Neuropeptides最新文献

{"title":"Immunohistochemical determination of the excitatory and inhibitory axonal endings contacting NUCB2/nesfatin-1 neurons","authors":"Aynura Aghayeva,&nbsp;Duygu Gok Yurtseven,&nbsp;Nursel Hasanoglu Akbulut,&nbsp;Ozhan Eyigor","doi":"10.1016/j.npep.2023.102401","DOIUrl":"10.1016/j.npep.2023.102401","url":null,"abstract":"<div><p>Nesfatin-1 is an anorexigenic peptide suppressing food intake and is synthesized and secreted by neurons located in the hypothalamus. Our study was aimed to demonstrate the effect of excitatory and inhibitory neurotransmitters on NUCB2/nesfatin-1 neurons. In this context, dual peroxidase immunohistochemistry staining was performed using NUCB2/nesfatin-1 primary antibody with each of the primary antibodies of vesicular transporter proteins applied as markers for neurons using glutamate, acetylcholine, and GABA as neurotransmitters. In double labeling applied on floating sections, the NUCB2/nesfatin-1 reaction was determined in brown color with diaminobenzidine, while vesicular carrier proteins were marked in black. Slides were analyzed to determine the ratio of nesfatin-1 neurons in the three hypothalamic nucleus in contact with a relevant vesicular carrier protein. The ratios of NUCB2/nesfatin-1 neurons with the innervation were compared among neurotransmitters. In addition, possible gender differences between males and females were examined. The difference in the number of VGLUT2-contacting NUCB2/nesfatin-1 neurons was significantly higher in males when compared to females. When both genders were compared in different nuclei, it was seen that there was no statistical significance in terms of the percentage of NUCB2/nesfatin-1 neuron apposition with VGLUT3. The statistical evaluation showed that number of NUCB2/nesfatin-1 neurons receiving GABAergic innervation is higher in males when compared to females (*<em>p</em> ≤ 0.05; <em>p</em> = 0.045). When the axonal contact of vesicular neurotransmitter transporter proteins was compared between the neurotransmitters, it was determined that the most prominent innervation is GABAergic. In the supraoptic region, no contacts of VAChT-containing axons were found on NUCB2/nesfatin-1 neurons in both female and male subjects. In conclusion, it is understood that both excitatory and inhibitory neurons can innervate the NUCB2/nesfatin-1 neurons and the glutamatergic system is effective in the excitatory innervation while the GABAergic system plays a role in the inhibitory mechanism.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"103 ","pages":"Article 102401"},"PeriodicalIF":2.9,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143417923000823/pdfft?md5=176b747a2df34b78779d0777d53f9d32&pid=1-s2.0-S0143417923000823-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139035428","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":"CircBUB1 activates the PI3K/AKT signaling pathway to promote the migration and invasion of glioblastoma cells","authors":"Runan Zhang, Dongmei Wu, Ying Wang, Liping Wu, Guowei Gao, Dayong Shan","doi":"10.1016/j.npep.2023.102400","DOIUrl":"https://doi.org/10.1016/j.npep.2023.102400","url":null,"abstract":"<h3>Background</h3><p>Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid growth and resistance to treatment, leading to poor survival rates. The molecular mechanisms underlying GBM progression remain unclear, necessitating further research. This study focuses on the role of circBUB1, a circular RNA, in GBM cell migration and invasion, and the associated molecular mechanisms.</p><h3>Methods</h3><p>RNA/protein expression was detected using RT-qPCR/western blot assay. Transwell and wound healing assays were conducted to assess GBM cell migration and invasion. Detailed mechanistic analyses were carried out to understand the role of circBUB1 in GBM cells.</p><h3>Results</h3><p>CircBUB1 was found to be highly expressed and functioned as an oncogene in GBM cells. Functional assays revealed that knockdown of circBUB1 suppressed the migration and invasion of GBM cells. Mechanistic analyses showed that circBUB1 sequestered miR-1296-5p, thereby elevating TRIM14 expression. TRIM14 was also found to promote PTEN ubiquitination, ultimately leading to the down-regulation of PTEN protein and activation of the PI3K/AKT signaling pathway. Through rescue assays, this study confirmed that circBUB1 promoted GBM cell migration and invasion by reducing PTEN protein levels.</p><h3>Conclusion</h3><p>Our findings indicate that circBUB1 activates the PI3K/AKT signaling pathway, promoting the migration and invasion of GBM cells via the miR-1296-5p/TRIM14 axis. This provides new insights into the molecular mechanisms of GBM progression and potential therapeutic targets.</p>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"19 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138690805","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 somatostatin, a somatostatin agonist, and an antagonist, on a putative migraine trigger pathway","authors":"Geoffrey A. Lambert ,&nbsp;Alessandro S. Zagami","doi":"10.1016/j.npep.2023.102399","DOIUrl":"10.1016/j.npep.2023.102399","url":null,"abstract":"<div><h3>Objective</h3><p>To determine whether somatostatin (SST) could be a cortico-brainstem neurotransmitter involved in producing the headache of migraine.</p></div><div><h3>Background</h3><p>There is evidence to support the idea that a cortico-brainstem-trigeminal nucleus neuraxis might be responsible for producing migraine headache; we have suggested that SST may be one of the neurotransmitters involved.</p></div><div><h3>Methods</h3><p>Rats were anesthetised and prepared for recording neurons in either the periaqueductal gray matter (PAG) or nucleus raphe magnus (NRM), as well as the trigeminal nucleus caudalis (TNC). The dura mater and facial skin were stimulated electrically or mechanically. SST, the SST agonist L054264 and the SST antagonist CYN54806 were injected intravenously, by microinjection, or by iontophoresis into the PAG or NRM. Cortical neuronal activity was provoked by cortical spreading depression (CSD) or light flash (LF) and was monitored by recording cortical blood flow (CBF).</p></div><div><h3>Results</h3><p>Intravenous injection of SST: (a) selectively decreased the responses of TNC neurons to stimulation of the dura, but not skin, for up to 5 h; (b) decreased the ongoing discharge rate of TNC neurons while simultaneously increasing the discharge rate of neurons in either brainstem nucleus and; (c) prevented, or reversed, the effect of CSD and LF on brainstem and trigeminal neuron discharge rates. CSD and LF decreased the discharge rate of neurons in both brainstem nuclei and increased the discharge rate of TNC neurons. These effects were reversed by L054264 and mimicked by CYN54806. Injections of L054264 into the PAG or NRM reduced the response of TNC neurons to dural stimulation and skin stimulation differentially, depending on the nucleus injected. Injections of CYN54806 into either brainstem nucleus potentiated the responses of TNC neurons to dural and skin stimulation, but without a marked differential effect.</p></div><div><h3>Conclusions</h3><p>These results imply that SST could be a neurotransmitter in a pathway responsible for migraine pain.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"103 ","pages":"Article 102399"},"PeriodicalIF":2.9,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S014341792300080X/pdfft?md5=d52cfad0b3101d4f39777e5b79ba3e38&pid=1-s2.0-S014341792300080X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138579172","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":"New fraternine analogues: Evaluation of the antiparkinsonian effect in the model of Parkinson's disease","authors":"Andréia Biolchi Mayer ,&nbsp;Henrique de Oliveira Amaral ,&nbsp;Danilo Gustavo R. de Oliveira ,&nbsp;Gabriel Avohay Alves Campos ,&nbsp;Priscilla Galante Ribeiro ,&nbsp;Solange Cristina Rego Fernandes ,&nbsp;Adolfo Carlos Barros de Souza ,&nbsp;Raffael Júnio Araújo de Castro ,&nbsp;Anamélia Lorenzetti Bocca ,&nbsp;Márcia Renata Mortari","doi":"10.1016/j.npep.2023.102390","DOIUrl":"10.1016/j.npep.2023.102390","url":null,"abstract":"<div><p>Venom-derived peptides are important sources for the development of new therapeutic molecules, especially due to their broad pharmacological activity. Previously, our research group identified a novel natural peptide, named fraternine, with promising effects for the treatment of Parkinson's disease. In the present paper, we synthesized three peptides bioinspired in fraternine: fra-10, fra-14, and fra-24. They were tested in the 6-OHDA-induced model of parkinsonism, quantifying motor coordination, levels of TH+ neurons in the <em>substantia nigra pars compacta</em> (SN), and inflammation mediators TNF-α, IL-6, and IL-1ß in the cortex. Peptides fra-14 and fra-10 improved the motor coordination in relation to 6-OHDA lesioned animals. However, most of the peptides were toxic in the doses applied. All three peptides reduced the intensity of the lesion induced rotations in the apomorphine test. Fra-24 higher dose increased the number of TH+ neurons in SN and reduced the concentration of TNF-α in the cortex of 6-OHDA lesioned mice. Overall, only the peptide fra-24 presented a neuroprotection effect on dopaminergic neurons of SN and a reduction of cytokine TNF-α levels, making it worthy of consideration for the treatment of PD.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"103 ","pages":"Article 102390"},"PeriodicalIF":2.9,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143417923000719/pdfft?md5=c496fa6bb627804800a78cf237e1f4da&pid=1-s2.0-S0143417923000719-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135714404","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":"Effect of valproic acid combined with transplantation of olfactory ensheathing cells modified by neurotrophic 3 gene on nerve protection and repair after traumatic brain injury","authors":"Haiming Li ,&nbsp;Zhijie Yin ,&nbsp;Shuangzhu Yue ,&nbsp;Yunying An ,&nbsp;Xiaoyin Wang ,&nbsp;Shifang Zhou ,&nbsp;Lei Meng ,&nbsp;Baozhe Jin","doi":"10.1016/j.npep.2023.102389","DOIUrl":"10.1016/j.npep.2023.102389","url":null,"abstract":"<div><h3>Background</h3><p>Traumatic brain injury (TBI) often leads to cognitive and neurological dysfunction. Valproic acid (VPA) has a neuroprotective effect in acute central nervous system diseases; the neurotrophin 3 gene (NT-3) can maintain the survival of neurons, and olfactory ensheathing cells (OECs) can promote the growth of nerve axons. This study aimed to evaluate the restorative effect of VPA combined with NT-3 modified OECs (NT-3-OECs) on neurological function after TBI.</p></div><div><h3>Methods</h3><p>The neurological severity score (NSS) of rats was evaluated on the 1st, 7th, 14th, and 28th day after TBI modeling and corresponding intervention. Hematoxylin-eosin (HE) staining, p75 nerve growth factor receptor (P75), glial fibrillary acidic protein (GFAP), and neurofilament protein (NF)staining, and argyrophilic staining were used to observe the morphology of brain tissue 28 days after modeling. Moreover, TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect the apoptosis rate of neurons. The changes in synapses and mitochondria in the injured area were observed by electron microscope.</p></div><div><h3>Results</h3><p>NT-3-OECs transplantation can increase the content of NT-3 in brain tissue, and NT-3-OECs can survive for &gt;28 days. The NSS score of the TBI-VPA-NT-3-OECs group 28 days after cell transplantation was significantly lower than that of the other model treatment groups (<em>P</em> &lt; 0.05). The morphological structure of the brain tissue was more complete, and the neurofilament fibers were neatly arranged, achieving better results than those of the other groups. The apoptosis rate of nerve cells in the TBI-VPA-NT-3-OECs group was significantly lower than in the other treatment groups (<em>P</em> &lt; 0.05). Furthermore, the number of synapses in the combined intervention group was significantly higher than in the other treatment groups, and the mitochondrial structure was more complete.</p></div><div><h3>Conclusion</h3><p>NT-3-OECs have good biological function, and VPA combined with NT-3-OECs transplantation can effectively improve the prognosis of TBI rats.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"103 ","pages":"Article 102389"},"PeriodicalIF":2.9,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143417923000707/pdfft?md5=a98bf69cb4847868e487fb1ce0a72898&pid=1-s2.0-S0143417923000707-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72014934","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":"Cross talk about the role of Neuropeptide Y in CNS disorders and diseases","authors":"Rajeshwari Bale,&nbsp;Gaurav Doshi","doi":"10.1016/j.npep.2023.102388","DOIUrl":"10.1016/j.npep.2023.102388","url":null,"abstract":"<div><p>A peptide composed of a 36 amino acid called Neuropeptide Y (NPY) is employed in a variety of physiological processes to manage and treat conditions affecting the endocrine, circulatory, respiratory, digestive, and neurological systems. NPY naturally binds to G-protein coupled receptors, activating the Y-receptors (Y1-Y5 and y6). The findings on numerous therapeutic applications of NPY for CNS disease are presented in this review by the authors. New targets for treating diseases will be revealed by medication combinations that target NPY and its receptors. This review is mainly focused on disorders such as anxiety, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Machado Joseph disease, multiple sclerosis, schizophrenia, depression, migraine, alcohol use disorder, and substance use disorder. The findings from the preclinical studies and clinical studies covered in this article may help create efficient therapeutic plans to treat neurological conditions on the one hand and psychiatric disorders on the other. They may also open the door to the creation of novel NPY receptor ligands as medications to treat these conditions.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102388"},"PeriodicalIF":2.9,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425492","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 use of intranasal oxytocin in the treatment of eating disorders","authors":"Magda Malewska-Kasprzak,&nbsp;Katarzyna Jowik,&nbsp;Marta Tyszkiewicz-Nwafor","doi":"10.1016/j.npep.2023.102387","DOIUrl":"10.1016/j.npep.2023.102387","url":null,"abstract":"<div><p>Oxytocin (OXT) is a hypothalamic peptide that plays a number of roles in the body, being involved in labor and lactation, as well as cognitive-emotional processes and social behavior. In recent years, knowledge of the physiology of OXT has been repeatedly used to explore its potential role in the treatment of numerous diseases, identifying a significant role for OXT in appetite regulation, eating behavior, weight regulation, and food-related beliefs. In this review we provide an overview of publications on this topic, but due to the wealth of research, we have limited our focus to studies based on the use of intranasal OXT in psychiatric diseases, with a particular focus on the role of oxytocin in eating disorders and obesity. Accumulating evidence that OXT intranasal supplementation may provide some therapeutic benefit seems promising. In individuals with autistic spectrum disorders (ASD) and schizophrenia, OXT may affect core deficits, improving social cognition and reducing symptom severity in schizophrenia. Dysregulation of serum and CSF OXT levels, as well as polymorphisms of its genes, may affect emotion perception in patients with eating disorders and correlate with co-occurring depressive and anxiety disorders. Nevertheless, there are still many critical questions regarding the pharmacokinetics and pharmacodynamics of intranasal OXT that can only be answered in larger randomized controlled trials.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102387"},"PeriodicalIF":2.9,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41207244","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":"Neuroprotective effect of the PACAP-ADNP axis on SOD1G93A mutant motor neuron death induced by trophic factors deprivation","authors":"Benedetta Magrì ,&nbsp;Agata Grazia D'Amico ,&nbsp;Grazia Maugeri ,&nbsp;Giovanna Morello ,&nbsp;Valentina La Cognata ,&nbsp;Salvatore Saccone ,&nbsp;Concetta Federico ,&nbsp;Sebastiano Cavallaro ,&nbsp;Velia D'Agata","doi":"10.1016/j.npep.2023.102386","DOIUrl":"10.1016/j.npep.2023.102386","url":null,"abstract":"<div><p><span>Amyotrophic lateral Sclerosis (ALS) is a </span>neurodegenerative disease<span><span> characterized by progressive degeneration of motor neurons in the </span>central nervous system<span><span>. Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) account for approximately in 20% of familial ALS cases. The pathological mechanisms underlying the toxicity induced by mutated SOD1 are still unknown. However, it has been hypothesized that oxidative stress (OS) has a crucial role in motor neuron degeneration in ALS patients. Moreover, it has been described that SOD1 mutation interferes expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a protective key modulator against OS and </span>reactive oxygen species (ROS) formation.</span></span></p><p><span>The protective effect of pituitary adenylate cyclase-activating peptide (PACAP) has been demonstrated in various neurological disorders<span>, including ALS. Some of its effects are mediated by the stimulation of an intracellular factor known as activity-dependent protein (ADNP). The role of PACAP-ADNP axis on mutated SOD1 motor neuron degeneration has not been explored, yet. The present study aimed to investigate whether PACAP prevented apoptotic cell death induced by growth factor deprivation through ADNP activation and whether the </span></span>peptidergic axis can counteract the OS insult.</p><p>By using an in vitro model of ALS, we demonstrated that PACAP by binding to PAC1 receptor (PAC1R) prevented motor neuron death induced by serum deprivation through induction of the ADNP expression<span> via PKC stimulation. Furthermore, we have also demonstrated that the PACAP/ADNP axis counteracted ROS formation by inducing translocation of the Nfr2 from the cytoplasm to the nucleus. In conclusion, our study provides new insights regarding the protective role of PACAP-ADNP in ALS.</span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102386"},"PeriodicalIF":2.9,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680249","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":"CDNF overexpression prevents motor-cognitive dysfunction by intrastriatal CPP-based delivery system in a Parkinson's disease animal model","authors":"Sheila A. Villa-Cedillo ,&nbsp;Daniel Matta-Yee-Chig ,&nbsp;Adolfo Soto-Domínguez ,&nbsp;Humberto Rodríguez-Rocha ,&nbsp;Aracely García-García ,&nbsp;Carlos R. Montes-de-Oca-Saucedo ,&nbsp;María de Jesús Loera-Arias ,&nbsp;Jesús Valdés ,&nbsp;Odila Saucedo-Cárdenas","doi":"10.1016/j.npep.2023.102385","DOIUrl":"10.1016/j.npep.2023.102385","url":null,"abstract":"<div><p><span><span><span><span>Parkinson's disease<span><span> (PD) is characterized by the loss of dopaminergic neurons in the </span>substantia nigra pars compact (SNpc), and no effective </span></span>treatment<span> has yet been established to prevent PD. Neurotrophic factors<span>, such as cerebral dopamine neurotrophic factor (CDNF), have shown a neuroprotective effect on dopaminergic neurons. Previously, we developed a cell-penetrating-peptide-based delivery system that includes Asn194Lys mutation in the rabies virus glycoprotein-9R peptide (mRVG9R), which demonstrated a higher delivery rate than the wild-type. In this study, using a mouse PD-like model, we evaluated the intrastriatal mRVG9R-KP-CDNF gene therapy through motor and </span></span></span>cognitive tests<span> and brain cell analysis. The mRVG9R-KP-CDNF complex was injected into the striatum on days 0 and 20. To induce the PD-like model, mice were intraperitoneally administered Paraquat (PQ) twice a week for 6 weeks. Our findings demonstrate that mRVG9R-KP-CDNF gene therapy effectively protects brain cells from PQ toxicity and prevents motor and </span></span>cognitive dysfunction<span> in mice. We propose that the mRVG9R-KP-CDNF complex inhibits astrogliosis<span><span> and microglia activation, safeguarding dopaminergic neurons and </span>oligodendrocytes from PQ-induced damage. This study presents an efficient CDNF delivery system, protecting neurons and glia in the </span></span></span>nigrostriatal pathway<span> from PQ-induced damage, which is known to lead to motor and cognitive dysfunction in neurodegenerative diseases such as PD.</span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"102 ","pages":"Article 102385"},"PeriodicalIF":2.9,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41207242","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":"Apelin receptor antagonist (ML221) treatment has a stimulatory effect on the testicular proliferation, antioxidants system and steroidogenesis in adult mice","authors":"Milirani Das,&nbsp;Guruswami Gurusubramanian,&nbsp;Vikas Kumar Roy","doi":"10.1016/j.npep.2023.102354","DOIUrl":"10.1016/j.npep.2023.102354","url":null,"abstract":"<div><p><span><span><span>The expression of apelin<span> and its receptor (APJ) has been shown in the hypothalamus-pituitary-testicular axis. It has also been suggested apelin and APJ are neuropeptide factors. The presence of apelin and APJ in the </span></span>seminiferous tubules and </span>interstitium<span> might be predicted to act as a local regulator of testicular activity, although the function is not well known in the mice testis. In the present study, we have investigated the effects of APJ, antagonist, ML221 on the </span></span>gonadotropin<span><span> levels, testicular steroidogenesis, proliferation, </span>apoptosis<span> and antioxidant system. Our results showed that inhibition of APJ by ML221 increased the sperm concentration, circulating testosterone, FSH, LH levels and intra-testicular testosterone concentration. Furthermore, ML221 treatment<span><span><span> stimulates the germ cell proliferation and antioxidant system in the testis. The expression of BCL2, </span>AR<span><span> was up-regulated whereas, the expression of BAX and active caspase3 was down-regulated after ML221 treatment. Immunohistocehmical analysis of AR also showed increase abundance in the spermatogonia, primary </span>spermatocytes<span> and Leydig cells of 150 μg/kg dose group. These findings suggest that in adult testis, the apelin system might have an inhibitory role in germ cell proliferation and a stimulatory role in apoptosis. It might also be suggested that the apelin system could be involved in the disposal mechanism for damaged germ cells during </span></span></span>spermatogenesis via the down-regulation of AR.</span></span></span></p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"101 ","pages":"Article 102354"},"PeriodicalIF":2.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166597","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}