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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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Reward monitoring in the frontopolar cortex of macaques

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Scientific Reports 2025年第1期15卷 1-14页

作者： Ferrucci, Lorenzo Ceccarelli, Francesco Londei, Fabrizio Arena, Giulia Elyasizad, Leyla Nougaret, Simon Genovesio, Aldo Department of Physiology and Pharmacology Sapienza University of Rome Piazzale Aldo Moro 5 Rome 00185 Italy Institute of Biochemistry and Cell Biology (IBBC) National Research Council of Italy (CNR) Via Ramarini 32 Monterotondo Scalo Rome 00015 Italy Behavioral Neuroscience PhD Program Sapienza University Rome Italy Institut de Neurosciences de La Timone UMR 7289 Centre National de La Recherche Scientifique and Aix-Marseille Universite Marseille France Department of Pharmaceutical Sciences University of Piemonte Orientale Novara Italy

Reward processing involves several prefrontal cortex areas, enabling individuals to learn from behavioral outcomes and shape decisions. However, the role of the frontopolar cortex (FPC) in these processes remains unclear due to limited single-neuron research. In this study, we recorded neural activity from the FPC of two macaques performing a fast-learning task, the object-in-place reward task, which examined how reward size affects learning. Results showed that FPC feedback monitoring activity extends to the value of specific choices. Moreover, once the association between scenes and reward had been learned, FPC neural activity before choice reflected the future animal’s behavior to stay or to switch on their previous behavioral strategy, i.e., to choose the same target or the other one. These results suggest that FPC neurons integrated information for action monitoring and later reprocessed it to decide the best behavioral strategy to adopt, determining whether to maintain or change the action plan. © The Author(s) 2025.

关键词： Area 10 Explore-exploit Frontal pole Learning Monkey Reward

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Atlas of Gray Matter Volume Differences Across Psychiatric Conditions: A Systematic Review With a Novel Meta-Analysis That Considers Co-Occurring Disorders

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Biological Psychiatry 2025年

作者： Fortea, Lydia Ortuño, Maria De Prisco, Michele Oliva, Vincenzo Albajes-Eizagirre, Anton Fortea, Adriana Madero, Santiago Solanes, Aleix Vilajosana, Enric Yao, Yuanwei Del Fabro, Lorenzo Solé, Eduard Verdolini, Norma Farré-Colomés, Alvar Serra-Blasco, Maria Picó-Pérez, Maria Lukito, Steve Wise, Toby Carlisi, Christina Arnone, Danilo Kempton, Matthew J. Hauson, Alexander Omar Wollman, Scott Soriano-Mas, Carles Rubia, Katya Norman, Luke Fusar-Poli, Paolo Mataix-Cols, David Valentí, Marc Via, Esther Cardoner, Narcis Solmi, Marco Zhang, Jintao Pan, Pinglei Shin, Jae Il Fullana, Miquel A. Vieta, Eduard Radua, Joaquim Institut d'Investigacions Biomèdiques August Pi I Sunyer Barcelona Spain Department of Medicine University of Barcelona Institute of Neuroscience Barcelona Spain Centro de Investigación Biomédica en Red de Salud Mental Instituto de Salud Carlos III Madrid Spain Bipolar and Depressive Disorders Unit Hospital Clínic Barcelona Spain Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy Psychiatric and Psychology Service Hospital Clínic Barcelona Spain Schizophrenia Unit Hospital Clínic Barcelona Spain Department of Psychology The University of Hong Kong Hong Kong Department of Systems Neuroscience University Medical Center Hamburg-Eppendorf Hamburg Germany Department of Pathophysiology and Transplantation University of Milan Milan Italy Local Health Unit Umbria 1 Department of Mental Health Mental Health Center of Perugia Perugia Italy Department of Addictive Behaviour and Addiction Medicine Central Institute of Mental Health Medical Faculty of Mannheim Heidelberg University Mannheim Germany eHealth ICOnnecta't Program and Psycho-Oncology Service Institut Català d'Oncologia L'Hospitalet de Llobregat Spain Psycho-oncology and Digital Health Group Health Services Research in Cancer Institut d'Investigació Biomèdica de Bellvitge L'Hospitalet del Llobregat Spain Live and Health Sciences Research Institute University of Minho Braga Portugal ICVS/3B's PT Government Associate Laboratory Guimarães Braga Portugal Departamento de Psicología Básica Universitat Jaume I Castelló de la Plana Spain Department of Child and Adolescent Psychiatry Institute of Psychology Psychiatry and Neuroscience King's College London London United Kingdom Department of Neuroimaging Institute of Psychiatry Psychology & Neurosciences King's College London London United Kingdom Division of Psychology and Language Sciences University College London London United Kingdom Centre for Affective Disorders Psychological Medicine King's College London Londo

Background: Regional gray matter volume (GMV) differences between individuals with mental disorders and comparison participants may be confounded by co-occurring disorders. To disentangle disorder-specific GMV correlates, we conducted a large-scale multidisorder meta-analysis using a novel approach that explicitly models co-occurring disorders. Methods: We systematically reviewed voxel-based morphometry studies indexed in PubMed and Scopus up to January 2023 that compared adults with major mental disorders (anorexia nervosa, schizophrenia spectrum, anxiety, bipolar, major depressive, obsessive-compulsive, and posttraumatic stress disorders plus attention-deficit/hyperactivity, autism spectrum, and borderline personality disorders) with comparison participants. Two authors independently extracted data and assessed quality using the Newcastle-Ottawa Scale. We derived GMV correlates for each disorder using: 1) a multidisorder meta-analysis that accounted for all co-occurring mental disorders simultaneously and 2) separate standard meta-analyses for each disorder in which co-occurring disorders were ignored. We assessed the alterations’ extent, intensity (effect size), and specificity (interdisorder correlations and transdiagnostic alterations) for both approaches. Results: We included 433 studies (499 datasets) involving 19,718 patients and 16,441 comparison participants (51% female, ages 20–67 years). We provide GMV correlate maps for each disorder using both approaches. The novel approach, which accounted for co-occurring disorders, produced GMV correlates that were more focal and disorder specific (less correlated across disorders and fewer transdiagnostic abnormalities). Conclusions: This work offers the most comprehensive atlas of GMV correlates across major mental disorders. Modeling co-occurring disorders yielded more specific correlates, supporting this approach's validity. The atlas NIfTI maps are available online. © 2024 Society of Biological Psychiatry

关键词： Anxiety disorders Comorbidity Gray matter volume Major depressive disorder Meta-analysis Psychiatric conditions

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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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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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IMPACT OF PSYCHOSIS SUBTYPES ON DISEASE PROGRESSION IN ALZHEIMER’S DISEASE: NONLINEAR MIXED EFFECT (NLME) MODELLING OF ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE (ADNI2) DATA

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Alzheimer's & Dementia 2017年第7期13卷 P1064-P1065页

作者： Fabrizia D'Antonio Suzanne Reeves Yucheng Sheng Carlo de Lena Robert J. Howard Julie Bertrand Sapienza University of Rome Rome Italy University College London London United Kingdom PhD Program in Behavioral Neuroscience Sapienza University of Rome Rome Italy Inserm University Paris Diderot Paris France

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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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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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