Neuropeptides最新文献

{"title":"The activity of cholinergic neurons in the basal forebrain interferes with anesthesia-arousal process of propofol","authors":"Cai-hua Feng ,&nbsp;Xiao-Nan Du ,&nbsp;Zhi Wang ,&nbsp;Ting Wu ,&nbsp;Li-Na Zhang","doi":"10.1016/j.npep.2024.102449","DOIUrl":"10.1016/j.npep.2024.102449","url":null,"abstract":"<div><p>Previous research has demonstrated that basal forebrain (BF) regulates arousal during propofol anesthesia. However, as the BF comprises cholinergic neurons alongside two other types of neurons, the specific role of cholinergic neurons has not been definitively elucidated. In our study, calcium signal imaging was utilized to monitor the real-time activities of cholinergic neurons in the BF during propofol anesthesia. Additionally, we selectively stimulated these neurons to investigate EEG and behavioral responses during propofol anesthesia. Furthermore, we specifically lesioned cholinergic neurons in the BF to investigate the sensitivity to propofol and the induction time. The results revealed that propofol suppressed calcium signals of cholinergic neurons within the BF following intraperitoneal injection. Notably, upon recovery of the righting reflex, the calcium signals partially recovered. Spectral analysis of the EEG elucidated that optical stimulation of cholinergic neurons led to a decrease in δ power underlie propofol anesthesia. Conversely, depletion of cholinergic neurons in the BF enhanced sensitivity to propofol and shortened the induction time. These findings clarify the role of cholinergic neurons in the anesthesia-arousal process, as well as the depth and the sensitivity of propofol anesthesia.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"107 ","pages":"Article 102449"},"PeriodicalIF":2.5,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143417924000489/pdfft?md5=2954f2a19297b9c76679046ebce2f747&pid=1-s2.0-S0143417924000489-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141409489","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":"MP-13, a novel chimeric peptide of morphiceptin and pepcan-9, produces potent antinociception with limited side effects","authors":"Chenxi Mei ,&nbsp;Jing Zhang ,&nbsp;Zhanyu Niu ,&nbsp;Jerine Peter Simon ,&nbsp;Tong Yang ,&nbsp;Mingmin Huang ,&nbsp;Zhonghua Zhang ,&nbsp;Lanxia Zhou ,&nbsp;Shouliang Dong","doi":"10.1016/j.npep.2024.102440","DOIUrl":"10.1016/j.npep.2024.102440","url":null,"abstract":"<div><p>Pharmacological investigations have substantiated the potential of bifunctional opioid/cannabinoid agonists in delivering potent analgesia while minimizing adverse reactions. Peptide modulators of cannabinoid receptors, known as pepcans, have been investigated before. In this study, we designed a series of chimeric peptides based on pepcans and morphiceptin (YPFP-NH₂). Here, we combined injections of pepcans and morphiceptin to investigate the combination treatment of opioids and cannabis and compared the analgesic effect with chimeric compounds. Subsequently, we employed computational docking to screen the compounds against opioid and cannabinoid receptors, along with an acute pain model, to identify the most promising peptide. Among these peptides, MP-13, a morphiceptin and pepcan-9 (PVNFKLLSH) construct, exhibited superior supraspinal analgesic efficacy in the tail-flick test, with an ED₅₀ value at 1.43 nmol/mouse, outperforming its parent peptides and other chimeric analogs. Additionally, MP-13 displayed potent analgesic activity mediated by mu-opioid receptor (MOR), delta-opioid receptor (DOR), and cannabinoid type 1 (CB1) receptor pathways. Furthermore, MP-13 did not induce psychological dependence and gastrointestinal motility inhibition at the effective analgesic doses, and it maintained non-tolerance-forming antinociception throughout a 7-day treatment regimen, with an unaltered count of microglial cells in the periaqueductal gray region, supporting this observation. Moreover, intracerebroventricular administration of MP-13 demonstrated dose-dependent antinociception in murine models of neuropathic, inflammatory, and visceral pain. Our findings provide promising insights for the development of opioid/cannabinoid peptide agonists, addressing a crucial gap in the field and holding significant potential for future research and development.</p></div><div><h3>Perspective</h3><p>This article offers insights into the combination treatment of pepcans with morphiceptin. Among the chimeric peptides, MP-13 exhibited potent analgesic effects in a series of preclinical pain models with a favorable side-effect profile.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"107 ","pages":"Article 102440"},"PeriodicalIF":2.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321313","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":"Chronic unpredictable stress (CUS) reduced phoenixin expression, induced abnormal sperm and testis morphology in male rats","authors":"Zahra Isnaini Mohamed,&nbsp;Mageswary Sivalingam,&nbsp;Ammu K. Radhakrishnan,&nbsp;Faizul Jaafar,&nbsp;Syafiq Asnawi Zainal Abidin","doi":"10.1016/j.npep.2024.102447","DOIUrl":"https://doi.org/10.1016/j.npep.2024.102447","url":null,"abstract":"<div><p>Chronic stress caused by prolonged emotional pressure can lead to various physiological issues, including reproductive dysfunction. Although reproductive problems can also induce chronic stress, the impact of chronic stress-induced reproductive dysfunction remains contentious. This study investigates the effects of chronic unpredictable stress (CUS) on reproductive neuropeptides, sperm quality, and testicular morphology. Sixteen twelve-week-old Sprague Dawley rats were divided into two groups: a non-stress control group and a CUS-induced group. The CUS regimen involved various stressors over 28 days, with both groups undergoing behavioural assessments through sucrose-preference and forced-swim tests. Hypothalamic gene expression levels of <em>CRH, PNX, GPR173, kisspeptin, GnRH, GnIH</em>, and <em>spexin</em> neuropeptides were measured via qPCR, while plasma cortisol, luteinizing hormone (LH), and testosterone concentrations were quantified using ELISA. Seminal fluid and testis samples were collected for sperm analysis and histopathological evaluation, respectively. Results showed altered behaviours in CUS-induced rats, reflecting stress impacts. Hypothalamic <em>corticotropin-releasing hormone</em> (<em>CRH</em>) expression and plasma cortisol levels were significantly higher in CUS-induced rats compared to controls (<em>p</em> &lt; 0.05). Conversely, <em>phoenixin</em> (<em>PNX</em>) expression decreased in the CUS group (p &lt; 0.05), while <em>kisspeptin, spexin</em>, and <em>gonadotropin-inhibitory hormone (GnIH)</em> levels showed no significant differences between groups. Despite a significant increase in <em>GnRH</em> expression (<em>p</em> &lt; 0.05), plasma LH and testosterone concentrations were significantly lower (p &lt; 0.05) in CUS-induced rats. Histopathological analysis revealed abnormal testis morphology in CUS-induced rats, including disrupted architecture, visible interstitial spaces between seminiferous tubules, and absence of spermatogenesis. In conclusion, CUS affects reproductive function by modulating <em>PNX</em> and <em>GnRH</em> expression, influencing cortisol levels, and subsequently reducing plasma LH and testosterone concentrations. This study highlights the complex interplay between chronic stress and reproductive health, emphasizing the significant impact of stress on reproductive functions.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"107 ","pages":"Article 102447"},"PeriodicalIF":2.9,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143417924000465/pdfft?md5=16f41a83157ab3f756fdb1ce7389ed12&pid=1-s2.0-S0143417924000465-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141313689","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":"Effects of an herbal adaptogen feed-additive on feeding-related hypothalamic neuropeptides in chronic cyclic heat-stressed chickens","authors":"Elizabeth S. Greene,&nbsp;Maryam Afkhami Ardakani,&nbsp;Sami Dridi","doi":"10.1016/j.npep.2024.102439","DOIUrl":"10.1016/j.npep.2024.102439","url":null,"abstract":"<div><p>Heat stress (HS) is a global serious issue in the poultry industry with numerous adverse effects, including increased stress, depressed feed intake (FI), poor growth performance and higher mortality. Herbal adaptogens, plant extracts considered as stress response modifiers, are metabolic regulators that improve an organism's ability to adapt to and minimize damage from environmental stresses. Previously, we showed that herbal adaptogen supplementation increased FI and body weight (BW) of broiler (meat-type) chickens reared under HS conditions. Therefore, we hypothesized that these effects may be mediated through modulation of hypothalamic feeding-related neuropeptides. Male Cobb 500 chicks were reared in 12 environmental chambers with three diets: a corn-soybean-based diet (C) and two herbal adaptogen-supplemented diets at 500 g/1000 kg (NR-PHY-500) and 1 kg/1000 kg (NR-PHY-1000). Broilers in 9 chambers were exposed to chronic cyclic HS (35 °C for 8 h/day) from d29 to d42, while 3 chambers were maintained at 24 °C (thermoneutral, TN) for all 42 days. Hypothalamic samples were collected on d42 from each group, both before the onset of HS (Pre-HS) that day and after 3 h of HS (post-HS). Hypothalamic expressions of neuropeptide Y (NPY) receptors Y4 and Y7, Corticotropin-releasing hormone (CRH), orexin receptor 1 (ORXR1), melanocortin receptors (MC1R, MC4R, and MC5R), visfatin and neurosecretory protein GL (NPGL) genes were significantly upregulated by adaptogen supplementation. The hypothalamic expression of MC2R was affect by period, with a significant upregulation during post-HS phase. There was a significant period by treatment interaction for hypothalamic orexin and adiponectin expression. The hypothalamic expression of NPY, Y1, Y2, Y5, Y6, proopiomelanocortin (POMC), cocaine and amphetamine regulated transcript (CART), agouti-related peptide (AgRP), ORXR2, AdipR1/2, MC3R, and ghrelin was not affected by diet supplementation nor by HS exposure.</p><p>In conclusion, these findings suggest that in-feed supplementation of adaptogen might improve FI and growth via modulation of hypothalamic feeding-related neuropeptides in heat-stressed broilers.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"106 ","pages":"Article 102439"},"PeriodicalIF":2.9,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094049","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 phenotypic changes of Schwann cells promote the functional repair of nerve injury","authors":"Shufen Liao ,&nbsp;Yan Chen ,&nbsp;Yin Luo ,&nbsp;Mengqi Zhang ,&nbsp;Jun Min","doi":"10.1016/j.npep.2024.102438","DOIUrl":"10.1016/j.npep.2024.102438","url":null,"abstract":"<div><p>Functional recovery after nerve injury is a significant challenge due to the complex nature of nerve injury repair and the non-regeneration of neurons. Schwann cells (SCs), play a crucial role in the nerve injury repair process because of their high plasticity, secretion, and migration abilities. Upon nerve injury, SCs undergo a phenotypic change and redifferentiate into a repair phenotype, which helps in healing by recruiting phagocytes, removing myelin fragments, promoting axon regeneration, and facilitating myelin formation. However, the repair phenotype can be unstable, limiting the effectiveness of the repair. Recent research has found that transplantation of SCs can be an effective treatment option, therefore, it is essential to comprehend the phenotypic changes of SCs and clarify the related mechanisms to develop the transplantation therapy further.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"106 ","pages":"Article 102438"},"PeriodicalIF":2.9,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945472","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":"A Na+ channel receptor of FMRFamide in the cephalopod Sepiella japonica: Identification, characterisation, and expression profiling during different stages of gonadal development","authors":"Hui-Min Cao ,&nbsp;Jun-Hong Wu ,&nbsp;Shuang Li,&nbsp;Xu Zhou,&nbsp;Li-Bing Zheng,&nbsp;Chang-Feng Chi","doi":"10.1016/j.npep.2024.102437","DOIUrl":"10.1016/j.npep.2024.102437","url":null,"abstract":"<div><p>FMRFamide, a member of the neuropeptide family, is involved in numerous physiological processes. FMRFamide-activated sodium channels (FaNaCs) are a family of non-voltage-gated, amiloride-sensitive, Na⁺-selective channels triggered by the neuropeptide FMRFamide. In the present study, the full-length cDNA of the FaNaC receptor of <em>Sepiella japonica</em> (<em>SjFaNaC</em>) was cloned. The cDNA of <em>SjFaNaC</em> was 3004 bp long with an open reading frame (ORF) of 1812 bp, encoding 603 amino acid residues with no signal peptide at the N-terminus. Sequence analysis indicated that <em>Sj</em>FaNaC shared a high identity with other cephalopods FaNaCs and formed a sister clade with bivalves. The protein structure was predicted using SWISS-MODEL with <em>Ac</em>FaNaC as the template. Quantitative real-time PCR (qRT-PCR) revealed that <em>SjFaNaC</em> transcripts were highly expressed in both female and male reproductive organs, as well as in the optic lobe and brain of the central nervous system (CNS). Results of <em>in situ</em> hybridisation (ISH) showed that <em>SjFaNaC</em> mRNA was mainly distributed in the medulla and deep retina of the optic lobe and in both the supraesophageal and subesophageal masses of the brain. Subcellular localisation indicated that the <em>Sj</em>FaNaC protein was localised intracellularly and on the cell surface of HEK293T cells. In summary, these findings may lay the foundation for future exploration of the functions of <em>Sj</em>FaNaC in cephalopods.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"106 ","pages":"Article 102437"},"PeriodicalIF":2.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141026726","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":"V-ATPase B2 promotes microglial phagocytosis of myelin debris by inactivating the MAPK signaling pathway","authors":"Yao Li ,&nbsp;Yuhan Dai ,&nbsp;Lan Chu","doi":"10.1016/j.npep.2024.102436","DOIUrl":"https://doi.org/10.1016/j.npep.2024.102436","url":null,"abstract":"<div><p>Microglial phagocytosis of myelin debris is a crucial process for promoting myelin regeneration in conditions such as multiple sclerosis (MS). Vacuolar-ATPase B2 (V-ATPase B2) has been implicated in various cellular processes, but its role in microglial phagocytosis and its potential impact on MS-related responses remain unclear. In this study, we employed BV-2 murine microglial cells to investigate the influence of V-ATPase B2 on the phagocytosis of myelin debris by microglia. The results revealed that V-ATPase B2 expression increased in response to myelin debris exposure. Overexpression of V-ATPase B2 significantly enhanced BV-2 phagocytosis of myelin debris. Additionally, V-ATPase B2 overexpression shifted microglial polarization towards an anti-inflammatory M2 phenotype, coupled with decreased lysosomal pH and enhanced lysosome degradation capacity. Moreover, endoplasmic reticulum (ER) stress inhibitor, 4-PBA, reversed the effects of V-ATPase B2 silencing on ER stress, M2 polarization, and lysosomal degradation of BV-2 cells. The MAPK pathway was inhibited upon V-ATPase B2 overexpression, contributing to heightened myelin debris clearance by BV-2 cells. Notably, MAPK pathway inhibition partially attenuated the inhibitory effects of V-ATPase B2 knockdown on myelin debris clearance. In conclusion, our findings reveal a pivotal role for V-ATPase B2 in promoting microglial phagocytosis of myelin debris by regulating microglial polarization and lysosomal function via the MAPK signaling pathway, suggesting that targeting V-ATPase B2 may hold therapeutic potential for enhancing myelin debris clearance and modulating microglial responses in MS and related neuroinflammatory disorders.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"106 ","pages":"Article 102436"},"PeriodicalIF":2.9,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905787","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":"Fat mass and obesity-associated protein regulates RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion","authors":"Yanqing Wang ,&nbsp;Zimei Wu ,&nbsp;Yuyang He ,&nbsp;Xiaoying Zeng ,&nbsp;Zijuan Gu ,&nbsp;Xianxi Zhou ,&nbsp;Wenwen Si ,&nbsp;Dongfeng Chen","doi":"10.1016/j.npep.2024.102428","DOIUrl":"https://doi.org/10.1016/j.npep.2024.102428","url":null,"abstract":"<div><p>RNA methylation can epigenetically regulate learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of Vascular dementia (VD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus in models of VD. Through prediction and dual-luciferase reporters validation studies, we observed that miRNA-711 was upregulated after VD and could bind to the 3′-untranslated region of FTO mRNA and regulate its expression in vitro. Methylated RNA immunoprecipitation (MeRIP)-qPCR assay and functional study confirmed that Syn1 was an important target gene of FTO. This suggests that FTO is an important regulator of Syn1. FTO upregulation by inhibition of miR-711 in the hippocampus relieves synaptic association protein and synapse deterioration in vivo, whereas FTO downregulation by miR-711 agomir in the hippocampus leads to aggravate the synapse deterioration. FTO upregulation by inhibition of miR-711 relieves cognitive impairment of rats VD model, whereas FTO downregulation by miR-711 deteriorate cognitive impairment. Our findings suggest that FTO is a regulator of a mechanism underlying RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"105 ","pages":"Article 102428"},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351831","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":"Pharmacological profile of agmatine: An in-depth overview","authors":"Hira Rafi ,&nbsp;Hamna Rafiq ,&nbsp;Muhammad Farhan","doi":"10.1016/j.npep.2024.102429","DOIUrl":"https://doi.org/10.1016/j.npep.2024.102429","url":null,"abstract":"<div><p>Agmatine, a naturally occurring polyamine derived from arginine via arginine decarboxylase, has been shown to play multifaceted roles in the mammalian body, impacting a wide range of physiological and pathological processes. This comprehensive review delineates the significant insights into agmatine's pharmacological profile, emphasizing its structure and metabolism, neurotransmission and regulation, and pharmacokinetics and function. Agmatine's biosynthesis is highly conserved across species, highlighting its fundamental role in cellular functions. In the brain, comparable to established neurotransmitters, agmatine acts as a neuromodulator, influencing the regulation, metabolism, and reabsorption of neurotransmitters that are key to mood disorders, learning, cognition, and the management of anxiety and depression. Beyond its neuromodulatory functions, agmatine exhibits protective effects across various cellular and systemic contexts, including neuroprotection, nephroprotection, cardioprotection, and cytoprotection, suggesting a broad therapeutic potential.</p><p>The review explores agmatine's interaction with multiple receptor systems, including NMDA, α2-adrenoceptors, and imidazoline receptors, elucidating its role in enhancing cell viability, neuronal protection, and synaptic plasticity. Such interactions underpin agmatine's potential in treating neurological diseases and mood disorders, among other conditions. Furthermore, agmatine's pharmacokinetics, including its absorption, distribution, metabolism, and excretion, are discussed, underlining the complexity of its action and the potential for therapeutic application. The safety and efficacy of agmatine supplementation, demonstrated through various animal and human studies, affirm its potential as a beneficial therapeutic agent.</p><p>Conclusively, the diverse physiological and therapeutic effects of agmatine, spanning neurotransmission, protection against cellular damage, and modulation of various receptor pathways, position it as a promising candidate for further research and clinical application. This review underscores the imperative for continued exploration into agmatine's mechanisms of action and its potential in pharmacology and medicine, promising advances in the treatment of numerous conditions.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"105 ","pages":"Article 102429"},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140543763","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":"Neurocircuitry underlying the actions of glucagon-like peptide 1 and peptide YY3–36 in the suppression of food, drug-seeking, and anxiogenesis","authors":"Yasmina Dumiaty,&nbsp;Brett M. Underwood,&nbsp;Jenny Phy-Lim,&nbsp;Melissa J. Chee","doi":"10.1016/j.npep.2024.102427","DOIUrl":"https://doi.org/10.1016/j.npep.2024.102427","url":null,"abstract":"<div><p>Obesity is a critical health condition worldwide that increases the risks of comorbid chronic diseases, but it can be managed with weight loss. However, conventional interventions relying on diet and exercise are inadequate for achieving and maintaining weight loss, thus there is significant market interest for pharmaceutical anti-obesity agents. For decades, receptor agonists for the gut peptide glucagon-like peptide 1 (GLP-1) featured prominently in anti-obesity medications by suppressing appetite and food reward to elicit rapid weight loss. As the neurocircuitry underlying food motivation overlaps with that for drugs of abuse, GLP-1 receptor agonism has also been shown to decrease substance use and relapse, thus its therapeutic potential may extend beyond weight management to treat addictions. However, as prolonged use of anti-obesity drugs may increase the risk of mood-related disorders like anxiety and depression, and individuals taking GLP-1-based medication commonly report feeling demotivated, the long-term safety of such drugs is an ongoing concern. Interestingly, current research now focuses on dual agonist approaches that include GLP-1 receptor agonism to enable synergistic effects on weight loss or associated functions. GLP-1 is secreted from the same intestinal cells as the anorectic gut peptide, Peptide YY₃_–₃₆ (PYY₃_–₃₆), thus this review assessed the therapeutic potential and underlying neural circuits targeted by PYY₃_–₃₆ when administered independently or in combination with GLP-1 to curb the appetite for food or drugs of abuse like opiates, alcohol, and nicotine. Additionally, we also reviewed animal and human studies to assess the impact, if any, for GLP-1 and/or PYY₃_–₃₆ on mood-related behaviors in relation to anxiety and depression. As dual agonists targeting GLP-1 and PYY₃_–₃₆ may produce synergistic effects, they can be effective at lower doses and offer an alternative approach for therapeutic benefits while mitigating undesirable side effects.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"105 ","pages":"Article 102427"},"PeriodicalIF":2.9,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S014341792400026X/pdfft?md5=e5b0a1bb8019f231bc08035df63b0fa1&pid=1-s2.0-S014341792400026X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140345284","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}