ability to organize into structured aggregates such as nanofibers, nanotubes, nanoribbons, and nanovesicles. These intricate structures are linked to neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Prion disease, Huntington's disease, and type II diabetes. Peptide nano assembly can be guided by external stimuli, such as temperature, pH, ultrasound, electric and magnetic fields. In this review, the discussion will be centred around the various factors that influence the self-assembly of peptides alongside therapeutic interventions that align with the fundamental principles of thermodynamics and kinetics to modulate the aggregation characteristics of peptide self-assembly.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102517"},"PeriodicalIF":2.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670407","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":"Molecular mechanisms of GDNF/GFRA1/RET and PI3K/AKT/ERK signaling interplay in neuroprotection: Therapeutic strategies for treating neurological disorders","authors":"MD Nasiruddin Khan ,&nbsp;Divya Choudhary ,&nbsp;Sidharth Mehan ,&nbsp;Zuber Khan ,&nbsp;Ghanshyam Das Gupta ,&nbsp;Acharan S. Narula","doi":"10.1016/j.npep.2025.102516","DOIUrl":"10.1016/j.npep.2025.102516","url":null,"abstract":"<div><div>Neurological disorders, marked by progressive neuronal degeneration, impair essential cognitive functions like memory and motor coordination… This manuscript explores the significant roles of glial cell line-derived neurotrophic factor (GDNF), its co-receptors (GFRA1), and the receptor tyrosine kinase (RET) in mediating neuronal survival and function in various neurodegenerative conditions. The interplay between pivotal signaling pathways—PI3K/AKT and ERK1/2—facilitated by GDNF/GFRA1/RET, is emphasized for its neuroprotective effects. Dysregulation of these pathways is implicated in neurodegenerative and neuropsychiatric processes, with overactivation of GSK3β contributing to neuronal damage and apoptosis. Experimental evidence supports that activation of the RET receptor by GDNF enhances AKT signaling, promoting cell survival by inhibiting apoptotic pathways—therapeutic strategies incorporating GDNF delivery and RET activation present promising neuronal protection and regeneration options. Furthermore, inhibition of GSK3β demonstrates potential in ameliorating tau-related pathologies, while small molecule RET agonists may enhance therapeutic efficacy. This review explores the knowledge of GDNF/GFRA1/RET and PI3K/AKT/ERK1/2 associated signaling cascades, underscoring their significance in neuroprotection and therapeutic targeting to combat neurodegenerative diseases. Emerging approaches such as gene therapy and small-molecule RET agonists may offer novel avenues for treatment, although challenges like targeted delivery across the blood-brain barrier remain pertinent.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102516"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637309","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":"Bioactive peptides as multipotent molecules bespoke and designed for Alzheimer's disease","authors":"Ana Mesias,&nbsp;Sandra Borges,&nbsp;Manuela Pintado,&nbsp;Sara Baptista-Silva","doi":"10.1016/j.npep.2025.102515","DOIUrl":"10.1016/j.npep.2025.102515","url":null,"abstract":"<div><div>In an increasingly aging world where neurodegenerative diseases (NDs) are exponentially rising, research into more effective and innovative treatments seems paramount. Bioactive peptides (BPs) emerge as promising compounds with revolutionary potential in the treatment of NDs, particularly in well-known conditions like Alzheimer's disease (AD). The biological potential of these compounds is primarily attributed to their drug development advantages such as enhanced penetration, low toxicity, and rapid clearance, as well as, their antioxidant, and anti-inflammatory properties bio-linked to the neuroprotective effect, able to attenuate the multifactorial pathologies of AD. BPs can be sourced from common dietary origins, like animals, plants, marine, and from emerging sources like edible insects. However, to isolate an active BP with beneficial biological effects it must first be released from its parent protein, followed by a synthesis-flow. While <em>in silico</em> approaches can predict a BP's potential bioactivity and structural characteristics, <em>in vitro</em>, cell-based, and <em>in vivo</em> assays should be conducted to ensure these properties. The blood-brain-barrier (BBB) microenvironment and permeability in health or disease state are key factors to consider since they can limit the ability of circulating therapeutical agents, including BPs, to reach the brain. This review focuses on the bioactivity properties of BPs from different dietary protein sources and explores their beneficial effect and neuroprotective activity in AD, unraveling new paths of treatment.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102515"},"PeriodicalIF":2.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563444","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":"Ginsenoside Rg1 improves autophagy dysfunction to ameliorate Alzheimer's disease via targeting FGR proto-oncogene","authors":"Qiankun Quan ,&nbsp;Xinxin Ma ,&nbsp;JianJun Feng ,&nbsp;Wanni Li ,&nbsp;Xi Li","doi":"10.1016/j.npep.2025.102514","DOIUrl":"10.1016/j.npep.2025.102514","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegeneration driven by beta-amyloid (Aβ) deposits in the brain involving autophagy dysfunction. Ginsenoside Rg1, a pharmacologically active compound found in ginseng, has possible therapeutic effects for AD. This study discovered that FGR proto-oncogene (FGR) was a therapeutic target of Rg1 in AD and it was possibly involved in autophagy. C57BL/6 J mice were injected with 5 μL (1 μg/mL) Aβ_1–42 in the right lateral ventricle to establish an AD model. AD mouse hippocampus had high FGR expression. Intragastrically administered Rg1 (40 mg/kg) decreased FGR protein levels in AD mice's hippocampus and improved memory function in AD mice. Both sides of the mice hippocampal fissure were administered with 2 μL lentiviral particles (1 × 10⁷ TU) containing FGR overexpression plasmids. FGR overexpression rendered Rg1 ineffectual in restoring memory function and reducing hippocampal neuron damage. We injected 2 μL lentiviral particles (1 × 10⁷ TU) containing short hairpin RNA plasmids targeting FGR to the mice hippocampal fissures. FGR knockdown improved spatial memory function of AD mice, reduced hippocampal neuron apoptosis, and prevented Aβ accumulation. HT22 cells were transfected with small interfering RNA targeting FGR. FGR knockdown increased the viability of Aβ_1–42 treated HT22 cells. BACE1 and LC3II/I protein levels were decreased and p62 and SIRT1 were increased in AD mice and cells with FGR knockdown. LC3 was down-regulated after inhibiting FGR expression in Aβ_1–42 treated hippocampal neurons. In conclusion, Rg1 exerts anti-AD functions by targeting FGR and downregulating its expression.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102514"},"PeriodicalIF":2.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592338","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":"BDNF-mediated depressor response by direct baroreceptor activation benefits for prevention and control of hypertension in high-latitude cold region","authors":"Yan Feng ,&nbsp;Lei Yin ,&nbsp;Ying Li","doi":"10.1016/j.npep.2025.102506","DOIUrl":"10.1016/j.npep.2025.102506","url":null,"abstract":"<div><div>Brian-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling impacts on neuronal and cardiovascular physiology; however, its role in neurocontrol of circulation via baroreflex afferent pathway is largely unknown. Gene and protein expression of BDNF/TrkB were detected in the nodose (NG) and nucleus of tractus solitary (NTS) and expression levels were higher in male compared with female rats, which is relevant well with the blood pressure (BP, males &gt; females in average). Microinjection of BDNF into NG dose-dependently reduced BP and this reduction was more dramatic in shamed control vs. renovascular hypertension (RVH) model rats, which partially inhibited in the presence of TrkB inhibitor K252a, indicating that BDNF-TrkB tends to lower BP under physiological and hypertensive conditions due presumably to a negative feed-back control by BP or compensatory mechanism. To answer this question, expression profiles for BDNF-TrkB were tested in the tissue of NG and NTS collected from RVH model rats. Consistently, the expression of both BDNF-TrkB were significantly up-regulated in RVH model alone with the elevation of BP. Taken these data together, our observation provides direct evidence showing the fundamental role of BDNF-TrkB signaling in autonomic control of BP regulation through baroreflex afferent function, potentially dominant role of BDNF-TrkB-mediated BP reduction in vivo baroreceptor activation due to distinct cellular mechanism compared with their role in the NTS, which extends our understanding of activity-dependent or compensatory mechanism of BDNF-TrkB in response to BP change, and sheds new light of BDNF-TrkB as potential target in prevention and control of hypertension in cold-region.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"111 ","pages":"Article 102506"},"PeriodicalIF":2.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534406","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":"Mechanistic role of proteins and peptides in Management of Neurodegenerative Disorders","authors":"Saumya Awasthi ,&nbsp;Prafulla Chandra Tiwari ,&nbsp;Srishti Awasthi ,&nbsp;Arpit Dwivedi ,&nbsp;Shikha Srivastava","doi":"10.1016/j.npep.2025.102505","DOIUrl":"10.1016/j.npep.2025.102505","url":null,"abstract":"<div><div>Proteins and peptides have emerged as significant contributors in the management of neurodegenerative disorders due to their diverse biological functions. These biomolecules influence various cellular processes, including cellular repair, inflammation reduction, and neuronal survival, which are crucial for mitigating the effects of diseases such as Alzheimer's, Parkinson's, and Amyotrophic Lateral Sclerosis (ALS). By interacting with specific cellular receptors, proteins and peptides like neurotrophic factors, cytokines, and enzyme inhibitors promote neurogenesis, reduce oxidative stress, and enhance synaptic plasticity. Nevertheless, till certain limitations and challenges do exist to deliver these fragile therapeutic bioactives. Moreover, targeted delivery systems, such as nanoparticles and biomolecular carriers, are being developed to improve the bioavailability and specificity of these protein-based therapeutics, ensuring efficient crossing of the blood-brain barrier. This review explores the mechanistic pathways through which these biomolecules act, emphasizing their potential to modify disease progression and improve the quality of life in patients with neurodegenerative conditions. Overall, proteins and peptides are not only seen as promising therapeutic agents but also as foundational tools in advancing personalized medicine in the field of neurodegenerative disorders.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"110 ","pages":"Article 102505"},"PeriodicalIF":2.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420506","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":"Modulation of temporoammonic-CA1 synapses by neuropeptide Y is through Y1 receptors in mice","authors":"Mariana A. Cortes ,&nbsp;Aundrea F. Bartley ,&nbsp;Qin Li ,&nbsp;Taylor R. Davis ,&nbsp;Stephen E. Cunningham ,&nbsp;Mary Anne Garner ,&nbsp;Patric J. Perez ,&nbsp;Adela C. Harvey ,&nbsp;Alecia K. Gross ,&nbsp;Lynn E. Dobrunz","doi":"10.1016/j.npep.2025.102504","DOIUrl":"10.1016/j.npep.2025.102504","url":null,"abstract":"<div><div>Reduced levels of neuropeptide Y (NPY), an abundant neuromodulator in the brain, are linked to multiple neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). The CA1 region of hippocampus is important for anxiety regulation and highly expresses NPY. Injecting NPY into CA1 is anxiolytic and alleviates behavioral symptoms in a model of traumatic stress; these anxiolytic effects are blocked by a Y1 receptor antagonist. However the location of Y1Rs that mediate NPY's anxiolytic effects in CA1 remains unclear. CA1 receives inputs from entorhinal cortex through the temporammonic pathway (TA), which is important for fear learning and sensitive to stress. Our lab previously showed that NPY reduces TA-evoked synaptic responses, however, the subtype of NPY receptor mediating this reduction is unknown. Here we demonstrate that in mice both exogenous (bath-applied) and endogenously-released NPY act through Y1 receptors in the TA pathway. This is the first demonstration of Y1 receptor-mediated effect on synaptic function in CA1. Interestingly, chronic overexpression of NPY (in NPY-expressing interneurons) impairs the sensitivity of the TA-evoked synaptic response to a Y1 receptor agonist. However, the long-known NPY Y2 receptor-mediated effect on the Schaffer collateral (SC) pathway is unaffected by NPY overexpression. Therefore, NPY can have a pathway-specific impact on synaptic transmission in CA1 based on the differential expression of NPY receptors and their response to overexpression of NPY. Our results demonstrating that NPY acts at Y1 receptors in the TA pathway are consistent with the idea that the TA pathway underlies the anxiolytic effects of NPY in CA1.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"110 ","pages":"Article 102504"},"PeriodicalIF":2.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402962","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}