Neuropharmacology最新文献_第10页

CD38-mediated oxytocin signaling in paraventricular nucleus contributes to empathic pain 室旁核中cd38介导的催产素信号与共情疼痛有关。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-13 DOI: 10.1016/j.neuropharm.2025.110301

Xinying Zhang , Zifeng Wu , Siqi Yang , Yuanyuan Wang , Suwan Hu , Yawei Ji , Qi Zhang , Yuchen Bu , Chenqi Jiang , Jingyao Huang , Haoran Wang , Di Wang , Chaoli Huang , Peng Jiang , Cunming Liu , Xiaolin Yang , Chun Yang , Ling Yang , Riyue Jiang

{"title":"CD38-mediated oxytocin signaling in paraventricular nucleus contributes to empathic pain","authors":"Xinying Zhang , Zifeng Wu , Siqi Yang , Yuanyuan Wang , Suwan Hu , Yawei Ji , Qi Zhang , Yuchen Bu , Chenqi Jiang , Jingyao Huang , Haoran Wang , Di Wang , Chaoli Huang , Peng Jiang , Cunming Liu , Xiaolin Yang , Chun Yang , Ling Yang , Riyue Jiang","doi":"10.1016/j.neuropharm.2025.110301","DOIUrl":"10.1016/j.neuropharm.2025.110301","url":null,"abstract":"<div><div>Empathy plays a crucial role in social communication and the perception of affective states and behavioral processes. In this study, we observed that empathic interaction with a mouse experiencing pain resulted in decreased mechanical pain thresholds and anxiety-like behaviors in its bystander, though the underlying mechanisms remain unknown. We demonstrated that CD38 expression in the paraventricular nucleus (PVN) was upregulated during empathic pain, and the pain and emotions of CD38 knockout (CD38KO) mice as bystanders were not affected. Furthermore, fiber photometry recordings indicated that calcium activities of PVN neurons were increased during empathic pain. Interestingly, direct chemogenetic inhibition of PVN neurons attenuated the hyperalgesia and anxiety-like behaviors associated with empathic pain. In contrast, activating PVN neurons through chemogenetics in CD38KO mice induced hyperalgesia and anxiety-like effects in empathic pain. Oxytocin levels in PVN were upregulated during empathic pain, while CD38KO mice inhibit the upregulation in OXT levels, confirming that CD38 is involved in releasing brain OXT and that the CD38-OXT system in the PVN plays a role in empathic pain. Collectively, CD38-mediated oxytocin signaling in PVN is closely linked to empathic pain through its effect on the activation of PVN neurons, and it could be viable targets for novel empathic behavior interventions.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"267 ","pages":"Article 110301"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008897","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

Effects of chronic ethanol exposure on dorsal medial striatal neurons receiving convergent inputs from the orbitofrontal cortex and basolateral amygdala 慢性乙醇暴露对接受眶额皮质和杏仁核基底外侧趋同输入的背内侧纹状体神经元的影响。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-13 DOI: 10.1016/j.neuropharm.2025.110303

Sudarat Nimitvilai-Roberts , Marcelo F. Lopez , John J. Woodward

{"title":"Effects of chronic ethanol exposure on dorsal medial striatal neurons receiving convergent inputs from the orbitofrontal cortex and basolateral amygdala","authors":"Sudarat Nimitvilai-Roberts , Marcelo F. Lopez , John J. Woodward","doi":"10.1016/j.neuropharm.2025.110303","DOIUrl":"10.1016/j.neuropharm.2025.110303","url":null,"abstract":"<div><div>Alcohol use disorder is associated with altered function of cortical-amygdala-striatal circuits such as the orbitofrontal cortex (OFC), basolateral amygdala (BLA) and their connections to the dorsal medial striatum (DMS) shown to be involved in goal-directed actions. Using retrobead tracing, we previously reported enhanced excitability of DMS-projecting OFC neurons in mice following 3-to-7-day withdrawal from chronic intermittent ethanol (CIE) exposure. In the same animals, spiking of DMS-projecting BLA neurons was decreased at 3-days post-withdrawal followed by an increase in firing at 7- and 14-days. In the current study, we used transsynaptic labeling and slice electrophysiology to investigate the effects of CIE exposure on DMS neurons that receive convergent inputs from the OFC and BLA. Mice were infused with anterograde transsynaptic AAVs in the OFC (AAV1-Cre) and BLA (AAV1-Flpo) and a Cre-On/Flp-On-YFP AAV in the DMS followed by 4 weekly cycles of Air or CIE vapor exposure. Current-clamp recordings of YFP + DMS<sup>OFC−BLA</sup> neurons showed three distinct patterns of firing: regular spiking, regular spiking followed by depolarization block and regular spiking with the appearance of broadened action potentials and plateau potentials at higher current steps (termed FANS). In both male and female mice, withdrawal from CIE exposure significantly increased the excitability of regular spiking neurons as compared to air controls. More subtle effects were observed on FANS neurons with both increases and decreases in firing that were current step and sex-dependent. These findings add to a growing literature demonstrating how neurons within cortical-amygdala-striatal circuits implicated in compulsive/habitual behaviors are impacted by chronic alcohol exposure.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"267 ","pages":"Article 110303"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008900","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

Berberine ameliorates seizure activity and cardiac dysfunction in pentylenetetrazol-kindling seizures in rats: Modulation of sigma1 receptor, Akt/eNOS signaling, and ferroptosis 小檗碱改善戊四唑点燃大鼠癫痫发作的癫痫活动和心功能障碍：调节sigma1受体、Akt/eNOS信号和铁下垂。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-10 DOI: 10.1016/j.neuropharm.2025.110295

Shrouk M. Basiouny , Hala F. Zaki , Shimaa M. Elshazly , Ahmed F. Mohamed

{"title":"Berberine ameliorates seizure activity and cardiac dysfunction in pentylenetetrazol-kindling seizures in rats: Modulation of sigma1 receptor, Akt/eNOS signaling, and ferroptosis","authors":"Shrouk M. Basiouny , Hala F. Zaki , Shimaa M. Elshazly , Ahmed F. Mohamed","doi":"10.1016/j.neuropharm.2025.110295","DOIUrl":"10.1016/j.neuropharm.2025.110295","url":null,"abstract":"<div><div>Seizures can lead to cardiac dysfunction. Multiple pathways contribute to this phenomenon, of which the chaperone sigma-1 receptor (S1R) signaling represents a promising nexus between the abnormalities seen in both epilepsy and ensuing cardiac complications. The study explored the potential of Berberine (BER), a promising S1R agonist, in treating epilepsy and associated cardiac abnormalities in a pentylenetetrazol (PTZ) kindling rat model of epilepsy. Male Wistar albino rats received PTZ (35 mg/kg) every other day alone, with BER, with phenytoin (PHT), with both BER and PHT and with both BER and an S1R blocker (NE-100) over 27 days. BER decreased seizure severity and improved hemodynamic parameters. Histopathological abnormalities were more pronounced in the PTZ, and blocker group than in other groups, in heart tissue. In cardiac tissue, BER enhanced the AKT/eNOS signaling pathway and mitigated ferroptosis by boosting the cystine/glutamate transporter/Glutathione/Glutathione Peroxidase 4 (XCT/GSH/GPX4) system and ferritin heavy chain-1 (FTH-1) expression, while reducing iron and Transferrin receptor protein 1 (TFR1) levels. Such effects were largely negated by NE-100 pretreatment. In conclusion, BER shows protective effects on cardiac dysfunction induced by the PTZ kindling model by acting as an S1R agonist and influencing the AKT/eNOS signaling pathway and ferroptosis.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"267 ","pages":"Article 110295"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971514","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 novel miR_146-Tfdp2 axis antagonizes METH induced neuron apoptosis and cell cycle abnormalities in tree shrew 新型miR_146-Tfdp2轴拮抗甲基醚诱导的树鼩神经元凋亡和细胞周期异常。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-09 DOI: 10.1016/j.neuropharm.2025.110300

Shuwei Zhang , Chan Wang , Jianxing Liu , Liu Liu , Lin Miao , Haowei Wang , Yunqing Tian , Hao Cheng , Juan Li , Xiaofeng Zeng

{"title":"The novel miR_146-Tfdp2 axis antagonizes METH induced neuron apoptosis and cell cycle abnormalities in tree shrew","authors":"Shuwei Zhang , Chan Wang , Jianxing Liu , Liu Liu , Lin Miao , Haowei Wang , Yunqing Tian , Hao Cheng , Juan Li , Xiaofeng Zeng","doi":"10.1016/j.neuropharm.2025.110300","DOIUrl":"10.1016/j.neuropharm.2025.110300","url":null,"abstract":"<div><div>Methamphetamine (METH) is a synthetic drug with potent addictive, relapse, and neurotoxic properties. METH abuse contributes to severe damage to the central nervous system, potentially causing cognitive impairments, behavioral changes, and neurodegenerative diseases. METH-induced neuronal damage is closely related to apoptosis and cell cycle abnormalities, while gene expression regulator microRNAs (miRNAs) may play extensive roles in this progress, but the specific mechanisms remain unclear. We found that the novel miRNA 146 (miR_146) was downregulated in METH-induced apoptosis and cell cycle arrest in tree shrew primary neurons, while the expression of its target gene <em>Tfdp2</em> was increased after METH exposure. Overexpression of miR_146 or silencing of <em>Tfdp2</em> significantly alleviated METH-induced cell cycle arrest and apoptosis in primary tree shrew neurons. These findings provide new insights into the role of the miR_146-<em>Tfdp2</em> axis in METH-induced neurotoxic injury and offer a theoretical basis for miR_146 as potential therapeutic targets in drug abuse.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"267 ","pages":"Article 110300"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966128","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

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