Neuropharmacology最新文献_第3页

Multi-functional memantine nitrate attenuated cognitive impairment in models of vascular dementia and Alzheimer's disease through neuroprotection and increased cerebral blood flow

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-11 DOI: 10.1016/j.neuropharm.2025.110410

Guangying Chen , Kexin Zhang , Minghua Sun , Ningqing Xie , Liangmiao Wu , Guiliang Zhang , Baojian Guo , Chunhui Huang , Maggie Pui Man Hoi , Gaoxiao Zhang , Changzheng Shi , Yewei Sun , Zaijun Zhang , Yuqiang Wang

{"title":"Multi-functional memantine nitrate attenuated cognitive impairment in models of vascular dementia and Alzheimer's disease through neuroprotection and increased cerebral blood flow","authors":"Guangying Chen , Kexin Zhang , Minghua Sun , Ningqing Xie , Liangmiao Wu , Guiliang Zhang , Baojian Guo , Chunhui Huang , Maggie Pui Man Hoi , Gaoxiao Zhang , Changzheng Shi , Yewei Sun , Zaijun Zhang , Yuqiang Wang","doi":"10.1016/j.neuropharm.2025.110410","DOIUrl":"10.1016/j.neuropharm.2025.110410","url":null,"abstract":"<div><div>Alzheimer's disease (AD) and vascular dementia (VaD) are two prevalent forms of dementia. VaD is linked to cerebrovascular lesions, such as those from white matter ischemia and chronic cerebral hypoperfusion, which can also occur in AD. Nitric oxide (NO) regulates cerebral blood flow (CBF) in the central nervous system. Memantine is an NMDA receptor antagonist approved for AD treatment. This study investigated the efficacy and molecular mechanism of MN-08, a novel memantine nitrate, in one VaD model (2VO) and two AD models (APP/PS1 mice and Aβ1-42-induced mice). MN-08 increased CBF, ameliorated cognitive and memory functions in VaD and AD, and was more effective than memantine. MN-08 increased the survival rate of CA1 neurons and mitigated white matter lesions and axonal damage. Moreover, MN-08 protected neurons from OGD-induced loss and promoted axonal outgrowth in the hippocampus by upregulating phosphorylated Akt (p-Akt), glycogen synthase kinase-3β (p-GSK3β), and high-molecular-weight neurofilaments (p-NFH). The beneficial effects of MN-08 were attenuated by carboxy-PTIO, a potent NO scavenger, suggesting that MN-08-derived NO may alleviate cognitive impairment from cerebral hypoperfusion. Taken together, our studies demonstrate that MN-08 is a promising therapeutic agent for the treatment of dementia including VaD and AD.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"272 ","pages":"Article 110410"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625423","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

Exploring serotonergic psychedelics as a treatment for personality disorders

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-11 DOI: 10.1016/j.neuropharm.2025.110413

Brennan M. Carrithers , Daniel E. Roberts , Brandon M. Weiss , Jacob D. King , Robin L. Carhart-Harris , Alexandra R. Gordon , Broc A. Pagni , Miltiadis Moreau , Stephen Ross , Richard J. Zeifman

{"title":"Exploring serotonergic psychedelics as a treatment for personality disorders","authors":"Brennan M. Carrithers , Daniel E. Roberts , Brandon M. Weiss , Jacob D. King , Robin L. Carhart-Harris , Alexandra R. Gordon , Broc A. Pagni , Miltiadis Moreau , Stephen Ross , Richard J. Zeifman","doi":"10.1016/j.neuropharm.2025.110413","DOIUrl":"10.1016/j.neuropharm.2025.110413","url":null,"abstract":"<div><div>Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy could hold potential for addressing core features of PDs through shared mechanisms of personality modulation. Although historical literature and observational studies suggest the potential clinical utility of psychedelics in treating PDs, rigorous research is lacking, and individuals with PDs are often excluded from modern psychedelic therapy trials. In the present review, we first discuss research on the effects of psychedelics in individuals with a PD through the conventional lens of the Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.; DSM-5-TR) categorical model. Next, using the dimensional DSM Alternative Model of Personality Disorders (DSM-AMPD) as a framework, we examine how psychedelics may affect self-functioning, interpersonal functioning, and pathological personality traits. We conclude by discussing the clinical relevance of psychedelic therapy as a treatment for personality pathology, including safety considerations, gaps and limitations, and recommendations for approaching psychedelic therapy within these more complex clinical populations.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"272 ","pages":"Article 110413"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625419","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

Electrophysiological analysis of paraventricular thalamic neurons co-expressing kappa and mu opioid receptors

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-10 DOI: 10.1016/j.neuropharm.2025.110407

E.J. Kuijer , S.J. Bailey , D.J. Heal , S. Smith , S. Wonnacott , C.P. Bailey

{"title":"Electrophysiological analysis of paraventricular thalamic neurons co-expressing kappa and mu opioid receptors","authors":"E.J. Kuijer , S.J. Bailey , D.J. Heal , S. Smith , S. Wonnacott , C.P. Bailey","doi":"10.1016/j.neuropharm.2025.110407","DOIUrl":"10.1016/j.neuropharm.2025.110407","url":null,"abstract":"<div><div>The paraventricular thalamus (PVT) is a central node in the integration of stress- and reward-related information that may serve as a pivotal site for opioid receptors to exert their effects. Kappa opioid receptors (KOPrs) and mu opioid receptors (MOPrs) have dissociable and opposing roles in circuits of stress and reward. Interestingly, both are highly expressed in the PVT, however it is not known how aversive KOPr and rewarding MOPr signalling converges to dictate PVT activity and, by proxy, whole brain effects. We have investigated the function of KOPrs and MOPrs in single PVT neurons using whole-cell voltage-clamp recordings in brain slices from female and male mice (4–8 weeks). The majority of PVT neurons (69 %) co-expressed KOPr and MOPr. Activation of either receptor produced outward K<sup>+</sup> currents, with no age and sex differences. In neurons co-expressing both opioid receptors, the MOPr-induced K<sup>+</sup> current reversed around the theoretical equilibrium potential, whilst the KOPr current did not reverse at any holding potential tested. Furthermore, investigation of apparent inward currents produced by MOPr inverse agonists suggested the presence of tonically active MOPrs, predominantly in the anterior PVT. Activation of both KOPrs and MOPrs decreased glutamatergic input to PVT neurons by around 40 %, whereas only KOPr activation decreased GABAergic input, by 46 %. Together these data suggest that the balance of activation of KOPrs and MOPrs in the PVT plays a critical role in integrating stress- and reward-related signals.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"272 ","pages":"Article 110407"},"PeriodicalIF":4.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616433","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

Oxytocin receptors within the caudal lateral septum regulate social approach-avoidance, long-term social discrimination, and anxiety-like behaviors in adult male and female rats

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-10 DOI: 10.1016/j.neuropharm.2025.110409

Fardad Pirri , Cheryl M. McCormick

{"title":"Oxytocin receptors within the caudal lateral septum regulate social approach-avoidance, long-term social discrimination, and anxiety-like behaviors in adult male and female rats","authors":"Fardad Pirri , Cheryl M. McCormick","doi":"10.1016/j.neuropharm.2025.110409","DOIUrl":"10.1016/j.neuropharm.2025.110409","url":null,"abstract":"<div><div>OTR signaling promotes social approach or facilitates social avoidance, depending on the brain region involved. The lateral septum plays a critical role in regulating social interactions and memory. We investigated the role of OTR signaling in the caudodorsal lateral septum (LSc.d) in modulating social approach-avoidance behavior, long-term social discrimination memory, and anxiety-like behaviors in adult rats. Local infusion of the selective OTR antagonist L-368,899 (1 μg/0.5 μl) into the LSc.d decreased social approach, increased social vigilance, and reduced long-term social discrimination memory in both sexes. Administration of the biased OTR/Gq agonist carbetocin (0.5 μg/0.5 μl) reduced social approach and long-term social discrimination memory in both sexes, and had anxiogenic effects (increased latency to consume palatable food in test arena) only in males. In contrast, the full OTR agonist TGOT (50 ng/0.5 μl) had no effect on social approach or long-term social discrimination memory, and decreased latency to consume palatable food (anxiolytic effect). The results indicate that the oxytocin system can both promote and inhibit social behaviors depending on the differential activation of G-protein subunits and β-arrestins, as well as the pivotal role of the LS in modulating social and anxiety-like behavior in rats.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110409"},"PeriodicalIF":4.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610943","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

Side effects of microdosing lysergic acid diethylamide and psilocybin: A systematic review of potential physiological and psychiatric outcomes 麦角酰二乙胺和迷幻药的副作用：对潜在生理和精神结果的系统回顾。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-07 DOI: 10.1016/j.neuropharm.2025.110402

Stefan Modzelewski , Anna Stankiewicz , Napoleon Waszkiewicz , Kacper Łukasiewicz

{"title":"Side effects of microdosing lysergic acid diethylamide and psilocybin: A systematic review of potential physiological and psychiatric outcomes","authors":"Stefan Modzelewski , Anna Stankiewicz , Napoleon Waszkiewicz , Kacper Łukasiewicz","doi":"10.1016/j.neuropharm.2025.110402","DOIUrl":"10.1016/j.neuropharm.2025.110402","url":null,"abstract":"<div><h3>Objective</h3><div>Psychedelics are gaining renewed attention, especially through the practice of microdosing, where low doses are taken regularly. Microdosing lysergic acid diethylamide (LSD) and psilocybin is used by both healthy individuals and those with mental health conditions to improve daily functioning, reduce anxiety, and enhance mood and cognition. However, there is limited information about the side effects of this practice. This review aimed to collect and characterize the side effects of psychedelic microdosing.</div></div><div><h3>Methods</h3><div>We conducted a systematic review of original papers from PubMed, Web of Science, and Scopus (accessed August 03, 2024) that reported side effects of microdosing LSD and psilocybin. Non-English papers, non-original studies, studies without typical microdosing doses, or those lacking descriptions of side effects were excluded. Our methodology has been developed in accordance with PRISMA guidelines. Because side effects were assessed heterogeneously in these papers, we did not perform a bias evaluation.</div></div><div><h3>Results</h3><div>We included 31 studies, 15 of which we classified as laboratory studies with higher quality evidence, and 14 studies with lower quality evidence, as well as 2 clinical cases. Side effects were typically dose-dependent, mild, and short-lived. Common adverse effects included increased blood pressure, anxiety, and cognitive impairment.</div></div><div><h3>Discussion</h3><div>This review is limited by the heterogeneity in reporting side effects and the short duration of many studies. Future studies should transparently and systematically present a description of side effects.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110402"},"PeriodicalIF":4.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586389","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

Neurotransmitter imbalance and amygdala synaptic plasticity in lumbar disc herniation-induced chronic pain and related emotional Disturbances:A multi-omics analysis

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-06 DOI: 10.1016/j.neuropharm.2025.110405

Zhenyu Huang , Haibo Tan , Yuanfei Fu , Huanxin Xie , Huangsheng Tan , Kun Gao , Hongkan Lou

{"title":"Neurotransmitter imbalance and amygdala synaptic plasticity in lumbar disc herniation-induced chronic pain and related emotional Disturbances:A multi-omics analysis","authors":"Zhenyu Huang , Haibo Tan , Yuanfei Fu , Huanxin Xie , Huangsheng Tan , Kun Gao , Hongkan Lou","doi":"10.1016/j.neuropharm.2025.110405","DOIUrl":"10.1016/j.neuropharm.2025.110405","url":null,"abstract":"<div><div>Chronic pain due to lumbar disc herniation (LDH) significantly impairs quality of life and is often accompanied by emotional disturbances, such as anxiety and depression. Despite the recognition of these comorbidities, the underlying neural mechanisms remain unclear. This study investigates the role of neurotransmitter imbalances and key regulatory molecules in LDH-induced chronic pain and related emotional disturbances, with a focus on synaptic plasticity in the amygdala. A rat model of LDH was developed using male Sprague-Dawley rats. Behavioral assessments were conducted to evaluate pain hypersensitivity, anxiety, and depression-like behaviors. Cerebrospinal fluid (CSF) metabolomics and amygdala transcriptomics were employed to analyze neurotransmitter profiles and gene expression. In vitro experiments were conducted to explore the role of PRKCG in synaptic plasticity. Behavioral tests showed significant pain hypersensitivity and anxiety- and depression-like behavior in LDH rats. Metabolomic analysis revealed altered levels of glutamate and γ-aminobutyric acid (GABA) in the CSF, indicating neurotransmitter imbalances. Transcriptomic profiling identified changes in genes related to synaptic plasticity, including PRKCG. PRKCG knockdown led to reduced CAMKII phosphorylation and GRIA1 expression, supporting its role in modulating synaptic plasticity. This study provides evidence that neurotransmitter imbalances and alterations in synaptic plasticity within the amygdala may contribute to the persistence of chronic pain and associated emotional disturbances in LDH. PRKCG may represent a novel therapeutic target for treating both chronic pain and related emotional disturbances.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110405"},"PeriodicalIF":4.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586388","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

Role of endocannabinoid neurotransmission in the insular cortex on cardiovascular, autonomic and behavioral responses evoked by acute restraint stress in rats

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-04 DOI: 10.1016/j.neuropharm.2025.110404

Ivaldo J.A. Belem-Filho , Ana C.V. Godoy , Cristiane Busnardo , Alana T. Frias , Helio Zangrossi Jr. , Bruno Del Bianco Borges , Ana C.F. Herval , Fernando M.A. Correa , Carlos C. Crestani , Fernando H.F. Alves

{"title":"Role of endocannabinoid neurotransmission in the insular cortex on cardiovascular, autonomic and behavioral responses evoked by acute restraint stress in rats","authors":"Ivaldo J.A. Belem-Filho , Ana C.V. Godoy , Cristiane Busnardo , Alana T. Frias , Helio Zangrossi Jr. , Bruno Del Bianco Borges , Ana C.F. Herval , Fernando M.A. Correa , Carlos C. Crestani , Fernando H.F. Alves","doi":"10.1016/j.neuropharm.2025.110404","DOIUrl":"10.1016/j.neuropharm.2025.110404","url":null,"abstract":"<div><div>This study aimed to investigate the role of endocannabinoid mechanisms present within the insular cortex (IC) on cardiovascular, autonomic and anxiogenic-like responses evoked by an acute session of restraint in rats. For this, bilateral guide cannulas directed to the IC were implanted in male Wistar rats for intrabrain microinjection of the selective CB<sub>1</sub> receptor antagonist AM251, the selective TRPV1 receptor antagonist capsazepine, the fatty acid amide hydrolase (FAAH) inhibitor URB597 or the monoacylglycerol lipase (MAGL) inhibitor JZL184. The effects of pharmacological treatments were evaluated on restraint-evoked increases in blood pressure and heart rate, sympathetically-mediated cutaneous vasoconstriction and in delayed anxiogenic-like effect assessed 24h after stress exposure in the elevated plus maze (EPM) and open field (OF). We observed that acute restraint stress decreased the exploration of both EPM open arms and OF center region in animals treated with vehicle into the IC, thus indicating an anxiogenic-like effect. Inhibition of MAGL within the IC evoked by local treatment with JZL184 avoided the restraint-evoked anxiogenic effect. IC treatment with JZL184 also attenuated the tachycardia during restraint. The other pharmacological treatments did not modify the cardiovascular, autonomic and behavioral responses evoked by restraint. Taken together, these findings suggest that endocannabinoid neurotransmission in the IC, potentially acting through the endocannabinoid 2-arachidonoylglycerol, plays an inhibitory role in both tachycardia and anxiogenic-like effect evoked by stressful events.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110404"},"PeriodicalIF":4.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563665","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

Cuprizone-induced demyelination provokes abnormal intrinsic properties and excitatory synaptic transmission in the male mouse anterior cingulate cortex

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-03 DOI: 10.1016/j.neuropharm.2025.110403

Ryo Kawabata , Shinji Yamamoto , Nana Kamimura , Ikuko Yao , Keisuke Yoshikawa , Kohei Koga

{"title":"Cuprizone-induced demyelination provokes abnormal intrinsic properties and excitatory synaptic transmission in the male mouse anterior cingulate cortex","authors":"Ryo Kawabata , Shinji Yamamoto , Nana Kamimura , Ikuko Yao , Keisuke Yoshikawa , Kohei Koga","doi":"10.1016/j.neuropharm.2025.110403","DOIUrl":"10.1016/j.neuropharm.2025.110403","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Demyelination in the CNS provokes hyperalgesia, negative emotions, and/or cognitive impairment. Cuprizone (CPZ)-induced demyelination is a major demyelinating disease model for rodents. The anterior cingulate cortex (ACC) is a brain region that is responsible for higher brain functions related to MS symptoms. However, little is known whether CPZ exposure induces demyelination in the ACC coincides with changes to intrinsic neuron properties and synaptic transmission. In this study, we first examined if CPZ exposure induces demyelination in the male mouse ACC. CPZ exposure induced demyelination in the ACC and decreased body weight. In addition, demyelination altered intrinsic properties and excitatory synaptic transmission in layer II/III pyramidal neurons from the ACC as indicated by whole-cell patch-clamp in brain slice preparations. CPZ exposure decreased the frequency of action potentials due to increasing rheobase. At the synapse level, CPZ exposure also suppressed evoked excitatory synaptic transmission to the ACC. Finally, CPZ exposure also changed the kinetics of AMPA and NMDA receptors. These results suggest that CPZ exposure induces demyelination in the ACC coinciding with changes in intrinsic properties, action potentials and excitatory synaptic transmission.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110403"},"PeriodicalIF":4.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552644","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 novel ferroptosis inhibitor phenothiazine derivative reduces cell death and alleviates neurological impairments after cerebral hemorrhage

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-02 DOI: 10.1016/j.neuropharm.2025.110399

Bing-Qiao Wang , Yu-Fan Ma , Ru Chen , Guo-Qing Zhang , Qi Xie , Chang-Xiong Gong , Xiao-feng Cheng , Qin Zhang , Yuan Zhao , Shuang Zhang , Zhao-You Meng , Yi-Liang Fang , Cheng-Kang He , Yan-Jie Huang , Sen Lin , Qing-Wu Yang

{"title":"A novel ferroptosis inhibitor phenothiazine derivative reduces cell death and alleviates neurological impairments after cerebral hemorrhage","authors":"Bing-Qiao Wang , Yu-Fan Ma , Ru Chen , Guo-Qing Zhang , Qi Xie , Chang-Xiong Gong , Xiao-feng Cheng , Qin Zhang , Yuan Zhao , Shuang Zhang , Zhao-You Meng , Yi-Liang Fang , Cheng-Kang He , Yan-Jie Huang , Sen Lin , Qing-Wu Yang","doi":"10.1016/j.neuropharm.2025.110399","DOIUrl":"10.1016/j.neuropharm.2025.110399","url":null,"abstract":"<div><div>The precise etiology of brain injury induced by intracerebral hemorrhage (ICH) remains unclear. Currently, there are no effective therapeutic options available to slow down or prevent the progression of the disease. An increasing body of evidence suggests that ferroptosis plays a significant role in the development of injury related to ICH. Furthermore, pharmacological inhibition of ferroptosis has been identified as a promising therapeutic target for ICH injury. The compound 2-(1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)-10H-phenothiazine (compound-51), a derivative of promethazine, has been demonstrated to exhibit anti-ferroptosis and antioxidant properties. The aim of this study is to investigate the role and mechanism of action of compound-51 in a rat model of ICH. The <em>in vivo</em> experiments demonstrated that compound-51 significantly alleviated neurological impairments, reduced brain edema, and decreased hematoma volume. At the cellular level, compound-51 was observed to significantly enhance cellular survival and inhibit ferroptosis. Furthermore, compound-51 demonstrated a more pronounced therapeutic effect than Fer-1, without causing any injury to the heart, kidney, or liver. <em>In vitro</em> experiments demonstrated that compound-51 significantly increased cell viability and intracellular GPX4 levels, while reducing lipid peroxidation and oxidized glutathione levels. Collectively, these findings indicate that compound-51 exhibits a pronounced anti-ferroptosis function and alleviates neurological impairments in an ICH model, suggesting its potential as a new therapeutic agent for the treatment of ICH.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110399"},"PeriodicalIF":4.6,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552643","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

Corrigendum to “Enriched environment mitigates cognitive impairment in pre-adolescent mice following repeated neonatal sevoflurane exposure by reducing TTBK1 expression and Tau phosphorylation” [Neuropharmacology 268 (2025) 110327]

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-02-28 DOI: 10.1016/j.neuropharm.2025.110388

Yang Yu , Jiafeng Yu , Banglin Wu , Yuanlin Wang , Yun Li , Yongyan Yang , Yonghao Yu , Jingyu Feng

引用次数: 0