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Brain-derived neurotrophic factor in main neurodegenerative diseases

Neural Regeneration Research 2023年第3期18卷 554-555页

作者： Serena Camuso Sonia Canterini Division of Neuroscience Department of PsychologyUniversity La SapienzaRomeItaly PhD Program in Behavioral Neuroscience Sapienza University of RomeRomeItaly

Discovered in pig brains in 1982,the brain-derived neurotrophic factor(BDNF)is one of the most studied and characterized neurotrophins in the central nervous *** recent years,BDNF has received considerable attention for its importance in the development and maintenance of normal brain *** is because BDNF plays an important role in crucial functions of the nervous system,such as the survival,differentiation,and maturation of neurons and glial cells as well as the actions of neuroprotection in adverse conditions,such as glutamatergic overstimulation,cerebral ischemia,hypoglycemia,and neurotoxicity(Kowiański et al.,2018).

关键词： stimulation diseases

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Genome-wide association analysis identifies APOE as a mitophagy modifier in Lewy body disease

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Alzheimer's and Dementia 2025年第4期21卷 e70198页

作者： Hou, Xu Heckman, Michael G. Fiesel, Fabienne C. Koga, Shunsuke Soto-Beasley, Alexandra I. Watzlawik, Jens O. Zhao, Jing Valentino, Rebecca R. Johnson, Patrick W. White, Launia J. Quicksall, Zachary S. Reddy, Joseph S. Bras, Jose Guerreiro, Rita Zhao, Na Bu, Guojun Dickson, Dennis W. Ross, Owen A. Springer, Wolfdieter Department of Neuroscience Mayo Clinic Jacksonville FL United States Division of Clinical Trials and Biostatistics Mayo Clinic Jacksonville FL United States Neuroscience PhD Program Mayo Clinic Graduate School of Biomedical Sciences Jacksonville FL United States Department of Quantitative Health Sciences Mayo Clinic Jacksonville FL United States Department of Neurodegenerative Science Van Andel Institute Grand Rapids MI United States Division of Psychiatry and Behavioral Medicine Michigan State University College of Human Medicine Grand Rapids MI United States

INTRODUCTION: Phosphorylated ubiquitin (p-S65-Ub) is generated during PINK1-PRKN mitophagy as a specific marker of mitochondrial damage. Despite the widespread deposition of p-S65-Ub in aged and diseased human brain, the genetic contribution to its accumulation remains unclear. METHODS: To identify novel mitophagy regulators, we performed a genome-wide association study using p-S65-Ub level as a quantitative trait in 1012 autopsy-confirmed Lewy body disease (LBD) samples. RESULTS: We identified a significant genome-wide association with p-S65-Ub for rs429358 (apolipoprotein E ε4 [APOE4]) and a suggestive association for rs6480922 (ZMIZ1). APOE4 was associated with higher p-S65-Ub levels and greater neuropathological burden. Functional validation in mouse and human induced pluripotent stem cell (iPSC) models confirmed APOE4-mediated mitophagy alterations. Intriguingly, ZMIZ1 rs6480922 was associated with lower p-S65-Ub levels, reduced neuropathological load, and increased brain weight, indicating a potential protective role. DISCUSSION: Our findings underscore the importance of mitochondrial quality control in LBD pathogenesis and nominate regulators that may contribute to disease risk or resilience. Highlights: p-S65-Ub levels were used as a quantitative marker of mitochondrial damage. A GWAS identified two genetic variants that modify mitophagy in LBD autopsy brain. APOE4 was associated with increased p-S65-Ub accumulation and neuropathology. APOE4 altered mitophagy via pathology-dependent and pathology-independent mechanisms. ZMIZ1 was linked to reduced p-S65-Ub and neuropathology indicative of protection. © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

关键词： autophagy GWAS mitochondria Parkin Parkinson's disease phosphorylated ubiquitin PINK1 PRKN ubiquitin ZMIZ1

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Social environment affects the vulnerability to adolescent-onset depression and determines antidepressant efficacy in a preclinical model

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neuroscience Applied 2023年 2卷

作者： N. Ciano Albanese A. Reccagni C. Barezzi F. Marsili S. Poggini I. Branchi Istituto Superiore di Sanità Center for Behavioral Sciences and Mental Health Rome Italy Sapienza University of Rome PhD program in Clinical-experimental Neuroscience and Psychiatry Rome Italy

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Social isolation in adolescence leads to different cognitive and emotional dysfunctions in males and females: a preclinical study

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neuroscience Applied 2022年 1卷

作者： N. Ciano Albanese A. Reccagni C. Barezzi S. Poggini I. Branchi Istituto Superiore di Sanità Center for Behavioral Sciences and Mental Health Rome Italy Sapienza University of Rome PhD program in Behavioral Neurosciences Rome Italy Sapienza University of Rome PhD program in Clinical-experimental Neuroscience and Psychiatry Rome Italy

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Different subjective experiences of the environment are associated to different fluoxetine treatment outcomes

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neuroscience Applied 2022年 1卷

作者： C. Delli Colli S. Poggini G. Matte Bon N. Ciano Albanese E. Castrén I. Branchi Istituto Superiore di Sanità Center for Behavioral Sciences and Mental Health Roma Italy Sapienza University of Rome PhD program in Behavioral Neuroscience Roma Italy Neuroscience Center University of Helsinki Helsinki Finland

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

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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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Network analysis of stress response vulnerability in a mouse model of major depressive disorder

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neuroscience Applied 2024年 3卷

作者： A. Viglione C. Delli Colli F. Marsili S. Poggini T.M. Milewki K.M. Mahach V. Manzi A. Poleggi J.P. Curley I. Branchi Istituto Superiore di Sanità Center for Behavioral Sciences and Mental Health Rome Italy Sapienza University of Rome PhD program in Pharmacology and Toxicology Rome Italy University of Texas at Austin Psychology Department Austin United States Istituto Superiore di Sanità Department of Cell Biology and Neuroscience Rome Italy

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Motor inhibition parameters are reflected in the kinetic and kinematic of gait initiation in a step version of the Stop Signal Task

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Gait & Posture 2022年 97卷 9-9页

作者： Fiori, L. Marc, I.B. Ramawat, S. Tatarelli, A. Varrecchia, T. Chini, G. Ranavolo, A. Draicchio, F. Pani, P. Ferraina, S. Brunamonti, E. Department of Physiology and Pharmacology Sapienza University of Rome Rome Italy PhD program in Behavioral Neuroscience Sapienza University of Rome Rome Italy Department of Occupational and Environmental Medicine Epidemiology and Hygiene INAIL Department of Human Neurosciences Sapienza University of Rome Rome Italy

IntroductionInteracting with a continuously changing environment may necessitate cancelling a programmed movement, such as a step, after an environmental change to avoid errors and possible falls. This cancellation is successful if it occurs during the few milliseconds from the Anticipatory Postural Adjustments (APA) that precede the step onset, a period in which the center of mass (CoM) and the center of pressure (CoP) can still be aligned. Here we studied the inhibition of steps by the means of Stop Signal Task (SST), a behavioral task matched with a theoretical model developed to study the behavioral and physiological correlates of simple response inhibition [1], e.g., pressing a button. Aim of the present work was investigating if and how the inhibition of a complex multi-effectors movement as in step, accomplishes the assumptions of the model developed for simpler movements and if it is they are reflected in the time evolution of CoM and CoP. Methods12 healthy subjects (age: 33.3±7.1 y; weight: 69.3±17 kg; height: 169.7±8.2 cm) were required to initiate 300 walks from a stationary position (Go trials; GT) in response to the onset of an ahead pointing arrow (Go signal) on a pc monitor, and to interrupt the movement when in 30% of the trials (Stop trials; ST), a road stop signal (Stop signal) replaced the arrow after a variable time, determined using a behavioral tracking staircase algorithm [2]. A stereo-photogrammetric motion analysis system (SMART-DX 6000: BTS) and eight dynamometer platforms (Kistler 9286B; Kistler) were used to detect the kinematic and dynamic parameters of gait initiation. Ad-hoc analysis algorithms were developed by the MATLAB software (R2019b 9.7; MathWorks) to track the time evolution of CoM and CoP trajectories and capture the related reaction times (RT) for GT, error stop trials (eST), and correct stop trials (cST), and to conduct the statistical analysis. ResultsFig. 1 displays the CoM (left upper panels) and CoP (left lower panels) t

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Time moderates the interplay between 5-HTTLPR and stress on depression risk – Gene x environment interaction as dynamic process

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neuroscience Applied 2022年 1卷

作者： C. Delli Colli M. Borgi S. Poggini F. Chiarotti F. Cirulli B.W.J.H. Penninx F. Benedetti B. Vai I. Branchi Sapienza University of Rome PhD program in Pharmacology and Toxicology- Department of Physiology and Pharmacology “Vittorio Erspamer” Roma Italy Istituto Superiore di Sanità Center for Behavioral Sciences and Mental Health Roma Italy Amsterdam UMC- Vrije Universiteit Department of Psychiatry Amsterdam Netherlands- The IRCCS San Raffaele Scientific Institute Psychiatry & Clinical Psychobiology- Division of Neuroscience Milano Italy

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P.861Gender-specific involvement of Methyl-CpG binding protein 2 in vulnerability to stress: evidence from a healthy cohort

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European Neuropsychopharmacology 2020年 40卷 S477-S478页

作者： Cosentino, L. Zidda, F. Witt, S. De Filippis, B. Flor, H. Istituto Superiore di Sanità Center for Behavioral Sciences and Mental Health Rome Italy Sapenza University of Roma PhD program in Behavioral Neuroscience Roma Italy Central Institute of Mental Health- Medical Faculty Mannheim- Heidelberg University Department of Cognitive and Clinical Neuroscience Mannheim Germany Central Institute of Mental Health- Medical Faculty Mannheim- Heidelberg University Department of Genetic Epidemiology in Psychiatry Mannheim Germany

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