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

{"title":"Sigma-1 Receptor Activation by Fluvoxamine Ameliorates ER Stress, Synaptic Dysfunction and Behavioral Deficits in a Ketamine Model of Schizophrenia.","authors":"Mariam K Ahmed, Kareem Abdou, Weam W Ibrahim, Ahmed F Mohamed, Noha A El-Boghdady","doi":"10.1007/s11481-025-10231-4","DOIUrl":"10.1007/s11481-025-10231-4","url":null,"abstract":"<p><p>Endoplasmic reticulum (ER) stress and misfolded proteins accumulation are recognized as central factors in the development of psychiatric disorders. This study evaluated the potential therapeutic effect of fluvoxamine, a potent sigma-1 receptor agonist in alleviating protein misfolding and the subsequent ER stress in ketamine-induced model of schizophrenia. NE100 hydrochloride, a sigma-1 receptor blocker, was used to investigate the role of this receptor in fluvoxamine-mediated effects. Rat model of schizophrenia was induced by intraperitoneal administration of ketamine (30 mg/kg/day) for 5 consecutive days. Then, rats were treated with fluvoxamine (30 mg/kg/day, p.o), with or without NE100 (1 mg/kg/day, i.p), for 14 days. Fluvoxamine improved the learning abilities, cognitive flexibility, and sociability functions of ketamine-subjected rats as evidenced in Morris water maze and three-chamber social interaction tests. It mitigated ketamine-induced inhibition of nNOS/PSD-95/NMDAR signaling pathway, thus augmented the function of parvalbumin-GABAergic neurons as indicated by increasing the prefrontal cortical levels of parvalbumin and GAD67. Fluvoxamine also attenuated the prefrontal cortical production of unfolded protein response markers, namely, IRE-1, PERK, and ATF-6, highlighting its ability to alleviate ER stress. Further, it exerted anti-apoptotic and anti-inflammatory effects as shown by lowering Iba-1, tumor necrosis factor-α (TNF-α), Bax, and caspase-12 levels contrary to elevating Bcl-2. Additionally, it attenuated the histopathological alterations in prefrontal cortical neurons. Noteworthy, the co-administration of NE100 reduced the advantageous effects of fluvoxamine, indicating the involvement of sigma-1 receptor in mediating the observed antipsychotic effects. Thus, sigma-1-mediated signaling pathways could be therapeutic targets for preventing or slowing schizophrenia progression.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"76"},"PeriodicalIF":3.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710115","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":"Pyrroloquinoline Quinone Preconditioning Alleviates Ischemic Cerebral Injury Through Antioxidant and Anti-Inflammatory Mechanisms.","authors":"Lifang Xiao, Mengyao Wang, Jingjing Li, Haoran Wang, Niu Pu, Xitong Bo, Fuxiang Chen, Yilong Zhou, Qiong Cheng","doi":"10.1007/s11481-025-10234-1","DOIUrl":"10.1007/s11481-025-10234-1","url":null,"abstract":"<p><p>The underlying pathological mechanism of ischemic stroke is complex, with oxidative stress and inflammation being two key factors that are intertwined and mutually influential. They also serve as important potential targets for the intervention of cerebral ischemia. Pyrroloquinoline quinone (PQQ) is known for its neuroprotective properties and the ability to modulate immune system function. Previous studies have demonstrated that PQQ mitigates brain infarction in rodent models of cerebral ischemia; however, the neuroprotective mechanisms underlying PQQ's effects against ischemic brain injury are not yet fully understood. This study used an MCAO rat model, an OGD model with SH-SY5Y cells, and an LPS-activated BV2 microglia model to investigate the neuroprotective functions of PQQ on brain ischemia. Using various experimental methods, including cell viability assays, oxidative stress damage assessments, inflammatory factor expression analysis, behavioral tests in animal models, and histological evaluations, we discovered that PQQ activates the nuclear translocation of Nrf2 in neurons, thereby enhancing downstream antioxidant responses. Additionally, PQQ inhibits NF-kB activation in microglia and suppresses their M1-type polarization, leading to decreased pro-inflammatory mediators' expression levels and reduced neural inflammatory damage. These results provide further insights into the neuroprotective mechanisms involved in PQQ's effects against cerebral ischemia and may offer evidence for its translational application in treating brain ischemia.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"75"},"PeriodicalIF":3.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692634","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":"Macroalgae Polysaccharides Enhance Brain Health by Mitigating Scopolamine-induced Oxidative Stress and Inflammation Via Nrf-2/TLR4/NF-kB Pathways.","authors":"Zahir Shah, Arshad Iqbal, Syed Lal Badshah, Mushtaq Ahmad Mir, Saima Sohni, Hammad Ullah, Shahid Ali Shah, Nasreena Bashir, Muhammad Ayaz, Maria Daglia","doi":"10.1007/s11481-025-10230-5","DOIUrl":"10.1007/s11481-025-10230-5","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disorder commonly associated with memory loss and difficulties in performing daily activities, particularly in the aging brain.</p><p><strong>Purpose of the study: </strong>This study aimed to evaluate the neuroprotective effects of macroalgae-derived polysaccharides from seaweed against scopolamine-induced amnesia, oxidative stress, and amyloid plaque (Aβ) production in rodents, following standard experimental protocols.</p><p><strong>Methods: </strong>Three novel polysaccharides were extracted from Chara vulgaris, Cladophora glomerata, and Spirogyra crassa, namely: methylated pectin-type polysaccharides (PS1), methylated pectin-type polysaccharides (homo galacturonan and rhamno galacturonan, PS2), Ulvan-type polysaccharide, and xyloglucan polysaccharides (PS3). These polysaccharides were characterized using a variety of analytical techniques, including SEM, FTIR, XRD, ¹H-NMR, and ¹³C-NMR. The polysaccharides were administered at a dose of 30 mg/kg to male albino mice exposed to scopolamine (1 mg/kg) for three weeks. To assess their neuroprotective effects, Morris Water Maze (MWM) and Y-maze tests, antioxidant enzyme assays (Catalase, GSH, LPO), and western blotting were performed.</p><p><strong>Results: </strong>The results showed that all three polysaccharides significantly (p ≤ 0.001) mitigated redox imbalance and reduced (p ≤ 0.001) microglial activation, thereby decreasing scopolamine-induced neuroinflammation and amyloid beta (Aβ) accumulation. Additionally, these polysaccharides improved neuronal synapses and cognitive function by modulating the NRf-2/TLR4/NF-kB signaling pathway.</p><p><strong>Data analysis: </strong>The data analysis and graph generation were performed using GraphPad Prism software, version 5.0, with a significance level set at a p-value of < 0.05.</p><p><strong>Conclusion: </strong>The findings highlighted the potential of these three novel natural polysaccharides as promising candidates for the treatment of scopolamine-induced oxidative stress-mediated neurodegenerative disorders, such as Alzheimer's disease.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"74"},"PeriodicalIF":3.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692633","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":"Erythropoietin (EPO) Alleviates Chronic Stress-Induced Depression by Modulating SIRT1-Mediated Mitochondrial Function.","authors":"Yanhua Luo, Tahir Ali, Yue Hu, Qichao Gong, Chengyou Zheng, Ling Li, Shupeng Li, Liangliang Hao","doi":"10.1007/s11481-025-10233-2","DOIUrl":"10.1007/s11481-025-10233-2","url":null,"abstract":"<p><p>Mitochondrial dysfunction is a hallmark of many psychiatric disorders, and SIRT1 signaling plays a critical role in regulating mitochondrial dynamics, function, and autophagy. This study investigated the interplays between erythropoietin (EPO), mitochondrial protection, and SIRT1 signaling in depression. Chronic restraint stress (CRS)- induced depression mouse model and CORT-treated HT22 cells were employed, which were subsequently treated with EPO. CRS mice exhibited depressive-like behaviors, which were alleviated by EPO treatment, as evidenced by decreased immobility and increased sucrose preference. EPO also enhanced mitochondrial function by stimulating mitophagy and improving mitochondrial homeostasis, as indicated by elevated ATP levels, reduced nitric oxide, and restored expression of mitochondrial-related genes in both the hippocampus of CRS mice and CORT-treated HT22 cells. Additionally, EPO restored suppressed SIRT1 expression, promoted dendritic spine density and synaptic gene expression in the hippocampus, increased p-STAT5 phosphorylation, and increased NAMPT expression and NAD + levels. Notably, pharmacological inhibition of SIRT1 via EX-527 counteracted EPO effects, exacerbating depressive symptoms and mitochondrial homeostasis. Furthermore, EX-527 treatment decreased ATP levels and mitochondrial DNA copy numbers in CRS + EPO-treated mice and reduced ATG5 expression. However, EX-527 did not significantly impact BNIP3, Parkin, PINK1, LC3B-II, Ace-FOXO1, or FOXO1 expression. EX-527 exposure significantly increased Ac-LC3B precipitation in the hippocampus of CRS + EPO-treated mice and the COXIV/LAMP1 ratio in the HT22 cells. In summary, these results suggested that EPO antidepressant effects were mediated through SIRT1 regulation, which influenced LC3B deacetylation, improving CRS-induced mitochondrial dysfunction and autophagy impairment.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"73"},"PeriodicalIF":3.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676757","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":"Magnolol Ameliorates Depression Through Modulating the TREM2-DOK3-ERK Pathway.","authors":"Zihang Guo, Huina Yang, Guoling Sun, Qiao Peng, Wenchang Zhao, Li Liu","doi":"10.1007/s11481-025-10229-y","DOIUrl":"10.1007/s11481-025-10229-y","url":null,"abstract":"<p><p>Depression is a mental disorder with a high incidence and high clinical cure rate but a low treatment acceptance rate and a high recurrence rate. Depression is often accompanied by neuroinflammation. Magnolol (MA), a pharmacologically active compound in Magnolia officinalis, has an antidepressant effect. The aim of this study was to investigate the molecular mechanism of the antidepressant effect of MA in mice and BV2 microglia. MA increased sugar water preference in the sucrose preference test (SPT) and inhibited immobility time in the forced swim test (FST) but did not affect distance travelled in the open field test (OFT). MA reduced the levels of proinflammatory cytokines (IL-6, TNF-α and IL-1β) and increased the expression levels of BDNF and IL-10 to promote neuronal survival. MA inhibited not only the amoeba-like morphology of hippocampal microglia but also iNOS expression in BV2 microglia. MA increased the expression of TREM2 and the p-DOK3/DOK3 ratio but decreased the p-ERK/ERK ratio. The knockdown of TREM2 led to a decrease in the p-DOK3/DOK3 ratio and an increase in the p-ERK/ERK ratio while also inducing microglial activation, promoting the production of inflammatory factors, and abrogating the protective effects of MA. Our study suggested that MA attenuated CUMS-induced depression-like behaviour and microglial activation by reducing ERK phosphorylation through increased TREM2 expression and DOK3 phosphorylation, which may provide new approaches for the treatment of depression.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"72"},"PeriodicalIF":3.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669114","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":"Activation of Hippocampal ACE2 Prevents the Dysbiosis-induced Depression-like Behavior in Mice by Enhanced Neurogenesis and Neuroprotection via Mas Receptor.","authors":"Kohei Takahashi, Osamu Nakagawasai, Kazuhiro Kurokawa, Kazuya Miyagawa, Atsumi Mochida-Saito, Hiroshi Takeda, Minoru Tsuji","doi":"10.1007/s11481-025-10232-3","DOIUrl":"10.1007/s11481-025-10232-3","url":null,"abstract":"<p><p>The association between gut microbiota imbalance and depression is well known; however, its underlying mechanisms remain unclear. Angiotensin (Ang)-converting enzyme 2 (ACE2) transforms Ang II into Ang (1-7), which exerts antidepressant effects via the Mas receptor (MasR). However, the role of ACE2 in dysbiosis-related depression in the brain remains unclear. In this study, we assessed changes in brain ACE2 expression and whether diminazene aceturate (DIZE), an ACE2 activator, alleviates depression-like behavior in an antibiotic-induced (ABX) dysbiosis mouse model. The tail suspension test revealed depression-like behavior in ABX mice. Western blotting and immunohistochemistry revealed decreased expression levels of ACE2, Ang (1-7), p-CAMKII, p-CREB, BDNF, synaptophysin, p-PPARγ, CD206, TREM2, and IL-10 and reduced neurogenesis in the dentate gyrus of the hippocampus. Iba1, CD86, iNOS, IL-1β, TNF-α, and cleaved caspase-3 levels were increased, indicating microglial activation in the hippocampus. MasR staining was observed in neurons and microglia in the hippocampus of ABX mice. Furthermore, p-CAMKII and p-CREB staining was observed in neurons, while p-PPARγ staining was observed in microglia in the hippocampus of ABX mice treated with DIZE. DIZE administration prevented ABX-induced changes, whereas the effects of DIZE were abolished by co-administration with A779, a MasR inhibitor. These findings suggest that hippocampal ACE2 expression plays a crucial role in dysbiosis-related depression associated with gut microbiota imbalance, potentially offering a target for therapeutic interventions.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"71"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661184","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":"Inhibition of oxidative stress, neuroinflammatory cytokines, and protein expressions contributes to the antipsychotic effects of geraniol in mice with ketamine-induced schizophrenia.","authors":"Christian I Uruaka, Benneth Ben-Azu, Noah A Omeiza, Emmanuel O Chidebe, Abayomi M Ajayi, Cletus B Lemii, Tamunobarabiye I Nonju, Udeme O Georgewill, Owunari A Georgewill","doi":"10.1007/s11481-025-10226-1","DOIUrl":"10.1007/s11481-025-10226-1","url":null,"abstract":"<p><p>Imbalances in redox and neuroinflammation are believed to play a role in the complex causes of schizophrenia, a widespread mental disorder characterized by abnormal behaviour. In this regard, we investigated the effects of geraniol, a natural compound with various medicinal uses, on ketamine-induced schizophrenia-like behaviour, oxidative stress and neuroinflammation in mice. We conducted three sets of experiments with adult male Swiss mice (n = 7): drug alone, preventive and reversal groups. The treatments included saline (10 mL/kg/p.o./day), geraniol (25, 50 and 100 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) for 14 days, along with ketamine (20 mg/kg/i.p./day) injections between days 8-14 in the preventive group, or ketamine administration for full 14 days before therapeutic intervention from days 8-14 in the reversal group. We measured behavioural hyperactivity, cognition and sociability. Additionally, brain oxidative/nitrergic imbalance, inflammatory cytokines (TNF-α, IL-6) and proteins (COX-2, iNOS, NF-κB) were determined in the striatum, prefrontal cortex, and hippocampus. KET administration was associated with schizophrenia-like symptoms as characterized by increased hyperlocomotion, impaired spatial memory and social withdrawal, particularly in the reversal group. This was exacerbated by redox imbalance and neuroinflammation in specific brain regions. However, geraniol (25, 50 and 100 mg/kg) treatment significantly prevented and reversed the brain's insults by restoring ketamine-induced decreases in glutathione, superoxide-dismutase and catalase activities, reduced malondialdehyde and nitrite contents along with TNF-α and IL-6 concentrations. Geraniol also suppressed NF-κB, COX-2 and iNOS expressions in the striatum, prefrontal-cortex and hippocampus. Geraniol shows neuroprotective and neurorestorative effects against schizophrenia-like symptoms by inhibiting oxidative stress, neuroinflammatory cytokines, and protein expression in mouse brains.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"70"},"PeriodicalIF":3.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556028","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":"Enhancing Neuroprotection Through Exercise: The Synergistic Effects of Bioactive Plant Compounds Via the CREB-BDNF Signaling Pathway.","authors":"Jing Li, Lili Sun, Fang Fang, Mohammadmatin Morshedi","doi":"10.1007/s11481-025-10228-z","DOIUrl":"10.1007/s11481-025-10228-z","url":null,"abstract":"<p><p>The hippocampus, a vital brain region, orchestrates numerous critical functions including memory, learning, stress response, and emotional regulation. Structural changes in the hippocampus due to prolonged stress exposure can precipitate cognitive decline and behavioral deficits. Recent studies have illuminated the restorative influence of physical fitness on the hippocampus; notably, exercise enhances memory, learning, hippocampal architecture, neurogenesis, and synaptic plasticity. A key mediator in these processes is the brain-derived neurotrophic factor (BDNF), which facilitates synaptic improvements and overall brain health following exercise. Concurrently, bioactive plant compounds such as curcumin, resveratrol, and crocin have emerged as potent therapeutic agents for neurodegenerative disorders, credited with improving memory, synaptic plasticity, and overall brain function, without the adverse effects associated with synthetic drugs. These natural compounds potentially exert their neuroprotective effects through various mechanisms including neurotransmitter regulation, oxidative stress alleviation, and stimulation of the BDNF-cyclic AMP response element binding protein (CREB) signaling pathway. Given the individual benefits of exercise and bioactive plant compounds, this review proposes a synergistic approach combining both modalities, aimed at developing novel, efficacious neuroprotective interventions. By harnessing the intertwined benefits of physical activity and plant-derived therapies, we outline a compelling case for their combined utility in fortifying hippocampal function and combating neurodegenerative conditions. In this review, we combined the benefits of exercise and therapy with bioactive plant components to create a neuroprotective drug.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"69"},"PeriodicalIF":3.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531436","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":"Stimulant Use, HIV, and Plasma Metabolites Among Men.","authors":"Emily M Cherenack, Michaela E Larson, Kevin Murray, Zachary J Mayer, Candace Guerrero, Courtney A Broedlow, Nichole R Klatt, Adam W Carrico","doi":"10.1007/s11481-025-10223-4","DOIUrl":"10.1007/s11481-025-10223-4","url":null,"abstract":"<p><p>Metabolomics can be used to identify biological targets to mitigate the negative impacts of HIV and stimulant use on neuroimmune and cardiometabolic functioning. However, studies are needed to characterize the plasma metabolome among sexual minority men (SMM) in the context of independent and co-occurring HIV and stimulant use. From 2020 to 2022, we collected plasma samples and assessed biologically confirmed HIV status and stimulant use among 61 community-recruited SMM in Miami, Florida. Cross-sectional bivariate analyses and multivariable regressions correcting for false discovery rate compared 390 mass spectrometry-based plasma metabolites across four HIV/stimulant use groups: (1) living without HIV and no stimulant use (HIV-STIM-), (2) living with HIV and no stimulant use (HIV + STIM-), (3) living without HIV with stimulant use (HIV-STIM +), and (4) living with HIV with stimulant use (HIV + STIM +). Six metabolites showed differences between HIV/stimulant use groups at p < 0.05 in both Kruskal-Wallis tests and linear regressions: choline, tryptophan, two lysophosphatidylcholines, one triacylglyceride, and one dihexosylceramide. After correcting for false discovery rate, in linear regressions controlling for BMI and age, the HIV + STIM + group had lower aspartic acid than the HIV-STIM- group, higher lysophosphatidylcholine a C18:1 than the HIV-STIM + group, and higher triacylglyceride(20:3_34:0) than the HIV-STIM- and HIV + STIM- groups. In SMM, co-occurring stimulant use and HIV were associated with perturbations in certain metabolites. Metabolites such as aspartic acid and lysophosphatidylcholines are potentially involved in immune dysregulation, addiction, energy use, and cardiovascular disease. Trials of interventions to reduce stimulant use could elucidate its causal relationship to metabolites.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"68"},"PeriodicalIF":3.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328002","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":"Puerarin Improves Cancer-Induced Bone Pain by Recovering Mitochondrial Dysfunction in the Spinal Cord.","authors":"Gege Sheng, Yin Wu, Hongyan Liu, Peigen Zhang, Zhipeng Zhang, Liangzhu Yu, Menglin Cheng, Haili Zhu","doi":"10.1007/s11481-025-10224-3","DOIUrl":"10.1007/s11481-025-10224-3","url":null,"abstract":"<p><p>Cancer metastases induce bone pain and central sensitization in the spinal cord. Mitochondrial dysfunction is associated with pian signal transmission and involved in cancer-induced bone pain. Pueratin (Pue) is a natural isoflavone compound that works as a potential natural neuroprotective agent. However, the mechanisms of Pue on cancer pain remain unclear. In this study, a cancer-induced bone pain (CIBP) rat model was established and Pue was administered intrathecally. As a result, CIBP model rats exhibited as the evoked mechanical pain, thermal pain, and spontaneous pain, the elevated neurological damage and mitochondrial dysfunction in the spinal cord. Pue administration improved pain related behaviors, decreased the neuronal activity, reduced NLRP3 inflammasome-mediated inflammation, and elevated mitochondrial dysfunction in the spinal cords of CIBP rats. Proteomical data showed that in the spinal synaptosomes, 59 differentially expressed proteins (DEPs) were significantly up-regulated while 128 DEPs were down-regulated. Among them, 5 genes were found to be overlapped for CIBP and Pue-potential targets and Src was belonged to the hub genes. Database analysis and experimental assay showed that Pue bound with Src at the affinity of 7.9 ± 0.2 µM, and decreased Src level and phosphorylation in the spinal cord of CIBP rats and in primary astrocytic cells. In addition, Pue also recovered levels of mitochondrial membrane potential and reactive oxygen species, and decreased inflammation in primary astrocytic cells. To summarize, Pue inhibits spinal Src activity, restores mitochondrial function, reduces central sensitization in the spinal cord, and relieves cancer-induced bone pain. This study may provide a basis for the application of Pue on the relief of cancer pain.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"67"},"PeriodicalIF":3.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259552","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}