Neuroscience Letters最新文献_第8页

Differential expression of TRPV1 and TRPM8 in the mouse trigeminal ganglion and spinal dorsal root ganglion TRPV1和TRPM8在小鼠三叉神经节和脊髓背根神经节中的差异表达。

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-20 Epub Date: 2025-10-10 DOI: 10.1016/j.neulet.2025.138413

Caifeng Shao , Jichao Wei , Hong-Yi Jia , Yu-Han Zhou , Mingwei Zhao , Kun Yang , Ming-Ming Zhang

引用次数: 0

Dexmedetomidine improves postoperative cognitive dysfunction via regulating Adrb2/Pkg 右美托咪定通过调节Adrb2/Pkg改善术后认知功能障碍：右美托咪定抗术后认知功能障碍。

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-20 Epub Date: 2025-10-01 DOI: 10.1016/j.neulet.2025.138406

Cuirong Chen , Hong Han , Hongzhe Li , Zitan Zhang , Yingbing Lv

{"title":"Dexmedetomidine improves postoperative cognitive dysfunction via regulating Adrb2/Pkg","authors":"Cuirong Chen , Hong Han , Hongzhe Li , Zitan Zhang , Yingbing Lv","doi":"10.1016/j.neulet.2025.138406","DOIUrl":"10.1016/j.neulet.2025.138406","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative cognitive dysfunction (POCD) refers to postoperative neurological complications in patients, thus affecting patients’ normal daily life.</div></div><div><h3>Purpose</h3><div>Our study aimed to confirm whether <em>Adrb2/Pkg</em> are involved in the protective effect of Dexmedetomidine (Dex) against POCD in rats.</div></div><div><h3>Methods</h3><div>The targets for Dex against POCD were screened by online databases. An POCD rat model was constructed, and the Morris water maze tests were conducted to evaluate the cognitive function of POCD rats. The inflammatory markers (IL-6, TNF-α, and IL-13) were recorded, and the levels of <em>Adrb2</em> and <em>Pkg</em> in hippocampus tissue were detected using RT-qPCR. The key targets <em>Adrb2/Pkg</em> were verified through the LPS-induced inflammatory BV-2 cell model.</div></div><div><h3>Results</h3><div>Network pharmacology analysis predicted that <em>Adrb2</em> and <em>Pkg</em> were the key genes of Dex against POCD. Dex treatment improved learning and memory skills of POCD rats. <em>In vitro</em> and <em>in vivo</em> experiments showed that Dex treatment alleviated inflammation, and upregulated <em>Adrb2</em> and <em>Pkg</em> mRNA levels of POCD rats and inflammatory BV-2 cell line. Silencing <em>Adrb2/Pkg</em> reversed the apoptosis suppression in LPS-induced inflammatory BV-2 cells caused by Dex.</div></div><div><h3>Conclusion</h3><div>The <em>Adrb2/Pkg</em> could potentially be the mechanism by which Dex protects POCD rats from cognitive impairment.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"868 ","pages":"Article 138406"},"PeriodicalIF":2.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Hydrogen sulfide protects against hippocampal neuronal apoptosis in aged rats with postoperative cognitive dysfunction by promoting m6A methylation 硫化氢通过促进m6A甲基化对术后认知功能障碍老年大鼠海马神经元凋亡的保护作用。

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-20 Epub Date: 2025-09-30 DOI: 10.1016/j.neulet.2025.138405

Bo Wang , YongPan Wen , Yonghong Tang , Min Li

{"title":"Hydrogen sulfide protects against hippocampal neuronal apoptosis in aged rats with postoperative cognitive dysfunction by promoting m6A methylation","authors":"Bo Wang , YongPan Wen , Yonghong Tang , Min Li","doi":"10.1016/j.neulet.2025.138405","DOIUrl":"10.1016/j.neulet.2025.138405","url":null,"abstract":"<div><h3>Purpose</h3><div>To explore the potential involvement of m6A methylation in the neuroprotective mechanism of H<sub>2</sub>S against hippocampus neuronal apoptosis in aged rats with POCD.</div></div><div><h3>Methods</h3><div>Sprague-Dawley rats (18–20 months) were subjected to anesthesia and laparotomy surgery to establish an animal model of POCD. The Open Field, Y-maze, and Novel Object Recognition tests assessed behavioral performance. Protein expression levels were analyzed using Western blot analysis, and neuronal apoptosis was analyzed using TUNEL staining.</div></div><div><h3>Results</h3><div>NaHS (100 μmol/kg) significantly increased the alternation ratio of the Y-maze test and the discrimination index of the NOR test, reduced hippocampal neuronal apoptosis, indicated by decreased TUNEL-positive neurons and modulated the expression of apoptosis-related protein markers (Bcl-2 was upregulated and Bax/Cleaved caspase-3 were downregulated). Furthermore, NaHS restored reduced m<sup>6</sup>A RNA methylation levels and corrected the disturbed expression of m<sup>6</sup>A-related enzymes (METTL3, METTL14, YTHDF1, YTHDF3, FTO, ALKBH5) in the hippocampus of aged rats with POCD.</div></div><div><h3>Conclusion</h3><div>H<sub>2</sub>S shows neuroprotective effects by mitigating hippocampal neuronal apoptosis and restoring m<sup>6</sup>A RNA methylation in the hippocampus of aged rats with POCD. These findings provide preclinical evidence that H<sub>2</sub>S may serve as a potential therapeutic agent for the prevention of POCD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"868 ","pages":"Article 138405"},"PeriodicalIF":2.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Mitochondrial dysfunction and aging can be alleviated by modulating calcineurin and cardiolipin dynamics following stroke 脑卒中后可通过调节钙调磷酸酶和心磷脂动态来缓解线粒体功能障碍和衰老。

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-20 Epub Date: 2025-10-06 DOI: 10.1016/j.neulet.2025.138410

Pallab Bhattacharya , Shailendra Saraf , Anirban Barik , Bijoyani Ghosh , Aishika Datta , Davendra Singh Malik

{"title":"Mitochondrial dysfunction and aging can be alleviated by modulating calcineurin and cardiolipin dynamics following stroke","authors":"Pallab Bhattacharya , Shailendra Saraf , Anirban Barik , Bijoyani Ghosh , Aishika Datta , Davendra Singh Malik","doi":"10.1016/j.neulet.2025.138410","DOIUrl":"10.1016/j.neulet.2025.138410","url":null,"abstract":"<div><div>The crucial influence of mitochondria in ischemic stroke pathophysiology presents many unexplored yet promising avenues for therapeutic strategies and clinical outcomes. Post-stroke mitochondrial dysfunction contributes to aggravated levels of calcium overload and apoptosis. This dysfunction is signified by disruption of the mitochondrial lipids such as cardiolipin, along with mitochondrial DNA mutation, leading to an imbalance in mitophagy. Calcium overload-mediated calcineurin overexpression has been reported to exacerbate mitochondrial damage and further contribute to neuronal apoptosis. In our study, we explored the alterations in the mitochondrial function following inhibition of the calcium-mediated calcineurin levels in post-stroke condition. In a rodent model of middle cerebral artery occlusion (MCAo), we observed that the inhibition of the calcium channels in post-stroke condition led to restored neuronal histology and viability following upregulation of the antioxidant levels. At the mitochondrial level, calcium channel inhibition downregulated calcineurin activation and normalized cardiolipin concentration, mitochondrial membrane potential, and respiratory control ratio in post-stroke condition. This inhibition also balanced the mitochondrial dynamics proteins and mitophagy towards neuronal recovery following ischemic stress. Moreover, it also normalized the expression of TERT, a key marker of mitochondrial health and aging. These findings highlight the role of calcium-mediated calcineurin in influencing mitochondrial dysfunction and aging in ischemic stroke. Thus, calcium channel inhibition offers a promising therapeutic strategy by preserving mitochondrial integrity and promoting neuroprotection following stroke.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"868 ","pages":"Article 138410"},"PeriodicalIF":2.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

GABAergic disinhibition through the STING-dependent autophagic pathway in the dorsal horn underlies diabetic neuropathic pain pathogenesis 糖尿病神经性疼痛的发病机制是通过背角中sting依赖的自噬途径解除gaba能抑制。

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-20 Epub Date: 2025-09-28 DOI: 10.1016/j.neulet.2025.138391

Ya-Jie Zhao , Hong-Zhen Bai , Yi-Na Wang , Yu-Kun Liu , Long-Biao Zhao , Zhao Li , Hui-Zhou Li , Xiu-Li Wang , Peng Liu

{"title":"GABAergic disinhibition through the STING-dependent autophagic pathway in the dorsal horn underlies diabetic neuropathic pain pathogenesis","authors":"Ya-Jie Zhao , Hong-Zhen Bai , Yi-Na Wang , Yu-Kun Liu , Long-Biao Zhao , Zhao Li , Hui-Zhou Li , Xiu-Li Wang , Peng Liu","doi":"10.1016/j.neulet.2025.138391","DOIUrl":"10.1016/j.neulet.2025.138391","url":null,"abstract":"<div><div>Our previous study demonstrated that STING/ATG5-mediated autophagy in the spinal dorsal horn contributes to diabetic neuropathic pain (DNP), although the underlying mechanisms remained unclear. In this study, we investigated how STING-driven autophagy leads to impaired spinal inhibition via lysosomal degradation of GABA receptors. In a rat model of DNP, spinal levels of STING and ATG5 were elevated, while P62, GABA<sub>A</sub> receptor, and GABA<sub>B</sub> receptor expression were reduced. Behavioral tests showed that intrathecal administration of a STING inhibitor increased mechanical pain thresholds and upregulated P62 and GABA receptors. Conversely, treatment with a STING agonist worsened hyperalgesia and further suppressed GABA receptor expression. Knockdown of ATG5 via siRNA similarly alleviated pain and restored GABA receptor levels. Interestingly, although the mTOR inhibitor rapamycin alleviated neuropathic pain, it unexpectedly increased spinal P62 expression compared to the DNP group. Administration of leupeptin, a lysosomal protease inhibitor, significantly increased paw withdrawal thresholds on days 1–3 and elevated GABA receptor expression, whereas the proteasomal inhibitor MG132 had no effect. These results demonstrate that STING/ATG5-mediated autophagy promotes DNP through autophagic-lysosomal degradation of GABA receptors, highlighting this pathway as a promising therapeutic target for treating diabetic neuropathic pain.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"868 ","pages":"Article 138391"},"PeriodicalIF":2.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Stable Traits, Adaptive Brains: links between Visual Homeostatic Plasticity and Personality 稳定特征，适应性大脑：视觉稳态可塑性与个性之间的联系。

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-20 Epub Date: 2025-10-10 DOI: 10.1016/j.neulet.2025.138414

Marina Baroni , Valentina Cesari , Angelo Gemignani , Maria Concetta Morrone , Claudia Lunghi , Danilo Menicucci

{"title":"Stable Traits, Adaptive Brains: links between Visual Homeostatic Plasticity and Personality","authors":"Marina Baroni , Valentina Cesari , Angelo Gemignani , Maria Concetta Morrone , Claudia Lunghi , Danilo Menicucci","doi":"10.1016/j.neulet.2025.138414","DOIUrl":"10.1016/j.neulet.2025.138414","url":null,"abstract":"<div><div>This study explores the relationship between personality traits and visual homeostatic plasticity, a neural mechanism maintaining stable the brain activity. Actually, personality may influence neuroplasticity, the general brain ability to adapt through experiences. Indeed, prior research links traits like openness to experience and neuroticism to Hebbian plasticity (experience-based synaptic strengthening), but any connections to homeostatic plasticity remain largely unexplored.</div><div>To probe homeostatic plasticity we tested the effect of short-term monocular deprivation in 24 healthy adults. Participants wore an eye patch for two hours, and underwent binocular rivalry tests measuring shifts in perceptual dominance. The deprivation index, reflecting homeostatic plasticity in the primary visual cortex, was analysed alongside personality traits assessed via the Big Five Questionnaire.</div><div>Results revealed a positive correlation between the deprivation index and conscientiousness but a negative correlation with emotional stability. Conscientious individuals, often goal-directed and self-regulated, showed reduced homeostatic plasticity, suggesting diminished mental flexibility. Conversely, higher emotional stability (lower neuroticism) enhanced homeostatic plasticity, aligning with findings that neuroticism reduces resilience, a potential link to impaired plasticity.</div><div>Overall, the study suggests that homeostatic plasticity, often limited to sensory adaptation, might reflect broader brain regulatory properties that appear to be linked to personality traits.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"868 ","pages":"Article 138414"},"PeriodicalIF":2.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Regional differences in oxytocin and vasopressin 1a receptor functionality in mouse embryonic brain development 小鼠胚胎脑发育中催产素和抗利尿激素1a受体功能的区域差异。

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-20 Epub Date: 2025-10-05 DOI: 10.1016/j.neulet.2025.138409

Elliot Sommer , Heather K. Caldwell

{"title":"Regional differences in oxytocin and vasopressin 1a receptor functionality in mouse embryonic brain development","authors":"Elliot Sommer , Heather K. Caldwell","doi":"10.1016/j.neulet.2025.138409","DOIUrl":"10.1016/j.neulet.2025.138409","url":null,"abstract":"<div><div>There is mounting evidence that the oxytocin (Oxt) and vasopressin (Avp) systems contribute to early brain development. Work from transgenic mouse models as well as pharmacological manipulation of the Oxt and Avp systems suggests that signaling through the Oxt receptor (Oxtr) and the Avp 1a receptor (Avpr1a) during embryonic brain development affects behavior in adulthood. Unfortunately, at this time, very little is known or understood about where in the brain Oxtr and Avpr1a occurs during embryonic development or what the downstream consequences may be. To help provide some answers, Oxtr- and Avpr1a-stimulated G-protein coupled receptor binding assays were performed using guanosine 5′-(γ-thio)triphosphate, a non-hydrolyzable analog of guanosine triphosphate, to determine the functionality of the Oxtr and Avpr1a in both sexes at embryonic day (E) 14.5, E16.5, and E18.5. Based on previous work, we hypothesized that the Oxtr and Avpr1a would be functional in both sexes by E16.5 and activated by Oxt and Avp, respectively. The data suggest that while the Oxtr and Avpr1a are functional in both sexes starting at E16.5, where in the brain they are functional is not fully aligned with where there is known receptor binding. For the Oxtr, at E16.5, functional binding was observed in the ventricular and subventricular zones of the cortical and septal neuroepithelium and the amygdalar area, this shifted by E18.5 with functional binding observed only in the ventricular and subventricular septal neuroepithelium and the amygdalar area, with no functional binding observed in the ventricular and subventricular cortical neuroepithelium. For the Avpr1a, at E16.5, functional binding was only observed in the ventral hypothalamic area but by E18.5 functional binding was observed across numerous brain regions. Taken together, these data suggest that Oxtr and Avpr1a signaling is positioned to have site-specific effects on mouse brain development starting at E16.5.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"868 ","pages":"Article 138409"},"PeriodicalIF":2.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Relationship between prefrontal oxygenation during task-set period and executive function in healthy older people: A near-infrared spectroscopy study 健康老年人任务设定期前额叶氧合与执行功能的关系：近红外光谱研究

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-20 Epub Date: 2025-09-27 DOI: 10.1016/j.neulet.2025.138395

Yumi Oboshi , Mitsuru Kikuchi , Yasuomi Ouchi

{"title":"Relationship between prefrontal oxygenation during task-set period and executive function in healthy older people: A near-infrared spectroscopy study","authors":"Yumi Oboshi , Mitsuru Kikuchi , Yasuomi Ouchi","doi":"10.1016/j.neulet.2025.138395","DOIUrl":"10.1016/j.neulet.2025.138395","url":null,"abstract":"<div><h3>Introduction</h3><div>In past research, we have examined the characteristics of brain activity caused by prefrontal task completion in healthy older adults in a simplified manner using a near-infrared spectroscopy device, with the aim of identifying methods of early intervention to prevent their cognitive decline. Previously, we reported that prefrontal oxygenation during pre-task preparation was greater in young adults than older adults, and that this greater activation was associated with better task performances in both groups. To extend this research, in the present study, we examined previous findings with task repetitions, as older adults take more time to become familiar new tasks.</div></div><div><h3>Methods</h3><div>We modified the working memory task with a clear task-set instruction and examined the change in the task-set and task-induced activation in 63 cognitively healthy older adults.</div></div><div><h3>Results</h3><div>Task-set activation did not increase even after three repetitions, and the task-induced activation was greater than task-set activation in most channels. The difference in degree between task-induced activation and task-set activation showed a reduction with task repetitions. Significant inverse correlations were observed between the prefrontal activation due to the task itself in the third session, i.e., after task repetitions and the reaction time of the Trail Making Test, which represents attentional function.</div></div><div><h3>Discussion</h3><div>These results indicate that continued activation by the task itself, which persists even after older adults become familiar with the task, may be associated with executive function decline.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"868 ","pages":"Article 138395"},"PeriodicalIF":2.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Dynamic current-clamp unveiling the indispensable interplay between Nav1.7 and Nav1.8 for shaping action potential trajectory and retaining neuroexcitation of visceral sensory neurons 动态电流钳揭示了Nav1.7和Nav1.8在形成动作电位轨迹和保持内脏感觉神经元神经兴奋方面不可或缺的相互作用。

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-01 Epub Date: 2025-09-20 DOI: 10.1016/j.neulet.2025.138387

Ying Li , Chen Zhang , Limin Han , Zhao Qian

{"title":"Dynamic current-clamp unveiling the indispensable interplay between Nav1.7 and Nav1.8 for shaping action potential trajectory and retaining neuroexcitation of visceral sensory neurons","authors":"Ying Li , Chen Zhang , Limin Han , Zhao Qian","doi":"10.1016/j.neulet.2025.138387","DOIUrl":"10.1016/j.neulet.2025.138387","url":null,"abstract":"<div><div>Tetrodotoxin (TTX)-sensitive/Nav1.7- and TTX-resistive/Nav1.8 Na<sup>+</sup> channels contribute to neuroexcitation in the sensory neurons of the nodose ganglion (NG); however, their specific roles remain debatable. Therefore, we aimed to study the action potential (AP) elicited from NG neurons isolated from adult rats and simulated by a dynamic current clamp (DCC) using gNa0/Nav1.7 and/or gNa1/Nav1.8 injection. We trained and tuned the voltage-dependent profiles of the Na<sup>+</sup> current generated from the DCC using the Hodgkin–Huxley/Vandenberg models to match the AP parameters elicited by a brief pulse. A- or C-type AP could be simulated using DCC by applying gNa0 or gNa0/gNa1 alongside reduced gNa0 to avoid overshooting the up-stroke. This indicates the indispensability of these two Na<sup>+</sup> channels for shaping the AP trajectory with tight orchestration. The hump over the repolarization period featuring C-type neurons could be generated using DCC by adding gNa1 in this cellular model. Furthermore, both A- and C-type repeated discharges can be simulated using gNa0 or gNa1 with a reduced gNa0. Similar experiments were performed on human embryonic kidney 293 cells with stable Nav1.7 expression to mimic A-type-like conditions for further verification. Both A- and C-type-like APs were simulated in this expression system by adding gNa0 or gNa0/gNa1. Therefore, Nav1.7/Nav1.8 is crucial in shaping the AP trajectory, with specific timing for Nav1.8 activation to retain neuroexcitation in the sensory nervous system. Additionally, this pilot study will establish a fundamental base for the pharmacological screening of targeted ion channels and validate the disease-based mechanism in cardiology and neuroscience.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138387"},"PeriodicalIF":2.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 angiotensin II type 2 receptor antagonist TDI05 alleviates the peripheral neuropathic pain 新型血管紧张素II型2受体拮抗剂TDI05可减轻周围神经性疼痛。

IF 2 4区医学

Neuroscience Letters Pub Date : 2025-11-01 Epub Date: 2025-08-28 DOI: 10.1016/j.neulet.2025.138369

Qilong Mao , Yu Zeng , Huining Liang , Siyu Hou , Qi Wang , Jiaxin Zhang , Zhou Lan , Hongjun Wang , Jing Wang , Hongmei Zhao

{"title":"A novel angiotensin II type 2 receptor antagonist TDI05 alleviates the peripheral neuropathic pain","authors":"Qilong Mao , Yu Zeng , Huining Liang , Siyu Hou , Qi Wang , Jiaxin Zhang , Zhou Lan , Hongjun Wang , Jing Wang , Hongmei Zhao","doi":"10.1016/j.neulet.2025.138369","DOIUrl":"10.1016/j.neulet.2025.138369","url":null,"abstract":"<div><div>Neuropathic pain is a debilitating chronic pain condition often associated with heightened inflammatory responses and increased angiotensin II type 2 receptor (AT<sub>2</sub>R) expression. This study systematically evaluated the therapeutic efficacy of TDI05, a novel AT<sub>2</sub>R antagonist, for treating neuropathic pain management. <em>In vitro</em> experiments using RAW 264.7 macrophages showed that TDI05 treatment significantly reduced AT<sub>2</sub>R expression at both the protein and mRNA levels, as determined by Western blotting and qPCR analysis, while CCK-8 assays confirmed its non-cytotoxicity. ELISA showed TDI05 reduced the production of inflammatory mediators (TNF-α, IL-1β, IL-8) by RAW 264.7 cells. Remarkably, in co-cultured systems with HT22 neuronal cells, these anti-inflammatory effects corresponded to significant down-regulation of pain-related ion channels transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1). <em>In vivo</em> validation utilizing three well-established rodent neuropathic pain models, TDI05 administration produced dose-dependent analgesic effects, significantly increasing mechanical withdrawal thresholds. Furthermore, immunofluorescence staining showed TDI05 reduced AT<sub>2</sub>R expression in sciatic nerve macrophages, while immunohistochemistry analysis confirmed suppression of TRPA1/TRPV1 expression in sensory neurons in the mouse spared nerve injury (SNI) model. Collectively, these findings establish TDI05 as a compelling therapeutic candidate for neuropathic pain treatment through AT<sub>2</sub>R-mediated inflammatory pathway inhibition and subsequent nociceptive TRP channel inhibition.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"867 ","pages":"Article 138369"},"PeriodicalIF":2.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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