Neuropeptides最新文献

{"title":"Neurobiochemical characteristics of arginine-rich peptides explain their potential therapeutic efficacy in neurodegenerative diseases","authors":"Sedigheh Eskandari ,&nbsp;Ameneh Rezayof ,&nbsp;S. Mohsen Asghari ,&nbsp;Shiva Hashemizadeh","doi":"10.1016/j.npep.2023.102356","DOIUrl":"10.1016/j.npep.2023.102356","url":null,"abstract":"<div><p><span>Neurodegenerative diseases<span><span>, including Alzheimer̕ s disease (AD), Parkinson̕ s disease (PD), Huntington̕ s disease (HD), and Amyotrophic Lateral Sclerosis (ALS) require special attention to find new potential </span>treatment<span> methods. This review aims to summarize the current knowledge of the relationship between the biochemical properties of arginine-rich peptides (ARPs) and their neuroprotective effects to deal with the harmful effects of risk factors. It seems that ARPs have portrayed a promising and fantastic landscape for treating neurodegeneration-associated disorders. With multimodal mechanisms of action, ARPs play various unprecedented roles, including as the novel delivery platforms for entering the </span></span></span>central nervous system<span><span><span> (CNS), the potent antagonists for calcium influx<span>, the invader molecules for targeting mitochondria, and the protein stabilizers. Interestingly, these peptides inhibit the proteolytic enzymes<span> and block protein aggregation to induce pro-survival signaling pathways. ARPs also serve as the scavengers of toxic molecules and the reducers of </span></span></span>oxidative stress<span><span> agents. They also have anti-inflammatory, antimicrobial, and anti-cancer properties. Moreover, by providing an efficient </span>nucleic acid delivery system, ARPs can play an essential role in developing various fields, including gene vaccines, gene therapy, gene editing, and imaging. ARP agents and ARP/cargo therapeutics can be raised as an emergent class of neurotherapeutics for </span></span>neurodegeneration<span>. Part of the aim of this review is to present recent advances in treating neurodegenerative diseases using ARPs as an emerging and powerful therapeutic tool. The applications and progress of ARPs-based nucleic acid delivery systems have also been discussed to highlight their usefulness as a broad-acting class of drugs.</span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"101 ","pages":"Article 102356"},"PeriodicalIF":2.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168557","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":"Effects of voluntary, and forced exercises on neurotrophic factors and cognitive function in animal models of Parkinson's disease","authors":"Forouzan Rafie ,&nbsp;Mohammad Amin Rajizadeh ,&nbsp;Mehdi Shahbazi ,&nbsp;Mohammad Pourranjbar ,&nbsp;Amir H. Nekouei ,&nbsp;Vahid Sheibani ,&nbsp;Daniel Peterson","doi":"10.1016/j.npep.2023.102357","DOIUrl":"10.1016/j.npep.2023.102357","url":null,"abstract":"<div><h3>Background</h3><p><span>Parkinson's disease<span> (PD) is one of the most common neurodegenerative diseases in the elderly. </span></span>Cognitive dysfunction<span> represents a common and challenging non-motor symptom for people with Parkinson's disease. The number of neurotrophic proteins in the brain is critical in neurodegenerative diseases such as Parkinson's. This research aims to compare the effects of two types of exercise, forced and voluntary, on spatial memory and learning and neurochemical factors (CDNF and BDNF).</span></p></div><div><h3>Methods</h3><p>In this research, 60 male rats were randomly divided into six groups (<em>n</em><span><span> = 10): the control (CTL) group without exercise, the Parkinson's groups without and with forced (FE) and voluntary (VE) exercises, and the sham groups (with voluntary and forced exercise). The animals in the forced exercise group were placed on the treadmill for four weeks (five days a week). At the same time, voluntary exercise training groups were placed in a special cage equipped with a rotating wheel. At the end of 4 weeks, learning and spatial memory were evaluated with the Morris water maze<span> test. BDNF and CDNF protein levels in the </span></span>hippocampus<span> were measured by the ELISA method.</span></span></p></div><div><h3>Results</h3><p>The results showed that although the PD group without exercise was at a significantly lower level than other groups in terms of cognitive function and neurochemical factors, both types of exercise, could improve these problems.</p></div><div><h3>Conclusion</h3><p>According to our results, 4 weeks of voluntary and forced exercises were all found to reverse the cognitive impairments of PD rats.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"101 ","pages":"Article 102357"},"PeriodicalIF":2.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10537783","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":"Improvement of actin dynamics and cognitive impairment in diabetes through troxerutin-mediated downregulation of TRPM7/CaN/cofilin","authors":"Hongyan Li ,&nbsp;Jie Li ,&nbsp;Pin Wang ,&nbsp;Fang Yuan ,&nbsp;Songyun Zhang","doi":"10.1016/j.npep.2023.102381","DOIUrl":"10.1016/j.npep.2023.102381","url":null,"abstract":"<div><p><span><span><span>Diabetic cognitive impairment is a central nervous </span>complication of diabetes mellitus. Its specific pathogenesis is unknown, and no effective </span>treatment strategy is currently available. An imbalance in actin dynamics is an important mechanism underlying cognitive impairment. </span>Transient receptor potential channel 7<span><span> (TRPM7) mediates actin dynamics imbalance through calcineurin (CaN) and </span>cofilin<span> cascades involved in various neurodegenerative diseases<span><span>. We previously demonstrated that TRPM7<span> expression is increased in diabetic cognitive impairment, and troxerutin has been shown to ameliorate diabetic cognitive impairment. However, the relationship between troxerutin and TRPM7 remains unclear. In this study, we hypothesize that troxerutin may improve diabetic cognitive impairment by enhancing actin dynamics through downregulation of the TRPM7/CaN/cofilin pathway. To test this hypothesis, we divided db/m and db/db mice into the following groups: normal control group (NC), normal + troxerutin group (NT), diabetic group (DM), diabetic + troxerutin group (DT) and diabetic + troxerutin + </span></span>bradykinin<span><span> group (DTB). The results showed that diabetic mice exhibited cognitive impairment at 17 weeks of age, TRPM7, CaN, cofilin and G-actin were highly expressed in the CA1 region of </span>hippocampus, while p-cofilin and F-actin expression decreased. Furthermore, hippocampal neuronal cellsshowed varying degrees of damage. The length of synaptic active zone, the width of synaptic cleft, and the number of synapses per high-power field were decreased. Troxerutin intervention alleviated these manifestations in the DT group; however, the effect of troxerutin was weakened in the DTB group. In conclusion, our findings suggest that diabetes leads to cognitive impairment, activation of the TRPM7/CaN/cofilin pathway, actin dynamics imbalance, and destruction of hippocampal neuronal cells and synapses. Troxerutin can downregulate TRPM7/CaN/cofilin, improve actin dynamics imbalance, and ameliorate cognitive impairment in diabetic mice. This study provides a new avenue for exploring and treating cognitive impairment in diabetes.</span></span></span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102381"},"PeriodicalIF":2.9,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41207243","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":"Neonatal oxytocin treatment alters levels of precursor and mature BDNF forms and modifies the expression of neuronal markers in the male rat hippocampus","authors":"Stanislava Bukatova ,&nbsp;Alexandra Reichova ,&nbsp;Zuzana Bacova ,&nbsp;Jan Bakos","doi":"10.1016/j.npep.2023.102384","DOIUrl":"10.1016/j.npep.2023.102384","url":null,"abstract":"<div><p><span><span><span><span>Neuropeptide oxytocin appears to be involved in the formation of hippocampal circuitry, underlying social memory and </span>behaviour. Recent studies point to the role of oxytocin in regulating the levels of </span>nerve growth factors that could influence </span>neurogenesis<span> and neuritogenesis<span> during the early stages of brain development. Therefore, the aim of the present study was to evaluate the early developmental effect of oxytocin administration (P2 and P3 days, two doses, 5 μg/pup, s.c.) on the expression of 1) brain-derived neurotrophic factor (BDNF) isoforms<span><span> and 2) GABAergic and glutamatergic<span> markers in the male rat hippocampus. Furthermore, we evaluated the branching of dendrites of primary hippocampal GABAergic and glutamatergic neurons in response to incubation with oxytocin (1 μM). We found that after oxytocin administration, levels of proBDNF increased on P5 and mBDNF on P7 in the </span></span>CA1 hippocampal region. We also observed a reduction in the expression of glutamatergic marker (</span></span></span></span><em>VGluT2</em>) on P7 compared to P5 in control and oxytocin treated rats. During the early developmental stages (P5, P7, P9) the expression of GABAergic markers (<em>Gad65</em> and <em>Gad67</em><span><span>) decreased regardless of oxytocin treatment<span>. Incubation in a presence of oxytocin reduced branching of glutamatergic hippocampal neurons and the opposite stimulatory effect of oxytocin was observed in GABAergic neurons. These findings suggest that oxytocin affects </span></span>neurotrophin isoforms in the male rat hippocampus in the early stages of development, which could explain changes in glutamatergic neurons and their morphology.</span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102384"},"PeriodicalIF":2.9,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41179573","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":"Dissecting the functional significance of HSP90AB1 and other heat shock proteins in countering glioblastomas and ependymomas using omics analysis and drug prediction using virtual screening","authors":"Sudhanshu Sharma,&nbsp;Pravir Kumar","doi":"10.1016/j.npep.2023.102383","DOIUrl":"10.1016/j.npep.2023.102383","url":null,"abstract":"<div><p><span>Heat shock proteins (HSPs) are the evolutionary family of proteins that are highly conserved and present widely in various organisms and play an array of important roles and cellular functions. Currently, very few or no studies are based on the systematic analysis of the HSPs in </span>Glioblastoma<span><span><span> (GBMs) and ependymomas. We performed an integrated </span>omics<span> analysis to predict the mutual regulatory differential HSP signatures that were associated with both glioblastoma and ependymomas. Further, we explored the various common dysregulated biological processes<span><span><span><span> operating in both the tumors, and were analyzed using functional enrichment, gene ontology along with the pathway analysis of the predicted HSPs. We established an </span>interactome network of protein-protein interaction (PPIN) to identify the hub HSPs that were commonly associated with GBMs and ependymoma. To understand the mutual molecular mechanism of the HSPs in both </span>malignancies, transcription factors, and </span>miRNAs<span> overlapping with both diseases were explored. Moreover, a transcription factor-miRNAs-HSPs coregulatory network was constructed along with the prediction of potential candidate </span></span></span></span>drugs<span> that were based on perturbation-induced gene expression analysis. Based on the RNA-sequencing data, HSP90AB1 was identified as the most promising target among other predicted HSPs. Finally, the ranking of the drugs was arranged based on various drug scores. In conclusion, this study gave a spotlight on the mutual targetable HSPs, biological pathways, and regulatory signatures associated with GBMs and ependymoma with an improved understanding of crosstalk involved. Additionally, the role of therapeutics was also explored against HSP90AB1. These findings could potentially be able to explain the interplay of HSP90AB1 and other HSPs within these two malignancies.</span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102383"},"PeriodicalIF":2.9,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41158424","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 regulatory effects of the apelin/APJ system on depression: A prospective therapeutic target","authors":"Yanjun Tian ,&nbsp;Ruihao Wang ,&nbsp;Lin Liu ,&nbsp;Wenhuan Zhang ,&nbsp;Haiqing Liu ,&nbsp;Liqing Jiang ,&nbsp;Yunlu Jiang","doi":"10.1016/j.npep.2023.102382","DOIUrl":"10.1016/j.npep.2023.102382","url":null,"abstract":"<div><p>Depression is a debilitating neuropsychological disorder characterized by high incidence, high recurrence, high suicide, and high disability rates, which poses serious threats to human health and imposes heavy psychological and economic burdens on family and society. The pathogenesis of depression is extremely complex, and its etiology is multifactorial. Mounting evidence suggests that apelin and apelin receptor APJ, which compose the apelin/APJ system, are related to the development of depression. However, the specific mechanism is still unclear, and research in this area in human is still insufficient. Acceleration of research into the regulatory effects and underlying mechanisms of the apelin/APJ system in depression may identify attractive therapeutic targets and contribute to the development of novel intervention strategies against this devastating psychological disorder. In this review, we mainly discuss the regulatory effects of apelin/APJ system on depression and its potential therapeutic applications.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102382"},"PeriodicalIF":2.9,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268679","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":"Mate calling alters expression of neuropeptide, cocaine- and amphetamine- regulated transcript (CART) in the brain of male frog Microhyla nilphamariensis","authors":"Shobha Bhargava ,&nbsp;Ketaki Shetye ,&nbsp;Swapnil Shewale ,&nbsp;Nitin Sawant ,&nbsp;Sneha Sagarkar ,&nbsp;Nishikant Subhedar","doi":"10.1016/j.npep.2023.102380","DOIUrl":"10.1016/j.npep.2023.102380","url":null,"abstract":"<div><p><span>Croaking is a unique component of reproductive behaviour<span> in amphibians which plays a key role in intraspecies communication and mate evaluation. While gonadal hormones are known to induce croaking, central regulation of sound production is less studied. Croaking is a dramatic, transient activity that sets apart an animal from non-croaking individuals. Herein, we aim at examining the profile of the neuropeptide cocaine- and amphetamine-regulated transcript (CART) in actively croaking and non-croaking frog </span></span><em>Microhyla nilphamariensis</em><span><span>. In anurans, this peptide is widely expressed in the areas inclusive of acoustical nuclei as well as areas relevant to reproduction. CART immunoreactivity<span><span> was far more in the preoptic area (POA), anteroventral </span>tegmentum (AV), ventral </span></span>hypothalamus<span><span><span> (vHy), pineal (P) and pituitary gland of croaking frog compared to non-croaking animals. On similar lines, tissue fragments collected from the mid region of the brain inclusive of POA, vHy, AV, pineal and pituitary gland of croaking frog showed upregulation of CART mRNA. However, CART immunoreactivity in the neuronal </span>perikarya of </span>raphe (Ra) was completely abolished during croaking activity. The data suggest that CART signaling in the brain may be an important player in mediating croaking behaviour in the frog.</span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102380"},"PeriodicalIF":2.9,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256589","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":"Reduced mastication during growth inhibits cognitive function by affecting trigeminal ganglia and modulating Wnt signaling pathway and ARHGAP33 molecular transmission","authors":"Eri Misawa-Omori,&nbsp;Hidemasa Okihara,&nbsp;Takuya Ogawa,&nbsp;Yasunori Abe,&nbsp;Chiho Kato,&nbsp;Hideyuki Ishidori,&nbsp;Akiyo Fujita,&nbsp;Satoshi Kokai,&nbsp;Takashi Ono","doi":"10.1016/j.npep.2023.102370","DOIUrl":"10.1016/j.npep.2023.102370","url":null,"abstract":"<div><p>Binding of brain-derived neurotrophic factor (BDNF) to its receptor tyrosine kinase B (TrkB) is essential for the development of the hippocampus, which regulates memory and learning. Decreased masticatory stimulation during growth reportedly increases BDNF expression while decreasing TrkB expression in the hippocampus. Increased BDNF expression is associated with Wnt family member 3A (Wnt3a) expression and decreased expression of Rho GTPase Activating Protein 33 (ARHGAP33), which regulates intracellular transport of TrkB. TrkB expression may be decreased at the cell surface and affects the hippocampus via BDNF/TrkB signaling. Mastication affects cerebral blood flow and the neural cascade that occurs through the trigeminal nerve and hippocampus. In the current study, we hypothesized that decreased masticatory stimulation reduces memory/learning in mice due to altered Wnt3a and ARHGAP33 expression, which are related to memory/learning functions in the hippocampus. To test this hypothesis, we fed mice a powdered diet until 14 weeks of age and analyzed the BDNF and TrkB mRNA expression in the right hippocampus using real-time polymerase chain reaction and Wnt3a and ARHGAP33 levels in the left hippocampus using western blotting. Furthermore, we used staining to assess BDNF and TrkB expression in the hippocampus and the number of nerve cells, the average size of each single cell and the area of intercellular spaces of the trigeminal ganglion (TG). We found that decreased masticatory stimulation affected the expression of BDNF, Wnt3a, ARHGAP33, and TrkB proteins in the hippocampus, as well as memory/learning. The experimental group showed significantly decreased numbers of neurons and increased the area of intercellular spaces in the TG. Our findings suggest that reduced masticatory stimulation during growth induces a decline in memory/learning by modulating molecular transmission mechanisms in the hippocampus and TG.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102370"},"PeriodicalIF":2.9,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10085261","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":"An inclusive study of recent advancements in Alzheimer's disease: A comprehensive review","authors":"Sukanya Singh ,&nbsp;Mitali Mahajan ,&nbsp;Dhawal Kumar,&nbsp;Kunika Singh,&nbsp;Mehvish Chowdhary,&nbsp;Amit","doi":"10.1016/j.npep.2023.102369","DOIUrl":"10.1016/j.npep.2023.102369","url":null,"abstract":"<div><p>Alzheimer's disease<span><span><span><span> (AD) has remained elusive in revealing its pathophysiology and mechanism of development. In this review paper, we attempt to highlight several theories that abound about the exact pathway of AD development. The number of cases worldwide has prompted a constant flow of research to detect high-risk patients, slow the progression of the disease and discover improved methods of </span>treatment that may prove effective. We shall focus on the two main classes of </span>drugs that are currently in use; and emerging ones with novel mechanisms that are under development. As of late there has also been increased attention towards factors that were previously thought to be unrelated to AD, such as the gut </span>microbiome, lifestyle habits, and diet. Studies have now shown that all these factors make an impact on AD progression, thus bringing to our attention more areas that could hold the key to combating this disease. This paper covers all the aforementioned factors concisely. We also briefly explore the relationship between mental health and AD, both before and after the diagnosis of the disease.</span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102369"},"PeriodicalIF":2.9,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414878","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":"Naloxone could limit morphine hypersensitivity: Considering the molecular mechanisms","authors":"Mojgan Baratzadeh ,&nbsp;Samira Danialy ,&nbsp;Shima Abtin ,&nbsp;Homa Manaheji","doi":"10.1016/j.npep.2023.102345","DOIUrl":"10.1016/j.npep.2023.102345","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Naloxone<span><span> has been used as an opioid antagonist to prevent multiple adverse side effects of opioid-like tolerance and </span>hyperalgesia. This study has investigated naloxone combined with morphine to limit pain </span></span>hypersensitivity. In addition, the expression of brain-derived neurotrophic factor (BDNF) and K</span>⁺ Cl⁻ cotransporter2 (KCC2) were also studied.</p></div><div><h3>Methods</h3><p><span><span>Forty-eight adult male Wistar rats (180–220 g) were divided into eight groups, with six rats in each group. Rats were divided into two tolerance and hyperalgesia groups; the sham group, the morphine group, the treatment group (naloxone along with morphine), and the sham group (naloxone along with saline) for eight consecutive days. Tail-flick test was performed on days 1, 5, and 8, and the plantar test on days 1 and 10. On days 8 and 10, the lumbar segments of the spinal cord were collected, and BDNF and KCC2 expression were analyzed using </span>western blotting and </span>immunohistochemistry, respectively.</p></div><div><h3>Results</h3><p>Results showed that tolerance and hyperalgesia developed following eight days of repeated morphine injection. BDNF expression significantly increased, but KCC2 was downregulated. Co-administration of naloxone and morphine decreased tolerance and hyperalgesia by decreasing BDNF and increasing KCC2 expression, respectively.</p></div><div><h3>Conclusion</h3><p>This study suggests that BDNF and KCC2 may be candidate molecules for decreased morphine tolerance and hyperalgesia.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"100 ","pages":"Article 102345"},"PeriodicalIF":2.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749388","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}