ASN NEURO最新文献

{"title":"Cortical Stimulation-Based Transcriptome Shifts on Parkinson's Disease Animal Model.","authors":"Johyeon Nam, Hongseong Shin, Chaeyeon You, Eunha Baeg, Jae Geun Kim, Sunggu Yang, Mi-Ryung Han","doi":"10.1080/17590914.2025.2513881","DOIUrl":"10.1080/17590914.2025.2513881","url":null,"abstract":"<p><p>Parkinson's disease is the second most prevalent neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons. Significant improvements in gait balance, particularly in step length and velocity, were observed with less invasive wireless cortical stimulation. Transcriptome sequencing was performed to demonstrate the cellular mechanism, specifically targeting the primary motor cortex, where stimulation was applied. Our findings indicated that 38 differentially expressed genes (DEGs), initially downregulated following Parkinson's disease induction, were subsequently restored to normal levels after cortical stimulation. These 38 DEGs are potential targets for the treatment of motor disorders in Parkinson's disease. These genes are implicated in crucial processes, such as astrocyte-mediated blood vessel development and microglia-mediated phagocytosis of damaged motor neurons, suggesting their significant roles in improving behavioral disorders. Moreover, these biomarkers not only facilitate the rapid and accurate diagnosis of Parkinson's disease but also assist in precision medicine approaches.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2513881"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Stages of Alcohol-Related Cerebral White Matter Degeneration Reviewed: Early-Stage Stress/Neuroinflammation Versus Late-Stage Impaired Insulin/IGF Signaling Through Akt-mTOR-Review.","authors":"Suzanne M de la Monte, Greg Sutherland","doi":"10.1080/17590914.2025.2573965","DOIUrl":"10.1080/17590914.2025.2573965","url":null,"abstract":"<p><p>Long-term effects of alcohol-related brain damage (ARBD) include neurocognitive and neurobehavioral dysfunctions with neurodegeneration. White matter (WM) is notably targeted across the lifespan yet relatively little is known about the stages, mechanisms, and consequences of myelin and axonal loss. In alcohol-related liver disease, early pathology is reversible, but with chronic heavy alcohol exposures, disease progresses with degeneration, and ultimately organ failure. Similarly, WM ARBD also develops in two broad stages. The early stages of WM ARBD are likely mediated by vascular dysfunction with tissue swelling, oligodendrocyte dysfunction, myelin loss, neuroinflammation, and oxidative stress. The chronic progressive stage is linked to metabolic dysfunction related to impairments in insulin and insulin-like growth factor signaling through Akt-mechanistic target of rapamycin (mTOR) pathways that mediate oligodendrocyte survival and function, myelin homeostasis, and blood-brain-barrier (BBB) integrity. We hypothesize that early-stage WM ARBD may be largely reversible by abstinence and anti-oxidant/anti-inflammatory measures, whereas late-stage ARBD requires strategies to restore WM/oligodendrocyte metabolic function via insulin sensitizer, antioxidant, anti-inflammatory, and myelin homeostasis/normalization support. Multi-pronged, overlapping but distinct therapeutic strategies are needed to reduce the impact and long-term health consequences of chronic progressive WM ARBD.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2573965"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Research on Exosomal miRNAs in Central Nervous System Diseases.","authors":"Guangli Feng, Xiaoqian Lan, Shiyi Qin, Yuting Shi, Qinxi Zhao, Qing Li, Lianmei Zhong","doi":"10.1080/17590914.2025.2465546","DOIUrl":"10.1080/17590914.2025.2465546","url":null,"abstract":"<p><p>Neurological diseases present a wide range of conditions, intricate diagnosis and treatment processes, and complex prognostic considerations. Therefore, research focusing on the diagnosis and treatment of these diseases is crucial. Exosomal miRNAs are small RNA molecules enclosed in membrane vesicles, released by cells and known to play roles in the development of various neurological disorders. They also serve as specific biomarkers for these conditions. Drawing on extensive research on exosomal miRNAs in diseases like stroke, Alzheimer's, epilepsy, Parkinson's, and neuroregeneration, this paper provides a comprehensive review of the relationship between exosomal miRNAs and neurological diseases. We strive to offer current and detailed theoretical understandings to help with the diagnosis and treatment of these disorders.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2465546"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurons Are Not All the Same: Diversity in Neuronal Populations and Their Intrinsic Responses to Spinal Cord Injury.","authors":"Justin R Siebert, Kiersten Kennedy, Donna J Osterhout","doi":"10.1080/17590914.2024.2440299","DOIUrl":"10.1080/17590914.2024.2440299","url":null,"abstract":"<p><p>Functional recovery following spinal cord injury will require the regeneration and repair of damaged neuronal pathways. It is well known that the tissue response to injury involves inflammation and the formation of a glial scar at the lesion site, which significantly impairs the capacity for neuronal regeneration and functional recovery. There are initial attempts by both supraspinal and intraspinal neurons to regenerate damaged axons, often influenced by the neighboring tissue pathology. Many experimental therapeutic strategies are targeted to further stimulate the initial axonal regrowth, with little consideration for the diversity of the affected neuronal populations. Notably, recent studies reveal that the neuronal response to injury is variable, based on multiple factors, including the location of the injury with respect to the neuronal cell bodies and the affected neuronal populations. New insights into regenerative mechanisms have shown that neurons are not homogenous but instead exhibit a wide array of diversity in their gene expression, physiology, and intrinsic responses to injury. Understanding this diverse intrinsic response is crucial, as complete functional recovery requires the successful coordinated regeneration and reorganization of various neuron pathways.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2440299"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Atg9 Phosphorylation Sites Regulate Autophagic Trafficking in Glia.","authors":"Linfang Wang, Shuanglong Yi, Shiping Zhang, Yu-Ting Tsai, Yi-Hsuan Cheng, Yu-Tung Lin, Chia-Ching Lin, Yi-Hua Lee, Honglei Wang, Margaret S Ho","doi":"10.1080/17590914.2024.2443442","DOIUrl":"10.1080/17590914.2024.2443442","url":null,"abstract":"<p><p>We previously identified a role for dAuxilin (dAux), the fly homolog of Cyclin G-associated kinase, in glial autophagy contributing to Parkinson's disease (PD). To further dissect the mechanism, we present evidence here that lack of glial dAux enhanced the phosphorylation of the autophagy-related protein Atg9 at two newly identified threonine residues, T62 and T69. The enhanced Atg9 phosphorylation in the absence of dAux promotes autophagosome formation and Atg9 trafficking to the autophagosomes in glia. Whereas the expression of the non-phosphorylatable Atg9 variants suppresses the lack of dAux-induced increase in both autophagosome formation and Atg9 trafficking to autophagosome, the expression of the phosphomimetic Atg9 variants restores the lack of Atg1-induced decrease in both events. In relation to pathophysiology, Atg9 phosphorylation at T62 and T69 contributes to dopaminergic neurodegeneration and locomotor dysfunction in a <i>Drosophila</i> PD model. Notably, increased expression of the master autophagy regulator Atg1 promotes dAux-Atg9 interaction. Thus, we have identified a dAux-Atg1-Atg9 axis relaying signals through the Atg9 phosphorylation at T62 and T69; these findings further elaborate the mechanism of dAux regulating glial autophagy and highlight the significance of protein degradation pathway in glia contributing to PD.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2443442"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G-Ratio Commentary-Why You've Been Doing It Wrong.","authors":"R Douglas Fields, Dipankar J Dutta","doi":"10.1080/17590914.2025.2486962","DOIUrl":"10.1080/17590914.2025.2486962","url":null,"abstract":"","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2486962"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of Iron in Ferroptosis, Necroptosis, and Pyroptosis as Potential Players in TBI Morbidity and Mortality.","authors":"Makenzie Nolt, James Connor","doi":"10.1080/17590914.2024.2394352","DOIUrl":"10.1080/17590914.2024.2394352","url":null,"abstract":"<p><p>Iron is a critical transition metal required to sustain a healthy central nervous system. Iron is involved in metabolic reactions, enzymatic activity, myelinogenesis, and oxygen transport. However, in several pathological conditions such as cancer, neurodegeneration, and neurotrauma iron becomes elevated. Excessive iron can have deleterious effects leading to reactive oxygen species (ROS) via the Fenton reaction. Iron-derived ROS are known to drive several mechanisms such as cell death pathways including ferroptosis, necroptosis, and pyroptosis. Excessive iron present in the post-traumatic brain could trigger these harmful pathways potentiating the high rates of morbidity and mortality. In the present review, we will discuss how iron plays an intricate role in initiating ferroptosis, necroptosis, and pyroptosis, examine their potential link to traumatic brain injury morbidity and mortality, and suggest therapeutic targets.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2394352"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Analysis of Early White Matter Damage in Cuprizone Mouse Model of Demyelination Using 7.0 T MRI Multiparametric Approach.","authors":"Emma Friesen, Maxina Sheft, Kamya Hari, Vanessa Palmer, Shenghua Zhu, Sheryl Herrera, Richard Buist, Depeng Jiang, Xin-Min Li, Marc R Del Bigio, Jonathan D Thiessen, Melanie Martin","doi":"10.1080/17590914.2024.2404366","DOIUrl":"10.1080/17590914.2024.2404366","url":null,"abstract":"<p><p>Magnetic Resonance Imaging (MRI) is commonly used to follow the progression of neurodegenerative conditions, including multiple sclerosis (MS). MRI is limited by a lack of correlation between imaging results and clinical presentations, referred to as the clinico-radiological paradox. Animal models are commonly used to mimic the progression of human neurodegeneration and as a tool to help resolve the paradox. Most studies focus on later stages of white matter (WM) damage whereas few focus on early stages when oligodendrocyte apoptosis has just begun. The current project focused on these time points, namely weeks 2 and 3 of cuprizone (CPZ) administration, a toxin which induces pathophysiology similar to MS. <i>In vivo</i> T₂-weighted (T₂W) and Magnetization Transfer Ratio (MTR) maps and <i>ex vivo</i> Diffusion Tensor Imaging (DTI), Magnetization Transfer Imaging (MTI), and relaxometry (T₁ and T₂) values were obtained at 7 T. Significant changes in T₂W signal intensity and non-significant changes in MTR were observed to correspond to early WM damage, whereas significant changes in both corresponded with full demyelination. Some DTI metrics decrease with simultaneous increase in others, indicating acute demyelination. MTI metrics T₂^A, T₂^B, <i>f</i> and R were observed to have contradictory changes across CPZ administration. T₁ relaxation times were observed to have stronger correlations to disease states during later stages of CPZ treatment, whereas T₂ had weak correlations to early WM damage. These results all suggest the need for multiple metrics and further studies at early and late time points of demyelination. Further research is required to continue investigating the interplay between various MR metrics during all weeks of CPZ administration.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2404366"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells.","authors":"Derek C Lee, Linh Ta, Purna Mukherjee, Tomas Duraj, Marek Domin, Bennett Greenwood, Srada Karmacharya, Niven R Narain, Michael Kiebish, Christos Chinopoulos, Thomas N Seyfried","doi":"10.1080/17590914.2024.2422268","DOIUrl":"10.1080/17590914.2024.2422268","url":null,"abstract":"<p><p>Energy is necessary for tumor cell viability and growth. Aerobic glucose-driven lactic acid fermentation is a common metabolic phenotype seen in most cancers including malignant gliomas. This metabolic phenotype is linked to abnormalities in mitochondrial structure and function. A luciferin-luciferase bioluminescence ATP assay was used to measure the influence of amino acids, glucose, and oxygen on ATP content and viability in mouse (VM-M3 and CT-2A) and human (U-87MG) glioma cells that differed in cell biology, genetic background, and species origin. Oxygen consumption was measured using the Resipher system. Extracellular lactate and succinate were measured as end products of the glycolysis and glutaminolysis pathways, respectively. The results showed that: (1) glutamine was a source of ATP content irrespective of oxygen. No other amino acid could replace glutamine in sustaining ATP content and viability; (2) ATP content persisted in the absence of glucose and under hypoxia, ruling out substantial contribution through either glycolysis or oxidative phosphorylation (OxPhos) under these conditions; (3) Mitochondrial complex IV inhibition showed that oxygen consumption was not an accurate measure for ATP production through OxPhos. The glutaminase inhibitor, 6-diazo-5-oxo-L-norleucine (DON), reduced ATP content and succinate export in cells grown in glutamine. The data suggests that mitochondrial substrate level phosphorylation in the glutamine-driven glutaminolysis pathway contributes to ATP content in these glioma cells. A new model is presented highlighting the synergistic interaction between the high-throughput glycolysis and glutaminolysis pathways that drive malignant glioma growth and maintain ATP content through the aerobic fermentation of both glucose and glutamine.</p>","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2422268"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robert Paul Skoff (1942-2023).","authors":"Joyce Benjamins, Pamela Knapp, Anne Boullerne","doi":"10.1080/17590914.2024.2393559","DOIUrl":"10.1080/17590914.2024.2393559","url":null,"abstract":"","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2393559"},"PeriodicalIF":3.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}