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Translational models of stress and resilience: An applied neuroscience methodology review

neuroscience Applied 2024年 3卷

作者： Albayrak, Zeynep Seda Vaz, Andreia Bordes, Joeri Ünlü, Selen Sep, Milou S.C. Vinkers, Christiaan H. Pinto, Luisa Yapici-Eser, Hale Koç University Hospital Department of Child and Adolescent Psychiatry Istanbul Turkey Koç University Graduate School of Health Sciences Neuroscience PhD Program Koç University Istanbul Turkey Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho Campus de Gualtar Braga 4710-057 Portugal ICVS/3B's–PT Government Associate Laboratory Braga 4710-057 Portugal Bn'ML Behavioral and Molecular Lab Campus de Gualtar Braga 4710-057 Portugal Neurocentre Magendie INSERM 1215 Université de Bordeaux Bordeaux France Koç University School of Medicine İstanbul Turkey Department of Psychiatry Amsterdam University Medical Centers Location Vrije Universiteit Amsterdam Netherlands GGZ InGeest Mental Health Care Amsterdam Netherlands Amsterdam Neuroscience Mood Anxiety Psychosis Sleep & Stress Program Amsterdam Netherlands Amsterdam Public Health Mental Health Program Amsterdam Netherlands Department of Psychiatry and Department of Anatomy and Neurosciences Amsterdam University Medical Center Location VUMC Amsterdam Netherlands Academic Working Place Depression GGZ InGeest Amsterdam Netherlands Amsterdam Neuroscience (Mood Anxiety Psychosis Stress & Sleep Program) and Amsterdam Public Health (Mental Health Program) Research Institutes Amsterdam Netherlands Koç University School of Medicine Department of Psychiatry İstanbul Turkey

Stress, encompassing psychological, physical, and physiological challenges, is an important factor affecting an individual's well-being and potentially leading to psychiatric, neurodegenerative, immune, and metabolic disorders. However, not everyone exposed to stress develops these conditions, highlighting the concept of resilience. Resilience is a dynamic process categorized into four dimensions: pre-existing resilience capacity, ongoing resilience processes, post-stress resilience outcomes, and recovery from psychopathologies. These dimensions involve genomic, cellular, and systemic interactions influenced by genetic factors, early life experiences, adult life experiences in addition to community/environmental factors, and health behaviors. The biological response to stress encompasses endocrine, autonomic, immunological, and behavioral components, modulated by stressor characteristics and individual traits. Due to the limitations in studying stress and resilience in humans, translational models using rodents and cell cultures are essential. Rodent models include acute, chronic, and traumatic stress paradigms, aiding the study of stress-related behavioral and molecular outcomes. Additionally, early life stress models, such as prenatal stress and maternal separation, provide insights into developmental impacts. In this review, first, rodent models for lifelong stress exposure will be summarized considering their validity, advantages, and limitations. Subsequently, an overview of models designed to enhance resilience capacity and process in rodents, and later the behavioral models employed to study the outcomes of resilience will be given. Lastly, the focus will be shifted to cell culture and iPSCs models. Finally, future considerations focused on improving translational models used to study stress and resilience will be discussed. It is aimed to provide an overview of designs for translational stress and resilience models to access more effective translational biom

关键词： Acute stress Behavior Chronic stress Resilience Rodent Stress

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MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice

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Molecular therapy. Nucleic acids 2023年 32卷 144-160页

作者： Tai-Heng Chen Shih-Hsin Chang Yu-Fu Wu Ya-Ping Yen Fang-Yu Hsu Yen-Chung Chen Yang Ming Ho-Chiang Hsu Yi-Ching Su Sheng-Tang Wong Jui-Hung Hung Shih-Hwa Chiou Yuh-Jyh Jong Jun-An Chen PhD Program in Translational Medicine Kaohsiung Medical University Kaohsiung 80708 and Academia Sinica Taipei 11529 Taiwan. Institute of Molecular Biology Academia Sinica Taipei 11529 Taiwan. Department of Pediatrics Kaohsiung Medical University Kaohsiung 80708 Taiwan. School of Post-Baccalaureate Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Neuroscience Program of Academia Sinica Academia Sinica Taipei 11529 Taiwan. Department of Computer Science National Yang Ming Chiao Tung University Hsinchu 30093 Taiwan. Institute of Pharmacology School of Medicine National Yang Ming Chiao Tung University Taipei 11221 Taiwan. Innovative Cellular Therapy Center Department of Medical Research Taipei Veterans General Hospital Taipei 11217 Taiwan. Department of Laboratory Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Translational Research Center of Neuromuscular Diseases Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung 80708 Taiwan. Graduate Institute of Clinical Medicine College of Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung 80708 Taiwan. Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu 30093 Taiwan.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.

关键词： ASO MT: Non-coding RNAs MiR34 SMA biomarker microRNA nusinersen spinal muscular atrophy

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srp54 promotes motor neuron development and is required for motility in zebrafish

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neuroscience 2025年 579卷 24-34页

作者： Nikaela Losievski Pooja Kamath Ashley Fox Natalie M Aloi Megan C Baird Amy Everest Thomas L Gallagher Sharon L Amacher Stephen J Kolb Department of Neurology The Ohio State University Wexner Medical Center Columbus OH USA Neuroscience Graduate Program The Ohio State University Columbus OH USA. Department of Neurology The Ohio State University Wexner Medical Center Columbus OH USA. Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus OH USA. English Department PhD Program in Writing Rhetoric and Literacy The Ohio State University Columbus OH USA. Department of Molecular Genetics The Ohio State University Columbus OH USA. Department of Molecular Genetics The Ohio State University Columbus OH USA Center for RNA Biology The Ohio State University Columbus OH USA. Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus OH USA Center for RNA Biology The Ohio State University Columbus OH USA Center for Muscle Health and Neuromuscular Disorders The Ohio State University and Nationwide Children's Hospital Columbus OH USA. Center for Muscle Health and Neuromuscular Disorders The Ohio State University and Nationwide Children's Hospital Columbus OH USA. Electronic address: Stephen.Kolb@osumc.edu.

The signal recognition particle (SRP) is a highly conserved ribonucleoprotein (RNP) that translocates a subset of secreted and integral membrane proteins to the endoplasmic reticulum for proper localization. The most conserved SRP protein component, SRP54, has been implicated in the molecular etiology of spinal muscular atrophy (SMA). A key feature of SMA is the selective loss of motor neurons; however, the mechanism underlying this selectivity is unknown. SMA arises from deficient levels of the ubiquitously expressed Survival of Motor Neuron (SMN) protein. SMN is proposed to assemble the SRP, and SMN deficiency in SMA may attenuate SRP function and contribute to motor neuron death in patients. Using zebrafish embryos homozygous for a srp54 nonsense mutation (srp54), we investigated the requirement of Srp54 protein in motor axon development. The first grossly distinguishable phenotype observed in srp54 embryos was reduced motility at 30 h postfertilization (hpf). Additionally, we detected reduced length and branching of caudal primary motor axons in srp54 embryos compared to srp54 and srp54 siblings at 30 hpf, suggesting that defective motor neurons may contribute to the observed immotility. We also examined additional neural, secretory, and migratory cell types at 30 hpf to assess whether motor neurons are especially vulnerable to Srp54 deficiency. Of the cell types evaluated, only the hatching gland had distinct expression pattern alterations in srp54 embryos at this developmental stage. Our findings suggest that Srp54 deficiency results in motor neuron developmental defects and support the hypothesis that SRP54 may influence motor neuron selectivity in SMA.

关键词： Central nervous system Hatching gland Neurodevelopment Signal recognition particle Spinal muscular atrophy

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BIOS-02. RECAPITULATE TUMOR DIVERSION AND SPATIAL PATTERNING IN GLIOBLASTOMA BACKGROUND

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Neuro-Oncology 2023年第SUPPLEMENT_5期25卷 v20-v20页

作者： Lo, Wei-Lun Khoa, Hoang Dang Ta Chuang, Jian-Ying Division of Neurosurgery Shuang-Ho Hospital New Taipei City New Taipei Taiwan (Republic of China) PhD Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei Taipei Taiwan (Republic of China) International Master Program in Medical Neuroscience Taipei Medical University Taipei Taiwan (Republic of China)

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Symmetries and synchronization from whole-neural activity in C. elegans connectome: Integration of functional and structural networks

arXiv

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arXiv 2024年

作者： Avila, Bryant Augusto, Pedro Phillips, David Gili, Tommaso Zimmer, Manuel Makse, Hernán A. Levich Institute and Physics Department City College of New York New YorkNY10031 United States Vienna Austria Vienna Biocenter PhD Program Doctoral School the University of Vienna Medical University of Vienna Vienna Austria Mechanical Engineering Department University of New Mexico AlbuquerqueNM87131 United States Networks Unit IMT Scuola Alti Studi Lucca Piazza San Francesco 15 Lucca55100 Italy Department of Radiology Neuroradiology Service Memorial Sloan Kettering Cancer Center New YorkNY10065 United States CUNY Neuroscience Graduate Center City University of New York New YorkNY10031 United States

Understanding the dynamical behavior of complex systems from their underlying network architectures is a long-standing question in complexity theory. Therefore, many metrics have been devised to extract network features like motifs, centrality, and modularity measures. It has previously been proposed that network symmetries are of particular importance since they are expected to underly the synchronization of a system’s units, which is ubiquitously observed in nervous system activity patterns. However, perfectly symmetrical structures are difficult to assess in noisy measurements of biological systems, like neuronal connectomes. Here, we devise a principled method to infer network symmetries from combined connectome and neuronal activity data. Using nervous system-wide population activity recordings of the *** backward locomotor system, we infer structures in the connectome called fibration symmetries, which can explain which group of neurons synchronize their activity. Our analysis suggests functional building blocks in the animal’s motor periphery, providing new testable hypotheses on how descending interneuron circuits communicate with the motor periphery to control behavior. Our approach opens a new door to exploring the structure-function relations in other complex systems, like the nervous systems of larger animals. © 2024, CC BY.

关键词： Synchronization

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Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update

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Journal of biomedical science 2023年第1期30卷 83页

作者： Li-Kai Huang Yi-Chun Kuan Ho-Wei Lin Chaur-Jong Hu PhD Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University No. 291 Zhong Zheng Road Zhonghe District New Taipei City Taiwan. Taipei Neuroscience Institute Taipei Medical University New Taipei City Taiwan. Dementia Center and Department of Neurology Shuang-Ho Hospital Taipei Medical University New Taipei City Taiwan. Department of Neurology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. Department of Biomedical Engineering National Taiwan University Taipei Taiwan. School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. PhD Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University No. 291 Zhong Zheng Road Zhonghe District New Taipei City Taiwan. chaurjongh@tmu.edu.tw. Taipei Neuroscience Institute Taipei Medical University New Taipei City Taiwan. chaurjongh@tmu.edu.tw. Dementia Center and Department of Neurology Shuang-Ho Hospital Taipei Medical University New Taipei City Taiwan. chaurjongh@tmu.edu.tw. Department of Neurology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. chaurjongh@tmu.edu.tw.

Alzheimer's disease (AD) is the leading cause of dementia, presenting a significant unmet medical need worldwide. The pathogenesis of AD involves various pathophysiological events, including the accumulation of amyloid and tau, neuro-inflammation, and neuronal injury. Clinical trials focusing on new drugs for AD were documented in 2020, but subsequent developments have emerged since then. Notably, the US-FDA has approved Aducanumab and Lecanemab, both antibodies targeting amyloid, marking the end of a nearly two-decade period without new AD drugs. In this comprehensive report, we review all trials listed in ***, elucidating their underlying mechanisms and study designs. Ongoing clinical trials are investigating numerous promising new drugs for AD. The main trends in these trials involve pathophysiology-based, disease-modifying therapies and the recruitment of participants in earlier stages of the disease. These trends underscore the significance of conducting fundamental research on pathophysiology, prevention, and intervention prior to the occurrence of brain damage caused by AD.

关键词： Alzheimer disease Anti-amyloid Anti-tau Clinical trials Cognitive enhancement Neuroinflammation Neuroprotection

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Differences in bipolar disorder type I and type II exposed to childhood trauma: A retrospective cohort study

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Journal of Affective Disorders Reports 2025年 19卷 100869-100869页

作者： Guillen-Burgos, Hernán F Gálvez-Flórez, Juan F Moreno-Lopez, Sergio Kwan, Angela T.H. Gomez, Oscar González-Haddad, Gerardo McIntyre, Roger S. Universidad Simon Bolivar Centro de Investigaciones en Ciencias de la Vida Center for Clinical and Translational Research Barranquilla Colombia Faculty of Medicine Center for Clinical and Translational Research Universidad El Bosque Bogotá D.C. Colombia Department of Psychiatry and Mental Health PhD Program of Neuroscience Hospital Universitario San Ignacio Pontificia Universidad Javeriana Bogotá D.C. Colombia School of Medicine Universidad de Los Andes Bogotá D.C. Colombia Faculty of Medicine University of Ottawa Ottawa K1H 8L1 ON Canada Division of Alcohol Drugs and Addiction McLean Hospital Harvard Medical School Boston MA United States Department of Psychiatry University of Toronto Toronto M5T 1R8 ON Canada

Background: Childhood trauma (CT) exposure is associated with a more pernicious course in bipolar disorder (BD). However, few studies have reported differences between BD I and BD II regarding CT exposure. We explore the differences in the CT trajectories in bipolar disorders. Methods: A retrospective cohort study of individuals with BD (BD I = 73 vs BD II = 73) was carried out. Early age at onset (EAO) and suicide ideation/behavior were used as severity outcomes. Timespan between EAO and treatment was documented and the associations between CT and comorbid alcohol used disorder (AUD), anxiety disorders (AD), and post-traumatic stress disorder (PTSD) were also described. Univariate, bivariate analyses, and a Poisson regression model with bootstrap resampling were used. Results: Higher scores of CT, physical abuse (PA), and sexual abuse (SA) were statistically significant for BD II than BD I (p < 0.001, p = 0.048, p < 0.001, respectively). Early age at onset, suicide ideation/behavior and treatment delay were associated with CT in both BD I and BD II. However, AUD and PTSD showed association with CT only for BD I. Limitations: Sample size, non-comparison control group, and recall bias. Conclusions: There are differences in CT subtype exposure between BD I and BD II with regards to early age onset, suicide ideation/behavior, delayed time to treatment, and comorbid mental disorders. These results claim for early access to strategies such as CT exposure screening in individuals with BD to detect possible pernicious course and improve the quality of life and clinical outcomes. © 2024

关键词： Bipolar disorder Childhood trauma Early age onset Mental comorbidities Suicide ideation/behavior Treatment delay

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Construction of dual Z-scheme Ag3VO4–BiVO4/InVO4 photocatalysts using vanadium source from spent catalysts for contaminated water treatment and bacterial inactivation

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Chemosphere 2024年 363卷 142746页

作者： Lee, Kuen-Chan Hsu, Shih-Chieh Huang, Jen-Hsien Wang, Kuan-Syun Pang, Wei Kong Hu, Chih-Wei Jiang, Yi-Jhen Cho, Er-Chieh Weng, Huei Chu Liu, Ting-Yu Department of Science Education National Taipei University of Education No. 134 Sec. 2 Heping E. Road Da-an District Taipei City106 Taiwan PhD Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University 250 Wuxing Street Taipei City110 Taiwan Department of Chemical and Materials Engineering Tamkang University No. 151 Yingzhuan Road Tamsui District New Taipei City25137 Taiwan Department of Green Material Technology Green Technology Research Institute CPC Corporation No.2 Zuonan Rd. Nanzi District Kaohsiung City81126 Taiwan Department of Materials Engineering Ming Chi University of Technology New Taipei City243303 Taiwan Faculty of Engineering Institute for Superconducting & Electronic Materials University of Wollongong WollongongNSW Australia National Synchrotron Radiation Research Center 101 Hsin-Ann Road Hsinchu Science Park Hsinchu30076 Taiwan School of Pharmacy College of Pharmacy Taipei Medical University 250 Wuxing Street Taipei City110 Taiwan Department of Mechanical Engineering Chung Yuan Christian University No. 200 Chungpei Road Chungli District Taoyuan City32023 Taiwan Department of Chemical Engineering and Materials Science Yuan Ze University Taoyuan City32003 Taiwan College of Engineering & Center for Sustainability and Energy Technologies Chang Gung University Taoyuan33302 Taiwan

Vanadate-based photocatalysts have recently attracted substantial attention owing to their outstanding photocatalytic activity for degrading organic pollutants and generating energy via photocatalytic processes. However, the relatively high price of vanadium has hindered the development of vanadate-based photocatalysts for various applications. Spent catalysts obtained from oil refineries typically contain a significant quantity of vanadium, making them valuable for recovery and utilization as precursors for the production of high-value-added photocatalysts. In this study, we transformed the V present in spent catalysts produced by the petrochemical industry into ternary vanadate-based photocatalysts [BiVO4/InVO4/Ag3VO4 (BVO/IVO/AVO, respectively)] designed for water remediation. The ternary composites revealed an enhanced photocatalytic capability, which was 1.42 and 5.1 times higher than those of the binary BVO/IVO and pristine AVO due to the facilitated charge separation. The ternary photocatalysts not only effectively treated wastewater containing various organic dyes, such as methylene blue (MB), rhodamine 6G (R6G), and brilliant green (BG), but also exhibited remarkable photocatalytic performance in the degradation of antibiotics, reduction of Cr(VI), and bacterial inactivation. This paper proposes a feasible route for recycling industrial waste as a source of vanadium to produce highly efficient vanadate-based photocatalysts. © 2024 Elsevier Ltd

关键词： Water pollution

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Correction to: ALS Cognitive Behavioral Screen‑Phone Version (ALS‑CBS™‑PhV): norms, psychometrics, and diagnostics in an Italian population sample

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Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2023年第1期44卷 419页

作者： Edoardo Nicolò Aiello Antonella Esposito Ilaria Giannone Lorenzo Diana Susan Woolley Jennifer Murphy Georgia Christodoulou Lucio Tremolizzo Nadia Bolognini Ildebrando Appollonio PhD Program in Neuroscience School of Medicine and Surgery University of Milano-Bicocca Monza Italy. e.aiello5@campus.unimib.it. Department of Psychology University of Milano-Bicocca Milan Italy. PhD Program in Neuroscience School of Medicine and Surgery University of Milano-Bicocca Monza Italy. Sutter Pacific Medical Foundation San Francisco CA USA. Biogen Cambridge MA USA. Institute for Health Promotion and Disease Prevention Research Keck School of Medicine University of Southern California Los Angeles CA USA. Neurology Section School of Medicine and Surgery University of Milano-Bicocca Monza Italy. Neuropsychological Laboratory IRCCS Istituto Auxologico Italiano Milan Italy.

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Correction to: Metachromatic leukodystrophy with late adult-onset: diagnostic clues and differences from other genetic leukoencephalopathies with dementia

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Journal of neurology 2021年第5期268卷 1977-1979页

作者： Chiara Benzoni Marco Moscatelli Silvia Fenu Anna Venerando Ettore Salsano Unit of Rare Neurodegenerative and Neurometabolic Diseases Fondazione IRCCS Istituto Neurologico Carlo Besta Via Celoria 11 Milan 20133 Italy. chiara.benzoni1@unimi.it. Unit of Neuroradiology Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy. Unit of Rare Neurodegenerative and Neurometabolic Diseases Fondazione IRCCS Istituto Neurologico Carlo Besta Via Celoria 11 Milan 20133 Italy. Unit of Medical Genetics and Neurogenetics Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy. Neuroscience PhD Program University of Milano-Bicocca Monza Italy.

The original version of this article unfortunately contained a mistake.

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