Journal of Experimental Neuroscience最新文献_第2页

New Mechanisms of DNA Repair Defects in Fused in Sarcoma-Associated Neurodegeneration: Stage Set for DNA Repair-Based Therapeutics? 肉瘤相关神经退行性疾病融合DNA修复缺陷的新机制:DNA修复治疗的阶段?

Journal of Experimental Neuroscience Pub Date : 2019-06-10 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519856358

Haibo Wang, Muralidhar L Hegde

{"title":"New Mechanisms of DNA Repair Defects in Fused in Sarcoma-Associated Neurodegeneration: Stage Set for DNA Repair-Based Therapeutics?","authors":"Haibo Wang, Muralidhar L Hegde","doi":"10.1177/1179069519856358","DOIUrl":"https://doi.org/10.1177/1179069519856358","url":null,"abstract":"Genome damage and defective DNA repair are etiologically linked to several neurodegenerative disorders, including fused in sarcoma (FUS)-associated amyotrophic lateral sclerosis (ALS). However, the underlying mechanisms remain enigmatic, which is a roadblock for exploiting genome repair-targeted therapies. Our recent studies identified defects in DNA nick ligation and oxidative damage repair caused by mutations in the RNA/DNA-binding protein FUS in familial ALS patients. In healthy neurons, FUS protects the genome by facilitating PARP1-dependent recruitment of XRCC1/DNA Ligase IIIα (LigIII) to oxidized genome sites and activating LigIII via direct interaction. This is a critical step in the repair of oxidative genome damage, a foremost challenge for postmitotic neurons due to their high oxygen consumption. We discovered that mutant FUS significantly inhibited the recruitment of XRCC1/LigIII to DNA strand breaks, causing defects in DNA ligation during the repair of oxidative DNA damage, which contributed to neurodegeneration. While the FUS loss of function was responsible for the repair defects, increased oxidative genome damage due to mutant FUS aggregation could exacerbate the phenomenon. We highlight how these new molecular insights into previously undescribed DNA repair defect linked to FUS-associated neurodegeneration could provide an important opportunity for exploring DNA repair-based therapeutic avenues.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"13 ","pages":"1179069519856358"},"PeriodicalIF":0.0,"publicationDate":"2019-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519856358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37344709","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}

引用次数: 22

Rev-erbs and Glia-Implications for Neurodegenerative Diseases. Rev-erbs和神经胶质对神经退行性疾病的影响。

Journal of Experimental Neuroscience Pub Date : 2019-06-04 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519853233

Percy Griffin, Julie M Dimitry, Erik S Musiek

引用次数: 1

Dissecting Static and Dynamic Functional Connectivity: Example From the Autism Spectrum. 剖析静态和动态功能连接:来自自闭症谱系的例子。

Journal of Experimental Neuroscience Pub Date : 2019-05-29 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519851809

Tonya White, Vince D Calhoun

{"title":"Dissecting Static and Dynamic Functional Connectivity: Example From the Autism Spectrum.","authors":"Tonya White, Vince D Calhoun","doi":"10.1177/1179069519851809","DOIUrl":"https://doi.org/10.1177/1179069519851809","url":null,"abstract":"The ability to measure the intrinsic functional architecture of the brain has grown exponentially over the last 2 decades. Measures of intrinsic connectivity within the brain, typically measured using resting-state functional magnetic resonance imaging (MRI), have evolved from primarily \"static\" approaches, to include dynamic measures of functional connectivity. Measures of dynamic functional connectivity expand the assumptions to allow brain regions to have temporally different patterns of communication between different regions. That is, connections within the brain can differentially fire between different regions at different times, and these differences can be quantified. Applying approaches that measure the dynamic characteristics of functional brain connectivity have been fruitful in identifying differences during brain development and psychopathology. We provide a brief overview of static and dynamic measures of functional connectivity and illustrate the synergy in applying these approaches to identify both age-related differences in children and differences between typically developing children and children with autistic symptoms.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"13 ","pages":"1179069519851809"},"PeriodicalIF":0.0,"publicationDate":"2019-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519851809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37338549","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}

引用次数: 8

Proposed Therapies for Pantothenate-Kinase-Associated Neurodegeneration. 泛酸激酶相关神经退行性变的建议治疗方法。

Journal of Experimental Neuroscience Pub Date : 2019-05-23 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519851118

Suzanne Jackowski

引用次数: 12

A Mechanism for the Development of Chronic Traumatic Encephalopathy From Persistent Traumatic Brain Injury. 持续性外伤性脑损伤并发慢性外伤性脑病的机制研究。

Journal of Experimental Neuroscience Pub Date : 2019-05-20 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519849935

Melissa Demock, Steven Kornguth

{"title":"A Mechanism for the Development of Chronic Traumatic Encephalopathy From Persistent Traumatic Brain Injury.","authors":"Melissa Demock, Steven Kornguth","doi":"10.1177/1179069519849935","DOIUrl":"https://doi.org/10.1177/1179069519849935","url":null,"abstract":"A mechanism that describes the progression of traumatic brain injury (TBI) to end-stage chronic traumatic encephalopathy (CTE) is offered in this article. This mechanism is based upon the observed increase in the concentration of both tau protein and of human leukocyte antigen (HLA) class I proteins; the HLA increase is expressed on the cell membrane of neural cells. These events follow the inflammatory responses caused by the repetitive TBI. Associated inflammatory changes include macrophage entry into the brain parenchyma from increased permeability of the blood-brain barrier (BBB) and microglial activation at the base of the sulci. The release of interferon gamma from the microglia and macrophages induces the marked increased expression of HLA class I proteins by the neural cells and subsequent redistribution of the tau proteins to the glial and neuronal surface. In those individuals with highly expressed HLA class I C, the high level of HLA binds tau protein electrostatically. The ionic region of HLA class I C (amino acid positions 50-90) binds to the oppositely charged ionic region of tau (amino acid positions 93-133). These interactions thereby shift the cellular localization of the tau and orient the tau spatially so that the cross-linking sites of tau (275-280 and 306-311) are aligned. This alignment facilitates the cross-linking of tau to form the intracellular and extracellular microfibrils of tau, the primary physiological characteristic of tauopathy. Following endocytosis of the membrane HLA/tau complex, these microfibrils accumulate and produce a tau-storage-like disease. Therefore, tauopathy is the secondary collateral process of brain injury, resulting from the substantial increase in tau and HLA expression on neural cells. This proposed mechanism suggests several potential targets for mitigating the clinical progression of TBI to CTE.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"13 ","pages":"1179069519849935"},"PeriodicalIF":0.0,"publicationDate":"2019-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519849935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37074540","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}

引用次数: 7

Mosaic APP Gene Recombination in Alzheimer's Disease-What's Next? 阿尔茨海默病中的Mosaic APP基因重组——下一步是什么?

Journal of Experimental Neuroscience Pub Date : 2019-05-16 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519849669

Ming-Hsiang Lee, Jerold Chun

{"title":"Mosaic APP Gene Recombination in Alzheimer's Disease-What's Next?","authors":"Ming-Hsiang Lee, Jerold Chun","doi":"10.1177/1179069519849669","DOIUrl":"https://doi.org/10.1177/1179069519849669","url":null,"abstract":"A first example of somatic gene recombination (SGR) within the human brain was recently reported, involving the well-known Alzheimer's disease (AD)-related gene amyloid precursor protein (APP). SGR was characterized by the creation of APP genomic complementary DNA (gencDNA) sequences that were identified in prefrontal cortical neurons from both normal and sporadic Alzheimer's disease (SAD) brains. Notably, SGR in SAD appeared to become dysregulated, producing many more numbers and forms of APP gencDNAs, including 11 single-nucleotide variations (SNVs) that are considered pathogenic APP mutations when they occur in families, yet are present mosaically among SAD neurons. APP gene transcription, reverse transcriptase (RT) activity, and DNA strand-breaks were shown to be three key factors required for APP gencDNA production. Many mechanistic details remain to be determined, particularly how APP gencDNAs are involved in AD initiation and progression. The possibility of reducing disease-related SGR through the use of RT inhibitors that are already FDA-approved for HIV and Hepatitis B treatment represents both a testable hypothesis for AD clinical trials and a genuine therapeutic option, where none currently exists, for AD patients.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"13 ","pages":"1179069519849669"},"PeriodicalIF":0.0,"publicationDate":"2019-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519849669","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37074537","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}

引用次数: 6

The Role of Body-Related Afferent Signals in Human Sense of Agency. 身体相关传入信号在人的代理感中的作用。

Journal of Experimental Neuroscience Pub Date : 2019-05-16 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519849907

Maria Pyasik, Tiziano Furlanetto, Lorenzo Pia

引用次数: 16

Sex Differences in Animal Models of Traumatic Brain Injury. 创伤性脑损伤动物模型的性别差异。

Journal of Experimental Neuroscience Pub Date : 2019-05-13 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519844020

Todd G Rubin, Michael L Lipton

引用次数: 50

Investigating the Subcortical Route to the Amygdala Across Species and in Disordered Fear Responses. 研究跨物种和无序恐惧反应中杏仁核的皮质下途径。

Journal of Experimental Neuroscience Pub Date : 2019-05-01 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519846445

Jessica McFadyen

{"title":"Investigating the Subcortical Route to the Amygdala Across Species and in Disordered Fear Responses.","authors":"Jessica McFadyen","doi":"10.1177/1179069519846445","DOIUrl":"10.1177/1179069519846445","url":null,"abstract":"Over the past few decades, evidence has come to light that there is a rapid subcortical shortcut that transmits visual information to the amygdala, effectively bypassing the visual cortex. This pathway purportedly runs from the superior colliculus to the amygdala via the pulvinar, and thus presents a methodological challenge to study noninvasively in the human brain. Here, we present our recent work where we reliably reconstructed the white matter structure and directional flow of neural signal along this pathway in over 600 healthy young adults. Critically, we found structure-function relationships for the pulvinar-amygdala connection, where people with greater fibre density had stronger functional neural coupling and were also better at recognising fearful facial expressions. These results tie together recent anatomical evidence from other visual primates with very recent optogenetic research on rodents demonstrating a functional role of this pathway in producing fear responses. Here, we discuss how this pathway might operate alongside other thalamo-cortical circuits (such as pulvinar to middle temporal area) and how its structure and function may change according to the sensory input it receives. This newly established circuit might play a potentially important role in autism and/or anxiety disorders.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"13 ","pages":"1179069519846445"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519846445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37225641","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}

引用次数: 21

Myo-granules Connect Physiology and Pathophysiology. 肌颗粒连接生理学和病理生理学。

Journal of Experimental Neuroscience Pub Date : 2019-04-12 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519842157

Alicia A Cutler, Theodore Eugene Ewachiw, Giulia A Corbet, Roy Parker, Brad B Olwin

引用次数: 0