6 results on '"A. Zatcepin"'
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2. Depletion and activation of microglia impact metabolic connectivity of the mouse brain
- Author
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Gnörich, Johannes, Reifschneider, Anika, Wind, Karin, Zatcepin, Artem, Kunte, Sebastian T., Beumers, Philipp, Bartos, Laura M., Wiedemann, Thomas, Grosch, Maximilian, Xiang, Xianyuan, Fard, Maryam K., Ruch, Francois, Werner, Georg, Koehler, Mara, Slemann, Luna, Hummel, Selina, Briel, Nils, Blume, Tanja, Shi, Yuan, Biechele, Gloria, Beyer, Leonie, Eckenweber, Florian, Scheifele, Maximilian, Bartenstein, Peter, Albert, Nathalie L., Herms, Jochen, Tahirovic, Sabina, Haass, Christian, Capell, Anja, Ziegler, Sibylle, and Brendel, Matthias
- Published
- 2023
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3. [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data
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Ballweg, Anna, Klaus, Carolin, Vogler, Letizia, Katzdobler, Sabrina, Wind, Karin, Zatcepin, Artem, Ziegler, Sibylle I., Secgin, Birkan, Eckenweber, Florian, Bohr, Bernd, Bernhardt, Alexander, Fietzek, Urban, Rauchmann, Boris-Stephan, Stoecklein, Sophia, Quach, Stefanie, Beyer, Leonie, Scheifele, Maximilian, Simmet, Marcel, Joseph, Emanuel, Lindner, Simon, Berg, Isabella, Koglin, Norman, Mueller, Andre, Stephens, Andrew W., Bartenstein, Peter, Tonn, Joerg C., Albert, Nathalie L., Kümpfel, Tania, Kerschensteiner, Martin, Perneczky, Robert, Levin, Johannes, Paeger, Lars, Herms, Jochen, and Brendel, Matthias
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- 2023
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4. Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
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Xia, Dan, Lianoglou, Steve, Sandmann, Thomas, Calvert, Meredith, Suh, Jung H., Thomsen, Elliot, Dugas, Jason, Pizzo, Michelle E., DeVos, Sarah L., Earr, Timothy K., Lin, Chia-Ching, Davis, Sonnet, Ha, Connie, Leung, Amy Wing-Sze, Nguyen, Hoang, Chau, Roni, Yulyaningsih, Ernie, Lopez, Isabel, Solanoy, Hilda, Masoud, Shababa T., Liang, Chun-chi, Lin, Karin, Astarita, Giuseppe, Khoury, Nathalie, Zuchero, Joy Yu, Thorne, Robert G., Shen, Kevin, Miller, Stephanie, Palop, Jorge J., Garceau, Dylan, Sasner, Michael, Whitesell, Jennifer D., Harris, Julie A., Hummel, Selina, Gnörich, Johannes, Wind, Karin, Kunze, Lea, Zatcepin, Artem, Brendel, Matthias, Willem, Michael, Haass, Christian, Barnett, Daniel, Zimmer, Till S., Orr, Anna G., Scearce-Levie, Kimberly, Lewcock, Joseph W., Di Paolo, Gilbert, and Sanchez, Pascal E.
- Published
- 2022
- Full Text
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5. Depletion and activation of microglia impact metabolic connectivity of the mouse brain
- Author
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Johannes Gnörich, Anika Reifschneider, Karin Wind, Artem Zatcepin, Sebastian T. Kunte, Philipp Beumers, Laura M. Bartos, Thomas Wiedemann, Maximilian Grosch, Xianyuan Xiang, Maryam K. Fard, Francois Ruch, Georg Werner, Mara Koehler, Luna Slemann, Selina Hummel, Nils Briel, Tanja Blume, Yuan Shi, Gloria Biechele, Leonie Beyer, Florian Eckenweber, Maximilian Scheifele, Peter Bartenstein, Nathalie L. Albert, Jochen Herms, Sabina Tahirovic, Christian Haass, Anja Capell, Sibylle Ziegler, and Matthias Brendel
- Subjects
FDG–PET ,Membrane Glycoproteins ,General Neuroscience ,metabolism [Progranulins] ,Immunology ,metabolism [Receptors, Immunologic] ,metabolism [Microglia] ,Cellular and Molecular Neuroscience ,Mice ,Metabolic connectivity ,scRadiotracing ,Progranulins ,Trem2 protein, mouse ,Neurology ,metabolism [Brain] ,Fluorodeoxyglucose F18 ,Positron-Emission Tomography ,metabolism [Fluorodeoxyglucose F18] ,Animals ,ddc:610 ,Microglia ,Neurodegeneration ,Receptors, Immunologic ,metabolism [Membrane Glycoproteins] - Abstract
Aim We aimed to investigate the impact of microglial activity and microglial FDG uptake on metabolic connectivity, since microglial activation states determine FDG–PET alterations. Metabolic connectivity refers to a concept of interacting metabolic brain regions and receives growing interest in approaching complex cerebral metabolic networks in neurodegenerative diseases. However, underlying sources of metabolic connectivity remain to be elucidated. Materials and methods We analyzed metabolic networks measured by interregional correlation coefficients (ICCs) of FDG–PET scans in WT mice and in mice with mutations in progranulin (Grn) or triggering receptor expressed on myeloid cells 2 (Trem2) knockouts (−/−) as well as in double mutant Grn−/−/Trem2−/− mice. We selected those rodent models as they represent opposite microglial signatures with disease associated microglia in Grn−/− mice and microglia locked in a homeostatic state in Trem2−/− mice; however, both resulting in lower glucose uptake of the brain. The direct influence of microglia on metabolic networks was further determined by microglia depletion using a CSF1R inhibitor in WT mice at two different ages. Within maps of global mean scaled regional FDG uptake, 24 pre-established volumes of interest were applied and assigned to either cortical or subcortical networks. ICCs of all region pairs were calculated and z-transformed prior to group comparisons. FDG uptake of neurons, microglia, and astrocytes was determined in Grn−/− and WT mice via assessment of single cell tracer uptake (scRadiotracing). Results Microglia depletion by CSF1R inhibition resulted in a strong decrease of metabolic connectivity defined by decrease of mean cortical ICCs in WT mice at both ages studied (6–7 m; p = 0.0148, 9–10 m; p = 0.0191), when compared to vehicle-treated age-matched WT mice. Grn−/−, Trem2−/− and Grn−/−/Trem2−/− mice all displayed reduced FDG–PET signals when compared to WT mice. However, when analyzing metabolic networks, a distinct increase of ICCs was observed in Grn−/− mice when compared to WT mice in cortical (p p Trem2−/− mice did not show significant alterations in metabolic connectivity when compared to WT. Furthermore, the increased metabolic connectivity in Grn−/− mice was completely suppressed in Grn−/−/Trem2−/− mice. Grn−/− mice exhibited a severe loss of neuronal FDG uptake (− 61%, p Grn−/− vs. 22% in WT). Conclusions Presence, absence, and activation of microglia have a strong impact on metabolic connectivity of the mouse brain. Enhanced metabolic connectivity is associated with increased microglial FDG allocation.
- Published
- 2023
6. [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data.
- Author
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Ballweg, Anna, Klaus, Carolin, Vogler, Letizia, Katzdobler, Sabrina, Wind, Karin, Zatcepin, Artem, Ziegler, Sibylle I., Secgin, Birkan, Eckenweber, Florian, Bohr, Bernd, Bernhardt, Alexander, Fietzek, Urban, Rauchmann, Boris-Stephan, Stoecklein, Sophia, Quach, Stefanie, Beyer, Leonie, Scheifele, Maximilian, Simmet, Marcel, Joseph, Emanuel, and Lindner, Simon
- Subjects
POSITRON emission tomography ,GLIAL fibrillary acidic protein ,NEURODEGENERATION ,GLIOSIS ,ALZHEIMER'S disease - Abstract
Objectives: Reactive gliosis is a common pathological hallmark of CNS pathology resulting from neurodegeneration and neuroinflammation. In this study we investigate the capability of a novel monoamine oxidase B (MAO-B) PET ligand to monitor reactive astrogliosis in a transgenic mouse model of Alzheimer's disease (AD). Furthermore, we performed a pilot study in patients with a range of neurodegenerative and neuroinflammatory conditions. Methods: A cross-sectional cohort of 24 transgenic (PS2APP) and 25 wild-type mice (age range: 4.3–21.0 months) underwent 60 min dynamic [
18 F]fluorodeprenyl-D2 ([18 F]F-DED), static 18 kDa translocator protein (TSPO, [18 F]GE-180) and β-amyloid ([18 F]florbetaben) PET imaging. Quantification was performed via image derived input function (IDIF, cardiac input), simplified non-invasive reference tissue modelling (SRTM2, DVR) and late-phase standardized uptake value ratios (SUVr). Immunohistochemical (IHC) analyses of glial fibrillary acidic protein (GFAP) and MAO-B were performed to validate PET imaging by gold standard assessments. Patients belonging to the Alzheimer's disease continuum (AD, n = 2), Parkinson's disease (PD, n = 2), multiple system atrophy (MSA, n = 2), autoimmune encephalitis (n = 1), oligodendroglioma (n = 1) and one healthy control underwent 60 min dynamic [18 F]F-DED PET and the data were analyzed using equivalent quantification strategies. Results: We selected the cerebellum as a pseudo-reference region based on the immunohistochemical comparison of age-matched PS2APP and WT mice. Subsequent PET imaging revealed that PS2APP mice showed elevated hippocampal and thalamic [18 F]F-DED DVR when compared to age-matched WT mice at 5 months (thalamus: + 4.3%; p = 0.048), 13 months (hippocampus: + 7.6%, p = 0.022) and 19 months (hippocampus: + 12.3%, p < 0.0001; thalamus: + 15.2%, p < 0.0001). Specific [18 F]F-DED DVR increases of PS2APP mice occurred earlier when compared to signal alterations in TSPO and β-amyloid PET and [18 F]F-DED DVR correlated with quantitative immunohistochemistry (hippocampus: R = 0.720, p < 0.001; thalamus: R = 0.727, p = 0.002). Preliminary experience in patients showed [18 F]F-DED VT and SUVr patterns, matching the expected topology of reactive astrogliosis in neurodegenerative (MSA) and neuroinflammatory conditions, whereas the patient with oligodendroglioma and the healthy control indicated [18 F]F-DED binding following the known physiological MAO-B expression in brain. Conclusions: [18 F]F-DED PET imaging is a promising approach to assess reactive astrogliosis in AD mouse models and patients with neurological diseases. [ABSTRACT FROM AUTHOR]- Published
- 2023
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