IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-01-24 DOI: 10.1080/17590914.2024.2445624

Alexander Gow

{"title":"Understanding the Myelin g Ratio from First Principles, Its Derivation, Uses and Artifacts.","authors":"Alexander Gow","doi":"10.1080/17590914.2024.2445624","DOIUrl":"10.1080/17590914.2024.2445624","url":null,"abstract":"In light of the increasing importance for measuring myelin g ratios - the ratio of axon-to-fiber (axon + myelin) diameters in myelin internodes - to understand normal physiology, disease states, repair mechanisms and myelin plasticity, there is urgent need to minimize processing and statistical artifacts in current methodologies. Many contemporary studies fall prey to a variety of artifacts, reducing study outcome robustness and slowing development of novel therapeutics. Underlying causes stem from a lack of understanding of the myelin g ratio, which has persisted more than a century. An extended exploratory data analysis from first principles (the axon-fiber diameter relation) is presented herein and has major consequences for interpreting published g ratio studies. Indeed, a model of the myelin internode naturally emerges because of (1) the strong positive correlation between axon and fiber diameters and (2) the demonstration that the relation between these variables is one of direct proportionality. From this model, a robust framework for data analysis, interpretation and understanding allows specific predictions about myelin internode structure under normal physiological conditions. Further, the model establishes that a regression fit to g ratio plots has zero slope, and it identifies the underlying causes of several data processing artifacts that can be mitigated by plotting g ratios against fiber diameter (not axon diameter). Hypothesis testing can then be used for extending the model and evaluating myelin internodal properties under pathophysiological conditions (forthcoming). For without a statistical model as anchor, hypothesis testing is aimless like a rudderless ship on the ocean.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2445624"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031981","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}

引用次数: 0

A Statistically-Robust Model of the Axomyelin Unit under Normal Physiologic Conditions with Application to Disease States. 正常生理条件下Axomyelin单元的统计鲁棒模型及其在疾病状态中的应用。

IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-01-30 DOI: 10.1080/17590914.2024.2447336

Alexander Gow, Jeffrey L Dupree, Douglas L Feinstein, Anne Boullerne

{"title":"A Statistically-Robust Model of the Axomyelin Unit under Normal Physiologic Conditions with Application to Disease States.","authors":"Alexander Gow, Jeffrey L Dupree, Douglas L Feinstein, Anne Boullerne","doi":"10.1080/17590914.2024.2447336","DOIUrl":"10.1080/17590914.2024.2447336","url":null,"abstract":"Despite tremendous progress in characterizing the myriad cellular structures in the nervous system, a full appreciation of the interdependent and intricate interactions between these structures is as yet unfulfilled. Indeed, few more so than the interaction between the myelin internode and its ensheathed axon. More than a half-century after the ultrastructural characterization of this axomyelin unit, we lack a reliable understanding of the physiological properties, the significance and consequence of pathobiological processes, and the means to gauge success or failure of interventions designed to mitigate disease. Herein, we highlight shortcomings in the most common statistical procedures used to characterize the myelin g ratio, with particular emphasis on the underlying principles of simple linear regression. These shortcomings lead to insensitive detection and/or ambiguous interpretation of normal physiology, disease mechanisms and remedial methodologies. To address these problems, we syndicate insights from early seminal myelin studies and use a statistical model of the axomyelin unit that is established in Gow (2025). Herein, we develop and demonstrate a statistically-robust analysis pipeline with which to examine and interpret axomyelin physiology and pathobiology in two disease states, experimental autoimmune encephalomyelitis and the rumpshaker mouse model of leukodystrophy. On a cautionary note, our pipeline is a relatively simple and streamlined approach that is not necessarily a panacea for all g ratio analyses. Rather, it approximates a minimum effort needed to elucidate departures from normal physiology and to determine if more comprehensive studies may lead to deeper insights.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2447336"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063471","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}

引用次数: 0

A Brain Endothelial Cell Caveolin-1/CXCL10 Axis Promotes T Cell Transcellular Migration Across the Blood-Brain Barrier. 脑内皮细胞小窝蛋白-1/CXCL10轴促进T细胞跨血脑屏障的细胞迁移

IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-03-10 DOI: 10.1080/17590914.2025.2472070

Troy N Trevino, Ali A Almousawi, Remy Martins-Goncalves, Andrea Ochoa-Raya, KaReisha F Robinson, Genesis L Abad, Leon M Tai, Suellen D Oliveira, Richard D Minshall, Sarah E Lutz

{"title":"A Brain Endothelial Cell Caveolin-1/CXCL10 Axis Promotes T Cell Transcellular Migration Across the Blood-Brain Barrier.","authors":"Troy N Trevino, Ali A Almousawi, Remy Martins-Goncalves, Andrea Ochoa-Raya, KaReisha F Robinson, Genesis L Abad, Leon M Tai, Suellen D Oliveira, Richard D Minshall, Sarah E Lutz","doi":"10.1080/17590914.2025.2472070","DOIUrl":"10.1080/17590914.2025.2472070","url":null,"abstract":"The mechanisms that govern whether T cells cross blood-brain barrier (BBB) endothelium by transcellular versus paracellular routes are unclear. Caveolin-1 is a membrane scaffolding and signaling protein associated with transcellular transmigration through the endothelial cytoplasm. Here, we report that the neuroinflammatory chemokine CXCL10 induced transcellular, caveolar transmigration of CXCR3+ CD4+ T cells. Specifically, data revealed that CXCL10-induced transcellular transmigration requires expression of Caveolin-1 and ICAM-1 in brain endothelial cells and of the CXCL10 receptor, CXCR3, and LFA-1 in T cells. Moreover, Caveolin-1 promoted CXCL10 aggregation into brain endothelial cytoplasmic stores, providing a mechanism for activation and recruitment of CXCR3+ T cells to migrate at cytoplasmic locations, distal to cell-cell junctions. Consistent with our in vitro data, genetic ablation of Caveolin-1 reduces infiltration of CXCR3+ CD4+ T cells into the CNS in experimental autoimmune encephalomyelitis. Our findings establish a novel mechanism by which brain endothelial cells utilize Caveolin-1 dependent CXCL10 intracellular stores to license T cells for transcellular migration across the blood-brain barrier.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2472070"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596193","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}

引用次数: 0

P-glycoprotein and Alzheimer's Disease: Threats and Opportunities. p -糖蛋白与阿尔茨海默病：威胁与机遇。

IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-04-23 DOI: 10.1080/17590914.2025.2495632

Joseph Jr Asante, Steven W Barger

引用次数: 0

Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5. 性别影响HIV-1 Tat转基因小鼠的认知结果：CCR5的作用

IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-01-13 DOI: 10.1080/17590914.2024.2447338

Chloe A Simons, Sarah Kim, Yun K Hahn, Ama Boake-Agyei, Sara R Nass, Phu Vo, Kurt F Hauser, Pamela E Knapp

{"title":"Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5.","authors":"Chloe A Simons, Sarah Kim, Yun K Hahn, Ama Boake-Agyei, Sara R Nass, Phu Vo, Kurt F Hauser, Pamela E Knapp","doi":"10.1080/17590914.2024.2447338","DOIUrl":"10.1080/17590914.2024.2447338","url":null,"abstract":"People living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND), even though combination antiretroviral therapy (cART) suppresses HIV replication. HIV-1 transactivator of transcription (HIV-1 Tat) contributes to the development of HAND through neuroinflammatory and neurotoxic mechanisms. C-C chemokine 5 receptor (CCR5) is important in immune cell targeting and is a co-receptor for HIV viral entry into CD4+ cells. Notably, CCR5 has been implicated in cognition unrelated to HIV infection. Inhibition of CCR5 has been shown to improve learning and memory. To test whether CCR5 is involved in cognitive changes in HAND, we used a non-infectious, transgenic model in which HIV-1 Tat is inducibly expressed. Well-powered cohorts of male and female mice were placed on a diet containing doxycycline to induce Tat expression for 8-wks. Males showed Tat-mediated deficits in the Barnes maze test of spatial learning and memory; females showed no impairments. Deficits in the males were fully reversed by the CCR5 antagonist, maraviroc (MVC). Tat-mediated deficits were not found in novel object recognition or contextual fear conditioning in either sex. Based on earlier work, we hypothesized that MVC might increase brain-derived neurotrophic factor (BDNF), which is essential in maintaining synaptodendritic function. MVC did increase the mBDNF to proBDNF ratio in males, perhaps contributing to improved cognition.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2447338"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977399","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}

引用次数: 0

Assessment of Phase-Dependent Alterations in Cortical Glycolytic and Mitochondrial Metabolism Following Ischemic Stroke. 缺血性脑卒中后皮质糖酵解和线粒体代谢阶段依赖性改变的评估。

IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-04-10 DOI: 10.1080/17590914.2025.2488935

Shokofeh Rahimpour, Ethan Meadows, John M Hollander, Kate Karelina, Candice M Brown

{"title":"Assessment of Phase-Dependent Alterations in Cortical Glycolytic and Mitochondrial Metabolism Following Ischemic Stroke.","authors":"Shokofeh Rahimpour, Ethan Meadows, John M Hollander, Kate Karelina, Candice M Brown","doi":"10.1080/17590914.2025.2488935","DOIUrl":"https://doi.org/10.1080/17590914.2025.2488935","url":null,"abstract":"Maintaining optimal brain metabolism supports neuronal function, synaptic communication, and cognitive processes. During ischemic stroke, brain metabolism and cellular bioenergetics within the neurovascular unit are disrupted, emphasizing the significance of understanding the physiology and pathology of the stroke brain. The objective of this study was to quantify and compare phase-dependent changes in glycolysis and oxidative phosphorylation following ischemic stroke by using the Seahorse XFe24 Analyzer. Since there are limited established methods to quantify glycolytic activity in brain tissue, we optimized the accuracy and reproducibility of extracellular acidification rate (ECAR) measurement by increasing the incubation time following exposure to each reagent. Following optimization, we quantified both ECAR and the oxygen consumption rate (OCR), a measure of oxidative phosphorylation, in cortical brain tissue punches corresponding to the penumbra from mice subjected to ischemic stroke. ECAR and OCR were quantified in tissue punches from the injured (ipsilateral) and the non-injured (contralateral) hemispheres at 48 hours, 7 days, and 14 days post-stroke. Normalized ECAR measurements showed elevated glycolytic activity in the ipsilateral and contralateral hemispheres at 7 days post-stroke compared to other time points. In contrast, normalized OCR measurements showed a modest increase in basal respiration within the ipsilateral hemispheres between 48 hours and 14 days post-stroke. In summary, the results demonstrate that ischemic stroke results in a distinct phase-dependent metabolic phenotype in both cortical hemispheres that persists up to 14 days after injury.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2488935"},"PeriodicalIF":3.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975226","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}

引用次数: 0

Advances in Research on Exosomal miRNAs in Central Nervous System Diseases. 外泌体mirna在中枢神经系统疾病中的研究进展

IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-04-01 DOI: 10.1080/17590914.2025.2465546

Guangli Feng, Xiaoqian Lan, Shiyi Qin, Yuting Shi, Qinxi Zhao, Qing Li, Lianmei Zhong

引用次数: 0

G-Ratio Commentary-Why You've Been Doing It Wrong. G-Ratio评论——为什么你一直做错了。

IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-04-07 DOI: 10.1080/17590914.2025.2486962

R Douglas Fields, Dipankar J Dutta

引用次数: 0

Neurons Are Not All the Same: Diversity in Neuronal Populations and Their Intrinsic Responses to Spinal Cord Injury. 神经元并不完全相同：神经元种群的多样性及其对脊髓损伤的内在反应。

IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-01-16 DOI: 10.1080/17590914.2024.2440299

Justin R Siebert, Kiersten Kennedy, Donna J Osterhout

{"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":"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.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2440299"},"PeriodicalIF":3.9,"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}

引用次数: 0

New Atg9 Phosphorylation Sites Regulate Autophagic Trafficking in Glia. 新的Atg9磷酸化位点调节神经胶质细胞的自噬运输。

IF 3.9 4区医学

ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-01-14 DOI: 10.1080/17590914.2024.2443442

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

{"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":"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 Drosophila 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.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"17 1","pages":"2443442"},"PeriodicalIF":3.9,"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}

引用次数: 0

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