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A Commentary on TDP-43 and DNA Damage Response in Amyotrophic Lateral Sclerosis. TDP-43与肌萎缩侧索硬化症DNA损伤反应的研究进展
Journal of Experimental Neuroscience Pub Date : 2019-10-10 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519880166
Joy Mitra, Muralidhar L Hegde
{"title":"A Commentary on TDP-43 and DNA Damage Response in Amyotrophic Lateral Sclerosis.","authors":"Joy Mitra, Muralidhar L Hegde","doi":"10.1177/1179069519880166","DOIUrl":"10.1177/1179069519880166","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a devastating, motor neuron degenerative disease without any cure. About 95% of the ALS patients feature abnormalities in the RNA/DNA-binding protein, TDP-43, involving its nucleo-cytoplasmic mislocalization in spinal motor neurons. How TDP-43 pathology triggers neuronal apoptosis remains unclear. In a recent study, we reported for the first time that TDP-43 participates in the DNA damage response (DDR) in neurons, and its nuclear clearance in spinal motor neurons caused DNA double-strand break (DSB) repair defects in ALS. We documented that TDP-43 was a key component of the non-homologous end joining (NHEJ) pathway of DSB repair, which is likely the major pathway for repair of DSBs in post-mitotic neurons. We have also uncovered molecular insights into the role of TDP-43 in DSB repair and showed that TDP-43 acts as a scaffold in recruiting the XRCC4/DNA Ligase 4 complex at DSB damage sites and thus regulates a critical rate-limiting function in DSB repair. Significant DSB accumulation in the genomes of TDP-43-depleted, human neural stem cell-derived motor neurons as well as in ALS patient spinal cords with TDP-43 pathology, strongly supported a TDP-43 involvement in genome maintenance and toxicity-induced genome repair defects in ALS. In this commentary, we highlight our findings that have uncovered a link between TDP-43 pathology and impaired DNA repair and suggest potential possibilities for DNA repair-targeted therapies for TDP-43-ALS.</p>","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":"1179069519880166"},"PeriodicalIF":0.0,"publicationDate":"2019-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48834786","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: 0
Blast-Related Traumatic Brain Injury: Current Concepts and Research Considerations. 爆炸性颅脑损伤的概念与研究思路
Journal of Experimental Neuroscience Pub Date : 2019-09-12 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519872213
Daniel W Bryden, Jessica I Tilghman, Sidney R Hinds
{"title":"Blast-Related Traumatic Brain Injury: Current Concepts and Research Considerations.","authors":"Daniel W Bryden, Jessica I Tilghman, Sidney R Hinds","doi":"10.1177/1179069519872213","DOIUrl":"10.1177/1179069519872213","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a well-known consequence of participation in activities such as military combat or collision sports. But the wide variability in eliciting circumstances and injury severities makes the study of TBI as a uniform disease state impossible. Military Service members are under additional, unique threats such as exposure to explosive blast and its unique effects on the body. This review is aimed toward TBI researchers, as it covers important concepts and considerations for studying blast-induced head trauma. These include the comparability of blast-induced head trauma to other mechanisms of TBI, whether blast overpressure induces measureable biomarkers, and whether a biodosimeter can link blast exposure to health outcomes, using acute radiation exposure as a corollary. This examination is contextualized by the understanding of concussive events and their psychological effects throughout the past century's wars, as well as the variables that predict sustaining a TBI and those that precipitate or exacerbate psychological conditions. Disclaimer: The views expressed in this article are solely the views of the authors and not those of the Department of Defense Blast Injury Research Coordinating Office, US Army Medical Research and Development Command, US Army Futures Command, US Army, or the Department of Defense.</p>","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":"1179069519872213"},"PeriodicalIF":0.0,"publicationDate":"2019-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49482575","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: 0
Future Directions in Examining Neurological Adaptation to Bilingual Experiences 双语经验神经适应研究的未来方向
Journal of Experimental Neuroscience Pub Date : 2019-09-01 DOI: 10.1177/1179069519876597
V. DeLuca
{"title":"Future Directions in Examining Neurological Adaptation to Bilingual Experiences","authors":"V. DeLuca","doi":"10.1177/1179069519876597","DOIUrl":"https://doi.org/10.1177/1179069519876597","url":null,"abstract":"In recent years, research examining the neurocognitive effects of bilingualism has undergone a shift in focus towards examining the neurocognitive effects of individual differences within specific aspects of language experience. The DeLuca et al study advances this direction in showing a specificity of neural adaptations to separate aspects of language experience. However, this approach is an early step of several in towards a more comprehensive understanding of the nature of neural adaptation to bilingual language use. This commentary discusses several future directions worth further consideration in research examining bilingualism-induced neuroplasticity.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519876597","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45011847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Walking Function After Cervical Contusion and Distraction Spinal Cord Injuries in Rats. 大鼠颈挫伤和脊髓牵张损伤后的行走功能。
Journal of Experimental Neuroscience Pub Date : 2019-08-19 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519869615
Yue Guo, Hai Hu, Jingchao Wang, Meiyan Zhang, Kinon Chen
{"title":"Walking Function After Cervical Contusion and Distraction Spinal Cord Injuries in Rats.","authors":"Yue Guo,&nbsp;Hai Hu,&nbsp;Jingchao Wang,&nbsp;Meiyan Zhang,&nbsp;Kinon Chen","doi":"10.1177/1179069519869615","DOIUrl":"https://doi.org/10.1177/1179069519869615","url":null,"abstract":"<p><p>This study examines and compares the walking function in contusion and distraction spinal cord injury (SCI) mechanisms. Moderate contusion and distraction SCIs were surgically induced between C5 and C6 in Sprague-Dawley male rats. The CatWalk system was used to perform gait analysis of walkway walking. The ladder rung walking test was used to quantify skilled locomotor movements of ladder rung walking. It was found that the inter-paw coordination, paw support, front paw kinematics, hind paw kinematics, and skilled movements were significantly different before and after contusion and distraction. Step sequence duration, diagonal support, forelimb intensity, forelimb duty cycle, forelimb paw angle, and forelimb swing speed were more greatly affected in distraction than in contusion at 2 weeks post-injury, whereas hindlimb stand was more greatly affected in contusion than in distraction at 8 weeks post-injury. After 8 weeks post-injury, diagonal coupling-variation, girdle coupling-variation, ipsilateral coupling-mean, forelimb maximum contact at, forelimb intensity, forelimb paw angle, and number of forelimb misplacements recovered to normal in contusion but not in distraction, whereas step sequence duration, ipsilateral coupling-variation, forelimb stand, forelimb duty cycle, hindlimb swing duration, hindlimb swing speed, and number of forelimb slips recovered to normal in distraction but not in contusion. Some of the behavioral outcomes, but not the others, were linearly correlated with the histological outcomes. In conclusion, walking deficits and recovery can be affected by the type of common traumatic SCI.</p>","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"13 ","pages":"1179069519869615"},"PeriodicalIF":0.0,"publicationDate":"2019-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519869615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41202958","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: 12
Discovering Conserved Properties of Brain Organization Through Multimodal Integration and Interspecies Comparison. 通过多模式整合和物种间比较发现大脑组织的保守性
Journal of Experimental Neuroscience Pub Date : 2019-07-09 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519862047
Ben D Fulcher
{"title":"Discovering Conserved Properties of Brain Organization Through Multimodal Integration and Interspecies Comparison.","authors":"Ben D Fulcher","doi":"10.1177/1179069519862047","DOIUrl":"10.1177/1179069519862047","url":null,"abstract":"<p><p>The primate cerebral cortex is broadly organized along hierarchical processing streams underpinned by corresponding variation in the brain's microstructure and interareal connectivity patterns. Fulcher et al. recently demonstrated that a similar organization exists in the mouse cortex by combining independent datasets of cytoarchitecture, gene expression, cell densities, and long-range axonal connectivity. Using the T1w:T2w magnetic resonance imaging map as a common spatial reference for data-driven comparison of cortical gradients between mouse and human, we highlighted a common hierarchical expression pattern of numerous brain-related genes, providing new understanding of how systematic structural variation shapes functional specialization in mammalian brains. Reflecting on these findings, here we discuss how open neuroscience datasets, combined with advanced neuroinformatics approaches, will be crucial in the ongoing search for organization principles of brain structure. We explore the promises and challenges of integrative studies and argue that a tighter collaboration between experimental, statistical, and theoretical neuroscientists is needed to drive progress further.</p>","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":"1179069519862047"},"PeriodicalIF":0.0,"publicationDate":"2019-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46720124","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: 0
Synchronous Interactions Foster Empathy 同步互动培养同理心
Journal of Experimental Neuroscience Pub Date : 2019-07-01 DOI: 10.1177/1179069519865799
Jonathan Levy, R. Feldman
{"title":"Synchronous Interactions Foster Empathy","authors":"Jonathan Levy, R. Feldman","doi":"10.1177/1179069519865799","DOIUrl":"https://doi.org/10.1177/1179069519865799","url":null,"abstract":"Despite growing interest in the neuroscience of empathy, very little is known about the developmental processes that foster the neural maturation of an empathic response. Here, we suggest that the synchronous interaction shapes and fosters the ability to empathize with others. We argue that this intriguing relationship between synchrony and empathy expands beyond the mother-child relationship to social relationships in general. It will be important to further explore this relationship in more social settings and to probe the biological mechanisms, which may underlie it. Advancing research on the relationship between these two social processes may support the work of practitioners, psychologists, and educators in moderating the devastating outcomes of mental disorders and promoting social maturity and growth.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519865799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42101374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Anti-Aggregation Property of Allicin by In Vitro and Molecular Docking Studies 大蒜素抗聚集性的体外及分子对接研究
Journal of Experimental Neuroscience Pub Date : 2019-07-01 DOI: 10.1177/1179069519866185
Suresh Kumar, Shivani Kumar, H. Ram
{"title":"Anti-Aggregation Property of Allicin by In Vitro and Molecular Docking Studies","authors":"Suresh Kumar, Shivani Kumar, H. Ram","doi":"10.1177/1179069519866185","DOIUrl":"https://doi.org/10.1177/1179069519866185","url":null,"abstract":"Amyloidogenesis is the process in which amyloid beta (Aβ) peptide aggregation results in plaque formation in central nervous system (CNS) are associated with many neurological diseases such as Alzheimer’s disease. The peptide aggregation initiated from peptide monomers results in formation of dimers, tetramers, fibrils, and protofibrils. The ability of allicin, a lipid-soluble volatile organosulfur biological compound, present in freshly crushed garlic (Allium sativum L.) to inhibit fibril formation by the Aβ peptide in vitro was investigated in the present study. Inhibition of fibrillogenesis was measured by a Thioflavin T (ThT) fluorescence assay and visualized by transmission electron microscopy (TEM). The molecular interaction between allicin and Aβ peptide was also demonstrated by in silico studies. The results show that allicin strongly inhibited Aβ fibrils by 97% at 300 µM, compared with control (Aβ only) (P < .001). These results were further validated by visual of fibril formation by transmission microscopy and molecular interaction of amyloid peptide with allicin by molecular docking. Aβ forms favourable hydrophobic interaction with Ile32, Met35, Val36, and Val39, and oxygen of allicin forms hydrogen bond with the amino acid residue Lys28. Allicin anti-amyloidogenic property suggests that this naturally occurring compound may have potential to ameliorate and prevent Alzheimer’s disease.","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519866185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47913087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Adult Neurogenesis and the Promise of Adult Neural Stem Cells. 成体神经发生和成体神经干细胞的前景。
Journal of Experimental Neuroscience Pub Date : 2019-06-27 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519856876
Hiyaa S Ghosh
{"title":"Adult Neurogenesis and the Promise of Adult Neural Stem Cells.","authors":"Hiyaa S Ghosh","doi":"10.1177/1179069519856876","DOIUrl":"https://doi.org/10.1177/1179069519856876","url":null,"abstract":"<p><p>The adult brain, even though largely postmitotic, is now known to have dividing cells that can make both glia and neurons. Of these, the precursor cells that have the potential to make new neurons in the adult brain have attracted great attention from researchers, anticipating their therapeutic potential for neurodegenerative conditions. In this review, I will focus on adult neurogenesis, from the perspective of the overall neurogenic potential in the adult brain, current understanding of the 'adult neural stem cell', and the importance of <i>niche</i> as a decisive factor for neurogenesis under homeostasis and pathologic conditions.</p>","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"13 ","pages":"1179069519856876"},"PeriodicalIF":0.0,"publicationDate":"2019-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519856876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37404714","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: 34
What Is Excitation/Inhibition and How Is It Regulated? A Case of the Elephant and the Wisemen. 什么是兴奋/抑制?它是如何调节的?大象和智者的故事。
Journal of Experimental Neuroscience Pub Date : 2019-06-23 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519859371
Hai-Yan He, Hollis T Cline
{"title":"What Is Excitation/Inhibition and How Is It Regulated? A Case of the Elephant and the Wisemen.","authors":"Hai-Yan He,&nbsp;Hollis T Cline","doi":"10.1177/1179069519859371","DOIUrl":"https://doi.org/10.1177/1179069519859371","url":null,"abstract":"<p><p>The balance between excitation and inhibition in neuronal circuits has drawn more and more attention in recent years, due to its proposed multifaceted functions in the normal neural circuit as well as its potential roles in the etiology of many neurological disorders. Here, we discuss the importance of clearly defining excitation/inhibition by experimental measurements and the implications of some recent studies to our understanding of the regulation of excitation/inhibition at the neuronal level.</p>","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"13 ","pages":"1179069519859371"},"PeriodicalIF":0.0,"publicationDate":"2019-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519859371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37377801","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: 33
Potential Mechanisms Driving Mitochondrial Motility Impairments in Developing Iron-Deficient Neurons. 发育中缺铁神经元线粒体运动障碍的潜在机制
Journal of Experimental Neuroscience Pub Date : 2019-06-20 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519858351
Thomas W Bastian
{"title":"Potential Mechanisms Driving Mitochondrial Motility Impairments in Developing Iron-Deficient Neurons.","authors":"Thomas W Bastian","doi":"10.1177/1179069519858351","DOIUrl":"https://doi.org/10.1177/1179069519858351","url":null,"abstract":"<p><p>Brain development is highly demanding energetically, requiring neurons to have tightly regulated and highly dynamic metabolic machinery to achieve their ultimately complex cellular architecture. Mitochondria are the main source of neuronal adenosine 5'-triphosphate (ATP) and regulate critical neurodevelopmental processes including calcium signaling, iron homeostasis, oxidative stress, and apoptosis. Metabolic perturbations during critical neurodevelopmental windows impair neurological function not only acutely during the period of rapid growth/development, but also in adulthood long after the early-life insult has been rectified. Our laboratory uses iron deficiency (ID), the most common nutrient deficiency, as a model of early-life metabolic disruptions of neuronal metabolism because iron has a central role in mitochondrial function. Recently, we published that ID reduces hippocampal neuronal dendritic mitochondrial motility and size. In this commentary, we delve deeper into speculation about potential cellular mechanisms that drive the effects of neuronal ID on mitochondrial dynamics and quality control pathways. We propose that understanding the basic cellular biology of how mitochondria respond and adapt to ID and other metabolic perturbations during brain development may be a key factor in designing strategies to reduce the risk of later-life psychiatric, cognitive, and neurodegenerative disorders associated with early-life ID.</p>","PeriodicalId":15817,"journal":{"name":"Journal of Experimental Neuroscience","volume":"13 ","pages":"1179069519858351"},"PeriodicalIF":0.0,"publicationDate":"2019-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519858351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37377799","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: 3
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