Molecular and Cellular Neuroscience最新文献

{"title":"Interweaving microglial senescence and gut microbiome dynamics in Alzheimer's disease – Mechanisms and therapeutic frontiers","authors":"Akanksha Waghmare ,&nbsp;Sandip Rahangdale ,&nbsp;Kanchan Khare ,&nbsp;Brijesh Taksande ,&nbsp;Milind Umekar ,&nbsp;Shubhada Mangrulkar","doi":"10.1016/j.mcn.2026.104075","DOIUrl":"10.1016/j.mcn.2026.104075","url":null,"abstract":"<div><div>Alzheimer's disease (AD), a prevalent neurodegenerative disorder characterized by cognitive impairment and neuronal degeneration, is increasingly recognized as being driven not only by the traditional amyloid-beta and tau pathologies but also by persistent neuroinflammation and systemic immune dysregulation. Emerging evidence implicates microglia senescence and gut microbiota dysbiosis is critical contributors to the neuroinflammatory landscape. Senescent microglia marked by reduced phagocytic ability and a pro-inflammatory secretory profile, are unable to clear pathogenic stimuli, thereby intensifying neuronal damage. Simultaneously, gut dysbiosis, characterized by a reduction in beneficial bacteria and an increase in endotoxin-producing species, elevates systemic inflammation and compromises the intestinal and blood brain barrier. Microbial metabolites, such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS), affect microglial activation through the gut-brain axis, primarily via the TLR4/NF-κB and NLRP3 inflammasome pathways, thus promoting microglial senescence and exacerbating AD pathology. Therapeutic approaches that target these interacting pathways are rejuvenation of microglia with senolytics and stimulation of TREM2; regulation of gut microbiota with probiotics, prebiotics, lifestyle modification, dietary intervention; and fecal microbiota transplantation. Precision medicine approaches incorporating microbiome profiling and immunogenetic analysis will enhance these treatments. This review combines mechanistic insight into microglial aging and gut-brain interaction, emphasizes their synergistic role in AD pathogenesis, and delineates integrated therapeutic strategies. Dissection of the gut-microglia axis can reveal novel targets for early intervention to counteract neuroinflammation, improve cognitive function, and slow disease progression in AD.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"136 ","pages":"Article 104075"},"PeriodicalIF":2.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological regulation of adult brain neuroplasticity: Synergistic roles of neuropeptide signaling, psychedelics, and synaptic modulators","authors":"Mustafa M. Shokr ,&nbsp;Mohamed N. Fawzy ,&nbsp;Ahmed M. Abdelaziz","doi":"10.1016/j.mcn.2026.104076","DOIUrl":"10.1016/j.mcn.2026.104076","url":null,"abstract":"<div><div>Neuroplasticity refers to the ability of the brain to modify synaptic connections and reorganize neural circuits, underpinning cognitive function, emotional regulation, and recovery from injury. Recent advances have redefined adult neuroplasticity as more dynamic and therapeutically accessible than previously thought, spurring investigation into pharmacological interventions that can augment these adaptive processes. This review dissects current evidence for drug strategies targeting synaptic modulators (NMDA, AMPA, and GABA receptors), neuropeptide systems (including BDNF, oxytocin, vasopressin), and psychedelic compounds (psilocybin, LSD, ketamine), integrating insights from cellular, preclinical, and clinical studies. We detail how these agents modulate molecular pathways governing synaptic transmission, dendritic remodeling, and gene expression linked to neuronal growth and resilience. Highlighted findings include the rapid-acting antidepressant effects of NMDA antagonists, the structural and functional reorganization induced by classic psychedelics via 5-HT2A receptor activation, and the neurorestorative roles of neuropeptides in synaptic and network adaptation. Alongside these advances, we critically address safety, ethical considerations, and the risk of maladaptive plasticity, underscoring the importance of dosing, patient selection, and controlled therapeutic environments. Non-hallucinogenic neuroplastogens and combinatorial approaches that are still emerging offer new avenues to fine-tune plasticity with an improved safety profile. The collective evidence positions neuroplasticity-targeting pharmacology as a promising and complex frontier for the treatment of neuropsychiatric and neurodegenerative disorders in adulthood.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"136 ","pages":"Article 104076"},"PeriodicalIF":2.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"haFGF14–154 attenuates Aβ1–42-induced neurotoxicity by facilitating BDNF maturation in a neuron-astrocyte co-culture system","authors":"Dong Peng ,&nbsp;Luyi Wu ,&nbsp;Lei Zhang ,&nbsp;Hongxia Chen ,&nbsp;Bo Hu ,&nbsp;Qihao Zhang ,&nbsp;Yadong Huang","doi":"10.1016/j.mcn.2025.104056","DOIUrl":"10.1016/j.mcn.2025.104056","url":null,"abstract":"<div><div>haFGF₁₄_–₁₅₄ improves cognitive impairment in animal models of Alzheimer's disease (AD), but the effects and mechanisms of astrocytes on the neuroprotection mediated by haFGF₁₄_–₁₅₄ remain unclear. Here, a neuron-astrocyte co-culture system was established to investigate the functions of astrocytes. The results showed that astrocytes strengthened the protective effect of haFGF₁₄_–₁₅₄ on Aβ₁_–₄₂-treated neurons. This enhanced protective function of haFGF₁₄_–₁₅₄ correlates with phenotypic transition in astrocytes, as demonstrated by the suppression of Aβ₁_–₄₂-induced A1-like genes and the elevation of A2-like markers <em>in vitro</em>. These observations are consistent with the reduction of GFAP and C3 levels in the hippocampus and prefrontal cortex of APP/PS1 mice treated with haFGF₁₄_–₁₅₄. haFGF₁₄_–₁₅₄ modified the function of astrocytes by activating the AKT/CREB/BDNF pathway, thereby promoting neurite growth. Moreover, haFGF₁₄_–₁₅₄ up-regulated the expression of Furin and MMP9 in astrocytes, leading to the processing of pro-BDNF. This effect was replicated in APP/PS1 mice administered with haFGF₁₄_–₁₅₄. Compared to the Aβ group, the BDNF level in the co-culture system supernatant was increased, while the IL-1β level was decreased following haFGF₁₄_–₁₅₄ treatment. Additionally, haFGF₁₄_–₁₅₄ inhibited neuronal apoptosis in the co-culture system, as evidenced by a decrease in pro-BDNF/P75^NTR, an increase in Bcl-2, and a reduction of Bad and Cleaved-caspase-3. In conclusion, current results demonstrate that astrocytes are crucial for mediating the protective effect of haFGF₁₄_–₁₅₄ against neuronal damage, and underline the importance of the AKT/CREB/BDNF pathway in promoting neurite growth and attenuating neuronal apoptosis.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104056"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of polarization dynamics in macrophages and microglia on the inflammatory microenvironment of spinal cord injury","authors":"Yue Hu,&nbsp;Jun Gao","doi":"10.1016/j.mcn.2025.104054","DOIUrl":"10.1016/j.mcn.2025.104054","url":null,"abstract":"<div><div>Spinal cord injury (SCI) triggers complex pathological processes—including neuroinflammation, glial scar formation, and impaired neuronal regeneration—that hinder recovery. Macrophages and microglia centrally regulate these processes through dynamic polarization states across a spectrum of pro−/anti-inflammatory phenotypes. While single-cell technologies reveal glial and immune heterogeneity and interactions in the SCI microenvironment, translating these insights into immunomodulatory therapies remains challenging. This review therefore examines mechanisms driving macrophage/microglia polarization in the microenvironment of SCI, focusing on their therapeutic targeting potential.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104054"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AstroGreen transgenic mouse illuminates the trafficking of astrocyte-derived extracellular vesicles","authors":"Lisa Nieland ,&nbsp;Edwina Abou Haidar ,&nbsp;David Rufino-Ramos ,&nbsp;Shilpa Prabhakar ,&nbsp;Youssef Samaha ,&nbsp;Koen Breyne ,&nbsp;Francis K. Fordjour ,&nbsp;Saumya Das ,&nbsp;Marike L.D. Broekman ,&nbsp;Stephen Gould ,&nbsp;Xandra O. Breakefield ,&nbsp;Erik R. Abels","doi":"10.1016/j.mcn.2025.104051","DOIUrl":"10.1016/j.mcn.2025.104051","url":null,"abstract":"<div><div>Astrocytes interact with neighboring cells by releasing extracellular vesicles (EVs). Tools to study astrocyte EV-mediated communication with other brain cells <em>in vivo</em> are essential<em>.</em> In this study, we crossed the Exomap1 transgenic mouse expressing Cre-activated human-specific CD81 (HsCD81) fused to the fluorescent protein mNeonGreen (HsCD81mNG), to a transgenic mouse expressing Cre under the astrocyte-expressing GFAP promoter resulting in <em>Exomap1</em>::<em>Gfap-Cre</em> mice, referred to here as AstroGreen. We characterized HsCD81mNG-expressing astrocytes and shedded EVs loaded with HsCD81mNG and Cre, both <em>in vitro</em> and in mouse brains. Using this model, we show that HsCD81mNG can be used to track EV content, production, and functional Cre transfer <em>in vitro</em> and in the brain, allowing evaluation of the interaction of astrocytes with neighboring cells mediated by EVs. We anticipate that this model will improve our understanding of astrocytes transferring EVs within their surroundings during normal physiological processes and in the context of neuropathological conditions.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104051"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stable apelin-13 analogues promote cell proliferation, differentiation and protect inflammation induced cell death","authors":"Priya Sharma ,&nbsp;Mary Erazo Bastidas ,&nbsp;Usman Ali ,&nbsp;Shivadas Sivasubramaniam ,&nbsp;Vadivel Parthsarathy","doi":"10.1016/j.mcn.2025.104036","DOIUrl":"10.1016/j.mcn.2025.104036","url":null,"abstract":"<div><div>Emerging evidence indicates that apelin, an adipokine, plays a critical role in numerous biological functions and may hold potential for therapeutic applications; however, its efficacy is constrained by rapid plasma degradation. Thus, the search for novel apelin analogues with reduced susceptibility to plasma degradation is ongoing. We have previously shown novel modified apelin-13 analogues, providing exciting opportunities for potential therapeutic development against Alzheimer's disease. In this study we explored novel insights into the neuroprotective effects of stable fatty acid modified (Lys8GluPAL) apelin-13-amide and amidated apelin-13 amide in mitigating cellular damage in SH-SY5Y neuroblastoma cells exposed to palmitic acid (PA) and lipopolysaccharide-induced (LPS) stress. Both apelin-13 analogues were found to modulate ER stress response and reduce oxidative stress by suppressing PA- and LPS-induced ROS production (36 % and 42 % reductions in GSH/GSG (<em>p</em> &lt; 0.005). The peptides attenuated apoptosis by reducing caspase 3/7 activity and restoring bcl2 expression (<em>p</em> &lt; 0.05) in cells treated with PA and LPS. They also downregulated pro-apoptotic genes, protected neurites from stress-induced damage, and promoted neurite outgrowth. The observed protective effects could be due to activation of the AMPK pathway, a critical regulator of cellular energy homeostasis and survival. These findings provide insight into novel, enzymatically stable apelin-13 analogues and highlight their potential to be developed as therapeutic agents against neuroinflammation and neurodegenerative disease, including Alzheimer's disease.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104036"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding aging through nitrogen containing compounds: A nutrigenomic insight","authors":"Spandana Rajendra Kopalli ,&nbsp;Nitu L. Wankhede ,&nbsp;Sushruta Koppula ,&nbsp;Brijesh Taksande ,&nbsp;Aman B. Upaganlawar ,&nbsp;Arifullah Mohammed ,&nbsp;Milind Umekar ,&nbsp;Mayur B. Kale","doi":"10.1016/j.mcn.2025.104055","DOIUrl":"10.1016/j.mcn.2025.104055","url":null,"abstract":"<div><div>Nitrogen compounds are increasingly recognized as key modulators in nutrigenomics, with profound implications for understanding and influencing the aging process. Traditionally central to human nutrition, these compounds are now understood to play critical roles in regulating gene expression, cellular signalling, and metabolic pathways that are essential for maintaining health during aging. Nitrogen-containing molecules, such as amino acids, polyamines, and nitric oxide, contribute to vital processes including protein synthesis, mitochondrial function, and oxidative stress management. These mechanisms are crucial for cellular homeostasis but become increasingly vulnerable to disruption during aging, leading to tissue degeneration and heightened susceptibility to age-related diseases. Disruptions in nitrogen metabolism can impair proteostasis, mitochondrial bioenergetics, and antioxidant defences, accelerating cellular decline. Recent research has expanded our understanding of how nitrogen compounds interact with nutrient-sensing pathways such as mTOR and AMPK, as well as epigenetic regulators that influence DNA repair, autophagy, and inflammation. These findings highlight the therapeutic potential of optimizing nitrogen metabolism to enhance health span and mitigate the effects of aging. The emerging field of nitrogen nutrigenomics offers promising opportunities for developing targeted nutritional strategies aimed at improving quality of life and delaying age-related decline. By integrating historical perspectives with contemporary discoveries, this review underscores the complex interplay between nitrogen compounds and aging while inspiring future research into innovative interventions that harness their benefits for longevity and well-being. Ultimately, optimizing nitrogen metabolism could pave the way for new approaches to extending health span and addressing age-related health challenges.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104055"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eprosartan alleviates the traumatic brain injury-induced multi-organ dysfunction syndrome in mice via AT1R/SNS/HMGB1 blockade and PDL-1 modulation","authors":"Manisha Thakur ,&nbsp;Sunil Sharma ,&nbsp;Neeru Vasudeva ,&nbsp;Paras Saini ,&nbsp;Deepika Lather ,&nbsp;Deepak Deepak","doi":"10.1016/j.mcn.2025.104035","DOIUrl":"10.1016/j.mcn.2025.104035","url":null,"abstract":"<div><div>Traumatic brain injury is not constrained only to the brain but delayed secondary events disturb the end organ functioning via intense response of three homeostatic mechanisms such as sympathetic activity, inflammation, and immunosuppression. Current study involved weight drop model to induce TBI in Swiss albino mice. Eprosartan was administered orally after 30–45 min post injury to mice in 0.35 mg/kg and 0.7 mg/kg doses. Mice were tested for neurobehavioral alterations and multiple organs, including brain, heart, lungs, liver, and kidney were excised for further edema, biochemical, inflammatory, catecholamine, gene expression and histopathological estimations at both acute and chronic phases of injury. Results highlighted that Epro improved neurobehavioral performance, maintained the BBB and lung integrity. It also ameliorated the oxidative stress as well as docking studies exhibited strong binding affinity of Epro for HMGB1 and PDL-1, that further supported by low tissue HMGB1 and serum IL-6 and TNF-α cytokines levels which halted the systemic hyperinflammation. Moreover, Epro treatment successfully restored the cardiac, hepatic and kidney function through stabilized serum biomarkers with declined plasma noradrenaline levels that subsides the sympathetic storm. Considerably, a bizarre cellular morphology was displayed by the organs in acute phase of injury whereas Epro reversed the morphological changes at chronic stage. Also, epro encouraged the PD-1/PDL-1 and IL-10 gene expression in the tissues that regulates immune response. Thus, it is concluded that Epro exerts its organ protective effect against MODS via AT₁/SNS pathway inhibition.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104035"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-based therapeutic approach for spinal cord injury: A review","authors":"Shuai Bai ,&nbsp;Rong Rong Qiang ,&nbsp;Rui Yang Liu ,&nbsp;De Jie Kang ,&nbsp;Yan Ling Yang","doi":"10.1016/j.mcn.2025.104048","DOIUrl":"10.1016/j.mcn.2025.104048","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a devastating neurological condition associated with high rates of disability and mortality, placing substantial burdens on patients, families, and healthcare systems. Current treatment strategies, including surgical decompression, pharmacological intervention, and rehabilitation, offer only limited functional recovery. Exosomes, extracellular vesicles with a double-membrane structure, range in diameter from 30 to 150 nm and play a key role in intercellular communication by transporting proteins, lipids, and nucleic acids. Recent studies have highlighted their potential as natural nanocarriers for the treatment of neurodegenerative disorders. Due to their low immunogenicity and multifunctional reparative properties, exosomes have shown considerable efficacy in promoting neurological recovery following SCI. They exert therapeutic effects through multiple mechanisms, including modulation of the inflammatory response, promoting axonal regeneration and angiogenesis, and inhibiting apoptosis. This review summarizes the pathophysiological mechanisms underlying SCI and elucidates the therapeutic roles of exosomes and exosomal microRNAs (<em>exo</em>-miR) in SCI repair. Furthermore, it discusses current challenges and prospects for the clinical translation of exosome-based therapies, aiming to provide valuable insights for future research and clinical applications.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104048"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agrimonolide exhibits anti-neuroinflammatory potential via TLR4-mediated pathways","authors":"Weiling Li ,&nbsp;Qian Peng ,&nbsp;Ping Sun ,&nbsp;Lingyi Xiang ,&nbsp;Yangxin Qi ,&nbsp;Xiansheng Ye ,&nbsp;Yingying Shi ,&nbsp;Song Hu ,&nbsp;Haifeng Chen ,&nbsp;Binlian Sun","doi":"10.1016/j.mcn.2025.104057","DOIUrl":"10.1016/j.mcn.2025.104057","url":null,"abstract":"<div><div>Microglial and astrocytic activation is the main reason for the neuroinflammatory responses, which damages neurons resulting in neurological disorders. Currently, there are few drugs that directly target neuroinflammation in clinical practice, which highlights the urgent need for effective inhibitors. In this study, we identified agrimonolide, from a screen of 40 compounds, as an inhibitor of glia activation, and further confirmed its efficacy in vitro and <em>in vivo</em>. In cellular models, agrimonolide significantly reduced the expression levels of proinflammatory cytokines (IL-1β, IL-6 and TNFα) in LPS stimulated BV2 cells and primary astrocytes. Mechanistic investigation revealed that agrimonolide suppresses the activation of both NF-κB and MAPK signaling pathways, combined the molecular docking results, it is suggested that agrimonolide may have multiple targets. In ICR mice, our measurements showed that agrimonolide treatment decreased LPS-induced glial activation, as evidenced by the protein levels of IBA-1 and GFAP. Additionally, it significantly inhibited the activation of TLR4-mediated signaling pathways. Our findings suggest that agrimonolide suppresses neuroinflammatory responses by inhibiting microglial and astrocytic activation, providing insight into potential treatment strategies for neuroinflammation-related diseases.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104057"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}