Neuroscience Letters最新文献

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Repeated exposure to motor imagery enhances focal brain activation during motor imagery practice after stroke 反复暴露于运动意象增强脑卒中后运动意象练习局灶性激活。
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-03-15 Epub Date: 2026-01-16 DOI: 10.1016/j.neulet.2026.138510
Sara M. Klick , Cristina Rubino , Justine R. Magnuson , Lauren Penko , Anjana Rajendran , Ronan Denyer , Christina B. Jones , Jordan Brocato , Chris Lamb , Cristina Schaurich , Lara A. Boyd , Sarah N. Kraeutner
{"title":"Repeated exposure to motor imagery enhances focal brain activation during motor imagery practice after stroke","authors":"Sara M. Klick ,&nbsp;Cristina Rubino ,&nbsp;Justine R. Magnuson ,&nbsp;Lauren Penko ,&nbsp;Anjana Rajendran ,&nbsp;Ronan Denyer ,&nbsp;Christina B. Jones ,&nbsp;Jordan Brocato ,&nbsp;Chris Lamb ,&nbsp;Cristina Schaurich ,&nbsp;Lara A. Boyd ,&nbsp;Sarah N. Kraeutner","doi":"10.1016/j.neulet.2026.138510","DOIUrl":"10.1016/j.neulet.2026.138510","url":null,"abstract":"<div><div>Stroke results in motor impairments of the upper limbs, linked to altered activation in sensorimotor regions. Motor imagery (MI; the mental rehearsal of movement) activates sensorimotor regions, providing the basis for its effectiveness as an intervention for motor recovery after stroke. Yet, the effect of repeated MI on brain activation after stroke is unexplored. In this study, thirty-three individuals with stroke (&gt;3 months) performed MI of an upper-limb movement using their paretic arm and hand across two sessions on two different days. Brain activation was obtained via functional magnetic resonance imaging (fMRI). Group-level contrasts revealed: 1) focal brain activation in Session 2 relative to Session 1, and 2) functional localization to sensorimotor regions. Together, these findings demonstrate that MI induces changes in brain activation after only two sessions in individuals with stroke, specifically encompassing activation in sensorimotor areas. Familiarizing individuals to MI prior to its use may improve applications of MI for learning and recovery.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138510"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998444","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
Differential neuroinflammatory trajectories in the hippocampus and prefrontal cortex after acute LPS administration 急性LPS处理后海马和前额皮质的不同神经炎症轨迹。
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-03-15 Epub Date: 2026-01-08 DOI: 10.1016/j.neulet.2026.138504
Zhouli Yue , Mengyuan Li , Jiahui Wang , Siqi Quan , Yiqi Wang , Zhanying Niu , Yucheng Li
{"title":"Differential neuroinflammatory trajectories in the hippocampus and prefrontal cortex after acute LPS administration","authors":"Zhouli Yue ,&nbsp;Mengyuan Li ,&nbsp;Jiahui Wang ,&nbsp;Siqi Quan ,&nbsp;Yiqi Wang ,&nbsp;Zhanying Niu ,&nbsp;Yucheng Li","doi":"10.1016/j.neulet.2026.138504","DOIUrl":"10.1016/j.neulet.2026.138504","url":null,"abstract":"<div><div>Neuroinflammation is a key pathological feature of central nervous system disorders, yet its temporal and regional dynamics remain poorly defined. In this study, we systematically investigated neuroinflammatory responses and neuronal injury in the hippocampus and prefrontal cortex following a single intraperitoneal injection of lipopolysaccharide (LPS, 1 mg/kg) in mice. Fifty-four male C57BL/6N mice were randomly divided into six groups, and serum and brain tissues were collected at 0, 3, 6, 12, 24, and 48 h after LPS administration. Cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA), neuronal injury was assessed by Nissl staining, and proteins expression was examined by Western blot. The results showed that peripheral cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), exhibited a rapid and transient increase, peaking at 3 h and returning to baseline within 24 h, whereas central inflammatory responses displayed marked region- and time-dependent differences. In the hippocampus, IL-1β showed delayed but sustained elevation, peaking at 12 h and accompanied by progressive neuronal injury. In contrast, the prefrontal cortex exhibited an early cytokines surge at 3 h, with prolonged IL-1β elevation, and a biphasic pattern of neuronal damage characterized by early injury, partial recovery, and delayed exacerbation. These spatiotemporal dynamics were paralleled by differential activation of the TLR4/MyD88/NF-κB pathway. These findings reveal that LPS-induced neuroinflammation is a heterogeneous and dynamic process rather than a uniform response, providing new insight into region-specific vulnerability and the dissociation between peripheral and central inflammatory kinetics.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138504"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949146","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
Dose-dependent impact of extremely low-frequency electromagnetic field (ELF-EMF) on the neuroplasticity in the hippocampus of adult rats 极低频电磁场(ELF-EMF)对成年大鼠海马神经可塑性的剂量依赖性影响
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-03-15 Epub Date: 2026-01-14 DOI: 10.1016/j.neulet.2026.138520
Maciej Klimiuk , Hanna Kletkiewicz , Joanna Wyszkowska , Karol Dokladny , Justyna Rogalska
{"title":"Dose-dependent impact of extremely low-frequency electromagnetic field (ELF-EMF) on the neuroplasticity in the hippocampus of adult rats","authors":"Maciej Klimiuk ,&nbsp;Hanna Kletkiewicz ,&nbsp;Joanna Wyszkowska ,&nbsp;Karol Dokladny ,&nbsp;Justyna Rogalska","doi":"10.1016/j.neulet.2026.138520","DOIUrl":"10.1016/j.neulet.2026.138520","url":null,"abstract":"<div><div>Extremely low-frequency electromagnetic field (ELF-EMF) therapy is gaining attention for its potential benefits in treating neurodegenerative conditions. However, the underlying molecular mechanisms responsible for the possible protective effects of ELF-EMF remain unclear. Our previous research revealed that ELF-EMF exposure can establish a new “set-point” for stress responses, with outcomes dependent on field intensity. Stress hormones have been shown to modulate hippocampal function and plasticity. Therefore, our study aimed to assess how ELF-EMF exposure affects the expression of transcripts related to hippocampal plasticity, including genes related to neurogenesis (BDNF, TrkB, GAP43), synaptic activity (PSD95, SYN1), and cell survival (Bcl-2, Bcl-xL, Bak1). Adult rats were exposed to ELF-EMF (50 Hz) at 1 mT and 7 mT intensities for three 7-day periods, 1 h/day, with 3-week break between each cycle. A subset of animals was sacrificed after each exposure to collect hippocampi. The relative expression of neural/synaptic genes and anti-/pro-survival factors was measured by real-time quantitative polymerase chain reaction. Our findings indicate that ELF-EMF exposure modulates mRNA expression of neural/synaptic genes and anti-/pro-survival factors. The direction and dynamics of changes depend on ELF-EMF intensity and the number of exposures. “Low-intensity” ELF-EMF (1 mT) increased pro-neuroplastic factors expression, while “high-intensity” ELF-EMF (7 mT) decreased them. In summary, “low-intensity” ELF-EMF enhances adaptive processes like neuroplasticity by eliciting a mild stress response, while “high-intensity” exposure disrupts homeostasis and brain function by inducing severe stress. Our findings indicate that the overall effects of ELF-EMF depend on the intricate interplay between stress reactions and long-term brain plasticity.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138520"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981695","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
The role of childhood trauma in hippocampal subfield alterations in lithium-treated type I bipolar disorder and healthy controls: A subfield volumetry MRI study 儿童创伤在锂治疗的I型双相情感障碍和健康对照者海马亚区改变中的作用:一项亚区容量MRI研究
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-03-15 Epub Date: 2026-01-04 DOI: 10.1016/j.neulet.2026.138503
Júnior Aparecido-de-Almeida , Marcio Gerhardt Soeiro-de-Souza
{"title":"The role of childhood trauma in hippocampal subfield alterations in lithium-treated type I bipolar disorder and healthy controls: A subfield volumetry MRI study","authors":"Júnior Aparecido-de-Almeida ,&nbsp;Marcio Gerhardt Soeiro-de-Souza","doi":"10.1016/j.neulet.2026.138503","DOIUrl":"10.1016/j.neulet.2026.138503","url":null,"abstract":"<div><h3>Background</h3><div>Type I bipolar disorder (BD-I) affects approximately 1% of the global population, and alterations in the morphology of the hippocampus, a cerebral region critical for memory and emotional regulation, may play an important role in its pathophysiology. Childhood Adversity (CA), including abuse and neglect, has been linked to structural hippocampal changes and elevated psychiatric risk, yet the impact of CA on hippocampal subfields in BD remains poorly understood.</div></div><div><h3>Methods</h3><div>Eighty‑five euthymic patients with BD-I on stable lithium therapy (age 18–40), and 59 healthy controls were assessed (both groups trauma-exposed with score of Childhood Trauma Questionnaire (CTQ) &gt; 25). Volumes of 12 hippocampal subfields were measured using FreeSurfer v6.0.0 and ENIGMA protocols. Partial correlations between CTQ subscale scores and subfield volumes were identified, controlling for age, sex, lithium use, and intracranial volume.</div></div><div><h3>Results</h3><div>In the BD-I group, higher physical neglect scores correlated with larger right hippocampal volumes: total hippocampus, CA1, hippocampal fissure, and presubiculum, whereas high emotional abuse scores were associated with increased left hippocampal fissure and subiculum volume. No significant associations were observed in controls, indicating specificity of trauma‑related alterations in BD-I.</div></div><div><h3>Conclusion</h3><div>Different CA subtypes yield distinct volumetric signatures in BD-I: physical neglect seems to drive expansion especially in right‑hemisphere subfields, while emotional abuse appears to enlarge the left subiculum. These findings highlight potential neuroplasticity biomarkers and may help inform early and targeted interventions.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138503"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912385","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
Electroacupuncture at GV20 and GV24 acupoints ameliorates migraine by blocking NLRP3-mediated pyroptosis via inhibiting the Piezo1 channel 电针GV20和GV24穴位通过抑制Piezo1通道阻断nlrp3介导的热凋亡来改善偏头痛。
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-03-15 Epub Date: 2026-01-06 DOI: 10.1016/j.neulet.2026.138505
Jianchang Luo , Liyao Feng , Wenbin Xu, Jiawang Lang, Luodan Wang, Zhipeng Zhao, Boxu Lang
{"title":"Electroacupuncture at GV20 and GV24 acupoints ameliorates migraine by blocking NLRP3-mediated pyroptosis via inhibiting the Piezo1 channel","authors":"Jianchang Luo ,&nbsp;Liyao Feng ,&nbsp;Wenbin Xu,&nbsp;Jiawang Lang,&nbsp;Luodan Wang,&nbsp;Zhipeng Zhao,&nbsp;Boxu Lang","doi":"10.1016/j.neulet.2026.138505","DOIUrl":"10.1016/j.neulet.2026.138505","url":null,"abstract":"<div><div>Migraine is a complex neuro-glio-vascular disorder, and electroacupuncture (EA) have been recommended as an alternative therapy for migraine. However, the mechanism of action of EA on GV20 (Baihui) and GV24 (Shenting) acupoints in treating migraine remains unclear. Thus, this study was performed to explore the potential mechanisms underlying the therapeutic influence of EA stimulation at GV20 and GV24 acupoints in the migraine treatment. After therapeutic effects of EA stimulation at GV20 and GV24 acupoints on migraine rat model established by dural electrical stimuli (DES) stimulation exploration, numerous approaches, such as qRT-PCR, immunofluorescence, and western blot, were applied to assess the expression of Piezo1 and pyroptosis-related proteins. Finally, Piezo1 activator (Yoda1) was used to confirm the involvement of Piezo1 channel in the treatment actions of EA stimulation at GV20 and GV24 acupoints on migraine. The results showed that EA stimulation at GV20 and GV24 acupoints forcefully alleviated the mechanical allodynia and central sensitization in rat model of migraine, also downregulated the expression of pro-inflammatory cytokines, containing TNF-α, IL-6, and IL-1β. In addition, EA stimulation at GV20 and GV24 acupoints also changed the expression of Piezo1 and pyroptosis-related proteins in rat model of migraine. Interestingly, treatment with the Yoda1 could reverse the therapeutic influences of EA stimulation at GV20 and GV24 acupoints in migraine rat model. Of note, the effect of EA stimulation at GV20 and GV24 acupoints on the expression of pyroptosis-related proteins could also be reverse by Yoda1 administration. This study emphasizes the EA efficacy at GV20 and GV24 acupoints on the migraine rat model established by DES stimulation, and proposes a mechanism involving inhibition of Piezo1 channel to block NLRP3-mediated pyroptosis in migraine.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138505"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934358","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
L17E cell-penetrating peptide enhances intranasal delivery of IgG to the cerebrospinal fluid in mice L17E细胞穿透肽增强小鼠脑脊液中IgG的鼻内递送。
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-03-15 Epub Date: 2026-01-17 DOI: 10.1016/j.neulet.2026.138521
Naoya Hashikawa, Taiki Terado, Takuya Noda, Riyo Kashimoto, Takumi Iima, Masamune Oro, Sora Tambara, Narumi Hashikawa-Hobara
{"title":"L17E cell-penetrating peptide enhances intranasal delivery of IgG to the cerebrospinal fluid in mice","authors":"Naoya Hashikawa,&nbsp;Taiki Terado,&nbsp;Takuya Noda,&nbsp;Riyo Kashimoto,&nbsp;Takumi Iima,&nbsp;Masamune Oro,&nbsp;Sora Tambara,&nbsp;Narumi Hashikawa-Hobara","doi":"10.1016/j.neulet.2026.138521","DOIUrl":"10.1016/j.neulet.2026.138521","url":null,"abstract":"<div><div>Antibody-based therapeutics are promising for treating central nervous system (CNS) diseases; however, brain delivery is severely restricted by the blood–brain barrier (BBB). Intranasal administration has gained attention as a noninvasive route proposed to reduce the impact of the BBB; however, the efficiency of delivering large biomolecules, such as antibodies, remains insufficiently characterized. This study aimed to investigate whether cell-penetrating peptides (CPPs) could increase detectable IgG levels in the cerebrospinal fluid (CSF) following intranasal administration in mice. Rabbit IgG was intranasally administered to ICR mice, either alone or in combination with CPPs (R9, Penetratin, or L17E). IgG levels in the CSF and serum were quantified by ELISA, and both time-course and dose-dependent effects were analyzed. IgG alone was not detected in the CSF, whereas serum IgG levels increased dose-dependently. Co-administration of Penetratin or L17E resulted in detectable CSF IgG levels, with L17E exceeding Penetratin. By contrast, no delivery was observed in the R9 group. Serum IgG levels also increased in the Penetratin and L17E groups. Time-course analysis with L17E showed that CSF IgG reached its highest measured level at 24 h and declined thereafter, whereas serum IgG reached higher levels at earlier time points and remained relatively stable. Dose–response analysis revealed linear increases in serum IgG, while CSF IgG levels depended on the concentration of L17E. These findings indicate that co-administration with amphipathic CPPs, particularly L17E, enables detectable IgG delivery to the CSF following intranasal administration in mice, although the underlying mechanisms and therapeutic relevance remain to be clarified.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138521"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003725","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
Chlorogenic acid exerts anti-inflammation and neuroprotective effect in pentylenetetrazole-induced epilepsy mouse model by regulating microglia polarization via Nrf2/HO-1 pathway 绿原酸通过Nrf2/HO-1通路调节小胶质细胞极化,在戊四唑致癫痫小鼠模型中发挥抗炎和神经保护作用
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-02-26 Epub Date: 2025-12-19 DOI: 10.1016/j.neulet.2025.138493
Yi Sun , Jiayu Wang , Aoyuan Zhang , Ankang Hu , Lianlian Wu
{"title":"Chlorogenic acid exerts anti-inflammation and neuroprotective effect in pentylenetetrazole-induced epilepsy mouse model by regulating microglia polarization via Nrf2/HO-1 pathway","authors":"Yi Sun ,&nbsp;Jiayu Wang ,&nbsp;Aoyuan Zhang ,&nbsp;Ankang Hu ,&nbsp;Lianlian Wu","doi":"10.1016/j.neulet.2025.138493","DOIUrl":"10.1016/j.neulet.2025.138493","url":null,"abstract":"<div><div>Chlorogenic acid (CGA) possesses diverse biological functions, including antioxidant, anti-inflammatory, and anti-apoptotic, both <em>in vitro and in vivo</em>. Recent studies have suggested that CGA also has neuroprotective effects. However, its potential to alleviate seizures and attenuate epilepsy-related neuropathology remains unclear. This study investigated the effects and underlying mechanisms of CGA in a pentylenetetrazole (PTZ)-induced epilepsy mouse model. CGA treatment significantly reduced epileptic seizures. Nissl and NeuN immunofluorescence staining revealed that CGA also significantly reduced neuronal damage. Furthermore, CGA promoted microglial polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype and suppressed neuroinflammation, evidenced by iNOS/IBA-1 and Arg-1/IBA-1 immunofluorescence and RT-PCR. BrdU staining revealed that CGA inhibited epilepsy-induced aberrant neurogenesis. In addition, behavioral tests showed improved cognitive performance following CGA treatment. Finally, western blot analysis indicated the activation of the Nrf2/HO-1 pathway, and Nrf2 knockdown reversed CGA’s effects. These findings suggest that CGA exerts anti-seizure and neuroprotective effects via microglial modulation through the Nrf2/HO-1 pathway.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"873 ","pages":"Article 138493"},"PeriodicalIF":2.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145799681","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
G protein-coupled receptor 17 promotes neuropathic pain in male mice by upregulating spinal NMDAR subunit expression G蛋白偶联受体17通过上调脊髓NMDAR亚基表达促进雄性小鼠神经性疼痛。
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-02-26 Epub Date: 2026-01-08 DOI: 10.1016/j.neulet.2026.138509
Biyun Li, Xueqin Xu, Qin Xiao, Kunyu Zhang, Xiuqin Yu, Yangqiao Xiao, Shuangshuang Lu, Wenjiao Jin, Panpan Sun, Longhui Li, Chunyu Ma, Zihao Lu, Yanqiong Wu, Changbin Ke
{"title":"G protein-coupled receptor 17 promotes neuropathic pain in male mice by upregulating spinal NMDAR subunit expression","authors":"Biyun Li,&nbsp;Xueqin Xu,&nbsp;Qin Xiao,&nbsp;Kunyu Zhang,&nbsp;Xiuqin Yu,&nbsp;Yangqiao Xiao,&nbsp;Shuangshuang Lu,&nbsp;Wenjiao Jin,&nbsp;Panpan Sun,&nbsp;Longhui Li,&nbsp;Chunyu Ma,&nbsp;Zihao Lu,&nbsp;Yanqiong Wu,&nbsp;Changbin Ke","doi":"10.1016/j.neulet.2026.138509","DOIUrl":"10.1016/j.neulet.2026.138509","url":null,"abstract":"<div><div>Neuropathic pain is a prevalent and debilitating chronic condition for which current treatments often provide inadequate relief. This constitutes a significant unmet clinical need, highlighting the importance of identifying novel molecular targets for more effective pharmacotherapy. Synaptic remodeling-mediated central sensitization is a key regulatory factor. Glutamate is a major excitatory transmitter in the central nervous system and binds to NMDA receptors in the postsynaptic membrane to promote synaptic remodeling. In C57 mice with spared nerve injury, it was noted that GPR17 and the GluN2A and GluN2B subunits of the NMDA receptor were elevated in the L4-L6 region of the spinal cord. Lentiviral knockdown of spinal GPR17 attenuated mechanical allodynia, suppressed astrocyte activation, and decreased levels of GluN2A and GluN2B subunits. GPR17 controls neuropathic pain, stimulates astrocyte activation, and NMDA receptor overexpression on neurons. Targeting GPR17 may represent a new therapeutic strategy for the management of neuropathic pain.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"873 ","pages":"Article 138509"},"PeriodicalIF":2.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949071","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
Antinociceptive role of IL-10/STAT3 signaling in trigeminal neuropathic pain male rat model through Pomc and β-endorphin IL-10/STAT3信号通过Pomc和β-内啡肽在三叉神经性疼痛雄性大鼠模型中的抗伤害感受作用
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-02-26 Epub Date: 2025-12-18 DOI: 10.1016/j.neulet.2025.138492
Lutfi Putra Perdana , Jaime Fabillar Jr , Dara Sari Arini , Swarnalakshmi Raman , Resmi Raju , Daisuke Ikutame , Masamitsu Oshima , Keiko Miyoshi , Yoshizo Matsuka
{"title":"Antinociceptive role of IL-10/STAT3 signaling in trigeminal neuropathic pain male rat model through Pomc and β-endorphin","authors":"Lutfi Putra Perdana ,&nbsp;Jaime Fabillar Jr ,&nbsp;Dara Sari Arini ,&nbsp;Swarnalakshmi Raman ,&nbsp;Resmi Raju ,&nbsp;Daisuke Ikutame ,&nbsp;Masamitsu Oshima ,&nbsp;Keiko Miyoshi ,&nbsp;Yoshizo Matsuka","doi":"10.1016/j.neulet.2025.138492","DOIUrl":"10.1016/j.neulet.2025.138492","url":null,"abstract":"<div><div>Interleukin-10 (IL-10) is a cytokine that can exert an analgesic effect on trigeminal neuropathic pain (TNP). However, its precise mechanism remains unclear. In this study, we investigated the antinociceptive effects of recombinant IL-10 (rIL-10) in a rat model of infraorbital nerve constriction. Using male Sprague-Dawley rats, we administered rIL-10 or phosphate-buffered saline to the intra-trigeminal ganglion and observed a peak analgesic effect at 4 h post-injection in the rIL-10 group. Real-time PCR demonstrated significant upregulation of the Proopiomelanocortin (<em>Pomc</em>) gene in rIL-10-treated rats, with immunofluorescence staining confirming increased expression of bioactive peptide β-endorphin (β-END) in the same group. <em>In situ</em> hybridization assay further localized <em>Pomc</em> expression to satellite glial cells and neurons in the trigeminal ganglion, with β-END exhibiting a similar distribution. To elucidate the signaling mechanism, we co-administered a STAT3 inhibitor, Stattic, which abolished the analgesic effect of rIL-10, suppressed <em>Pomc</em> upregulation, and reduced β-END expression. These findings indicate that the STAT3 pathway is a critical mediator of rIL-10-induced analgesia, with <em>Pomc</em> and β-END as potential molecular effectors.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"873 ","pages":"Article 138492"},"PeriodicalIF":2.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800526","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
Recovery from cuprizone induced incontinence is not dependent upon remyelination 铜酮引起的尿失禁的恢复不依赖于髓鞘再生。
IF 2 4区 医学
Neuroscience Letters Pub Date : 2026-02-26 Epub Date: 2025-12-21 DOI: 10.1016/j.neulet.2025.138494
Anirudhya Lahiri, Lucille E Papile, Zaenab Dhari, Jake T Lustig, Evan T Lombardo, Erica R Lavoie, Pearl A Sutter, Stephen J Crocker
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