Article
Cell Biology
Andrea Csemer, Adrienn Kovacs, Baneen Maamrah, Krisztina Pocsai, Kristof Korpas, Almos Klekner, Peter Szucs, Peter P. Nanasi, Balazs Pal
Summary: This study used slice electrophysiology to provide evidence that slow inward currents (SICs) can elicit synaptic plasticity by activating extrasynaptic NMDA receptors. The age dependence of SICs and their impact on synaptic plasticity were investigated in both murine and human cortical slices. The findings showed that SICs can induce moderate synaptic plasticity similar to spike timing-dependent plasticity, with a clear decline in SIC activity with aging and complete disappearance above a certain age cutoff. In conclusion, SICs likely play an important role in age-dependent physiological and pathological alterations of synaptic plasticity.
Article
Oncology
Clarissa A. Whitehead, Haoyun Fang, Huaqi Su, Andrew P. Morokoff, Andrew H. Kaye, Eric Hanssen, Cameron J. Nowell, Katharine J. Drummond, David W. Greening, Laura J. Vella, Theo Mantamadiotis, Stanley S. Stylli
Summary: In this study, it was found that glioblastoma cells promote invadopodia activity by secreting small extracellular vesicles (sEVs) containing matrix metalloproteinase MMP-2. Additionally, the invasiveness of cells and sEV secretion were increased after radiotherapy/temozolomide treatment. These findings reveal a relationship between sEVs and invadopodia, providing important insights into the functional capacity of sEVs in promoting glioblastoma cell invasion.
Article
Medical Laboratory Technology
Mengqi Su, Wenpeng Li, Yue Yuan, Siyao Liu, Chen Liang, He Liu, Ruixin Zhang, Yang Liu, Li Sun, Ying Wei, Chunlei Li, Xuejie Han, Hongting Hao, Xinbo Zhao, Yingchun Luo, Sen Yan, Zhenwei Pan, Yue Li
Summary: This study reveals the role of epididymal white adipose tissue (eWAT) in Ang II-induced cardiac fibrosis and dysfunction, indicating that adipocyte-derived exosomes mediate pathological communication between dysfunctional adipose tissue and the heart by transporting miR-23a-3p into cardiac fibroblasts, transforming fibroblasts into myofibroblasts, and promoting excessive collagen deposition by targeting RAP1. Therefore, preventing abnormal adipocyte exosome production, inhibiting miR-23a-3p biogenesis, and using a miR-23a-3p antagonist are novel strategies for treating cardiac fibrosis.
TRANSLATIONAL RESEARCH
(2022)
Article
Cell Biology
Alberto Lazari, Piergiorgio Salvan, Michiel Cottaar, Daniel Papp, Matthew F. S. Rushworth, Heidi Johansen-Berg
Summary: Evidence suggests that white matter plasticity in humans follows Hebb's rule. Stimulation of cortical areas leads to increased cortical excitability and a myelin marker in the stimulated fiber bundle, indicating the presence of Hebbian plasticity in human white matter fibers.
Article
Biochemical Research Methods
Beatriz Eymi Pimentel Mizusaki, Sally Si Ying Li, Rui Ponte Costa, Per Jesper Sjostrom
Summary: This study explored the functional differences between pre- and postsynaptically expressed long-term synaptic plasticity and found that they have complementary functions. Presynaptic plasticity mainly affects neurotransmitter release and short-term synaptic dynamics, while postsynaptic plasticity primarily influences synaptic gain. In different learning schemes, postsynaptic plasticity was more effective in regulating spike timing and frequency, while presynaptic plasticity adjusted the speed of learning. When combined with both pre- and postsynaptic expression, postsynaptic plasticity amplified the response range, and presynaptic plasticity controlled postsynaptic firing rates, contributing to activity homeostasis.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Danyang Huang, Yuehong Li, Zihan Ma, Hai Lin, Xiangdong Zhu, Yun Xiao, Xingdong Zhang
Summary: This study investigates how the viscoelasticity of collagen hydrogel regulates the cytoskeleton changes in mesenchymal stem cells (MSC) during chondrogenesis. Slower-relaxing hydrogels promote early chondrogenic differentiation but lead to myosin hyperactivation and cell apoptosis. In contrast, faster-relaxing hydrogels facilitate long-term chondrogenesis with reduced myosin hyperactivation and cell apoptosis.
Article
Oncology
Hannah K. K. Jackson, Christine Mitoko, Franziska Linke, Donald Macarthur, Ian D. D. Kerr, Beth Coyle
Summary: Through investigation and experimentation, it has been determined that metastatic medulloblastoma cells release significantly more extracellular vesicles, including exosomes rich in active MMP-2, which enhance the migration and invasiveness of primary medulloblastoma cells. This study demonstrates the crucial role of exosomes in medulloblastoma metastasis.
Article
Multidisciplinary Sciences
Yuzu Anazawa, Tomoki Kita, Rei Iguchi, Kumiko Hayashi, Shinsuke Niwa
Summary: Researchers have established Caenorhabditis elegans models for KIF1A-associated neuronal disorder (KAND) using CRISPR-Cas9 technology. They found that KIF1A mutations lead to reduced axonal transport and significantly impair the motility of heterodimeric motors composed of wild-type and mutant KIF1A.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Jinye Dai, Kif Liakath-Ali, Samantha Rose Golf, Thomas C. Sudhof
Summary: Studies have shown that in diverse neural circuits, signaling complexes formed by neurexin1(SS4+) and neurexin3(SS4+) with Cbln1/2 differentially control NMDA and AMPA receptors without regulating synapse or spine formation.
Article
Cell Biology
Kristin Metzdorf, Steffen Fricke, Maria Teresa Balia, Martin Korte, Marta Zagrebelsky
Summary: The balance between inhibitory and excitatory synaptic transmission is crucial for synaptic plasticity in neuronal networks. Nogo-A loss-of-function leads to an imbalance of AMPAR subunits, increased intracellular Ca2+ levels, and enhanced neuronal activation, contributing to a better understanding of the molecular mechanisms regulating excitation/inhibition balance and plasticity in the brain.
Article
Oncology
Liu Liu, Shasha Yin, Wenjian Gan
Summary: PRMT5 is overexpressed and activated in various types of cancer, including breast cancer. This study aims to understand the mechanism of how PRMT5 is dysregulated in cancer. The results show that TRAF6-mediated ubiquitination plays a key role in the regulation of PRMT5 activity and cell proliferation. Inhibiting TRAF6 could be a potential strategy for improving PRMT5 targeted therapy.
Article
Cell Biology
Aminu S. Jahun, Frederic Sorgeloos, Yasmin Chaudhry, Sabastine E. Arthur, Myra Hosmillo, Iliana Georgana, Rhys Izuagbe, Ian G. Goodfellow
Summary: The cGAS-STING pathway plays an important role in the interferon response against DNA viruses, and recent studies have shown its involvement in restriction of RNA viruses as well. This study demonstrates that the cGAS-STING pathway contributes to the interferon response against noroviruses, the common causes of infectious gastroenteritis worldwide. The findings also suggest that host genomic DNA can act as a damage-associated molecular pattern in cells infected with an RNA virus.
Article
Oncology
Maria V. Yusenko, Abhiruchi Biyanee, Mattias K. Andersson, Silke Radetzki, Jens P. von Kries, Goran Stenman, Karl-Heinz Klempnauer
Summary: Studies on MYB in human malignancies have identified it as a potential drug target for AML and ACC. While transcription factors are often considered hard to target, recent developments have shown successful targeting of MYB with low molecular weight compounds. The use of proteasome inhibitors to suppress oncogenic MYB activity opens up new possibilities for therapeutic approaches in MYB-driven cancers.
Article
Oncology
Rackhyun Park, Minsu Jang, Yea-In Park, Yeonjeong Park, Sim Namkoong, Jin Lee, Junsoo Park
Summary: This study demonstrates that elevated levels of CTRP1 in obesity significantly contribute to tumor progression, potentially by regulating the tumor suppressor p53. The molecular mechanisms linking obesity with cancer remain largely uninvestigated.
Article
Biochemistry & Molecular Biology
Joanna Agnieszka Komorowska-Mueller, Tanushka Rana, Bolanle Fatimat Olabiyi, Andreas Zimmer, Anne-Caroline Schmoele
Summary: CB2R plays a crucial role in cognitive functions and age-related microglial activity. Deletion of CB2R affects social memory and alters the morphology and activity of microglia in age-induced conditions.
Article
Biochemistry & Molecular Biology
Marta Orlando, Anton Dvorzhak, Felicitas Bruentgens, Marta Maglione, Benjamin R. Rost, Stephan J. Sigrist, Joerg Breustedt, Dietmar Schmitz
Summary: This study investigated the functional and structural changes associated with presynaptic potentiation induced by the adenylyl cyclase activator forskolin. Multi-modal imaging techniques revealed an increase in the surface area used for glutamate release, no change in the coupling distance between calcium channels and release sites, and rapid remodeling of synaptic ultrastructure at potentiated boutons. These findings suggest that early structural rearrangements enable long-term increase in synaptic strength.
Review
Biochemistry & Molecular Biology
Guendalina Bastioli, Maria Regoni, Federico Cazzaniga, Chiara Maria Giulia De Luca, Edoardo Bistaffa, Letizia Zanetti, Fabio Moda, Flavia Valtorta, Jenny Sassone
Summary: Parkinson's disease is a common neurodegenerative movement disorder characterized by the loss of dopamine neurons in the substantia nigra pars compacta. Clinical symptoms include bradykinesia, rigidity, resting tremors, and postural instability. While most cases of PD have sporadic onset, familial PD has been linked with rare genetic mutations, providing insight into the mechanism of dopamine neuron death in the disease.
Article
Clinical Neurology
Stefano Comai, Elisa Melloni, Cristina Lorenzi, Irene Bollettini, Benedetta Vai, Raffaella Zanardi, Cristina Colombo, Flavia Valtorta, Francesco Benedetti, Sara Poletti
Summary: Bipolar disorder (BD) patients showed higher levels of kynurenine (Kyn) and Kyn/tryptophan (Trp) ratio than major depression (MDD) patients, along with lower fractional anisotropy (FA) in several white matter tracts. Lower Trp levels were associated with more severe depressive symptoms and lower FA in specific brain regions, regardless of diagnosis. In BD patients, immune/inflammatory markers were selectively associated with Kyn/Trp ratio, suggesting a potential role of cytokines and Trp conversion into Kyn in affecting white matter microstructure.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Cell Biology
Elisa Savino, Fabrizia Claudia Guarnieri, Jin-Wu Tsai, Anna Corradi, Fabio Benfenati, Flavia Valtorta
Summary: Mutations in the PRRT2 gene are the main cause of various paroxysmal neurological diseases, affecting neurotransmitter release regulation and actin cytoskeleton dynamics during synaptogenesis. The PRRT2 protein plays a crucial role in growth cone morphology during neuronal development, with abnormal PRRT2 leading to changes in growth cone shape and actin cytoskeleton.
Article
Neurosciences
Barbara Imbrosci, Dietmar Schmitz, Marta Orlando
Summary: In this study, we developed an algorithm that utilizes convolutional neural networks (CNNs) to automatically detect and localize synaptic vesicles in electron micrographs, improving the efficiency of data collection. The algorithm performs well on synapses from different species and preparations, and provides a user interface for data analysis and proof-reading.
Article
Biochemistry & Molecular Biology
Fengxia Li, Eugenio F. Fornasiero, Tal M. Dankovich, Verena Kluever, Silvio O. Rizzoli
Summary: By systematically studying probes initially developed for electron microscopy, researchers found that antibodies coupled to 6 nm gold particles exhibit excellent labeling specificity and reliable detection threshold in nanoSIMS imaging. These tools enable accurate visualization and analysis of samples and can be easily combined with other imaging approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Verena Kluever, Belisa Russo, Sunit Mandad, Nisha Hemandhar Kumar, Mihai Alevra, Alessandro Ori, Silvio O. Rizzoli, Henning Urlaub, Anja Schneider, Eugenio F. Fornasiero
Summary: This study investigates the link between physiological aging and neurodegenerative disorders (NDDs) by studying protein turnover. The findings suggest that protein lifetimes are increased in aged brains and aging affects pathways associated with NDDs. A previously unknown alteration in proteostasis was also observed, indicating a metabolic adaptation that may precede neurodegeneration.
Article
Multidisciplinary Sciences
Maxim Katsenelson, Ilana Shapira, Eman Abbas, Kristina Jevdokimenko, Boaz Styr, Antonella Ruggiero, Saba Aid, Eugenio F. Fornasiero, Martin Holzenberger, Silvio O. Rizzoli, Inna Slutsky
Summary: This study reveals that insulin-like growth factor-1 receptor (IGF-1R) is a key regulator of firing rate homeostasis in central neural circuits. At the cellular level, IGF-1R interacts with the mitochondrial calcium uniporter complex (MCUc) and modulates the reliability of burst transfer, thereby affecting firing rate homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Eugenio F. Fornasiero, Jeffrey N. Savas
Summary: The orchestration and regulation of protein production and degradation are central to biological processes. Advances in proteomics have allowed estimation of protein lifetimes and interpretation of proteome changes in development, aging, and disease. This opinion article summarizes techniques, clarifies terminology, and provides insights for interpreting and validating protein turnover measurements. Overall, understanding protein lifetimes is essential for comprehending mammalian biology and defining the processes of life itself.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Matteo Moschetta, Tiziana Ravasenga, Antonio De Fusco, Luca Maragliano, Davide Aprile, Marta Orlando, Silvio Sacchetti, Silvia Casagrande, Gabriele Lignani, Anna Fassio, Pietro Baldelli, Fabio Benfenati
Summary: The study reveals that Synapsin I acts as a novel Ca2+ buffer in excitatory terminals, and blocking its binding to Ca2+ leads to abnormal neurotransmitter release and short-term plasticity. This finding sheds light on the physiological role of Ca2+ binding to SynI in the regulation of SV clustering and trafficking in nerve terminals.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Psychology, Biological
Riccardo Fesce
Summary: Several theories of consciousness have not been able to form a consensus theory due to inconsistent terminology and different objectives. This article aims to redefine terms and emphasize the role of emotions and imagination in the process.
PHYSIOLOGY & BEHAVIOR
(2023)
Article
Multidisciplinary Sciences
Erica Butti, Stefano Cattaneo, Marco Bacigaluppi, Marco Cambiaghi, Giulia Maria Scotti, Elena Brambilla, Francesca Ruffini, Giacomo Sferruzza, Maddalena Ripamonti, Fabio Simeoni, Laura Cacciaguerra, Aurora Zanghi, Angelo Quattrini, Riccardo Fesce, Paola Panina-Bordignon, Francesca Giannese, Davide Cittaro, Tanja Kuhlmann, Patrizia D'Adamo, Maria Assunta Rocca, Stefano Taverna, Gianvito Martino
Summary: In this study, the researchers provide evidence that adult neural stem/precursor cells in the brain regulate striatal function and support cognitive functions through the secretion of IGFBPL1.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Eugenio F. Fornasiero
Article
Neurosciences
Francesco Bolzoni, Beatrice Montanari, Veronica Farinelli, Paola Adamo, Federico Temporiti, Giorgia Marino, Riccardo Fesce, Roberto Gatti
Summary: The activation of MNS can be detected by observing non-visible postural adaptations. The Soleus muscle shows higher activation during dynamic postural adaptations, lower activation during static postures, and no activation during sitting. This observation suggests that mirror mechanisms can resonate with postural components of observed actions, even if they are not visible, indicating a potential role in motor recovery.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Kazi Atikur Rahman, Marta Orlando, Ayub Boulos, Ewa Andrzejak, Dietmar Schmitz, Noam E. Ziv, Harald Pruess, Craig C. Garner, Aleksandra Ichkova
Summary: Autoantibodies against NMDA receptors can cause internalization and loss of receptors, leading to the pathogenesis of NMDAR encephalitis. This study shows that microglia, a type of immune cells, play a role in removing the antibody-bound NMDARs, contributing to receptor and synapse loss. Mutations blocking the interaction between the antibody and microglia attenuate the loss of receptors and synapses, highlighting the critical involvement of microglia in autoimmune encephalitis.