Journal of integrative neuroscience最新文献

{"title":"Neuromodulation of the Cerebellum for Motor Applications: A Systematic Review.","authors":"Katherine G Warthen, Nicole C Walker, Bo Dehm Wicklund, Mia M Gonzalez, Nathan Ramirez, Stephanie C Gee, Hanaa Al-Dasouqi, Michelle R Madore","doi":"10.31083/j.jin2310195","DOIUrl":"10.31083/j.jin2310195","url":null,"abstract":"<p><strong>Background: </strong>Despite the connections and clear importance of the cerebellum in motor function, research utilizing cerebellar neuromodulation for treatment of movement disorders is still underdeveloped. Here we conduct a systematic review to investigate non-invasive neurostimulation of the cerebellum and its potential impact on motor systems and its function. Our aim is to give a general review of each neurostimulation study focusing on the cerebellum as a treatment target in the past five years at time of search, in order to update the field on current findings and inspire similar cerebellar neurostimulation research without unnecessary repetition.</p><p><strong>Methods: </strong>Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, our search included articles over the past five years that evaluated neurostimulation of the cerebellum (e.g., transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial alternating current stimulation, etc.). Inclusion criteria included: (1) neurostimulation (repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS)) of the cerebellum; (2) only original articles, and (3) outcomes focused on motor functions. Exclusion criteria included: (1) neurostimulation with the goal of targeting any brain structure other than the cerebellum and (2) reviews and conference abstracts.</p><p><strong>Results: </strong>The search revealed 82 distinct articles relevant to the research question. Included are 17 articles concerning rTMS, 56 articles concerning tDCS, and 9 articles concerning tACS. The majority of the studies are controlled trials of varying types, with 79, with two case studies and one pilot study.</p><p><strong>Conclusions: </strong>Many studies showed significant effects on motor function and circuitry via non-invasive neurostimulation of the cerebellum. Common targets of cerebellar neurostimulation include visuomotor control, stroke rehabilitation for improvements in balance and coordination, and motor skill acquisition. The field is still exploring ideal parameters of neurostimulation for each disorder or function of interest. Future research areas should include the inclusion of individual anatomy, including functional connectivity, and improving stimulation selectivity.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"195"},"PeriodicalIF":2.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper Overload Promotes β-amyloid Induced NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis in Alzheimer's Disease.","authors":"Min-Juan Zhu, Ling Zhang, Chang-Peng Wang","doi":"10.31083/j.jin2310194","DOIUrl":"https://doi.org/10.31083/j.jin2310194","url":null,"abstract":"<p><strong>Purpose: </strong>Alzheimer's disease (AD) is characterized by cognitive decline and abnormal protein accumulation. Copper imbalance and pyroptosis play significant roles in the pathogenesis of AD. Recent studies have suggested that dysregulated copper homeostasis contributed to β-amyloid accumulation, which may activate the NOD-like receptor protein 3 (NLRP3)-related pyroptosis pathway, promoting neuronal damages and AD progression. Therefore, the present study aims to investigates whether copper facilitates AD through exacerbating β-amyloid (Aβ) induced activation of NLRP3/Caspase-1/Gasdermin D (GSDMD)-mediated neuronal cell pyroptosis.</p><p><strong>Methods: </strong>Mouse hippocampal HT-22 cells were cultured with Aβ1-42 oligomer for 24 h as AD Model group. CuCl₂ treatment was administered to the AD cell model, and cell survivability levels were detected by Cell Counting Kit-8 (CCK-8), TdT-mediated dUTP nick end labeling (TUNEL), and other relevant kits. Mitochondrial function was evaluated using Mitochondrial membrane potential dye JC-1 and transmission electron microscopy (TEM). After intervention with the NLRP3 inhibitor MCC950, activation of the NLRP3/Caspase-1/GSDMD pathway by copper ions (Cu²⁺) was confirmed via Western Blot. Thioredoxin T (ThT) fluorescence assay was performed to observe the aggregation effect of Aβ induced by Cu²⁺ overload.</p><p><strong>Results: </strong>CuCl₂ treatment of the AD cell model resulted in up-regulation of the levels of Lactate Dehydrogenase (LDH), Interleukin-1β (IL-1β), and IL-18 expression, which indicated activation of pyroptosis. We observed a significant decrease in mitochondrial membrane potential, mitochondrial swelling, and loss of mitochondrial cristae by fluorescence microscopy and TEM. ThT fluorescence imaging showed that Cu²⁺ promoted Aβ aggregation and up-regulated NLRP3, apoptosis-associated speck-like protein containing a CARD (ACS), Caspase-1, Cleaved Caspase-1, GSDMD, and Gasdermin D N-terminal (GSDMD-NT). The NLRP3 inhibitor MCC950 partially reversed Cu²⁺-mediated pyroptosis in HT-22 cells.</p><p><strong>Conclusions: </strong>Exposure to copper ions disrupt mitochondrial copper homeostasis, promotes Aβ aggregation, and activates NLRP3 inflammasomes, further promoting the Aβ aggregation activated pyroptosis in AD cell models.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"194"},"PeriodicalIF":2.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Applications of Image Post-Processing 3D Visualisation for Cerebrovascular Diseases.","authors":"Jigen Dong, Shuai Zhou, Lipeng Jian, Lide Jin, Shengquan Huang","doi":"10.31083/j.jin2310193","DOIUrl":"https://doi.org/10.31083/j.jin2310193","url":null,"abstract":"<p><p>Intracranial vascular-related diseases are a common occurrence in neurosurgery. They have complex and diverse pathogeneses; further, their diagnosis and treatment remain unclear. Three-dimensional image post-processing technology is an emerging technology that involves converting a brain image scan into a digital model using image post-processing software, thus establishing a 3D view of the region of interest. Three-dimensional visualisation of the brains of patients with cerebrovascular diseases can allow a more intuitive examination of the local anatomy of the lesion as well as the adjacency between the lesion and peripheral nerves, brain tissue, and skull bones. Subsequently, this informs pre-operative planning, allows more accurate diagnosis of cerebrovascular diseases, and improves the safety of surgical treatment. This review summarised the current literature regarding cerebrovascular diseases and the application of 3D image post-processing technology in different cerebrovascular diseases.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"193"},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced GABA Levels in the ACC of Actively Drinking High Risk Individuals Compared to Recently Detoxified Alcohol-Dependent Patients.","authors":"Gianna Spitta, Tobias Gleich, Lea Mascarell Maricic, Annika Rosenthal, Florian Schubert, Semiha Aydin, Andreas Heinz, Jürgen Gallinat","doi":"10.31083/j.jin2310190","DOIUrl":"10.31083/j.jin2310190","url":null,"abstract":"<p><strong>Background: </strong>Acute gamma-aminobutyric acid (GABAergic) effects of alcohol consumption are well-known, whereas prior research has yielded inconsistent findings regarding on adaptations of the GABAergic neurotransmitter system to chronic alcohol use. Previous studies indicate either elevated or reduced GABA levels in cortical regions such as the anterior cingulate cortex (ACC) in persons with alcohol use disorder (AUD). We tested the hypothesis that active alcohol consumption compared to abstinence contributes to GABA levels as observed in prior research on chronic alcohol use.</p><p><strong>Methods: </strong>We investigated GABA levels in the ACC of 31 healthy controls (low risk, LR), 38 high risk individuals providing an active drinking pattern (high risk, HR) and 27 recently detoxified alcohol-dependent (AD) subjects via proton magnetic resonance spectroscopy (1H-MRS).</p><p><strong>Results: </strong>GABA levels in the ACC were significantly lower in HR compared with AD, but did neither differ between LR and AD nor between LR and HR. Also, we observed a quadratic effect indicating a distribution of GABA levels in the ACC as follows: LR > HR < AD. GABA levels were not associated with abstinence duration in AD.</p><p><strong>Conclusions: </strong>This study suggests that the GABAergic neurotransmitter system is blunted in AUD. More precisely GABA levels in the ACC seem to be higher in recently detoxified AD patients than in individuals at high risk which might suggest that GABA levels may increase after abstinence. No correlation was found between GABA levels and abstinence duration. Longitudinal studies are required to investigate alterations in the GABAergic system throughout the development and maintenance of AUD.</p><p><strong>Clinical trial registration: </strong>No: NCT02094196. Registered 20 March 2014, https://clinicaltrials.gov/study/NCT02094196.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"190"},"PeriodicalIF":2.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Selective Impairments of Total Sleep Deprivation on Alerting, Orienting, and Executive Control: Evidence from Event-Related Potentials.","authors":"Yuefang Dong, Lanxiang Wang, Lisha Luo, Yiran Wang, Tao Song, Yongcong Shao, Fubin Jiao, Guohua Shi","doi":"10.31083/j.jin2310191","DOIUrl":"10.31083/j.jin2310191","url":null,"abstract":"<p><strong>Background: </strong>Many studies have shown that total sleep deprivation (TSD) impairs the attention network, which includes three subcomponents as follows: alerting, orienting, and executive control. However, the specific attention network(s) damaged by TSD remains unclear.</p><p><strong>Methods: </strong>Twenty two participants were enrolled to complete the attention network test (ANT) before and after 36 h of TSD with simultaneous electroencephalography recordings.</p><p><strong>Results: </strong>The repeated-measures analysis of variance of the response time (RT) suggested that the interaction effect between sleep conditions (before versus after TSD) and target congruence (incongruent versus congruent target) was significant; that is, the RT of the incongruent target was longer than that of the congruent target, whereas this difference disappeared after TSD. Furthermore, the interaction effect of sustained potential (SP) amplitude between the sleep conditions and target congruence was significant; that is, the incongruent target invoked a less positive sustained potential amplitude after than before TSD; whereas that invoked by the congruent target was not.</p><p><strong>Conclusion: </strong>TSD selectively impairs attention networks. TSD affects the executive control network the most, which is followed by the alerting network rather than the orienting network. This provides a new perspective for understanding how shortened sleep affects attention.</p><p><strong>Clinical trial registration: </strong>No: ChiCTR2400088448. Registered 19 August 2024, https://www.chictr.org.cn.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"191"},"PeriodicalIF":2.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in Endogenous Stem Cell Populations in the Acute Phase of Blast-Induced Spinal Cord Injury.","authors":"David Valenti, Carly Norris, Margaret Yuan, Benita Luke, Rachel Thomas, Josiah Thomas, Susan Murphy, Pamela VandeVord, Kelly C S Roballo","doi":"10.31083/j.jin2310192","DOIUrl":"https://doi.org/10.31083/j.jin2310192","url":null,"abstract":"<p><strong>Background: </strong>Blast-induced spinal cord injury (bSCI) is prevalent among military populations and frequently leads to irreversible spinal cord tissue damage that manifests as sensorimotor and autonomic nervous system dysfunction. Clinical recovery from bSCI has been proven to be multifactorial, as it is heavily dependent on the function of numerous cell populations in the tissue environment, as well as extensive ongoing inflammatory processes. This varied recovery process is thought to be due to irreversible spinal cord damage after 72 hours post-injury. Stem cell therapy for spinal cord injuries has long been investigated due to these cells' proliferative nature, ability to enhance neuro-regeneration, neuroprotection, remyelination of axons, and modulation of the immune and inflammatory responses. Therefore, this study hypothesizes that the impaired function after injury is due to a lack of specific ectoderm and neural stem cell population activity at the injury site.</p><p><strong>Methods: </strong>This study aimed to elucidate changes in endogenous stem cell patterns by evaluating immunohistochemical staining densities of various stem cell markers using a preclinical thoracolumbar bSCI model. Analysis was performed 24-, 48-, and 72 hours following blast exposure. Behavior tests to assess sensory and mechanical functions were also performed.</p><p><strong>Results: </strong>The following Cluster of differentiation (CD) markers CD105, CD45, CD133, and Vimentin, Nanog homebox (NANOG), and sex determining region Y HMG-box 2 (SOX2) positive cell populations were significantly elevated with trending increases in Octamer-binding transcription factor 4 (OCT4) in the thoracolumbar region of spinal cord tissue at 72 hours following bSCI (<i>p</i> < 0.05). Behavior analyses showed significant decreases in paw withdrawal thresholds in the hind limbs and changes in locomotion at 48- and 72 hours post-injury (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>The significant increase in mesenchymal, pluripotent, and neural stem cell populations within the thoracolumbar region post-injury suggests that migratory patterns of stem cell populations are likely altered in response to bSCI. Behavioral deficits were consistent with those experienced by military personnel, such as increased pain-like behavior, reduced proprioception and coordination, and increased anxiety-like behavior post-bSCI, which underlines the translational capabilities of this model. While further research is vital to understand better the intrinsic and synergistic chemical and mechanical factors driving the migration of stem cells after traumatic injury, increased endogenous stem cell populations at the injury site indicate that stem cell-based treatments in patients suffering from bSCI could prove beneficial.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"192"},"PeriodicalIF":2.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"fNIRS Study of Brain Activation during Multiple Motor Control Conditions in Younger and Older Adults.","authors":"Duoduo Yu, Conghui Wei, Zhen Yuan, Jun Luo","doi":"10.31083/j.jin2310189","DOIUrl":"https://doi.org/10.31083/j.jin2310189","url":null,"abstract":"<p><strong>Background: </strong>Evidence suggests that aging contributes to decreased cerebral blood flow and brain oxyhemoglobin (HbO₂) in the association cortices during rest. However, the influence of aging on functional brain activation is still controversial. The objective of this study was to investigate the age-related dependence of HbO₂ across distinct motor control conditions in both primary and association cortices.</p><p><strong>Methods: </strong>Using functional near-infrared spectroscopy (fNIRS), this study assessed HbO₂ level changes within the primary somatosensory cortex (PSC), primary motor cortex (PMC), supplementary motor cortex (SMC), prefrontal cortex (PFC) and dorsolateral prefrontal cortex (DLPFC) under various motor control conditions. Analysis examined changes in the concentration of HbO₂ measured by fNIRS during rest, motor execution (ME), motor passivity (MP) and motor imagery (MI) with elbow flexion in 30 younger (21.5 ± 1.17 years old) and 30 older (60.9 ± 0.79 years old) adults.</p><p><strong>Results: </strong>During motor execution HbO₂ was higher in younger adults than older adults in bilateral PMC, bilateral PFC, left PSC, left SMC and left DLPFC (<i>p</i> < 0.05). During motor passivity, HbO₂ was higher in younger adults than older adults in bilateral PMC, left PSC and left SMC (<i>p</i> < 0.05). During motor imagery, HbO₂ was higher in younger adults than older adults in bilateral PFC and bilateral DLPFC (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>This study provided evidence that HbO₂ levels are different in the primary and association cortices during different motor control conditions in young and old adults and that HbO₂ levels in different brain regions under different motor control conditions can be influenced by age.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"189"},"PeriodicalIF":2.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Blood Biomarkers and Diagnosis Approaches for Neurodegenerative Dementias and Related Diseases.","authors":"Tomoki Sekimori, Kohji Fukunaga, David I Finkelstein, Ichiro Kawahata","doi":"10.31083/j.jin2310188","DOIUrl":"https://doi.org/10.31083/j.jin2310188","url":null,"abstract":"<p><p>Neurodegenerative dementias and related diseases, such as Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease have no fundamental cure yet. Degenerative proteins begin to accumulate before the onset of the symptoms of these diseases, and the early detection of these symptoms can lead to early therapeutic intervention. Therefore, early and simpler diagnostic methods are required. This review focuses on blood biomarkers, which are less expensive and easier to use than cerebrospinal fluid biomarkers and diagnostic imaging. A variety of approaches exist for establishing diagnostic methods for neurodegenerative dementias using blood biomarkers, such as disease differentiation using a single molecule, methods that combine multiple biomarkers, studies that search for important markers by comprehensively analyzing many molecules, and methods that combine other data. Finally, we discuss the future prospects for blood biomarker research based on the characteristics of each approach.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"188"},"PeriodicalIF":2.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Enlarged Perivascular Spaces and Early Acute Ischemic Stroke with Cognitive Impairment: A Cross-Sectional Study.","authors":"Yu Tu, Jiewei Peng, Xuan Gong, Peipei Zhu, Chengtao Zhang, Yuqi Liu, Rong Huang, Baizhu Li, Wenyan Zhuo","doi":"10.31083/j.jin2310187","DOIUrl":"10.31083/j.jin2310187","url":null,"abstract":"<p><strong>Background: </strong>Enlarged perivascular spaces (EPVSs) are commonly detected via magnetic resonance imaging. It is unclear whether EPVSs are associated with cognitive impairment within one month after an acute ischemic stroke (AIS) (i.e., early AIS with cognitive impairment (EAIS-CI)). This study explored the severity and location of EPVSs and their association with EAIS-CI severity and provides clinicians with early warning indicators before the onset of typical clinical symptoms in the Chinese population.</p><p><strong>Methods: </strong>The clinical data of 208 patients (176 AIS patients and 32 controls) were prospectively analyzed using the Montreal Cognitive Assessment Beijing version (MoCA-BJ) score as the primary group criterion and the Mini-Mental State Examination (MMSE) score as a supplementary criterion. When EPVS I as the main EPVS type detected by imaging, the basal ganglia (BG) is the area most severely affected. Statistical analysis was conducted on the relevant clinical data.</p><p><strong>Results: </strong>AIS patients were grouped based on MoCA-BJ scores. Age (<i>p</i> < 0.01), education level (<i>p</i> = 0.02), EPVS I as the main EPVS type (<i>p</i> < 0.01), the number of right-sided BG-EPVSs (<i>p</i> = 0.04), white matter hyperintensities (WMHs) (Fazekas scores: <i>p</i> = 0.02), brain atrophy (global cortical atrophy scores: <i>p</i> < 0.01, Koedam posterior atrophy visual scale scores: <i>p</i> = 0.01, medial temporal lobe atrophy scores: <i>p</i> < 0.01) and AIS lesion volume (<i>p</i> = 0.01) were significantly greater in the EAIS-CI group than in the EAIS without cognitive impairment group. The cognitive domains of attention (<i>p</i> = 0.04) and orientation (<i>p</i> < 0.01) were more closely associated with EPVS I as the main EPVS type. However, multivariate regression analysis did not identify EPVS I as the main EPVS type as the main risk factor for EAIS-CI (<i>p</i> = 0.098). Grouping by MMSE scores revealed that EPVS I as the main EPVS type was linked to low education level (<i>p</i> < 0.01) and was significantly associated with EAIS in individuals with cognitive dementia (<i>p</i> < 0.01).</p><p><strong>Conclusions: </strong>As a result of multiple factors, EAIS-CI is significantly associated with a low education level, BG-EPVS, WMHs, and worsening brain atrophy severity. Imaging markers, such as the severity of BG-EPVS, can assist in the early diagnosis and assessment of EAIS-CI.</p><p><strong>Clinical trial registration: </strong>The study was registered with the China Clinical Trial Registry (https://www.chictr.org.cn/), registration number: ChiCTR2000038819.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"187"},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin Mitigates Dopaminergic Neuron Degeneration and Restrains Microglial M1 Polarization by Inhibiting Toll Like Receptor 4.","authors":"Yangzhi Xie, Hao Zhang, Jiacheng Chen, Sicong Xu, Yan Luo","doi":"10.31083/j.jin2310185","DOIUrl":"https://doi.org/10.31083/j.jin2310185","url":null,"abstract":"<p><strong>Background: </strong>Luteolin is a natural flavonoid and its neuroprotective and anti-inflammatory effects have been confirmed to mitigate neurodegeneration. Despite these findings, the underlying mechanisms responsible for these effects remain unclear. Toll-like receptor 4 (TLR4) is widely distributed in microglia and plays a pivotal role in neuroinflammation and neurodegeneration. Here studies are outlined that aimed at determining the mechanisms responsible for the anti-inflammatory and neuroprotective actions of luteolin using a rodent model of Parkinson's disease (PD) and specifically focusing on the role of TLR4 in this process.</p><p><strong>Methods: </strong>The mouse model of PD used in this experiment was established through a single injection of lipopolysaccharide (LPS). Mice were then subsequently randomly allocated to either the luteolin or vehicle-treated group, then motor performance and dopaminergic neuronal injury were evaluated. BV2 microglial cells were treated with luteolin or vehicle saline prior to LPS challenge. MRNA expression of microglial specific marker ionized calcium-binding adapter molecule 1 (<i>IBA-1</i>) and M1/M2 polarization markers, as well as the abundance of indicated pro-inflammatory cytokines in the mesencephalic tissue and BV2 were quantified by real time-polymerase chain reaction (RT-PCR) and Enzyme-linked Immunosorbent Assay (ELISA), respectively. Cell viability and apoptosis of neuron-like PC12 cell line co-cultured with BV2 were detected. TLR4 RNA transcript and protein abundance in mesencephalic tissue and BV2 cells were detected. Nuclear factor kappa-gene binding (NF-κB) p65 subunit phosphorylation both <i>in vitro</i> and <i>in vivo</i> was evaluated by immunoblotting.</p><p><strong>Results: </strong>Luteolin treatment induced functional improvements and alleviated dopaminergic neuronal loss in the PD model. Luteolin inhibited apoptosis and promoted cell survival in PC12 cells. Luteolin treatment shifted microglial M1/M2 polarization towards an anti-inflammatory M2 phenotype both <i>in vitro and in vivo</i>. Finally, it was found that luteolin treatment significantly downregulated both <i>TLR4</i> mRNA and protein expression as well as restraining NF-κB p65 subunit phosphorylation.</p><p><strong>Conclusions: </strong>Luteolin restrained dopaminergic degeneration <i>in vitro</i> and <i>in vivo</i> by blocking TLR4-mediated neuroinflammation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"185"},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}