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The need for complexity models in psychiatry: enactive approaches are knocking on the door of traditional psychiatry

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Revista Colombiana de psiquiatria (English ed.) 2023年第4期52卷 269页

作者： Hernando Santamaría-García Director Doctorado de Neurociencias Pontifica Universidad Javeriana de Colombia PhD Program of Neuroscience Editor general de la Revista Colombiana de Psiquiatría. Electronic address: hernando.santamaria@javeriana.edu.c.

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Fabrication of hyaluronic acid with graphene quantum dot as a dual drug delivery system for cancer therapy

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FlatChem 2024年 44卷

作者： Lin, Joseph Lin, Jung-Hua Yeh, Tseng-Yu Zheng, Jia-Huei Cho, Er-Chieh Lee, Kuen-Chan Department of Science Education National Taipei University of Education No.134 Sec. 2 Heping E. Rd. Da-an District Taipei City 106 Taiwan School of Pharmacy College of Pharmacy Taipei Medical University 250 Wuxing Street Taipei City 110 Taiwan Master Program in Clinical Genomics and Proteomics College of Pharmacy Taipei Medical University 250 Wuxing Street Taipei City 110 Taiwan Cancer Center Wan Fang Hospital Taipei Medical University 110 Taiwan PhD Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei City 110 Taiwan

With recent advancements in nanomedicine, there has been growing interest in developing drug delivery systems with multifunctional capabilities. In this study, we developed a novel dual drug delivery system by combining two drug carriers via positive and negative electrostatic interactions. First, we modified polyethyleneimine (PEI) with graphene quantum dots (GQDs) to create a positively charged particle (GPI) with high drug loading efficiency and good dispersibility. Second, we embedded the pyrenebutyric acid structure in hyaluronic acid (HA) through EDC/NHS cross-linking and used TAK-632 as the hydrophobic drug to create negatively charged particles (HANPs) with hydrogel-like properties and the CD44 receptor. After the two components were constructed, the increase in the particle charge and simultaneous delivery of both drugs synergistically enhanced the therapeutic effect of this strategy. Qualitative tests confirmed the successful synthesis of the drug carrier, while the potential of this system as a cancer treatment strategy was evaluated in HCT116 cancer cells (through MTT cell viability assays) and in vivo mice xenograft experiments. Our results demonstrated that the dual drug delivery system, HANPs(TAK)/GPI(DOX), had a significant inhibitory effect on the growth of cancer cells both in vitro and in vivo, suggesting that this system is a promising candidate for a new type of treatment. © 2024 Elsevier B.V.

关键词： Dual drug delivery system Electrostatic interaction Graphene quantum dots Hydrophobic drug

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Brain age estimation by structural MRI in superagers: a BrainAGE approach in elderly people with youthful episodic memory

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Alzheimer's & Dementia 2022年第S5期18卷

作者： Marta Garo Pascual Christian Gaser Bryan A Strange CIEN Foundation Queen Sofia Foundation Alzheimer Centre Madrid Spain Centre for Biomedical Technology Universidad Politecnica de Madrid Madrid Spain PhD Program in Neuroscience Autonoma de Madrid University Madrid Spain Jena University Jena Germany

Background Age-related episodic memory decline is not the only trajectory of healthy ageing. Superagers are the living proof that an 80yo can have the memory of a 50-60yo. We aim to estimate the biological brain age of superagers using the BrainAGE approach to understand the underlying ageing process. In the context of normal ageing, resistance refers to the avoidance of ageing effects and will translate into a deceleration of the ageing process, whereas resilience is the successful coping with age-related changes and will translate into a similar estimated brain age and chronological age. We tested these hypotheses in this study. Method A sample of 63 superagers (mean age 81.8 years ± 1.8 std, 60.3% women) and 55 age-matched controls (mean age 82.4 years ± 1.9 std, 63.6% women) from the Vallecas Project cohort in Madrid, Spain, were selected according to their episodic memory score in the Free and Cued Selective Reminding Test. Superagers scored at or above the mean value of a 50-56yo person, whereas controls scored within one standard deviation for their age. BrainAGE (“Brain Age Gap Estimation”) aggregates to a single value the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (Franke and Gaser 2019). The BrainAGE score was calculated for both groups as the difference between chronological age and estimated brain age. Positive values indicate an acceleration of the ageing process and negative values indicate a deceleration of the ageing process. Result The BrainAGE score of superagers was -0.5 years, showing that their estimated brain age is lower than their chronological age whereas the estimated brain age of the control group is similar to their chronological age. The difference in BrainAGE between the superager and the control group is significant ( p = 1x10 -6 ). This result indicates a deceleration in the brain ageing process of superagers compared to

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Ludwigia octovalvis (Jacq.) P.H. Raven extract improves memory performance in mice with chronic kidney disease

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Phytomedicine Plus 2024年第2期4卷 100556-100556页

作者： Wang, Hao-Wei Huang, Yi-Hsuan Tung, Hsiao-Jou Lin, Wei-Sheng Chiu, Hao-Chieh Lin, Shuei-Liong Fan, Shou-Zen Wang, Pei-Yu Hsieh Yu Enterprise Co. Ltd. Taipei Taiwan Graduate Institute of Brain and Mind Sciences College of Medicine National Taiwan University Taipei Taiwan Department of Pediatrics Taipei Veterans General Hospital Taipei Taiwan Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine National Taiwan University Taipei Taiwan Graduate Institute of Physiology College of Medicine National Taiwan University Taipei Taiwan Department of Anesthesiology National Taiwan University Hospital National Taiwan University Taipei Taiwan Department of Anesthesiology En Chu Kong Hospital Taipei Taiwan Neurobiology and Cognitive Science Center National Taiwan University Taipei Taiwan PhD. Program in Translational Medicine National Taiwan University and Academia Sinica Taipei Taiwan PhD. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan

Background: Chronic kidney disease (CKD) is a significant global health concern often accompanied by cognitive impairment in affected patients. Ludwigia octovalvis extract (LOE) is a traditional medicine widely used for various conditions, including renal disease and its associated complications. However, the pharmacological effects and underlying mechanisms of LOE on CKD remain unclear. Methods: Adult male mice underwent a 4-week oral adenine-induced CKD model, followed by daily administration of either a vehicle, losartan, or LOE for 1 to 2 months. A battery of behavioral tests was conducted to examine CKD-associated cognitive impairments. Additionally, RNA sequencing, Golgi staining, and immunohistochemistry were performed to decipher the underlying mechanisms. Results: Neither losartan nor LOE supplementation could reverse adenine-induced kidney damage. However, during behavioral tests, both losartan and LOE treatments improved memory performance in mice without affecting emotional status and general locomotor activity. Transcriptome profiling and histological analyses revealed altered dendritic arborization and increased spine density of dentate granule cells, along with augmented adult hippocampal neurogenesis, contributing to the improved memory performance of mice treated with LOE. Conclusion: Our study provides comprehensive neurobehavioral and molecular evidence supporting the potential use of LOE for future CKD-associated memory dysfunction treatment. © 2024 The Author(s)

关键词： Adenine Cognitive dysfunction Neurogenesis

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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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Investigating white matter connectomes in amnestic and non-amnestic Alzheimer's disease clinical variants

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Alzheimer's & Dementia 2021年第S5期17卷

作者： Pandurang R. Bharne Nikolas G. Kinney Fulvio Da Re Nicola Spotorno Christopher A. Olm Philip Cook David J. Irwin Corey T. McMillan Murray Grossman Jeffrey S. Phillips Penn FTD Center University of Pennsylvania Philadelphia PA USA PhD Program in Neuroscience University of Milano-Bicocca Milan Italy School of Medicine and Surgery Milan Center for Neuroscience (NeuroMI) University of Milano-Bicocca Milan Italy Penn Image Computing and Science Laboratory University of Pennsylvania Philadelphia PA USA Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

Background Recent models propose that spread of Alzheimer's disease (AD) pathology may be mediated by white matter connectivity. AD clinical variants exhibit partially distinct patterns of gray matter atrophy. However, it is less clear whether phenotypic differences extend to patients' white matter connectomes. We hypothesized that white matter connectivity would differ between healthy controls, amnestic AD (aAD), and non-amnestic AD (naAD), including behavioral variant Alzheimer's disease (bvAD), logopenic-variant primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA). Method We examined white matter connectomes in 194 participants (controls=60, aAD=42, bvAD=25, lvPPA=39, PCA=28). All participants with dementia had evidence of AD pathologic change based on autopsy, Aβ 1–42 from cerebrospinal fluid, or [18] F-florbetaben positron emission tomography. T1-weighted and diffusion tensor images were collected using a 3 Tesla scanner. We calculated gray matter volume for cortical regions of interest and median fractional anisotropy (FA) for the tract connecting every pair of regions. Tracts with the most variable FA values across participants were excluded to yield graphs with 30% density. Linear regressions adjusted for sex and age were used to investigate group differences in degree and betweenness centrality as well as the relationship between gray matter volume and FA measures. Phenotypic differences in tractwise FA were evaluated using t-tests. Result Both node and edge metrics indicated significant (p<.05, corrected) widespread differences between patient groups and controls. In contrasts between disease groups, aAD patients had reduced degree in multiple occipital and inferior temporal regions; and higher betweenness centrality in bilateral frontal and parietal regions relative to naAD phenotypes. Tractwise FA values did not differ between patient groups. Across groups, endpoint gray matter volume was correlated with tractwise FA measures. Conclu

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06O NLRP3 inflammasome activation and altered mitophagy are key pathways in inclusion body myositis

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Neuromuscular Disorders 2024年 43卷 104441.10-104441.10页

作者： Naddaf, E. Nguyen, T. Watzlawik, J. Gao, H. Hou, X. Fiesel, F. Mandrekar, J. Kokesh, E. Harmsen, W. Lanza, I. Springer, W. Trushina, E. Department of Neurology Mayo Clinic Rochester USA Department of Neuroscience Mayo Clinic Jacksonville USA Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Rochester USA Neuroscience PhD Program Mayo Clinic Graduate School of Biomedical Sciences Jacksonville USA Department of Quantitative Health Sciences Mayo Clinic Rochester USA Division of Endocrinology and Metabolism Mayo Clinic Rochester USA

Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined. Inflammation and mitochondrial dysfunction are the most common histopathological findings. In this study, we aimed to explore the interplay between inflammation and mitochondrial dysfunction in IBM patients. We included 38 IBM patients and 22 age- and sex-matched controls without myopathy. Bulk RNA sequencing, Meso Scale Discovery ELISA, western blotting, histochemistry and immunohistochemistry were performed on frozen muscle samples from the study participants. We demonstrated activation of the NLRP3 inflammasome in IBM muscle samples, with the NLRP3 inflammasome pathway being the most upregulated pathway. On muscle histopathology, there was increased NRLP3 immunoreactivity in both inflammatory cells and muscle fibers. Mitophagy is critical for removing damaged mitochondria and preventing the formation of a vicious cycle of mitochondrial dysfunction—NLRP3 activation. In the IBM muscle samples, we showed altered mitophagy with elevated levels of p-S65-Ubiquitin, a mitophagy marker. Furthermore, p-S65-Ubiquitin aggregates accumulated in muscle fibers that were mostly type 2 and devoid of cytochrome-c-oxidase reactivity. Type 2 muscle fibers are known to be more prone to mitochondrial dysfunction. NLRP3 RNA levels correlated with p-S65-Ubiquitin levels. NLRP3 inflammasome is activated in IBM, along with altered mitophagy, potentially forming a self-sustaining vicious cycle. These findings could have potential therapeutic significance.

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AMYGDALA-FUSIFORM CROSS-FREQUENCY COUPLING FOR PROCESSING FACES AND EMOTIONAL EXPRESSION

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IBRO neuroscience Reports 2023年 15卷 S906-S906页

作者： Giulia Varotto Alba Peris-Yague Manuela Costa Antonio Gil-Nagel Rafael Toledano Stephan Moratti Bryan Strange University Politécnica de Madrid Laboratory For Clinical Neuroscience Center For Biomedical Technology Madrid Spain Universidad Autónoma de Madrid Phd Program In Neuroscience Madrid Spain Hospital Ruber International Neurology Madrid Spain Complutense University of Madrid Department Of Experimental Psychology Madrid Spain Reina Sofia Centre for Alzheimer's Research Neuroimaging madrid Spain

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Cover Image, Volume 28, Issue 7

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Hippocampus 2018年第7期28卷

作者： Ina P. Pavlova Shannon C. Shipley Marcos Lanio René Hen Christine A. Denny Division of Integrative Neuroscience Research Foundation for Mental Hygiene Inc. (RFMH)/New York State Psychiatric Institute (NYSPI) New York New York 10032 Department of Neuroscience MD-PhD Program College of Physicians and Surgeons Columbia University Medical Center New York New York 10032 Department of Psychiatry Columbia University New York New York 10032

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Effect size for the reduction of corticospinal excitability induced by transcranial static magnetic field stimulation

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Brain Stimulation 2023年第1期16卷 313-313页

作者： Pagge, Cristina Caballero-Insaurriaga, Jaime Oliviero, Antonio Foffani, Guglielmo Ammann, Claudia HM CINAC Hospital Universitario HM Puerta del Sur HM Hospitales Spain PhD program in Neuroscience Universidad Autónoma de Madrid Spain Hospital Nacional de Parapléjicos Toledo Spain CIBERNED Instituto de Salud Carlos III Madrid Spain

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