Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology最新文献

{"title":"Motor-Related Neural Dynamics are Modulated by Regular Cannabis Use Among People with HIV.","authors":"Lauren K Webert, Mikki Schantell, Lucy K Horne, Jason A John, Ryan Glesinger, Jennifer O'Neill, Maureen Kubat, Anna T Coutant, Grace C Ende, Sara H Bares, Pamela E May-Weeks, Tony W Wilson","doi":"10.1007/s11481-025-10219-0","DOIUrl":"10.1007/s11481-025-10219-0","url":null,"abstract":"<p><p>Recent work has shown that people with HIV (PWH) exhibit deficits in cognitive control and altered brain responses in the underlying cortical networks, and that regular cannabis use has a normalizing effect on these neural responses. However, the impact of regular cannabis use on the neural oscillatory dynamics underlying motor control deficits in PWH remains less understood. Herein, 102 control cannabis users, control nonusers, PWH who regularly use cannabis, and PWH who do not use cannabis performed a motor control task with and without interference during high-density magnetoencephalography. The resulting neural dynamics were examined using whole-brain, voxel-wise statistical analyses that examined the impact of HIV status, cannabis use, and their interaction on the neural oscillations serving motor control, spontaneous activity during the baseline period, and neurobehavioral relationships. Our key findings revealed cannabis-by-HIV group interactions in oscillatory gamma within the prefrontal cortices, higher-order motor areas, and other regions, with the non-using PWH typically exhibiting the strongest gamma interference responses. Cannabis-by-HIV interactions were also found for oscillatory beta in the dorsal premotor cortex. Spontaneous gamma during the baseline was elevated in PWH and suppressed in cannabis users in all regions exhibiting interaction effects and the left primary motor cortex, with spontaneous levels being correlated with behavioral performance. These findings suggest that regular cannabis use has a normalizing effect on the neural oscillations serving motor control and the abnormally elevated spontaneous gamma activity that has been widely replicated in PWH, which may suggest that cannabis has at least some therapeutic utility in PWH.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"63"},"PeriodicalIF":6.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Promotes B-Cell Maturation and Attenuates Post-Ischemic Immunodeficiency in a Murine Model of Transient Focal Cerebral Ischemia.","authors":"Shih-Huang Tai, Hao-Hsiang Hsu, Sheng-Yang Huang, Yu-Ning Chen, Liang-Yi Chen, Ai-Hua Lee, Ai-Chiang Lee, E-Jian Lee","doi":"10.1007/s11481-025-10222-5","DOIUrl":"https://doi.org/10.1007/s11481-025-10222-5","url":null,"abstract":"<p><p>In this study, we investigated the immunomodulatory effects of melatonin on B-cell maturation and its potential to mitigate immunodeficiency following transient focal cerebral ischemia in mice. Transient middle cerebral artery occlusion (MCAO) was induced in adult C57BL/6 mice, followed by melatonin administration. We evaluated the effects of melatonin on neutrophil infiltration, macrophage and microglial activation in the ischemic brain, and B-cell maturation in both the central nervous system and peripheral blood. Melatonin treatment significantly reduced pro-inflammatory cell infiltration in the ischemic hemisphere and promoted B-cell maturation, reflecting robust immunomodulatory activity. These immune changes coincided with improved neurological outcomes and reduced cerebral edema. Collectively, our findings suggest that melatonin may serve as a promising therapeutic candidate in ischemic stroke, addressing both immunodeficiency and neuronal injury.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"62"},"PeriodicalIF":6.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Sympathetic Nervous Influence on Hematopoiesis Up To Date.","authors":"Georges Maestroni","doi":"10.1007/s11481-025-10220-7","DOIUrl":"https://doi.org/10.1007/s11481-025-10220-7","url":null,"abstract":"<p><p>Hematopoiesis is a tightly regulated process taking place in specialized bone marrow structures called hematopoietic niches. In these structures, hematopoietic stem cells produce all hematopoietic lineages by their self-renewal and differentiation abilities. Sympathetic nerve fibers, entering the bone marrow in association with blood vessels, regulate on a circadian basis the hematopoietic stem cells and leukocytes migration in and out the bone marrow. This cellular traffic, that is mainly regulated by beta-adrenergic receptors expressed on mesenchymal stem cells, is needed to maintain an efficient hematopoietic niche and for immunosurveillance against infections. Both alpha- and beta-adrenergic receptors seem involved in the regeneration of hematopoiesis after myeloablative treatments. Likewise, the effects of psychogenic stress and of ageing on the hematopoietic system are also mediated by adrenergic signals. Yet, the exact mechanisms regulating hematopoietic regeneration and the differentiation ratio between lymphoid and myeloid cells are still obscure. A comprehensive understanding of the adrenergic influence on hematopoiesis holds the potential for novel therapeutic approaches in a variety of hematological diseases.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"61"},"PeriodicalIF":6.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNF-Stimulated Gene-6, Part of Extracellular Vesicles in Adipose Tissue-Derived Mesenchymal Stem Cell Concentrated Conditioned Medium, Affects Microglial Activity.","authors":"Mohammad Shahadat Hossain, Pratheepa Kumari Rasiah, Amritha T M Seetharaman, Dulce Alvarado, Megan Luo, James A Wohlschlegel, Mickey Pentecost, Rajashekhar Gangaraju","doi":"10.1007/s11481-025-10216-3","DOIUrl":"10.1007/s11481-025-10216-3","url":null,"abstract":"<p><p>Identifying the specific bioactive molecules produced by mesenchymal stem cells (MSCs) and the signaling pathways and cell types upon which they act is critical to developing MSC-based therapeutics for inflammatory diseases with high unmet needs. Our study aimed to investigate the impact of extracellular vesicle (EV)-derived TNF-Stimulated Gene-6 (TSG-6, from adipose tissue-derived mesenchymal stem cell concentrated conditioned medium, ASC-CCM or TSG-6 overexpression in ASC using ORF expression-ready clone) on microglia and its potential anti-inflammatory effects. EV but not non-vesicular secretome prepared by ultracentrifugation confirmed the expression of TSG-6 exclusively in the small EV (sEV) fraction. sEV ranged from 50-150 nm as determined by Zetasizer, demonstrated bilipid membrane evidenced by transmission electron microscopy, expressed positive exosomal (e.g. CD63) markers, and were endocytosed by BV2 cells confirmed by DiI fluorescently labeled exosomes. BV2 microglia cultured under serum-free conditions stimulated with TLR4 agonists (LPS and IFNγ) for 12 h in the presence of p-ASC-EV (sEV derived from ASC after cytokine stimulation) and TSG-6-ORF-EV significantly reduced nitrite release (p < 0.001), phagocytic activity (p < 0.001) and reduced CD44 expression (p < 0.05). CD44 knockdown in BV2 cells ablated TSG-6-ORF-EV mediated nitrite release, IL1β downregulation, and phagocytosis with TLR4 agonists. Our results revealed that under cytokine stimulation, the EV portion of ASC-CCM becomes enriched with TSG-6. Overexpressing TSG-6 in ASC leads to an increased concentration of TSG-6 in sEVs. This enriched EV fraction, containing TSG-6, regulates microglial dynamics through a feedback loop with CD44. EV-associated TSG-6 can influence immune cell behavior and signaling, mitigating excessive inflammation or immune dysfunction.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"60"},"PeriodicalIF":6.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIPK1: A Promising Target for Intervention Neuroinflammation.","authors":"Feixing Yan, Yujun Qiao, Shunli Pan, Anjuan Kang, Haile Chen, Yinliang Bai","doi":"10.1007/s11481-025-10208-3","DOIUrl":"https://doi.org/10.1007/s11481-025-10208-3","url":null,"abstract":"<p><p>Necroptosis is a novel mode of cell death that differs from traditional apoptosis, characterized by distinct molecular mechanisms and physiopathological features. Recent research has increasingly underscored the pivotal role of necroptosis in various neurological diseases, including stroke, Alzheimer's disease and multiple sclerosis. A defining hallmark of these conditions is neuroinflammation, a complex inflammatory response that critically influences neuronal survival. This review provides a comprehensive analysis of the mechanistic underpinnings of necroptosis and its intricate interplay with neuroinflammation, exploring the interrelationship between the two processes and their impact on neurological disorders. In addition, we discuss potential therapeutic strategies that target the intervention of necroptosis and neuroinflammation, offering novel avenues for intervention. By deepening our understanding of these interconnected processes, the development of more effective treatments approaches holds significant promise for improving patient outcomes in neurological disorders.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"59"},"PeriodicalIF":6.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Dapagliflozin's Influence on Autophagic Flux in Mania-like Behaviour: Insights from the LKB1/AMPK/LC3 Pathway in a Mouse Model.","authors":"Nada K Saleh, Sama M Farrag, Mohamed F El-Yamany, Ahmed S Kamel","doi":"10.1007/s11481-025-10218-1","DOIUrl":"10.1007/s11481-025-10218-1","url":null,"abstract":"<p><p>Mania-like episodes are neuropsychiatric disturbances associated with bipolar disorder (BD). Autophagic flux disturbance evolved as one of the molecular mechanisms implicated in mania. Recently, Dapagliflozin (DAPA) has corrected autophagic signaling in several neurological disorders. Yet, no endeavours examined the autophagic impact of DAPA in mania-like behaviours. This study aimed to investigate the effect of DAPA on disrupted autophagic pathways in a mouse model of mania-like behaviour. Mania-like behaviour was induced through paradoxical sleep deprivation (PSD) using the multiple-platform method for a duration of 36 h. Mice were divided into three groups, with DAPA (1 mg/kg/day, orally) administered for one week. Behavioural assessments were conducted on the 7th day. DAPA mitigated anxiety-like behaviour in the open field test and improved motor coordination and muscle tone in the rotarod test. Mechanistically, DAPA activated hippocampal autophagy-related markers; liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway, autophagy related gene 7 (ATG7), and microtubule-associated protein light chain 3II (LC3II). This was associated with reduced levels of the autophagosome receptor p62 protein, which subsequently enhanced GABA_A receptor-associated protein (GABARAP), facilitating the surface presentation of GABA_A receptors. Additionally, DAPA upregulated the GABA_B receptor R2 subunit through trophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Furthermore, DAPA mitigated elevated serum stress hormones and restored the balance between proinflammatory and anti-inflammatory cytokines in both cortical and hippocampal tissues. These findings highlight the role of autophagic flux modulation by DAPA and its therapeutic potential in mitigating mania-like behaviours.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"57"},"PeriodicalIF":6.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 Alters Inflammatory, Mitochondrial, and Protein Clearance Pathway Genes: Potential Implications for New-onset Parkinsonism in Patients.","authors":"Chukwunonso K Nwabufo","doi":"10.1007/s11481-025-10215-4","DOIUrl":"10.1007/s11481-025-10215-4","url":null,"abstract":"<p><p>Several preclinical and clinical studies have shown that SARS-CoV-2 infection is associated with new-onset Parkinson's disease (PD). The overall goal of this study is to uncover how the COVID-19 severity gradient impacts the conventional pathological pathway of PD to inform the identification of at-risk patients and the development of personalized treatment strategies. Transcriptomics analysis of 43 PD pathogenic genes was conducted on nasopharyngeal swabs from 50 COVID-19 patients with varying severity including 17 outpatients, 16 non-ICU, and 17 ICU patients, compared to 13 SARS-CoV-2 negative individuals. The study shows that COVID-19 severity gradient differentially dysregulates PD pathological genes. Dysfunctional lysosomal and mitochondrial processes in outpatients and non-ICU COVID-19 patients was identified as the convergent network of COVID-19-PD interactions. These dysfunctions were later abrogated by the upregulation of the ubiquitin-proteasome system and autophagy-lysosome system in ICU COVID-19 patients. A potential synergistic co-expression and clustering of protein clearance pathway genes with other pathological genes was observed in ICU patients, indicating a possible overlap in biological pathways. Dysregulation of the PD pathopharmacogene, SLC6A3 was observed in ICU patients, suggesting potential COVID-19-gene-drug interactions. Nasopharyngeal swabs express major PD pathological genes as well as clinically relevant drug processing genes, which could advance studies on PD, including diagnosis, pathogenesis, and the development of disease-modifying treatments. Outpatients and non-ICU COVID-19 patients may face a higher risk of developing new-onset PD, whereas ICU COVID-19 patients may be more susceptible to COVID-19-gene-drug interactions.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"58"},"PeriodicalIF":6.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonidine Ameliorates Neuroinflammation in the Rat Model of Tourette Syndrome.","authors":"Zhongling Ke, Yuxian Huang, Ang Wang, Yanhui Chen","doi":"10.1007/s11481-025-10214-5","DOIUrl":"https://doi.org/10.1007/s11481-025-10214-5","url":null,"abstract":"<p><p>Neuroinflammation plays a vital role in the etiology and pathogenesis of Tourette syndrome (TS). The postmortem report of TS patients clarified that IL-2 is elevated in the basal ganglia region, supporting neuroinflammation of TS. α₂ receptor agonist (clonidine) is one of the primary drugs for treating tic disorders; supported by clinical and animal experiments, α₂ receptor agonists have potential anti-inflammatory effects. This article aims to explore the impact of clonidine on neuroinflammation with TS and to reveal the possible mechanism of clonidine-mediated neuroinflammation with TS. Thirty P21 SD rats were randomly divided into a TS rat group (n = 20) and a normal control group (n = 10). After successful TS modelling, rats were randomly divided into the clonidine intervention group (n = 10) and the TS group (n = 10). The clonidine intervention group received clonidine 0.1 mg/kg by gavage daily for seven consecutive days. After behavioural evaluation on day 8, the brain was removed from the head. The striatum was separated from one side of the brain and subjected to ELISA to detect cytokines. The other side of the brain was subjected to immunohistochemical detection for microglial activation, and the integral optical density value was calculated using image software for comparison between the groups. Compared to the normal group, IL-2 cytokine levels in TS rats were significantly higher (P < 0.05). In the clonidine group, IL-2 levels (213.82 ± 121.48 pg/ml) were significantly lower than in the TS group (322.61 ± 79.27 pg/ml) (P < 0.05) but not significantly different from the normal control group (257.40 ± 95.80 pg/ml) (P > 0.05). Immunohistochemical analysis showed significant microglial activation in TS rats (IOD = 22.10 ± 6.67) compared to the normal group (IOD = 11.58 ± 4.36) (P < 0.05). Clonidine administration reduced microglial activation, with a significant difference between the TS + clonidine group (IOD = 15.97 ± 8.03) and TS rats (P < 0.05). Clonidine can suppress the neuroinflammatory response in Tourette syndrome, and its inhibitory effect on the neuroinflammatory response may be a potential beneficial effect of this treatment.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"56"},"PeriodicalIF":6.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limettin and PD98059 Mitigated Alzheimer's Disease Like Pathology Induced by Streptozotocin in Mouse Model: Role of p-ERK1/2/p-GSK-3β/p-CREB/BDNF Pathway.","authors":"Rofida M Hassan, Nesrine S Elsayed, Naglaa Assaf, Barbara Budzyńska, Krystyna Skalicka-Wożniak, Sherehan M Ibrahim","doi":"10.1007/s11481-025-10211-8","DOIUrl":"10.1007/s11481-025-10211-8","url":null,"abstract":"<p><p>Sporadic Alzheimer's disease (SAD) represents one of the major memory deficits that is characterized by tau hyperphosphorylation and amyloid beta (Aβ) deposition in the brain. Both are considered AD hallmarks which are mediated through neuroinflammation, oxidative stress, and cholinergic circuit interruption. This study aimed to show how limettin and PD98059 exert a neuroprotective effect against SAD and the possible role of the extracellular regulated kinase (p-ERK1/2) and glycogen synthase kinase-3 beta (p-GSK-3β) (Ser9)/cAMP-response element binding protein (p-CREB) (Ser133)/brain derived neurotrophic factor (BDNF) pathway. Control animals (Group I) received the vehicles, group II received PD98059 (10 mg/kg/i.p), while group III was administered limettin (15 mg/kg/i.p). Additionally, the other three groups received a single dose of streptozotocin (STZ; 3 mg/kg/ICV), where group IV served as the SAD group, while groups V and VI received PD98059 and limettin daily for 3 weeks, respectively. The SAD animals receiving PD98059 and limettin increased the number of arm entries, % alternations in Y-maze, with reduction in mean escape latency, increase in time spent in target quadrant and platform crossing in Morris Water Maze, compared to the SAD group. Additionally, PD98059 and limettin administration to the STZ group downregulated persistent activation of p-ERK1/2 which in turn increased p-GSK-3β (Ser9), leading to enhanced p-CREB (Ser133) and BDNF expressions, as well as reducing inflammatory markers viz., nuclear factor-kappa B and interleukin-6, leading to decreased Aβ deposition. Both treatments reduced immunohistochemical p-tau expression, brain edema, and increased intact neuron cells remarkably. Thus, based on these findings, PD98059 and limettin may have promising effects in protecting against SAD. Using blockers/inhibitory molecules are recommended to confirm effect through the corresponding pathway.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"55"},"PeriodicalIF":6.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COP1 Overexpression Attenuates Nociceptive Behaviors and Neuroinflammation in Cancer-Induced Bone Pain by Suppressing c/EBPβ.","authors":"Dan-Yang Li, Lin Liu, Shao-Jie Gao, Dai-Qiang Liu, Long-Qing Zhang, Jia-Yi Wu, Fan-He Song, Xin-Yi Dai, Ya-Qun Zhou, Wei Mei","doi":"10.1007/s11481-025-10217-2","DOIUrl":"https://doi.org/10.1007/s11481-025-10217-2","url":null,"abstract":"<p><p>Patients with advanced cancer often have bone metastases, causing bone destruction and cancer-induced bone pain (CIBP). The CCAAT/enhancer binding protein β (c/EBPβ) mediated the regulation of various pro-inflammatory molecules in microglia. To investigate the specific effect and regulatory mechanism of c/EBPβ in CIBP, a mice model of Lewis lung cancer (LLC) cells implantation was constructed. Our data demonstrated that the c/EBPβ was remarkably elevated in the spinal cord of CIBP mice. Specific knocking down c/EBPβ relieved the mechanical allodynia and thermal hyperalgesia of CIBP mice by suppressing the microglia activation and pro-inflammatory cytokines generation. Besides, overexpressing c/EBPβ could prompt severe pain behaviors with spinal neuroinflammation in naïve mice. Notably, the upstream regulator constitutive photomorphogenic 1 (COP1) was gradually reduced in the spinal cord of CIBP mice. Upregulating the expression of COP1 effectively alleviated the nociceptive behaviors of CIBP mice by inhibiting the accumulation of c/EBPβ and subsequent neuroinflammation. However, knocking down COP1 caused the rapid increase of c/EBPβ and exacerbation of spinal neuroinflammation, ultimately leading to behavioral damage in naïve mice. In conclusion, the absence of COP1 promoted the accumulation of c/EBPβ and neuroinflammatory molecules in the spinal cord of CIBP mice, which extends the future therapeutic approach for CIBP.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"54"},"PeriodicalIF":6.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}