Article
Multidisciplinary Sciences
Fujun Luo, Alessandra Sclip, Sean Merrill, Thomas C. Sudhof
Summary: This study shows that neurexins are essential for the localization and function of presynaptic GABA(B)-receptor signaling complexes. Deletion of neurexins results in decreased sensitivity of neurotransmitter release to GABA(B)-receptor activation and loss of GABA(B)-receptors from the presynaptic active zone. Neurexins play a crucial role in regulating presynaptic GABA(B) receptors at multiple central nervous system synapses.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Tim Fieblinger, Alberto Perez-Alvarez, Paul J. Lamothe-Molina, Christine E. Gee, Thomas G. Oertner
Summary: This study reveals the regulation of striatal excitatory neurons by phosphodiesterase PDE1 and cGMP, showing that blocking PDE1 activity can increase synaptic transmission and affect motor skill learning in mice.
Article
Multidisciplinary Sciences
Xiling Li, Chun Chien, Yifu Han, Zihan Sun, Xun Chen, Dion Dickman
Summary: The study revealed that the Glutamate-gated chloride channel (GluCl alpha) in Drosophila neurons plays a critical role in presynaptic homeostatic depression (PHD), driving the process through an activity-dependent anionic conductance.
Review
Pharmacology & Pharmacy
Anna Pittaluga
Summary: This review summarizes the results from synaptosome studies over the past 40 years, supporting the existence of auto and hetero NMDA receptors controlling the release of transmitters in the CNS of mammals. Additionally, immunochemical studies in isolated nerve endings confirm these functional observations.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
Michael J. Seibert, Chantell S. Evans, Kevin S. Stanley, Zhenyong Wu, Edwin R. Chapman
Summary: SYT9 is a Ca2+ sensor in neuroendocrine cells, but its function in neurons is unclear. In this study, it was found that SYT9 does not trigger rapid synaptic vesicle exocytosis in mouse cortical, hippocampal, or striatal neurons unless it is overexpressed. Loss of SYT9 in striatal neurons reduced the frequency of spontaneous neurotransmitter release events. Further investigation revealed that SYT9 is localized to dense-core vesicles containing substance P, and loss of SYT9 impaired SP release, causing the observed decrease in mini frequency. The study also showed that Ca2+ binding to the C2A domain of SYT9 triggered membrane fusion in vitro, and mutations disrupting this activity abolished SYT9's ability to regulate SP release and mini frequency. Therefore, it can be concluded that SYT9 indirectly regulates synaptic transmission in striatal neurons by controlling SP release.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biology
Tianzhi Li, Qiqi Cheng, Shen Wang, Cong Ma
Summary: Exocytosis of secretory vesicles relies on the interaction between Rabphilin 3A and SNAP-25, which promotes SNARE complex assembly and vesicle docking and fusion with the plasma membrane. This interaction is mediated by the N-terminal Rab-binding domain and C-terminal C(2)AB domain of Rabphilin 3A, as well as the C2B bottom alpha-helix of Rabphilin 3A and the N-peptide region of SNAP-25.
Article
Multidisciplinary Sciences
Yuni Kay, Bruce E. Herring
Summary: Efficient methods are lacking for studying proteins regulating presynaptic function, but the present study introduces an optical/electrophysiological method that utilizes optogenetics and simultaneous recordings of fiber volley amplitude to quantify synaptic efficacy. By inhibiting synaptotagmin 1 expression in CA3 pyramidal neurons, the study demonstrates a significant reduction in Schaffer collateral synapse function. This method aims to expedite understanding of molecular regulatory pathways governing presynaptic function.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Mario Lopez-Manzaneda, Andrea Fuentes-Moliz, Lucia Tabares
Summary: Presynaptic mitochondria play a critical role in regulating Ca2+ signaling during neurotransmitter release. They control the size and spread of Ca2+ wave during sustained electrical activity and also contribute to the regulation of fusion mode and kinetics of vesicle release and replenishment. This study provides insights into how mitochondria modulate the timing and reliability of neurotransmission during brief action potential trains in motor nerve terminals.
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2022)
Article
Neurosciences
Xin-Shen Wu, Shobana Subramanian, Yalan Zhang, Bo Shi, Jessica Xia, Tiansheng Li, Xiaoli Guo, Lynda El-Hassar, Klara Szigeti-Buck, Jorge Henao-Mejia, Richard A. Flavell, Tamas L. Horvath, Elizabeth A. Jonas, Leonard K. Kaczmarek, Ling-Gang Wu
Summary: Potassium channels play a crucial role in endocytosis and vesicle mobilization by organizing the F-actin cytoskeleton, in addition to their traditional role in ion conductance. Mutations in potassium channels that impair these non-conducting functions may contribute to various neurological disorders.
Article
Neurosciences
Peter H. Chipman, Richard D. Fetter, Lauren C. Panzera, Samuel J. Bergerson, Daniel Karmelic, Sae Yokoyama, Michael B. Hoppa, Graeme W. Davis
Summary: Homeostatic plasticity is a physiological process that counteracts neuronal perturbations in the brain. Acute AMPAR-specific antagonism can induce compensatory plasticity, leading to potentiation of presynaptic neurotransmitter release. This process can be induced within minutes and requires postsynaptic NMDARs.
Article
Multidisciplinary Sciences
Ying Lai, Giorgio Fois, Jose R. Flores, Michael J. Tuvim, Qiangjun Zhou, Kailu Yang, Jeremy Leitz, John Peters, Yunxiang Zhang, Richard A. Pfuetzner, Luis Esquivies, Philip Jones, Manfred Frick, Burton F. Dickey, Axel T. Brunger
Summary: Membrane fusion triggered by Ca2+ is important for synaptic neurotransmitter release and mucin secretion. A designed peptide can disrupt Ca2+-triggered membrane fusion, reduce stimulated mucin secretion, and alleviate mucus occlusion of mouse airways.
Article
Biochemistry & Molecular Biology
Kevin C. Courtney, Lanxi Wu, Taraknath Mandal, Mark Swift, Zhao Zhang, Mohammad Alaghemandi, Zhenyong Wu, Mazdak M. Bradberry, Claire Deo, Luke D. Lavis, Niels Volkmann, Dorit Hanein, Qiang Cui, Huan Bao, Edwin R. Chapman
Summary: The mammalian accessory protein complexin (Cpx) can remodel phospholipid bilayers, increasing the size and stability of SNARE-mediated fusion pores.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Lihao Ge, Wonchul Shin, Gianvito Arpino, Lisi Wei, Chung Yu Chan, Christopher K. E. Bleck, Weidong Zhao, Ling-Gang Wu
Summary: This study revealed the existence of sequential compound fusion and compound kiss-and-run mechanisms during vesicle fusion in excitable cells, which enhance exocytosis and endocytosis capacities, as well as dynamic ranges.
Article
Neurosciences
Haruki Odaka, Tadahiro Numakawa, Minami Soga, Jun Kido, Shiro Matsumoto, Ryutaro Kajihara, Toshika Okumiya, Naoki Tani, Yuki Tanoue, Takaichi Fukuda, Hirokazu Furuya, Takafumi Inoue, Takumi Era
Summary: Sialidosis is a neuropathic lysosomal storage disease characterized by a deficiency in the NEU1 gene, leading to abnormal accumulation of undigested sialyl-oligoconjugates. Our study using iPSCs and neural progenitor cells revealed disease-like phenotypes in sialidosis neurons, along with two distinct abnormalities in neuronal function. Comprehensive proteomics analysis showed reduction of SNARE proteins and glycolytic enzymes in synaptosomal fraction, with potential therapeutic strategies involving glycolysis bypass and modulation of AMPAR and L-type VDCC.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Timothy J. Hark, Nalini R. Rao, Charlotte Castillon, Tamara Basta, Samuel Smukowski, Huan Bao, Arun Upadhyay, Ewa Bomba-Warczak, Toshihiro Nomura, Eileen T. O'Toole, Garry P. Morgan, Laith Ali, Takashi Saito, Christelle Guillermier, Takaomi C. Saido, Matthew L. Steinhauser, Michael H. B. Stowell, Edwin R. Chapman, Anis Contractor, Jeffrey N. Savas
Summary: Protein turnover impairment at presynaptic terminals, particularly with synaptic vesicle-associated proteins, is observed at early stages of Alzheimer's disease. These impaired proteins interact with APP and Ab, leading to vulnerability of presynaptic terminals and manifestation of initial AD etiology.
Article
Biochemical Research Methods
Andrea J. Sterkenburg, Wouter T. R. Hooghiemstra, Iris Schmidt, Vasilis Ntziachristos, Wouter B. Nagengast, Dimitris Gorpas
Summary: Near-infrared fluorescence molecular endoscopy (NIR-FME) is an innovative technique for visualizing molecular processes in vivo. However, challenges in quality control and standardization hinder its clinical implementation. Standardization involves various parameters, with phantoms being useful tools.
JOURNAL OF BIOMEDICAL OPTICS
(2022)
Article
Biochemical Research Methods
Marwan Muhammad, Jaya Prakash, Evangelos Liapis, Vasilis Ntziachristos, Dominik Juestel
Summary: The weighted model-based algorithm presented in this article extends its capabilities to generate optoacoustic reconstructions with less distortions for partial-view geometry data, effectively mitigating reflection artifacts while also suppressing streaking artifacts in the presence of a strong optoacoustic chromophore. This method shows promise for improving the quality of partial-view multispectral optoacoustic tomography and enhancing the visualization of functional parameters such as tissue oxygenation.
JOURNAL OF BIOPHOTONICS
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Wido Heeman, Jasper Vonk, Vasilis Ntziachristos, Brian W. Pogue, Rudi A. J. O. Dierckx, Schelto Kruijff, Gooitzen M. van Dam
Summary: Fluorescence imaging is rapidly being applied in clinical care, with numerous clinical trials being conducted. A multidisciplinary approach is necessary to design a uniform fluorescence imaging protocol and ensure consistent data collection and reliable study outcomes.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Kanuj Mishra, Juan Pablo Fuenzalida-Werner, Francesca Pennacchietti, Robert Janowski, Andriy Chmyrov, Yuanhui Huang, Christian Zakian, Uwe Klemm, Ilaria Testa, Dierk Niessing, Vasilis Ntziachristos, Andre C. Stiel
Summary: Reversibly photo-switchable proteins have been utilized for super-resolution and optoacoustic imaging methods, and in this study, a prototype of a photo-switchable Ca2+ sensor was constructed based on GCaMP5G. The molecular mechanisms of the sensor were described at the structural level, demonstrating the ability to image calcium and other analytes at super-resolution and in vivo.
NATURE BIOTECHNOLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Sabrina Marcazzan, Marcos J. Braz Carvalho, Matthias Konrad, Julia Strangmann, Anna Tenditnaya, Theresa Baumeister, Roland M. Schmid, Hans-Juergen Wester, Vasilis Ntziachristos, Dimitris Gorpas, Timothy C. Wang, Margret Schottelius, Michael Quante
Summary: This preclinical study demonstrates that CXCR4-targeted fluorescence endoscopy using MK007 can detect dysplastic lesions in a mouse model of Barrett's esophagus.
Review
Pharmacology & Pharmacy
Nian Liu, Kanuj Mishra, Andre C. Stiel, Vipul Gujrati, Vasilis Ntziachristos
Summary: Optoacoustic imaging is a unique technique that provides high-resolution images of optical contrast for visualizing biological function in vivo. By detecting ultrasound waves generated through the conversion of light absorption to ultrasound, this method offers a range of applications in various biological and clinical fields.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Biochemical Research Methods
Arumugaraj Madasamy, Vipul Gujrati, Vasilis Ntziachristos, Jaya Prakash
Summary: This study aims to recover optical absorption maps using deep learning approaches by correcting for the influence of nonlinear optical fluence distribution. The results indicate that deep learning models can effectively compensate for nonlinear optical fluence distribution and improve the quality of optoacoustic images.
JOURNAL OF BIOMEDICAL OPTICS
(2022)
Review
Cardiac & Cardiovascular Systems
Masaru Seguchi, Alp Aytekin, Tobias Lenz, Philipp Nicol, Grace R. Klosterman, Alicia Beele, Emina Sabic, Lea Utsch, Aseel Alyaqoob, Dimitris Gorpas, Vasilis Ntziachristos, Farouc A. Jaffer, Philipp Rauschendorfer, Michael Joner
Summary: The progression of atherosclerotic plaque in coronary arteries involves complex cellular and molecular interactions. Atherosclerosis is now recognized as being driven by inflammation, with changes in plaque composition and molecular processes leading to increased vulnerability. While current intravascular imaging techniques can identify morphological features during plaque progression, they are unable to characterize the molecular profile of advanced atherosclerotic plaque. Hybrid imaging modalities are expected to provide additional information on plaque biology, aiding in the detection of high-risk patients and lesions. This article reviews existing literature on intravascular molecular imaging approaches and proposes clinically oriented applications, as well as future developments aimed at identifying patients at risk for cardiovascular events.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
(2022)
Article
Nanoscience & Nanotechnology
Nian Liu, Patrick O'Connor, Vipul Gujrati, Pia Anzenhofer, Uwe Klemm, Karin Kleigrewe, Michael Sattler, Oliver Plettenburg, Vasilis Ntziachristos
Summary: This study introduces CR880-based nanoparticles for deep tissue optoacoustic imaging and photothermal therapy. These nanoparticles exhibit high optoacoustic generation efficiency and photostability, and can be visualized in tumors with high image contrast. Moreover, they have high photothermal conversion efficiency for effective tumor elimination.
Article
Acoustics
Nikolina-Alexia Fasoula, Angelos Karlas, Olga Prokopchuk, Nikoletta Katsouli, Michail Bariotakis, Evangelos Liapis, Anna Goetz, Michael Kallmayer, Josefine Reber, Alexander Novotny, Helmut Friess, Marc Ringelhan, Roland Schmid, Hans -Henning Eckstein, Susanna Hofmann, Vasilis Ntziachristos
Summary: This study investigates whether multispectral optoacoustic tomography (MSOT) can detect and monitor hepatic steatosis by analyzing the spectral region around 930 nm. In a pilot study involving patients and mice, higher absorptions at 930 nm were observed in liver steatosis cases compared to healthy individuals, while no significant difference was observed in subcutaneous adipose tissue. This study suggests that MSOT has the potential to be a non-invasive and portable technique for detecting and monitoring hepatic steatosis in clinical settings, warranting further studies.
Article
Radiology, Nuclear Medicine & Medical Imaging
Milou E. Noltes, Maximilian Bader, Madelon J. H. Metman, Jasper Vonk, Pieter J. Steinkamp, Jan Kukacka, Henriette E. Westerlaan, Rudi A. J. O. Dierckx, Bettien M. van Hemel, Adrienne H. Brouwers, Gooitzen M. van Dam, Dominik Juestel, Vasilis Ntziachristos, Schelto Kruijff
Summary: This study examines the potential of multispectral optoacoustic tomography (MSOT) for risk stratification of thyroid nodules. The findings show a correlation between vascular patterns and thyroid malignancy, and identify malignant features in MSOT images that are verified by histopathology. However, mean oxygen saturation does not provide significant differences between benign and malignant thyroid nodules. Recommendations are made to consider optoacoustic features and chromophore quantification together for malignancy risk assessment.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Biochemical Research Methods
Philipp Rauschendorfer, Georg Wissmeyer, Farouc A. Jaffer, Dimitris Gorpas, Vasilis Ntziachristos
Summary: This article introduces a new method for attenuation correction in intravascular near-infrared fluorescence (NIRF) imaging. It utilizes a fluorophore-coated guidewire as a reference to measure blood attenuation in real-time during the NIRF examination. The method has been shown to significantly improve signal quality and accuracy in animal experiments.
JOURNAL OF BIOMEDICAL OPTICS
(2023)
Article
Multidisciplinary Sciences
Konxhe Kulaj, Alexandra Harger, Michaela Bauer, Oezuem S. Caliskan, Tilak Kumar Gupta, Dapi Menglin Chiang, Edward Milbank, Josefine Reber, Angelos Karlas, Petra Kotzbeck, David N. Sailer, Francesco Volta, Dominik Lutter, Sneha Prakash, Juliane Merl-Pham, Vasilis Ntziachristos, Hans Hauner, Michael W. Pfaffl, Matthias H. Tschoep, Timo D. Mueller, Stefanie M. Hauck, Benjamin D. Engel, Jantje M. Gerdes, Paul T. Pfluger, Natalie Krahmer, Kerstin Stemmer
Summary: Extracellular vesicles (EVs) derived from adipocytes transfer insulinotropic proteins to pancreatic β-cells, enhancing insulin secretion and glucose tolerance. This process is observed in insulin-resistant obese mice, suggesting that AdEVs play a role in informing β-cells about insulin resistance and increasing insulin demand.
NATURE COMMUNICATIONS
(2023)
Article
Nanoscience & Nanotechnology
Hailong He, Ludwig Englert, Vasilis Ntziachristos
Summary: Optical endoscopy is widely used for gastrointestinal diagnostics, but it only allows superficial inspection of the mucosa. To visualize deeper layers, optoacoustic endoscopy has been developed, which combines optical contrast with ultrasound to provide high-resolution imaging. This review focuses on the progress, current status, and potential applications of optoacoustic endoscopy.
Article
Acoustics
Angelos Karlas, Nikolina-Alexia Fasoula, Nikoletta Katsouli, Michael Kallmayer, Sabine Sieber, Sebastian Schmidt, Evangelos Liapis, Martin Halle, Hans-Henning Eckstein, Vasilis Ntziachristos
Summary: By using multispectral optoacoustic tomography (MSOT), this study imaged hemodynamics and oxygen kinetics within skeletal muscle during exercise. The results showed changes in blood volume and oxygen levels during different types of hand-grip exercises in healthy volunteers. Further analysis revealed insights into arteriovenous oxygen differences and muscle oxygen consumption. These findings highlight the potential implications of MSOT in muscle research and disease diagnostics.
