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

{"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":"https://doi.org/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":6.2,"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":"https://doi.org/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":6.2,"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":"https://doi.org/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":6.2,"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":6.2,"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":"https://doi.org/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":6.2,"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}

{"title":"The Dopaminergic and Anti-Neuroinflammatory Properties of Functionalized Nanoliposomes Containing Levodopa and Ibuprofen and Conjugated with Anti-Alpha-Synuclein Aptamer.","authors":"Sara Mostafa-Tehrani, Mostafa Saffari, Ebrahim Balali, Ramona Khadivi, Ali Jebali","doi":"10.1007/s11481-025-10227-0","DOIUrl":"https://doi.org/10.1007/s11481-025-10227-0","url":null,"abstract":"<p><p>The purpose of this study was to design, synthesize, characterize, and evaluate the functionalized nanoliposomes containing levodopa and ibuprofen and conjugated with Anti-alpha-synuclein aptamer (FNLLICAASA). In this study, different aptamer sequences were designed and the best aptamer was selected. Then, the FNLLICAASA was synthesized, characterized, and the amount of dopamine level changes in SH-SY5Y cells after exposure to FNLLICAASA was evaluated. Also, the interferon-gamma (INFG) expression was assessed. The binding of FNLLICAASA to SH-SY5Y cells was also investigated using a fluorescent microscope and flow cytometry. The results of molecular docking and molecular dynamics simulation showed that aptamer APT46 with GAGGAG sequence was the best-chosen aptamer. The FNLLICAASA have a size range of 120 to 310 nm with an average positive zeta potential of 30 mV. The dopamine level change was increased in treated SH-SY5Y nerve cells, indicating the dopaminergic property of FNLLICAASA. Also, the expression of INFG was decreased in treated SH-SY5Y nerve cells, indicating the anti-neuroinflammatory property of FNLLICAASA. The binding tests showed the targeted binding of synthesized nanoliposomes to alpha-synuclein molecules on the cell surface of SH-SY5Y cells.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"66"},"PeriodicalIF":6.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251160","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":"Extracellular Vesicles from Peripheral Blood Mononuclear Cells of Hyperammonemic Rats Induce Neuroinflammation in Hippocampus, Impairing Memory and Learning in Normal Rats.","authors":"Paula Izquierdo-Altarejos, Adrià López-Gramaje, Maria A Pedrosa, Valentina E Sebestyén, Lola Vazquez, Mar Martinez-Garcia, Marta Llansola, Vicente Felipo","doi":"10.1007/s11481-025-10225-2","DOIUrl":"https://doi.org/10.1007/s11481-025-10225-2","url":null,"abstract":"","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"65"},"PeriodicalIF":6.2,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251159","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":"Efficacy of 6-nitrobenzo[d]thiazol-2 Amine Derivative (N3) in Mitigating PTZ-Induced Epileptic Conditions Via Modulation of Inflammatory and Neuroprotective Pathways in-vivo Zebrafish.","authors":"Karthikeyan Ramamurthy, S P Ramya Ranjan Nayak, S Madesh, Siva Prasad Panda, K Manikandan, Rajakrishnan Rajagopal, Ahmed Alfarhan, Senthilkumar Palaniappan, Ajay Guru, M K Kathiravan, Jesu Arockiaraj","doi":"10.1007/s11481-025-10221-6","DOIUrl":"https://doi.org/10.1007/s11481-025-10221-6","url":null,"abstract":"<p><p>Epilepsy, a chronic neurological illness affecting 50 million people worldwide, causes recurring seizures due to abnormal brain activity. Current anti-epileptic medications have serious side effects and low efficacy, requiring alternative treatments. The current study investigated the anti-inflammatory, antioxidant, and neuroprotective effects of 6-nitrobenzo[d]thiazol-2-amine (N3) derivatives in a zebrafish larvae model of epilepsy caused by 6 mM pentylenetetrazole (PTZ). Furthermore, N3 was tested for its safety, potential to reduce oxidative stress, inflammation, and neurodegeneration, and effects on motor coordination and neurotransmitter levels. The study utilized in vitro hemolysis assays to evaluate the membrane-stabilizing properties of N3. Zebrafish larvae were pre-treated with N3 at varying concentrations and subsequently exposed to PTZ to induce epilepsy-like conditions. Antioxidant enzyme activities superoxide dismutase (SOD), catalase CAT), glutathione (GSH) levels, lactate dehydrogenase (LDH) activity, and reactive oxygen species (ROS) levels were analyzed. Gene expression for pro-inflammatory and neuroprotective markers was quantified using qPCR, while histological assessments were performed to evaluate amyloid plaque formation, collagen accumulation, and calcium deposition. Behavioral tests measured motor coordination, and gamma-aminobutyric acid (GABA) levels were quantified using high-performance liquid chromatography. N3 demonstrated dose-dependent hemolysis inhibition, confirming its membrane-stabilizing and anti-inflammatory properties up to 43.47 ± 1.36%. It enhanced antioxidant enzyme activities, increased GSH levels 0.76 ± 0.03 nmol/mg, reduced LDH and ROS levels 7.47 ± 0.07 U/mg protein, and suppressed pro-inflammatory gene expression. Histological analysis revealed reduced neurodegenerative markers, including amyloid plaques and calcium deposition. Behavioral improvements were observed, including enhanced motor coordination and increased GABA levels. The findings suggest that N3 derivatives have significant therapeutic potential in epilepsy by reducing oxidative stress, inflammation, and neurodegeneration. Further studies are needed to optimize dosing and confirm safety for clinical applications.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"64"},"PeriodicalIF":6.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236113","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":"Motor-Related Neural Dynamics are Modulated by Regular Cannabis Use Among People with HIV.","authors":"Lauren K Webert, Mikki Schantell, Lucy K Horne, Jason A John, Ryan Glesinger, Jennifer O'Neill, Maureen Kubat, Anna T Coutant, Grace C Ende, Sara H Bares, Pamela E May-Weeks, Tony W Wilson","doi":"10.1007/s11481-025-10219-0","DOIUrl":"10.1007/s11481-025-10219-0","url":null,"abstract":"<p><p>Recent work has shown that people with HIV (PWH) exhibit deficits in cognitive control and altered brain responses in the underlying cortical networks, and that regular cannabis use has a normalizing effect on these neural responses. However, the impact of regular cannabis use on the neural oscillatory dynamics underlying motor control deficits in PWH remains less understood. Herein, 102 control cannabis users, control nonusers, PWH who regularly use cannabis, and PWH who do not use cannabis performed a motor control task with and without interference during high-density magnetoencephalography. The resulting neural dynamics were examined using whole-brain, voxel-wise statistical analyses that examined the impact of HIV status, cannabis use, and their interaction on the neural oscillations serving motor control, spontaneous activity during the baseline period, and neurobehavioral relationships. Our key findings revealed cannabis-by-HIV group interactions in oscillatory gamma within the prefrontal cortices, higher-order motor areas, and other regions, with the non-using PWH typically exhibiting the strongest gamma interference responses. Cannabis-by-HIV interactions were also found for oscillatory beta in the dorsal premotor cortex. Spontaneous gamma during the baseline was elevated in PWH and suppressed in cannabis users in all regions exhibiting interaction effects and the left primary motor cortex, with spontaneous levels being correlated with behavioral performance. These findings suggest that regular cannabis use has a normalizing effect on the neural oscillations serving motor control and the abnormally elevated spontaneous gamma activity that has been widely replicated in PWH, which may suggest that cannabis has at least some therapeutic utility in PWH.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"63"},"PeriodicalIF":6.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}