Neuropharmacology最新文献_第10页

Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder 雌性叙利亚仓鼠对bremelanotide的分析，bremelanotide是一种美国FDA批准用于治疗女性性欲减退障碍的药物。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-09 DOI: 10.1016/j.neuropharm.2025.110299

Johnathan M. Borland , Abigail L. Kohut-Jackson , Anna C. Peyla , Megan AL. Hall , Paul G. Mermelstein , Robert L. Meisel

{"title":"Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder","authors":"Johnathan M. Borland , Abigail L. Kohut-Jackson , Anna C. Peyla , Megan AL. Hall , Paul G. Mermelstein , Robert L. Meisel","doi":"10.1016/j.neuropharm.2025.110299","DOIUrl":"10.1016/j.neuropharm.2025.110299","url":null,"abstract":"<div><div>Hypoactive sexual desire disorder (HSDD) is the most reported sexual dysfunction among premenopausal women worldwide. Bremelanotide, trade name Vyleesi, has been approved by the United States Food and Drug Administration to treat HSDD. However, despite approval, very little is known about its neurobiological mechanism of action. In this study, we utilized a female Syrian hamster model to investigate the effects of bremelanotide on melanocortin receptor expression in the mesolimbic dopamine system and sexual reward. We found that the majority of melanocortin 3 and 4 (MC4R) receptor mRNA is expressed in dopamine neurons in the ventral tegmental area (VTA). Fewer neurons express MC4R in the nucleus accumbens (NAc) or dorsal striatum, where they rarely colocalize with neurons expressing dopamine D1 or D2 receptors. Instead, MC4R mRNA is expressed in nucleus accumbens interneurons. Neither the low nor the high dose of bremelanotide had an effect on the expression of melanocortin receptor mRNA in the mesolimbic dopamine system. Finally, sexual experience resulted in a conditioned place preference (CPP) in female Syrian hamsters, though bremelanotide treatment failed to enhance sexual reward in this test. The results of this study are discussed in conjunction with similar studies in rats, with the conclusion that bremelanotide does not act on the VTA-NAc reward circuit and does not enhance the rewarding effects of sexual interactions.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"267 ","pages":"Article 110299"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Baicalin ameliorates neuroinflammation by targeting TLR4/MD2 complex on microglia via PI3K/AKT/NF-κB signaling pathway 黄芩苷通过PI3K/AKT/NF-κB信号通路靶向小胶质细胞上的TLR4/MD2复合物，改善神经炎症。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-09 DOI: 10.1016/j.neuropharm.2025.110296

Yufang Lu , Ruiying Zhou , Ruyi Zhu , Xue Wu , Jin Liu , Yue Ma , Xin Zhang , Yaling Zhang , Luting Yang , Yanhua Li , Yuan Zhang , Yaping Yan , Qian Zhang

{"title":"Baicalin ameliorates neuroinflammation by targeting TLR4/MD2 complex on microglia via PI3K/AKT/NF-κB signaling pathway","authors":"Yufang Lu , Ruiying Zhou , Ruyi Zhu , Xue Wu , Jin Liu , Yue Ma , Xin Zhang , Yaling Zhang , Luting Yang , Yanhua Li , Yuan Zhang , Yaping Yan , Qian Zhang","doi":"10.1016/j.neuropharm.2025.110296","DOIUrl":"10.1016/j.neuropharm.2025.110296","url":null,"abstract":"<div><div>This study aims to elucidate the target and mechanism of baicalin, a clinically utilized drug, in the treatment of neuroinflammatory diseases. Neuroinflammation, characterized by the activation of glial cells and the release of various pro-inflammatory cytokines, plays a critical role in the pathogenesis of various diseases, including spinal cord injury (SCI). The remission of such diseases is significantly dependent on the improvement of inflammatory microenvironment. Toll-like receptor 4/myeloid differentiation protein 2 (TLR4/MD2) complex plays an important role in pathogen recognition and innate immune activation. baicalin, a natural flavonoid, is renowned for its potent anti-inflammatory property. In this study, we discovered that baicalin significantly reduced the activation of glial cells and the levels of pro-inflammatory cytokines at the lesion site of SCI mice, thereby mitigating demyelination and neuronal damage. By directly occupying the active pocket of TLR4/MD2 complex on microglia, baicalin inhibited PI3K/AKT/NF-κB pathway, thereby exerting its anti-inflammatory effect. These findings were corroborated in mice induced by lipopolysaccharide, a TLR4 agonist. Furthermore, baicalin indirectly altered phenotype of astrocytes by reducing secretion of TNF-α, IL-1α, and C1q levels from microglia. Our work demonstrated that baicalin effectively alleviated neuroinflammation by directly targeting microglia and indirectly modulating astrocytes phenotype. As a natural flavonoid, baicalin holds significant potential as a therapeutic candidate for diseases characterized by neuroinflammation.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"267 ","pages":"Article 110296"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effects of social loss and isolation on partner odor investigation and dopamine and oxytocin receptor expression in female prairie voles 社会丧失和孤立对草原田鼠配偶气味调查及多巴胺和催产素受体表达的影响。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-06 DOI: 10.1016/j.neuropharm.2025.110298

Adrianna Kirckof , Emma Kneller , Erika M. Vitale , Michael A. Johnson , Adam S. Smith

{"title":"The effects of social loss and isolation on partner odor investigation and dopamine and oxytocin receptor expression in female prairie voles","authors":"Adrianna Kirckof , Emma Kneller , Erika M. Vitale , Michael A. Johnson , Adam S. Smith","doi":"10.1016/j.neuropharm.2025.110298","DOIUrl":"10.1016/j.neuropharm.2025.110298","url":null,"abstract":"<div><div>In humans, grief is characterized by intense sadness, intrusive thoughts of the deceased, and intense longing for reunion with the deceased. Human fMRI studies show hyperactivity in emotional pain and motivational centers of the brain when an individual is reminded of a deceased attachment figure, but the molecular underpinnings of these changes in activity are unknown. Prairie voles (<em>Microtus ochrogaster</em>), which establish lifelong social bonds between breeding pairs, also display distress and motivational shifts during periods of prolonged social loss, providing a model to investigate these behavioral and molecular changes at a mechanistic level. Here, a novel odor preference test was used to assess social vs non-social odor investigation, and a sucrose preference test was used to assess non-social, reward-driven motivation. Females that lost a male partner investigated partner- and food-associated cues significantly more than females that lost a female cagemate or remained intact with a male partner. However, females experiencing the loss of a male partner did not change investigation of stranger-associated cues. Western blotting revealed significant increases of dopamine receptor type 1 (DRD1) and oxytocin receptor protein content in specific brain regions in response to the loss of distinct social relationships. Such effects included an increase in DRD1 in the medial preoptic area of the hypothalamus (mPOA) in females experiencing loss of a male partner compared to all other conditions. Pharmacological antagonism of DRD1 in the mPOA blocked the loss-associated increase of investigation of the partner odor but did not affect investigation of food or stranger odors. This reveals a novel dopamine-mediated mechanism for partner-seeking behavior during periods of partner loss in female prairie voles.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"267 ","pages":"Article 110298"},"PeriodicalIF":4.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leveling up: Strategies for taking Neuropharmacology and us all to new heights 升级：将神经药理学和我们所有人带到新高度的策略。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-06 DOI: 10.1016/j.neuropharm.2025.110297

Jared W. Young Ph.D

引用次数: 0

Cholesterol metabolites modulate ionotropic P2X4 and P2X7 receptor current in microglia cells 胆固醇代谢物调节小胶质细胞中P2X4和P2X7受体电流。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-02 DOI: 10.1016/j.neuropharm.2024.110294

Michele Barraco , Eva Kudova , Claudio Bucolo , Lucia Ciranna , Maria Angela Sortino , Mariangela Chisari

{"title":"Cholesterol metabolites modulate ionotropic P2X4 and P2X7 receptor current in microglia cells","authors":"Michele Barraco , Eva Kudova , Claudio Bucolo , Lucia Ciranna , Maria Angela Sortino , Mariangela Chisari","doi":"10.1016/j.neuropharm.2024.110294","DOIUrl":"10.1016/j.neuropharm.2024.110294","url":null,"abstract":"<div><div>The central nervous system is a well-known steroidogenic tissue producing, among others, cholesterol metabolites such as neuroactive steroids, oxysterols and steroid hormones. It is well known that these endogenous molecules affect several receptor classes, including ionotropic GABAergic and NMDA glutamatergic receptors in neurons. It has been shown that also ionotropic purinergic (P2X) receptors are cholesterol metabolites’ targets. Among P2X receptors, purinergic P2X4 and P2X7 receptors are expressed in microglia, the innate immune cells involved in the brain inflammatory response. In this study, we explore the ionotropic purinergic receptors modulation by cholesterol metabolites in microglia. Patch-clamp experiments were performed in BV2 cells, a murine microglia cell line, to evaluate effects of cholesterol metabolites using micro- and nanomolar concentrations. About P2X4 receptor, we found that testosterone butyrate (20 μM and 200 nM) and allopregnanolone (10 μM and 100 nM) both potentiated its current, while neither 25-hydroxycholesterol (10 μM and 100 nM) nor 17β-estradiol (1 μM) showed any effects. On the other hand, P2X7 receptor current was potentiated by allopregnanolone (10 μM) and 25-hydroxycholesterol (10 μM and 100 nM). Taken together, our data show that modulation of either P2X4 and P2X7 current is affected differently by cholesterol metabolites, suggesting a structure-activity relationship among these players. Identifying the possible link between purinergic transmission, microglia and cholesterol metabolites will allow to define new targets for drug development to treat neuroinflammation.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"266 ","pages":"Article 110294"},"PeriodicalIF":4.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglial activation and neuroinflammation in acute and chronic cognitive deficits in sepsis 脓毒症患者急性和慢性认知缺陷中的小胶质细胞激活和神经炎症。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-31 DOI: 10.1016/j.neuropharm.2024.110285

Paul Denver , Colm Cunningham

{"title":"Microglial activation and neuroinflammation in acute and chronic cognitive deficits in sepsis","authors":"Paul Denver , Colm Cunningham","doi":"10.1016/j.neuropharm.2024.110285","DOIUrl":"10.1016/j.neuropharm.2024.110285","url":null,"abstract":"<div><div>Sepsis is characterised by dysregulated immune responses to infection, leading to multi-organ dysfunction and high rates of mortality. With increasing survival rates in recent years long-term neurological and psychiatric consequences have become more apparent in survivors. Many patients develop sepsis associated encephalopathy (SAE) which encompasses the profound but usually transient neuropsychiatric syndrome delirium but also new brain injury that emerges in the months and years post-sepsis. It is now clear that systemic inflammatory signals reach the brain during sepsis and that very significant neuroinflammation ensues. The major brain resident immune cell population, the microglia, has been implicated in acute and chronic cognitive dysfunction in animal models of sepsis based on a growing number of studies using bacterial endotoxin and in polymicrobial sepsis models such as cecal ligation and puncture. The current review explores the effects of sepsis on the brain, focussing on how systemic insults translate to microglial activation and neuroinflammation and how this disrupts neuronal function and integrity. We examine what has been demonstrated specifically with respect to microglial activation, revealing robust evidence for a role for neuroinflammation in sepsis-induced brain sequelae but less clear information on the extent of the specific microglial contribution to this, arising from findings using global knockout mice, non-selective drugs and treatments that equally target peripheral and central compartments. There is, nonetheless, clear evidence that microglia do become activated and do contribute to brain consequences of sepsis thus arguing for improved understanding of these neuroinflammatory processes toward the prevention and treatment of sepsis-induced brain dysfunction.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"267 ","pages":"Article 110285"},"PeriodicalIF":4.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A term as Editor-in-Chief of Neuropharmacology: Ups and downs and highs and lows 作为《神经药理学》主编的一个术语：起起落落，起起伏伏。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-30 DOI: 10.1016/j.neuropharm.2024.110270

Bruno G. Frenguelli

引用次数: 0

Thank you to our reviewers

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-30 DOI: 10.1016/j.neuropharm.2024.110274

引用次数: 0

Clozapine and rapamycin reverse behavioral abnormalities in an animal model of autoimmune schizophrenia 氯氮平和雷帕霉素逆转自身免疫性精神分裂症动物模型中的行为异常

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-27 DOI: 10.1016/j.neuropharm.2024.110286

Duilin Liu , Caiyun Zhu , Hui Wei

{"title":"Clozapine and rapamycin reverse behavioral abnormalities in an animal model of autoimmune schizophrenia","authors":"Duilin Liu , Caiyun Zhu , Hui Wei","doi":"10.1016/j.neuropharm.2024.110286","DOIUrl":"10.1016/j.neuropharm.2024.110286","url":null,"abstract":"<div><h3>Objective</h3><div>Autoantibody-associated psychosis represents a distinct disease subgroup of patients with schizophrenia with a suspected autoimmune origin. Although preliminary studies have suggested adjunctive drug treatment strategies targeting the immune system, further validation of these findings is warranted. Autoantibodies against SFT2D2 have been identified in patients with schizophrenia. ApoE<sup>−/−</sup> mice immunized with SFT2D2-peptides can be used as a model for testing immunotherapy in this subgroup of patients. We used the atypical antipsychotic drug clozapine and immunosuppressant rapamycin to test their effects in this mouse model.</div></div><div><h3>Methods</h3><div>The mice were evaluated for cognitive and schizophrenia-like behaviors. Following behavioral testing, brain samples were collected for analyzing specific pathological changes and dendritic spine formation.</div></div><div><h3>Results</h3><div>Clozapine and rapamycin reversed impaired pre-pulse inhibition, motor impairment, and improved cognitive ability in ApoE <sup>−/−</sup> mice exposed to anti-SFT2D2 immunoglobulin G. Immunohistochemical assays revealed that both clozapine and rapamycin significantly reduced activated microglial infiltration and restored neuronal dendritic spine density.</div></div><div><h3>Conclusions</h3><div>Our study results suggested that clozapine and rapamycin possess therapeutic benefits for managing autoimmune psychosis and provide mechanistic insights into immunotherapies involving immunosuppressive agents.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"266 ","pages":"Article 110286"},"PeriodicalIF":4.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Angiotensin 1-7 injected into the rat paraventricular nucleus of hypothalamus increases blood pressure and heart rate via various receptors 大鼠下丘脑室旁核注射血管紧张素1-7，可通过多种受体提高血压和心率。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-26 DOI: 10.1016/j.neuropharm.2024.110279

K. Mińczuk , E. Schlicker , A. Krzyżewska , B. Malinowska

{"title":"Angiotensin 1-7 injected into the rat paraventricular nucleus of hypothalamus increases blood pressure and heart rate via various receptors","authors":"K. Mińczuk , E. Schlicker , A. Krzyżewska , B. Malinowska","doi":"10.1016/j.neuropharm.2024.110279","DOIUrl":"10.1016/j.neuropharm.2024.110279","url":null,"abstract":"<div><div>Although angiotensin 1-7 (Ang 1–7) and its role as a part of the “protective” axis of the renin-angiotensin system are well described in the literature, the mechanisms of its angiotensin II-like pressor and tachycardic effects following its acute central administration are not fully understood. It was the aim of the present study to examine which receptors contribute to the aforementioned cardiovascular effects. Ang 1–7 and antagonists for glutamate, GABA, vasopressin, thromboxane A<sub>2</sub> (TP), α<sub>1</sub>-adrenergic, and P2X purinoceptors or modulators of oxidative stress were injected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anesthetized male Wistar rats. Acute injection of Ang 1–7 into the PVN increased blood pressure (BP) by about 15 mmHg and heart rate (HR) by about 14 beats/min. After preinjection with bicuculline (GABA<sub>A</sub> receptor antagonist), CNQX + D-AP5 (AMPA/kainate and NMDA receptor antagonists) and SQ29548 (TP receptor antagonist) the BP and HR reactions to Ang 1–7 were attenuated or abolished. The vasopressin V<sub>1A</sub> and V<sub>1B</sub> receptor antagonists conivaptan and nelivaptan, and the NADPH oxidase inhibitor apocynin even reversed the pressor and tachycardic effects of Ang 1–7. Antagonists of P2X (PPADS) and α<sub>1</sub>-adrenergic receptors (prazosin), the free radical scavenger tempol and the superoxide dismutase inhibitor DETC did not modify the cardiovascular effects of Ang 1–7. The (Mas receptor-related) rise in BP and HR evoked by Ang 1-7 administered to the rat PVN is linked to glutamate, vasopressin, GABA<sub>A</sub> and thromboxane receptors, and to oxidative stress, but does not seem to involve α<sub>1</sub>-adrenergic or P2X receptors.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"266 ","pages":"Article 110279"},"PeriodicalIF":4.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0