ASN NEURO最新文献_第3页

Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells. 氨基酸和葡萄糖发酵维持小鼠和人恶性胶质瘤细胞ATP含量。

IF 3.7 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-12-02 DOI: 10.1080/17590914.2024.2422268

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

{"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":"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.","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}

引用次数: 0

Robert Paul Skoff (1942-2023). 罗伯特·保罗·斯科夫（1942-2023）。

IF 3.9 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-09-05 DOI: 10.1080/17590914.2024.2393559

Joyce Benjamins, Pamela Knapp, Anne Boullerne

引用次数: 0

Diverse Responses of Oligodendrocytes to Different FGF-Family Members: Uncoupling Structure-Function Relationship Within FGF Subfamilies. 少突胶质细胞对不同 FGF 家族成员的不同反应：解耦 FGF 亚家族内的结构-功能关系。

IF 3.7 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-07-15 DOI: 10.1080/17590914.2024.2371163

Hebe M Guardiola-Diaz, Brett T DiBenedictis, Erealda Prendaj, Rashmi Bansal

{"title":"Diverse Responses of Oligodendrocytes to Different FGF-Family Members: Uncoupling Structure-Function Relationship Within FGF Subfamilies.","authors":"Hebe M Guardiola-Diaz, Brett T DiBenedictis, Erealda Prendaj, Rashmi Bansal","doi":"10.1080/17590914.2024.2371163","DOIUrl":"10.1080/17590914.2024.2371163","url":null,"abstract":"The fifteen canonical paracrine fibroblast growth factors (FGFs) are organized in five subfamilies that interact with four FGF-receptors (FGFRs) and heparan sulfate proteoglycan (HSPG) co-receptors. Many of these FGFs are expressed in CNS regions where oligodendrocyte (OL) progenitors originate, migrate or differentiate. FGF2 (basic FGF) is considered a prototype FGF and the information about the effects of FGF signaling on OL-lineage cells has evolved largely from the study of FGF2. However, other FGFs from four subfamilies ((FGF1 (FGF1,-2), FGF4 (FGF4,-5,-6), FGF8 (FGF8,-17,-18) and FGF9 (FGF9,-16,-20)) that can interact with the isoforms of FGFRs expressed in OL-lineage cells may also play important roles. We previously reported OL-responses to FGF8 family members. Here, we investigate the effects of members of the FGF1,-4, and -9 subfamilies on proliferation and differentiation of OL progenitors (OPCs), and on cell cycle re-entry and down-regulation of myelin proteins by mature OLs. We found that while FGF2 induced all these responses strongly, FGF4,-6,-9 could do so only transiently and in the presence of exogenous HSPGs, and that FGF5,-16,-20 could not do so even in the presence of heparin or at higher concentrations. Furthermore, we noted that structurally similar FGFs within subfamilies did not always show similarities in their biological effects on OL-lineage cells. Taken together, these studies reveal that FGFs differ in the way they regulate the OL-lineage cells, emphasizes the selectivity and importance of HSPGs as FGF co-receptors in OL-lineage cells and suggests that structural similarity among FGF-subfamily members may not always predict their overlapping biological functions.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2371163"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141722920","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

Pannexin1 Mediates Early-Life Seizure-Induced Social Behavior Deficits. Pannexin1介导早期癫痫发作诱发的社交行为缺陷

IF 3.7 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-07-16 DOI: 10.1080/17590914.2024.2371164

Price Obot, Antonio Cibelli, Jian Pan, Libor Velíšek, Jana Velíšková, Eliana Scemes

{"title":"Pannexin1 Mediates Early-Life Seizure-Induced Social Behavior Deficits.","authors":"Price Obot, Antonio Cibelli, Jian Pan, Libor Velíšek, Jana Velíšková, Eliana Scemes","doi":"10.1080/17590914.2024.2371164","DOIUrl":"10.1080/17590914.2024.2371164","url":null,"abstract":"There is a high co-morbidity between childhood epilepsy and autism spectrum disorder (ASD), with age of seizure onset being a critical determinant of behavioral outcomes. The interplay between these comorbidities has been investigated in animal models with results showing that the induction of seizures at early post-natal ages leads to learning and memory deficits and to autistic-like behavior in adulthood. Modifications of the excitation/inhibition (glutamate/GABA, ATP/adenosine) balance that follows early-life seizures (ELS) are thought to be the physiological events that underlie neuropsychiatric and neurodevelopmental disorders. Although alterations in purinergic/adenosinergic signaling have been implicated in seizures and ASD, it is unknown whether the ATP release channels, Pannexin1 (Panx1), contribute to ELS-induced behavior changes. To tackle this question, we used the ELS-kainic acid model in transgenic mice with global and cell type specific deletion of Panx1 to evaluate whether these channels were involved in behavioral deficits that occur later in life. Our studies show that ELS results in Panx1 dependent social behavior deficits and also in poor performance in a spatial memory test that does not involve Panx1. These findings provide support for a link between ELS and adult behavioral deficits. Moreover, we identify neuronal and not astrocyte Panx1 as a potential target to specifically limit astrogliosis and social behavioral deficits resultant from early-life seizures.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2371164"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141722921","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

Abnormal Regulation of Mitochondrial Sphingolipids during Aging and Alzheimer's Disease. 衰老和阿尔茨海默病过程中线粒体鞘磷脂的异常调节

IF 3.7 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-11-05 DOI: 10.1080/17590914.2024.2404367

Simone M Crivelli, Zainuddin Quadri, Ahmed Elsherbini, Hemendra J Vekaria, Patrick G Sullivan, Wenbo Zhi, Pilar Martinez-Martinez, Stefka D Spassieva, Erhard Bieberich

{"title":"Abnormal Regulation of Mitochondrial Sphingolipids during Aging and Alzheimer's Disease.","authors":"Simone M Crivelli, Zainuddin Quadri, Ahmed Elsherbini, Hemendra J Vekaria, Patrick G Sullivan, Wenbo Zhi, Pilar Martinez-Martinez, Stefka D Spassieva, Erhard Bieberich","doi":"10.1080/17590914.2024.2404367","DOIUrl":"10.1080/17590914.2024.2404367","url":null,"abstract":"During pathogenesis of Alzheimer's disease (AD), mitochondria suffer alterations that lead to low energy production and reactive oxygen species formation. However, the mechanism of impaired mitochondria homeostasis in AD is not fully understood. We hypothesized that abnormal sphingolipid metabolism in mitochondria could be one of the contributing factors to mitochondrial dysfunction. Synaptic and non-synaptic mitochondria were isolated from 5xFAD and wild type (WT) mice at 3 and 7 months using Ficoll gradient ultracentrifugation, and their function was analyzed using Seahorse assay. Additionally, mitochondria were analyzed using mass spectrometry for proteomics and sphingolipidomics analyses. Sphingolipid levels were also determined in synaptic and non-synaptic mitochondria isolated from AD patients and healthy controls. We found that synaptic mitochondria isolated from 3-months old 5xFAD mice manifest diminished oxygen consumption as compared to WT. Consistently, proteomics analysis showed that proteins related to respiratory electron transport and oxidative phosphorylation were altered in 5xFAD mice. When quantifying the main sphingolipids in mitochondria, we found that Cer 18:0, Cer 22:0, and Cer 24:1 were increased already at 3 months in 5xFAD mice. No increase in ceramides was detected in mitochondria isolated from AD patients. However, increased levels of sphingosine were found in both 5xFAD mice and AD patients when compared to respective controls. We report that the regulation of sphingolipids in mitochondria is abnormal at 3 months of age in 5xFAD mice, as indicated by the accumulation of long-chain ceramides, which increases with age. Sphingosine levels are increased in both the mitochondria of 5xFAD mice and AD patients. Our data suggest that the sphingolipid composition is dysregulated in mitochondria early during AD pathogenesis.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2404367"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581925","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

Robert Paul Skoff (1942-2023). 罗伯特-保罗-斯科夫（1942-2023）。

IF 3.9 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-09-05 DOI: 10.1080/17590914.2024.2393559

Joyce Benjamins, Pamela Knapp, Anne Boullerne

引用次数: 0

Editorial. 社论

IF 3.7 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-09-09 DOI: 10.1080/17590914.2024.2386884

Douglas L Feinstein

引用次数: 0

Evaluation of BR1 and BI30 AAVs for Brain Endothelial Tropism. BR1和BI30 aav对脑内皮性的评价。

IF 3.7 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-12-02 DOI: 10.1080/17590914.2024.2427953

Felecia M Marottoli, Deebika Balu, Rohan Chaudhary, Sarah E Lutz, Leon M Tai

{"title":"Evaluation of BR1 and BI30 AAVs for Brain Endothelial Tropism.","authors":"Felecia M Marottoli, Deebika Balu, Rohan Chaudhary, Sarah E Lutz, Leon M Tai","doi":"10.1080/17590914.2024.2427953","DOIUrl":"10.1080/17590914.2024.2427953","url":null,"abstract":"Brain endothelial cells are critical for homeostasis of the central nervous system. Novel adeno-associated viruses (AAV) with brain endothelial cell tropism have been developed and are beginning to be employed in mechanistic and therapeutic research. Studies using AAVs can be involved in terms of cost, time and personnel, and many groups, including our own, are not experts on the technology. Therefore, it is important to report data using AAVs with the research community as a guide for ongoing and future studies. Here, we detail our initial experience with the two most prevalent AAVs with tropism for brain endothelial cells, AAV-BR1 and AAV-BI30. One of our long-term goals is to express key proteins in brain endothelial cells and determine the impact on brain function. For method development, we administered AAV-BR1 and AAV-BI30 with a CMV-driven fluorescent reporter (CMV-P2A-mCherry) to wild-type mice intravenously (retro-orbital) and measured expression in brain and peripheral tissues by RT-PCR and immunostaining. We found that AAV-BR1 transduces neurons and endothelial cells in the brain, and the lung and liver, whereas AAV-BI30 transduces brain endothelial cells and peripheral tissue. Our data highlights the importance of using the AAV best suited to the scientific question.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2427953"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765669","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

Astrocytic Ephrin-B1 Regulates Oligodendrocyte Development and Myelination. 星形胶质细胞 Ephrin-B1 调控少突胶质细胞的发育和髓鞘化

IF 3.7 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-10-22 DOI: 10.1080/17590914.2024.2401753

Samantha N Sutley-Koury, Alyssa Anderson, Christopher Taitano-Johnson, Moyinoluwa Ajayi, Anna O Kulinich, Kimberly Contreras, Jasmin Regalado, Seema K Tiwari-Woodruff, Iryna M Ethell

{"title":"Astrocytic Ephrin-B1 Regulates Oligodendrocyte Development and Myelination.","authors":"Samantha N Sutley-Koury, Alyssa Anderson, Christopher Taitano-Johnson, Moyinoluwa Ajayi, Anna O Kulinich, Kimberly Contreras, Jasmin Regalado, Seema K Tiwari-Woodruff, Iryna M Ethell","doi":"10.1080/17590914.2024.2401753","DOIUrl":"10.1080/17590914.2024.2401753","url":null,"abstract":"Astrocytes have been implicated in oligodendrocyte development and myelination, however, the mechanisms by which astrocytes regulate oligodendrocytes remain unclear. Our findings suggest a new mechanism that regulates astrocyte-mediated oligodendrocyte development through ephrin-B1 signaling in astrocytes. Using a mouse model, we examined the role of astrocytic ephrin-B1 signaling in oligodendrocyte development by deleting ephrin-B1 specifically in astrocytes during the postnatal days (P)14-P28 period and used mRNA analysis, immunohistochemistry, and mouse behaviors to study its effects on oligodendrocytes and myelination. We found that deletion of astrocytic ephrin-B1 downregulated many genes associated with oligodendrocyte development, myelination, and lipid metabolism in the hippocampus and the corpus callosum. Additionally, we observed a reduced number of oligodendrocytes and impaired myelination in the corpus callosum of astrocyte-specific ephrin-B1 KO mice. Finally, our data show reduced motor strength in these mice exhibiting clasping phenotype and impaired performance in the rotarod test most likely due to impaired myelination. Our studies provide new evidence that astrocytic ephrin-B1 positively regulates oligodendrocyte development and myelination, potentially through astrocyte-oligodendrocyte interactions.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2401753"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493736","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

Dorsomedial Ventromedial Hypothalamic Nucleus Growth Hormone-Releasing Hormone Neuron Steroidogenic Factor-1 Gene Targets in Female Rat. 雌性大鼠下丘脑背内侧核生长激素释放激素神经元类固醇生成因子-1的基因靶点

IF 3.7 4区医学

ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-10-14 DOI: 10.1080/17590914.2024.2403345

Subash Sapkota, Sagor C Roy, Karen P Briski

{"title":"Dorsomedial Ventromedial Hypothalamic Nucleus Growth Hormone-Releasing Hormone Neuron Steroidogenic Factor-1 Gene Targets in Female Rat.","authors":"Subash Sapkota, Sagor C Roy, Karen P Briski","doi":"10.1080/17590914.2024.2403345","DOIUrl":"10.1080/17590914.2024.2403345","url":null,"abstract":"The prospect that the ventromedial hypothalamic nucleus (VMN) transcription factor steroidogenic factor-1/NR5A1 (SF-1) may exert sex-dimorphic control of glucose counterregulation is unresolved. Recent studies in male rats show that SF-1 regulates transcription of co-expressed hypoglycemia-sensitive neurochemicals in dorsomedial VMN growth hormone-releasing hormone (Ghrh) neurons. Gene knockdown and laser-catapult-microdissection/single-cell multiplex qPCR techniques were used here in a female rat model to determine if SF-1 control of Ghrh neuron transmitter marker, energy sensor, and estrogen receptor (ER) variant mRNAs varies according to sex. Data show that in females, hypoglycemia elicits a gain of SF-1 inhibitory control of VMNdm Ghrh neuron Ghrh and Ghrh-receptor gene profiles and loss of augmentation of glutaminase transcription; SF-1 gene silencing diminished eu- and hypoglycemic patterns of neuronal nitric oxide gene transcription. SF-1 imposes divergent control of baseline and hypoglycemic glutamate decarboxylase65 (GAD)-1 (stimulatory) versus GAD2 (inhibitory) mRNAs in that sex. SF-1 stimulates baseline VMNdm Ghrh neuron PRKAA1/AMPKα1 and PRKAA2/AMPKα2 gene expression, yet causes opposite changes in these gene profiles during hypoglycemia. SF-1 exerts glucose-dependent control of ER-alpha and G-protein-coupled ER-1 transcription, but blunts ER-beta gene profiles during eu- and hypoglycemia. In females, SF-1 knockdown did not affect hypercorticosteronemia or hyperglucagonemia, but blunted hypoglycemic suppression of growth hormone secretion. Results show that SF-1 expression is critical for female rat VMNdm Ghrh neuron counterregulatory neurochemical, AMPK catalytic subunit, and ER gene transcription responses to hypoglycemia. Sex differences in direction of SF-1 control of distinctive gene profiles may result in observed disparities in SF-1 regulation of counterregulatory hormone secretion between sexes.","PeriodicalId":8616,"journal":{"name":"ASN NEURO","volume":"16 1","pages":"2403345"},"PeriodicalIF":3.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456905","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