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

{"title":"Human Umbilical Cord Mesenchymal Stem Cells Ameliorated Chronic Unpredictable Mild Stress-Induced Depression and Anxiety by Alleviating Neuroinflammation.","authors":"Guangyang Liu, Li Miao, Haichen Niu, Herui Wang, Li Yan, Yaoyao Chen, Chenliang Zhang, Xin Li, Yi Mi, Liqiang Xu, Daohui Wang, Jingwen Zhou, Xiaodan Xu, Guo Li, Haomiao Long, Yongjun Liu","doi":"10.1007/s11481-025-10198-2","DOIUrl":"https://doi.org/10.1007/s11481-025-10198-2","url":null,"abstract":"<p><p>Inflammation, neurotransmitters, and apoptotic neurons are crucial elements in the progression of Major Depressive Disorder (MDD). Previous studies have demonstrated that mesenchymal stem cells (MSCs) had a positive impact on neuroinflammation and neuroprotection. In this context, human umbilical cord mesenchymal stem cells (hUC-MSCs) were administered into chronic unpredictable mild stress model (CUMS) mice to evaluate their effects on inflammation, neurotransmitters, microglia, neurons activation, and neuronal apoptosis. The distribution of hUC-MSCs within the brain was detected by CM-Dil-labelled hUC-MSCs. Our results indicated that hUC-MSCs infiltrated the brains of CUMS mice to protect the integrity of the blood-brain barrier (BBB). Furthermore, hUC-MSCs inhibited microglia activation to result in decreased inflammation levels and increased neurotransmitters, ultimately alleviating neuronal damage and regulating neuronal activity. These findings suggest that hUC-MSCs can maintain the BBB integrity and reduce neuroinflammation and neuronal damage, thereby effectively alleviating depression-like and anxiety-like behavior.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"45"},"PeriodicalIF":6.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030214","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":"Cranberry Extract Ameliorates Diabetic Cognitive Impairment in Rats Via LncRNA GAS-5 Downregulation and Pyroptosis Pathway Inhibition.","authors":"Mariam Ali Abo-Saif, Amany E Ragab, Iman M Talaat, Maha Saber-Ayad, Amera O Ibrahim, Hend Mostafa Selim","doi":"10.1007/s11481-025-10199-1","DOIUrl":"https://doi.org/10.1007/s11481-025-10199-1","url":null,"abstract":"<p><p>The pathophysiology of diabetes-induced brain injury involves pyroptosis, an inflammatory programmed cell death. This study aimed to investigate the potential protective effect of cranberry extract (CE) against diabetes-induced brain injury. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin in rats. Brain tissue samples were investigated for biochemical determination of the reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), and the quantitative RT-PCR for the gene expression of glial cell-derived neurotrophic factor (GDNF), lncRNA GAS-5, and pyroptosis markers. ELISA was used to determine the caspase-1 level and immunohistochemical staining for assessing IL-1β. Prophylactic dosing of the CE in diabetic rats improved cognitive behavior and significantly suppressed MDA concentration, pyroptosis genes expression (gasdermin D and caspase 1), and lncRNA GAS-5. In addition, CE significantly elevated GSH concentration, SOD activity, and gene expression of GDNF and markedly reduced IL-1β positive stained cells score in the brain. Phytochemical characterization of the CE by FT-IR and UPLC-PDA-MS/MS revealed cyanidin arabinoside, procyanidins, quercetin, and isorhamnetin as key components. CE protects against diabetes-induced cognitive dysfunction in rats by targeting redox-related signaling pathways and inducing an anti-inflammatory effect. LncRNA GAS-5 downregulation and pyroptosis pathway inhibition may contribute to its beneficial effects, suggesting its therapeutic potential.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"44"},"PeriodicalIF":6.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044085","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":"Novel Trajectories Towards Possible Effects of Semaglutide for Amelioration of Reserpine-induced Fibromyalgia in Rats: Contribution of cAMP/PKA/p-CREB and M1/M2 Microglia Polarization.","authors":"Mena Z Shafiek, Hala F Zaki, Ahmed F Mohamed, Weam W Ibrahim","doi":"10.1007/s11481-025-10196-4","DOIUrl":"https://doi.org/10.1007/s11481-025-10196-4","url":null,"abstract":"<p><p>Fibromyalgia (FM) is a pain disorder characterized by pervasive musculoskeletal pain associated with exhaustion, depression, and irregular sleep patterns. Semaglutide, an innovative glucagon-like peptide-1 (GLP-1) agonist, has shown analgesic effects by modulating pain hypersensitivity in animal models of inflammatory pain. The objective of this study is to ascertain semaglutide's therapeutic potential against FM-like symptoms caused by reserpine. Reserpine (1 mg/kg/day; SC) was administered into rats for 3 consecutive days, then they were treated daily with semaglutide intraperitoneally in low (5 nmol/kg), intermediate (10 nmol/kg), or high doses (20 nmol/kg), respectively, for 14 consecutive days. Semaglutide alleviated reserpine induced histopathological and immunohistopathological changes in spinal cord of rats evidenced by a remarkable rise in immuno-expression of cluster of differentiation 163 (CD163) contrary to a significant diminution in CD86 level as compared with reserpine group. Semaglutide also had an analgesic effect and improved motor incoordination, and depression brought on by reserpine. Furthermore, it had an anti-inflammatory impact via stimulating cyclic adenosine monophosphate (cAMP)/ protein kinase A (PKA)/ cAMP response element (CRE)-binding protein (CREB) signaling pathway and shifting M1/M2 macrophage polarization towards the M2. Semaglutide's anti-inflammatory actions were manifested through inhibition of inducible nitric oxide synthase and reduction in dorsal root ganglia concentrations of tumor necrosis factor-α together with elevation in the levels of arginase-1 and interleukin-4.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"43"},"PeriodicalIF":6.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058128","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":"The Role of Microglial Exosomes in Clozapine Treatment: Effect on Cognition in Schizophrenia.","authors":"Kyle Hewitt, Xu-Feng Huang","doi":"10.1007/s11481-024-10160-8","DOIUrl":"https://doi.org/10.1007/s11481-024-10160-8","url":null,"abstract":"<p><p>Schizophrenia is a complex neuropsychiatric disorder characterized by a spectrum of symptoms including cognitive impairments and psychotic episodes. Clozapine, an atypical antipsychotic drug, is a widely recognised treatment option for patients with drug-resistant schizophrenia, due to it having the highest efficacy out of all the antipsychotic drugs. Despite its efficacy, clozapine's impact on cognition and brain structure in schizophrenia patients remains a subject of ongoing research and debate, with accumulating evidence indicating negative impacts on cognitive performance and changes in brain volume. Changes in the immune system are linked to variations in cognitive functioning in schizophrenia. Previous research has indicated that microglia, the primary innate immune cells of the brain, have been associated with decreased cognitive performance when dysfunctional. Evidence suggests that brain structure may mediate the observed relationship between microglia and cognition. Microglial exosomes, integral to neuroinflammation and cellular communication, could provide insight into the neurobiological mechanisms underpinning the effects of clozapine treatment. This review focuses on the proposition that alterations in microglial exosome composition, particularly miRNAs, are involved in mediating clozapine's diverse effects on cognition by influencing brain macrostructure. This review aims to highlight new directions for future research that could lead to more effective and targeted therapeutic approaches in the management of schizophrenia.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"42"},"PeriodicalIF":6.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032167","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":"Abscisic Acid Rescues Behavior in Adult Female Mice in Attention Deficit Disorder with Hyperactivity Model of Dopamine Depletion by Regulating Microglia and Increasing Vesicular GABA Transporter Expression.","authors":"Maria Meseguer-Beltrán, Sandra Sánchez-Sarasúa, Nóra Kerekes, Marc Landry, Matías Real-López, Ana María Sánchez-Pérez","doi":"10.1007/s11481-025-10186-6","DOIUrl":"https://doi.org/10.1007/s11481-025-10186-6","url":null,"abstract":"<p><p>Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome typically diagnosed in childhood that may persist into adulthood. Its etiology encompasses both genetic and environmental factors, with genetic studies indicating catecholamine dysfunction and epidemiological evidence emphasizing neuroinflammation as a potential trigger. To investigate the roles of inflammation and development processes in ADHD, we conducted a longitudinal behavioral study using female Swiss mice with a dopamine deficit model. We explored the impact of neonatal dopaminergic lesions, treatment with abscisic acid (ABA)-an anti-inflammatory hormone-and developmental changes by comparing behavioral patterns in juvenile and adult mice. Postmortem analyses assessed neuroinflammation through microglial morphology, NLRP3, cytokine expression, and the excitatory/inhibitory (E/I) ratio in specific brain regions. Neonatal dopaminergic lesions induced hyperactivity and hypersensitivity in juvenile mice that persisted into adulthood. In adults, increased social interaction and memory impairment were observed in lesioned mice. Brain development mitigated impulsivity, while ABA treatment reduced locomotor activity, downregulated pain sensitivity, and influenced social interaction, although it did not completely resolve cognitive deficits in lesioned adult mice. In brain regions such as the anterior cingulate cortex (ACC), posterior insular cortex (pIC), and hippocampus, lesions significantly altered microglial morphology. In the ACC, lesions increased IL-1β and TNFα levels, decreased Arg1 mRNA levels, and disrupted the E/I balance. Importantly, ABA treatment restored microglial morphology, normalized IL-1β and Arg1 expression and upregulated vGAT levels. This study demonstrates that dopamine deficits lead to microglia alterations and E/I imbalance, contributing to ADHD symptoms. While some symptoms improve with brain development, targeting microglial health in specific brain regions emerges as a promising therapeutic approach for managing ADHD.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"39"},"PeriodicalIF":6.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047084","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":"Preparation and In vitro/In vivo Evaluation of Fingolimod hydrochloride Loaded Polymeric Mixed Nano-Micelles for Treatment of Multiple Sclerosis.","authors":"Ladan Dayani, Fatemeh Haddadi, Mehdi Aliomrani, Azade Taheri","doi":"10.1007/s11481-025-10203-8","DOIUrl":"https://doi.org/10.1007/s11481-025-10203-8","url":null,"abstract":"<p><p>Fingolimod (FYN) is one of the approved medicines for treatment of multiple sclerosis (MS) while exhibiting several side effects such as liver enzyme elevation and cardiac damage. This study was aimed to prepare the mixed micelles of ascorbyl palmitate (AP) and alpha-tocopherol polyethylene glycol succinate (TPGS) as a delivery system for FYN. The mixed micelles were prepared by thin film hydration method at different ratios of AP/TPGS. Saturation solubility of the micelles was compared with the pure drug. The optimized formulation was characterized by scanning electron microscopy (SEM) and subjected for stability study at 5 ± 3 °C for 3 months. The effect of the prepared fingolimod loaded micelles (FYN-Micelle) was finally assessed by experimental autoimmune encephalomyelitis (EAE) model at the dose of 0.3, 1, and 3 mg/kg of fingolimod, which was administrated intraperitoneally. The results indicated that the prepared mixed micelles at the AP/TPGS ratio of 1:5 showed a particle size, zeta potential, and an entrapment efficiency of 116.86 ± 2.41 nm, 23.61 ± 4.56 mV, and 63.28 ± 5.31%, respectively. Also, this formulation was stable after a 3-month incubation at 5 ± 3 °C. SEM images displayed an amorphous state of the drug in the micelles. Animal studies confirmed that this formulation at the dose of 1 mg/kg could enhance the myelin density of the brain while reducing cardiac and hepatic impairment. Therefore, these findings suggested that FYN-Micelle could be exploited as an effective delivery system for fingolimod hydrochloride to treat MS.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"41"},"PeriodicalIF":6.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025761","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":"Evaluation of the Anti-Inflammatory Effects of Novel Fatty Acid-Binding Protein 4 Inhibitors in Microglia.","authors":"Yi Ling Low, Ethan Kreutzer, Indu R Chandrashekaran, Luke A Adams, Jason Pun, Bradley C Doak, Yijun Pan, Jennifer L Short, Martin J Scanlon, Joseph A Nicolazzo","doi":"10.1007/s11481-025-10191-9","DOIUrl":"https://doi.org/10.1007/s11481-025-10191-9","url":null,"abstract":"<p><p>Fatty acid-binding protein 4 (FABP4) is a key lipid binding protein expressed in microglia, which has been demonstrated to play a critical role in microglial-mediated neuroinflammation, a component of many neurodegenerative diseases. Compounds able to inhibit the function of FABP4 have shown promise in reducing microglial-mediated neuroinflammation, however, their physicochemical properties would prevent their ability to be easily formulated and traverse the blood-brain barrier (BBB) in order to access microglial FABP4. To this end, this study assessed the ability of a series of FABP4 inhibitors, with more desirable physicochemical properties, to attenuate microglial inflammation in an in vitro setting. Four inhibitors with varying affinity to FABP4, as measured by isothermal titration calorimetry (MFP-0011462, MFP-0012314, MFP-0012318, and MFP-0012328), were assessed for their ability to induce toxicity and attenuate reactive oxygen species (ROS) generation and tumour necrosis factor-α (TNF-α) release from lipopolysaccharide (LPS)-activated BV-2 microglia. All FABP4 inhibitors were determined to be soluble in the aqueous buffers at the highest concentration used in the assays (100 µM). Isothermal titration calorimetry demonstrated that the compounds had varying affinities for FABP4 (K_D values of 316 nM to > 100 µM). The ability of FABP4 inhibitors to reduce LPS-mediated ROS production aligned with their K_D for FABP4, with the most effective inhibitor (MFP-0012328) also able to reduce TNF-α production (by RT-qPCR) and TNF-α release from LPS-activated BV-2 cells by 17% and 25%, respectively. These studies have demonstrated that a series of FABP4 inhibitors with more appropriate physicochemical properties for BBB penetration are able to reduce microglial-mediated inflammation, which may be of benefit in diseases where overactivation of microglia leads to neurodegeneration.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"40"},"PeriodicalIF":6.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060689","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":"Modafinil Ameliorated Fibromyalgia Syndrome in Rats by Modulating Mast Cells and Microglia Activation Through Dopamine/Substance P/MRGPRX/Histamine and PI3K/p-Akt/NF-κB Signaling Pathways.","authors":"Mennat-Allah M Kamal, Reham M Essam, Noha F Abdelkader, Hala F Zaki","doi":"10.1007/s11481-025-10194-6","DOIUrl":"https://doi.org/10.1007/s11481-025-10194-6","url":null,"abstract":"<p><p>Fibromyalgia syndrome (FMS) is characterized by prolonged, widespread musculoskeletal pain accompanied by various physical and psychological disturbances. Modafinil, a wake-promoting drug, manages pain symptoms in several diseases by inhibiting dopamine reuptake and exhibiting anti-inflammatory and immunomodulatory effects, including the impairment of cytokine production, microglia, and mast cell activation. Central inflammation may involve microglial activation, which is correlated with mast cell activation. Restoring dopamine levels and modulating the communication between mast cells and microglia may represent a promising approach to managing pain symptoms in FMS. Thus, this study intended to explore the interplay between brain mast cells and microglia as an underlying mechanism in the pathophysiology of FMS and how this interaction is controlled by modafinil, with a focus on dopamine/SP/MRGPRX2/histamine and PI3K/p-Akt/NF-κB signaling pathways. Rats were arbitrarily distributed between 4 groups. Group 1 served as normal control. Reserpine (1 mg/kg/day; s.c) was injected into the remaining groups for three consecutive days. In groups 3 and 4, modafinil (100 mg/kg/day; p.o) was administered either alone or in conjunction with haloperidol (1 mg/kg/day; ip), respectively, for the following 21 days. Modafinil ameliorated reserpine-induced thermal/mechanical allodynia (1.3-fold, 2.3-fold) and hyperalgesia (0.5-fold), attenuated depression (0.5-fold), and enhanced motor coordination (1.2-fold). It mitigated the histopathological alterations and increased dopamine levels in the thalamus of rats by 88.5%. Modafinil displayed anti-inflammatory effects via inhibiting mast cells and microglia activation, manifested by reductions in SP/MRGPRX2/IL-17/histamine (52%, 58%, 56.7%, and 63.7%) and PI3K/p-Akt/t-Akt/NF-κB/TNF-α/IL-6 (31.7%, 55.5%, 41%, 47.6%, and 76.9%), respectively. Ultimately, modafinil alleviated FMS behavioral, histopathological, and biochemical abnormalities and suppressed mast cell-microglial neuroinflammation in the thalamus of rats exposed to reserpine. This study highlights the potential of repurposing modafinil to improve FMS symptoms.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"38"},"PeriodicalIF":6.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999794","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":"Experimental autoimmune encephalomyelitis pathogenesis alters along animal age: impact of S100B expression.","authors":"Ana Rita Ribeiro, Raquel Pereira, Catarina Barros, Andreia Barateiro, Ainhoa Alberro, Afonso P Basto, Luís Graça, Maria Vaz Pinto, Fábio M F Santos, Pedro M P Gois, Susan E Howlett, Adelaide Fernandes","doi":"10.1007/s11481-025-10195-5","DOIUrl":"https://doi.org/10.1007/s11481-025-10195-5","url":null,"abstract":"<p><p>Multiple Sclerosis (MS) is the leading inflammatory and non-traumatic cause of disability in young adults, with late-onset MS emerging in middle-aged patients often resulting in poorer treatment responses and worse prognoses. The calcium-binding protein S100B is elevated in MS patients, and its targeting has shown promise in reducing disease severity in experimental autoimmune encephalomyelitis (EAE) models. However, most studies on MS pathology have focused on young animal models, leaving a gap in understanding the effects of age and S100B ablation on disease progression throughout the lifespan. This study aimed to characterize EAE in mice of different ages, examining demyelination, inflammation, and immune responses to determine whether S100B ablation could mitigate MS pathogenesis across the lifespan. EAE was induced in six cohorts of C57BL/6 mice: young adults (3 months), older adults (6 months), and middle-aged (12 months), including corresponding S100B knockout (KO) groups, followed for 23 days. Upon sacrifice, spinal cords were assessed via immunohistochemistry and Real-Time qPCR, while splenocytes were analyzed for immune cell characterization. Results indicated a more severe disease course in 12-month-old mice, marked by increased gliosis, inflammation, and impaired microglial phagocytic activity. Notably, S100B absence reduced gliosis and inflammatory markers across all ages, with 12-month-old S100B KO mice showing increased regulatory T cells. These findings highlight the exacerbating role of age and elevated S100B in MS progression, underscoring the importance of identifying age-specific MS markers and therapeutic targets.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"37"},"PeriodicalIF":6.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11997003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009091","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":"Antioxidant-Effective Quercetin Through Modulation of Brain Interleukin-13 Mitigates Autistic-Like Behaviors in the Propionic Acid-Induced Autism Model in Rats.","authors":"Kubilay Doğan Kılıç, Gökçen Garipoğlu, Burak Çakar, Yiğit Uyanıkgil, Oytun Erbaş","doi":"10.1007/s11481-025-10190-w","DOIUrl":"https://doi.org/10.1007/s11481-025-10190-w","url":null,"abstract":"<p><p>Overproduction of reactive oxygen species occurs when inflammation induces oxidative stress in macrophages and microglia, leading to a self-sustaining cycle of cellular damage and neuroinflammation. Oxidative stress and neuroinflammation are well-established contributors to the pathophysiology of autism spectrum disorders, which are associated with impaired neuronal function, neuronal loss, and behavioral deficits. Damaged cells, through microglial activation, release additional inflammatory mediators under conditions of oxidative stress, exacerbating neuronal damage. Quercetin, a powerful dietary antioxidant, has been shown to scavenge free radicals, reduce oxidative stress, and inhibit inflammatory pathways. Given these properties, we hypothesize that quercetin may improve learning and social skills in individuals with autism spectrum disorders by alleviating oxidative stress and reducing brain levels of inflammatory cytokines. In this study, an autism model was established in 30 rats by intraperitoneal injection of 250 mg/kg/day propionic acid (PPA) for five days. The study groups were as follows: Group 1: Normal ontrol (n = 10); Group 2: PPA + saline (PPAS, n = 10); Group 3: PPA + Quercetin (PPAQ, n = 10). All treatments were administered for 15 days. At the end of the treatment, histological and biochemical analyses of brain tissue and behavioral tests related to autistic-like behaviors were performed. Malondialdehyde, tumor necrosis factor-alpha, and interleukin-13 levels in brain homogenates were significantly higher in the PPAS group compared to the control group, indicating elevated oxidative stress and inflammation following PPA exposure. The PPAQ group significantly reduced oxidative stress parameters and inflammatory biomarkers, demonstrating its antioxidant and anti-inflammatory effects. This biochemical improvement was accompanied by preserving Purkinje cells and neuronal populations, significantly reduced in the PPAS group. Moreover, quercetin-treated rats exhibited improved social behavior and learning, which were severely impaired in the PPAS group. These findings, when interpreted together, suggest that quercetin exerts its neuroprotective effects by targeting oxidative stress and neuroinflammation, thereby preventing neuronal cell loss and alleviating behavioral deficits associated with autism spectrum disorders.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"36"},"PeriodicalIF":6.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054796","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}