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

{"title":"Green-synthesized Nanoparticles as Emerging Antidepressant and Anxiolytic Candidates: A Critical Review of Preclinical Evidence and Translational Prospects.","authors":"Meesala Krishna Murthy, Dibyaranjan Samal","doi":"10.1007/s11481-026-10323-9","DOIUrl":"https://doi.org/10.1007/s11481-026-10323-9","url":null,"abstract":"<p><p>The high incidence of depression and anxiety disorders worldwide, with figures of depression > 300 million and anxiety > 264 million, poses a serious challenge to health and wellness. Treatment is still limited by existing pharmacotherapies with delayed onset, adverse side effects, poor entry into the blood-brain barrier (BBB), and resistance in approximately 30% of patients. Green-synthesized nanoparticles (NPs) obtained via phytochemicals, microorganisms, and biomolecules are a promising sustainable route for neurotherapeutic applications. This critical review explores preclinical studies on the antidepressant and anxiolytic effects of green NPs, discussing their underlying mechanisms, translatability, and safety concerns in the context of the period 2015-2025. A comprehensive literature search on green synthesis, nanoparticles, Depression, Anxiety and Neurobehavioral outcomes was conducted using the Boolean operator in PubMed, Scopus, Web of Science, and Google Scholar. Evidence suggests that green NPs can facilitate both serotonergic and dopaminergic signal modulation, minimize neuroinflammation, recruit NFκB, activate antioxidant activity via the Nrf2/ HO-1 axis and induce neuroplasticity (Akt/CREB/BDNF axis). Their biogenic characteristics on the surface may enhance BBB transport and biocompatibility and reduce cytotoxicity and environmental persistence. However, there is still inadequate evidence regarding chronic toxicity, biodistribution, synthesis reproducibility, mechanistic validation and clinical evidence. Nano optimization by AI (as well as characterizing nanomaterials in a standardized manner), nanoinformatics and personalized nano-neuropharmacology in the future are required. Green NPs have promising therapeutic potential; however, this has mainly been demonstrated in preclinical studies.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225484","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":"Fraxetin Ameliorates Cognitive Impairment in STZ-Induced Mice: Involvement of Suppressed Microglial Hyperactivation and Improved Mitochondrial Dysfunction.","authors":"Jun Zhao, Yiming Bai, Chao Wang, Pengfei Guo, Zhe Wang, Guanhua Du, Ailin Liu","doi":"10.1007/s11481-026-10320-y","DOIUrl":"10.1007/s11481-026-10320-y","url":null,"abstract":"<p><p>Therapeutic for Alzheimer's disease (AD) remains a pressing medical challenge in the field of neuroscience. Natural compounds with structural diversity and multi-target regulatory properties have attracted increasing attention for the treatment of complex neurodegenerative disorders. ‌Fraxetin, previously identified through computer-aided virtual screening, C. elegans assays, and in vitro cellular models as a potential anti-AD natural compound, was further investigated in this study using established in vivo and in vitro systems to evaluate its efficacy in ameliorating cognitive function and elucidate underlying mechanisms. A sporadic AD mouse model was established by intracerebroventricular injection of STZ (3 mg/kg). Fraxetin (3, 10, and 30 mg/kg/day, po.) was administered until the mouse sacrifices. Cognitive performance was evaluated using the novel object recognition, passive avoidance, and Morris water maze tests. STZ induced cerebral energy metabolism disturbances accompanied by mitochondrial dysfunction, neuroinflammation, oxidative stress, neuronal and synaptic loss, and cholinergic system impairment. ‌Behavioral tests confirmed that fraxetin ameliorated cognitive deficits in STZ-induced mice. Further studies revealed that fraxetin preserved mitochondrial structural integrity and enhanced mitochondrial biogenesis, accompanied by upregulation of the Sirt1/PGC-1α/Nrf1/TFAM pathway. In parallel, fraxetin attenuated microglial overactivation and neuroinflammatory responses. Consistently, in LPS-stimulated BV2 microglial cells, fraxetin inhibited nitric oxide and inflammatory mediator release, which was associated with modulation of the TLR2/MYD88/NF-κB signaling pathway, while restoring cellular bioenergetic status, indicating coordinated regulation of inflammation-associated metabolic dysfunction. Importantly, fraxetin attenuated neurodegenerative alterations in STZ-treated mice, as evidenced by reduced neuronal loss and synaptic degeneration. These effects were associated with activation of the BDNF/TrkB/ERK/CREB neurotrophic pathway and inhibition of acetylcholinesterase activity, supporting preservation of synaptic and cholinergic function. This study provides experimental evidence supporting fraxetin as a promising natural multi-target candidate for the intervention of AD.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149571","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":"Dietary Supplementation with Omega-3 Fatty Acids Rescues Neurodevelopmental Deficits in a Combined Exposure Paradigm of Maternal Oxycodone Exposure and Chronic Stress.","authors":"Vamsi K Singu, Nghi M Nguyen, Alexander Ky, Victoria L Schaal, Pranavi Athota, Austin Gowen, Matthew VanOrmer, Olivia Loh, Ashley J Blount, Corrine Hanson, Sowmya V Yelamanchili, Ann Anderson-Berry, Gurudutt Pendyala","doi":"10.1007/s11481-026-10322-w","DOIUrl":"10.1007/s11481-026-10322-w","url":null,"abstract":"<p><p>In recent years, opioid abuse has become a major public health crisis affecting millions of individuals throughout the world. This widespread abuse of prescription opioids and dramatic increase in their availability have created the opioid epidemic. Further, oxycodone (oxy), which is prescribed for multiple types of pain, is gaining momentum as a pain reliever in pregnant women. Whilst successful in inducing analgesia, oxy freely passes through the placenta and can impact the overall development of the fetus in major ways. Currently, mechanisms that lead to impairment in the exposed offspring, including identification of biomarkers, are not well described. To fill this gap, our study utilizes a preclinical rodent model to test the therapeutic efficacy of omega-3 fatty acids (O3FA) in attenuating neurodevelopmental deficits in offspring exposed to chronic stress (CS) and oxy in utero which mirrors real-world cases of opioid use during pregnancy co-occurring with chronic psychosocial stress. Our results show that O3FA supplementation partially rescues phenotypic, biochemical, molecular, and behavioral endpoints. Notably, our proteomic study identified distinct key synaptic signatures, including functional pathways impacted in different treatment groups. Furthermore, RT-qPCR results identified key inflammatory markers whose expression was ameliorated by O3FA supplementation. Together, this study bridges an important knowledge gap pertinent to maternal-fetal health that reflects a combined exposure of oxy and CS that is clinically relevant and enumerates the therapeutic efficacy of O3FA in mitigating neurodevelopmental deficits in offspring exposed to in utero oxy and CS.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129529","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":"Beyond Histamine Blockade: Clemastine Fumarate as a Promoter of Myelin Regeneration, Inflammatory Regulation, and Neuroimmune Modulation in CNS Disorders.","authors":"Rohit Kumar Singh, Chandrayee Banerjee, Sidharth Mehan","doi":"10.1007/s11481-026-10321-x","DOIUrl":"10.1007/s11481-026-10321-x","url":null,"abstract":"<p><p>Clemastine fumarate, a first-generation H1 antihistamine, has emerged as a promising candidate for drug repurposing in neurodegenerative and neuropsychiatric disorders owing to its ability to cross the blood-brain barrier and interact with multiple central nervous system targets. Experimental studies indicate that clemastine promotes remyelination by stimulating the differentiation of oligodendrocyte precursor cells into mature, myelin-producing oligodendrocytes, thereby restoring myelin integrity and improving axonal function in experimental models. In addition to its remyelinating properties, preclinical evidence suggests that clemastine may attenuate neuroinflammation by modulating microglial activation and suppressing pro-inflammatory signalling pathways. These effects have been associated with improved structural and functional outcomes in experimental models of multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury, stroke, and several neuropsychiatric disorders. Mechanistically, clemastine primarily acts through muscarinic M1 receptor antagonism to promotes remyelination, while additional pathways including PI3K/Akt, ERK1/2, autophagy-related signalling, inflammasome modulation, and sigma-1 receptor signalling have been proposed based on experimental evidence but remain incompletely understood and require further mechanistic validation. Among the neurological disorders investigated multiple sclerosis currently has the strongest clinical evidence with early clinical trials demonstrating modest remyelinating activity. In contrast, evidence supporting the use of clemastine in other neurological disorders remains largely confined to preclinical studies. Several translational challenges also remain unresolved including dose optimisation, treatment timing, long-term safety, sedative and anticholinergic adverse effects, and patient selection. Future research should focus on refining pharmacokinetic properties, optimising dosing strategies, evaluating rational combination therapies, and identifying predictive biomarkers to facilitate clinical translation. Although current evidence highlights the therapeutic potential of clemastine fumarate, its application beyond multiple sclerosis remains investigational and will require rigorous mechanistic studies together with well-designed clinical trials before broader clinical use can be established.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129531","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":"Pharmacological Profiling of Mefenamic Acid Derivative (2-((2,3-dimethylphenyl)amino)phenyl)(4-ethylpiperazin-1-yl)methone) for its Antidepressant- and Anxiolytic-like Potential Using Corticosterone Induced Depression Model in Rodents.","authors":"Ishwar Purushottam Kokate, Thangaraj Devadoss, Vaishnavi G Thorat, Rayala Swetha, Rodda Susheela, Shvetank Bhatt","doi":"10.1007/s11481-026-10319-5","DOIUrl":"10.1007/s11481-026-10319-5","url":null,"abstract":"<p><p>Recent studies demonstrated that serotonergic system, specially 5-HT₃ receptor (5-HT₃R) plays major role in regulating mood and anxiety. The present study investigates antidepressant- and anxiolytic-like effects of a 5-HT₃ receptor antagonist (5-HT₃RA), (2-((2,3-dimethylphenyl)amino)phenyl)(4- ethylpiperazin-1-yl)methone) (MP-02), in mouse model of corticosterone-induced depression. Chronic administration of corticosterone (CORT) was done to induce depression- and anxiety-like behaviour in mice. It mimics stress-related pathophysiology due to involvement of HPA axis. Behavioural evaluations, such as spontaneous locomotor activity (SLA), forced swim test (FST), tail suspension test (TST), open field test (OFT), elevated plus maze (EPM), light and dark (L&D) test, sucrose preference test (SPT), were performed to assess antidepressant-and anxiolytic-like effects. Biochemical evaluations such as plasma CORT and serotonin, brain inflammatory marker and oxidative stress marker levels were measured in mouse brain. Administration of MP-02 led to significant reduction in immobility time during the FST and TST and increased % sucrose preference in SPT, which reflects antidepressant-like effect and it enhances the exploratory behaviour in OFT, EPM and L&D test which indicates anxiolytic-like effects. It also decreases the levels of plasma CORT and brain inflammatory markers TNF-α, IL-1β and oxidative stress marker, MDA and increases the levels of brain serotonin and anti-oxidant enzyme catalase and SOD. However, MP-02 was not affected the levels of BDNF in mouse brain. The present study demonstrated the potential antidepressant and anxiolytic-like effects of MP-02 in mice. The results were further supported by docking simulations, offering molecular insights into the understanding of the experimental results.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009481","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":"Sacral Nerve Modulation Alleviates Neuropathic Pelvic Pain Through Modulation of the Spinal Immune Microenvironment and Microglial Activation.","authors":"Jinming Zuo, Yang Wang, Lixin Yang, Yueshi Hu, Futian Zhang, Qiang Wang, Zhihua Cao, Qixin Duan","doi":"10.1007/s11481-026-10304-y","DOIUrl":"10.1007/s11481-026-10304-y","url":null,"abstract":"<p><p>To investigate the efficacy of sacral neuromodulation (SNM) in alleviating neuropathic pelvic pain (NPP) and its underlying neuroimmune mechanisms, focusing on microglial activation and the CX3CL1-CX3CR1 pathway. A rat model of NPP was established via pelvic nerve crush (PNC), followed by SNM intervention. Pain behaviors were assessed using von Frey filaments and thermal withdrawal latency testing. Microglial activation, inflammatory factor expression, and signaling pathway dynamics in the spinal dorsal horn were analyzed using immunofluorescence, Western blot, qRT-PCR, and ELISA. Transcriptome sequencing was used to identify key pathways modulated by SNM. Exogenous CX3CL1, LPS, minocycline, and PLX5622 were employed to validate the roles of microglia and the CX3CL1-CX3CR1 axis in SNM-induced analgesia. PNC rats exhibited stable lower abdominal mechanical hypersensitivity, accompanied by significant microglial activation and increased expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the spinal dorsal horn. SNM treatment ameliorated pain behaviors, suppressed microglial activation, reduced pro-inflammatory cytokine expression, and inhibited p38 and p65 phosphorylation. Transcriptome analysis revealed that SNM remodeled inflammation-related transcriptional profiles, notably suppressing the CX3CL1-CX3CR1 signaling axis. Exogenous CX3CL1 or LPS partially reversed SNM-induced analgesia and anti-inflammatory effects. Microglial depletion attenuated the PNC-induced pain phenotype, with no significant synergistic effect observed when combined with SNM. SNM alleviates NPP by inhibiting CX3CL1-CX3CR1-mediated microglial activation and downstream inflammatory signaling, thereby remodeling the spinal cord immune microenvironment. This study provides new evidence for the central immunological mechanism underlying SNM in treating chronic pelvic pain and suggests the CX3CL1-CX3CR1 axis as a potential target for combined neuromodulation therapy.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983527","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":"ELAVL3 Exacerbates Brain Injury and Cognitive Dysfunction in Mice After Cardiac Arrest by Increasing S100B mRNA Stability to Promote Microglia Activation.","authors":"XueQin Ji, Yan Xia, Yuan Zhao, Yang Wu, Peng Zhang","doi":"10.1007/s11481-026-10315-9","DOIUrl":"10.1007/s11481-026-10315-9","url":null,"abstract":"<p><strong>Background and aims: </strong>Microglial activation-driven neuroinflammation exacerbates secondary brain injury following cerebral ischemia/reperfusion (I/R). The underlying molecular regulators are not fully elucidated. We investigated the role of the RNA-binding protein ELAVL3 and its target S100B in post-ischemic microglial activation and subsequent neuronal injury.</p><p><strong>Methods: </strong>In vitro, BV-2 microglia were subjected to oxygen-glucose deprivation/reperfusion (OGD/R), and their conditioned medium was applied to HT22 neurons. In vivo, a mouse model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR) was utilized. Gene expression was modulated using small interfering RNA (siRNA), plasmids, and lentiviral vectors. The ELAVL3-S100B mRNA interaction was confirmed by RNA immunoprecipitation and luciferase assays. Neuronal injury, neuroinflammation, and cognitive outcomes were evaluated using molecular, histological, and behavioral analyses.</p><p><strong>Results: </strong>OGD/R induced pro-inflammatory activation in microglia, leading to neuronal apoptosis, oxidative stress, and mitochondrial damage. ELAVL3 and S100B were upregulated in activated microglia in vitro and in the hippocampus after CA/CPR. ELAVL3 directly bound the S100B 3'-untranslated region, enhancing its mRNA stability and protein expression. In vitro, ELAVL3 knockdown suppressed S100B, attenuated microglial activation, and protected neurons. In vivo, hippocampal knockdown of either ELAVL3 or S100B reduced neuroinflammation and improved cognitive function after CA/CPR. The neuroprotective effects of ELAVL3 knockdown were rescued by S100B overexpression.</p><p><strong>Conclusion: </strong>Our study identifies the ELAVL3/S100B axis as a key driver of post-ischemic neuroinflammation. ELAVL3 enhances S100B expression post-transcriptionally, promoting microglial-mediated neurotoxicity. Targeting this pathway may offer a potential therapeutic strategy for cerebral ischemic injuries.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957556","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":"Tamoxifen Modulates Spinal Cord Injury Repair Via CCL2/CCR2 Axis and its Mechanisms.","authors":"Xiangzi Wang, Xiao Liang, Yuqi Lin, Wuhua Pang, Yuhan Liu, Ziqi Wang, Bin Liu, Xuyi Chen","doi":"10.1007/s11481-026-10314-w","DOIUrl":"10.1007/s11481-026-10314-w","url":null,"abstract":"<p><p>Spinal cord injury (SCI) represents a profoundly serious neurological disorder characterized by limited self-repair capabilities and accompanied by secondary inflammatory damage, rendering its treatment a pressing challenge in the field of medical science research. During the acute phase of SCI, the expression levels of C-C motif chemokine ligand 2 (CCL2) and its receptor, chemokine receptor 2 (CCR2), are significantly upregulated. The CCL2/CCR2 axis plays a critical role in regulating microglial activation, inflammatory responses, and apoptotic cascades within the injured spinal cord microenvironment. Emerging evidence suggests that tamoxifen (TAM), a selective estrogen receptor modulator, may exert neuroprotective effects in SCI by pharmacologically inhibiting the activity of the CCL2/CCR2 axis. Targeting this axis through TAM administration represents a promising therapeutic strategy to mitigate post-injury pathological progression and improve outcomes in SCI models. This study aims to address the critical issue of secondary inflammatory damage hindering neural regeneration and repair following SCI. By investigating the regulatory effects of TAM on the CCL2/CCR2 axis and its downstream pathways, we seek to elucidate its molecular mechanisms and provide novel strategies for pharmacological intervention in secondary injuries associated with SCI. Utilizing bioinformatics techniques, we identified differentially expressed genes post-SCI and analyzed signaling pathways related to the CCL2/CCR2 axis. We assessed the expression levels of this axis following SCI and employed behavioral assays, RT-PCR, ELISA, and Western blotting to validate the effects of TAM administration on the CCL2/CCR2 axis, its downstream pathways, and molecular mechanisms in both LPS-induced microglial inflammation models and complete transection models of SCI. Furthermore, we utilized the CCR2 antagonist INCB3344 and the PPAR-γ antagonist GW9662 to further validate the relationships within these pathways. TAM significantly reduced the expression of the CCL2/CCR2 axis in both in vitro and in vivo models following injury. By modulating this axis, TAM decreased NF-κB pathway expression and inhibited the secretion of inflammatory factors, facilitating the transition of microglia from a pro-inflammatory to an anti-inflammatory phenotype while activating the PPAR-γ pathway. Additionally, the activation of PPAR-γ reciprocally inhibited the expression of the CCL2/CCR2 axis. TAM may significantly alleviate secondary inflammatory responses following SCI through its modulation of the CCL2/CCR2 signaling pathway, exhibiting anti-apoptotic and anti-inflammatory effects. The findings of this study provide a theoretical foundation and experimental basis for the clinical application of TAM in SCI treatment research.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957508","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":"Targeting Nav1.6: a promising strategy against cognitive impairment in maternal separation-sensitive mice.","authors":"Yaya Du, Jingcheng Yang, Hongwei Xiang, Ting Sun, Longfei Li, Le Yang, Fei Li, Lanxin Luo","doi":"10.1007/s11481-026-10316-8","DOIUrl":"10.1007/s11481-026-10316-8","url":null,"abstract":"<p><strong>Background: </strong>Maternal separation (MS) correlates with adult cognitive impairment and neuroinflammation. The voltage-gated sodium channel Nav1.6 is critical in neuroinflammatory and neurodegenerative processes, but its role in MS-induced cognitive impairment is unclear. This study investigated whether hippocampal AAV-shRNA-mediated Nav1.6 reduction protects against MS-induced cognitive deficits in mice, exploring mechanisms involving hippocampal neuroinflammation, autophagy-related markers, and apoptosis-related changes.</p><p><strong>Methods: </strong>C57BL/6 mice (male/female) were subjected to daily MS (3 h/day, postnatal days 1-21). Nav1.6 was knocked down via stereotactic injection of AAV-GP-2-SCN8A-mus into the hippocampus of MS-sensitive mice (6 weeks). Cognitive function was evaluated using Morris water maze, novel object recognition, Y-maze, and open field tests. Hippocampal synaptic plasticity (LTP), protein expressions (Nav1.6, LC3B, p62, PSD95, Syn, Bax, Bcl-2), and inflammatory cytokines were analyzed via electrophysiology, Western blotting, RT-PCR, and ELISA, respectively.</p><p><strong>Results: </strong>MS-sensitive mice exhibited significant cognitive deficits, reduced hippocampal synaptic plasticity, and increased Nav1.6 immunoreactivity in Iba1-positive cells. Hippocampal Nav1.6 reduction improved cognitive function, altered autophagy-related markers (reduced LC3B-II and elevated p62), altered apoptosis-related markers, and mitigated neuroinflammation (reduced IL-6, TNF-α, IL-1β).</p><p><strong>Conclusions: </strong>Hippocampal Nav1.6 reduction alleviates MS-induced cognitive impairment and is associated with modulation of autophagy- and apoptosis-related changes and neuroinflammatory responses, suggesting Nav1.6 as a potential therapeutic target for stress-related cognitive disorders.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882791","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":"6-gingerol Attenuates Inflammatory Response in Rats With Spinal Cord Injury by Reducing NLRP3-mediated Microglial Pyroptosis.","authors":"Junjie Li, Jinfeng Hu, Shuhan Liang, Jinxin Luo, Yaojian Rao","doi":"10.1007/s11481-026-10311-z","DOIUrl":"10.1007/s11481-026-10311-z","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a severe neurological disorder with limited therapeutic options. 6-gingerol, a major bioactive component of ginger, possesses anti-inflammatory and neuroprotective activities; however, its role in SCI remains incompletely understood. This study investigated the effects and underlying mechanisms of 6-gingerol in SCI-induced microglial pyroptosis. A rat SCI model was established and treated with 6-gingerol. Neurological function, histopathological changes, microglial activation, and pyroptosis were evaluated. An LPS/ATP-induced BV2 microglial pyroptosis model was used for in vitro mechanistic studies. Cell viability, LDH, pyroptosis-related proteins, and inflammatory cytokines were analyzed. The expression of EZH2, USP7, and FOXO3 was determined by qRT-PCR and Western blot. Chromatin immunoprecipitation was performed to evaluate EZH2 and H3K27me3 mediated regulation of the USP7 promoter, while co-immunoprecipitation and ubiquitination assays were used to examine the interaction between USP7 and FOXO3. 6-gingerol significantly improved locomotor recovery, attenuated spinal cord tissue damage, and reduced microglial pyroptosis and inflammatory response after SCI. Mechanistically, 6-gingerol suppressed EZH2 expression and reduced H3K27me3 enrichment at the USP7 promoter, thereby restoring USP7 expression. Increased USP7 enhanced FOXO3 deubiquitination and stabilization, leading to suppression of pyroptotic signaling. Furthermore, EZH2 overexpression, USP7 inhibition, or FOXO3 knockdown partially abolished the anti-pyroptotic effects of 6-gingerol in vitro, and EZH2 overexpression attenuated the neuroprotective effects of 6-gingerol in SCI rats. In conclusion, 6-gingerol treatment alleviates SCI-induced neuroinflammation and microglial pyroptosis through the EZH2/USP7/FOXO3 axis, highlighting a potential therapeutic strategy for SCI.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"21 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867099","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}