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206 results on '"Schifferer, Martina"'

1. T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis

Author

Kedia, Shreeya, Ji, Hao, Feng, Ruoqing, Androvic, Peter, Spieth, Lena, Liu, Lu, Franz, Jonas, Zdiarstek, Hanna, Anderson, Katrin Perez, Kaboglu, Cem, Liu, Qian, Mattugini, Nicola, Cherif, Fatma, Prtvar, Danilo, Cantuti-Castelvetri, Ludovico, Liesz, Arthur, Schifferer, Martina, Stadelmann, Christine, Tahirovic, Sabina, Gokce, Ozgun, and Simons, Mikael

Published
2024
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4. Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging

Author

Todorov-Völgyi, Katalin, González-Gallego, Judit, Müller, Stephan A., Beaufort, Nathalie, Malik, Rainer, Schifferer, Martina, Todorov, Mihail Ivilinov, Crusius, Dennis, Robinson, Sophie, Schmidt, Andree, Körbelin, Jakob, Bareyre, Florence, Ertürk, Ali, Haass, Christian, Simons, Mikael, Paquet, Dominik, Lichtenthaler, Stefan F., and Dichgans, Martin

Published
2024
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5. Apolipoprotein E aggregation in microglia initiates Alzheimer’s disease pathology by seeding β-amyloidosis

Author

Kaji, Seiji, Berghoff, Stefan A., Spieth, Lena, Schlaphoff, Lennart, Sasmita, Andrew O., Vitale, Simona, Büschgens, Luca, Kedia, Shreeya, Zirngibl, Martin, Nazarenko, Taisiia, Damkou, Alkmini, Hosang, Leon, Depp, Constanze, Kamp, Frits, Scholz, Patricia, Ewers, David, Giera, Martin, Ischebeck, Till, Wurst, Wolfgang, Wefers, Benedikt, Schifferer, Martina, Willem, Michael, Nave, Klaus-Armin, Haass, Christian, Arzberger, Thomas, Jäkel, Sarah, Wirths, Oliver, Saher, Gesine, and Simons, Mikael

Published
2024
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6. Validating a minipig model of reversible cerebral demyelination using human diagnostic modalities and electron microscopy

Author

Ancău, Mihai, Tanti, Goutam Kumar, Butenschoen, Vicki Marie, Gempt, Jens, Yakushev, Igor, Nekolla, Stephan, Mühlau, Mark, Scheunemann, Christian, Heininger, Sebastian, Löwe, Benjamin, Löwe, Erik, Baer, Silke, Fischer, Johannes, Reiser, Judith, Ayachit, Sai S., Liesche-Starnecker, Friederike, Schlegel, Jürgen, Matiasek, Kaspar, Schifferer, Martina, Kirschke, Jan S., Misgeld, Thomas, Lueth, Tim, and Hemmer, Bernhard

Published
2024
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10. Distinct molecular profiles of skull bone marrow in health and neurological disorders

Author

Kolabas, Zeynep Ilgin, Kuemmerle, Louis B., Perneczky, Robert, Förstera, Benjamin, Ulukaya, Selin, Ali, Mayar, Kapoor, Saketh, Bartos, Laura M., Büttner, Maren, Caliskan, Ozum Sehnaz, Rong, Zhouyi, Mai, Hongcheng, Höher, Luciano, Jeridi, Denise, Molbay, Muge, Khalin, Igor, Deligiannis, Ioannis K., Negwer, Moritz, Roberts, Kenny, Simats, Alba, Carofiglio, Olga, Todorov, Mihail I., Horvath, Izabela, Ozturk, Furkan, Hummel, Selina, Biechele, Gloria, Zatcepin, Artem, Unterrainer, Marcus, Gnörich, Johannes, Roodselaar, Jay, Shrouder, Joshua, Khosravani, Pardis, Tast, Benjamin, Richter, Lisa, Díaz-Marugán, Laura, Kaltenecker, Doris, Lux, Laurin, Chen, Ying, Zhao, Shan, Rauchmann, Boris-Stephan, Sterr, Michael, Kunze, Ines, Stanic, Karen, Kan, Vanessa W.Y., Besson-Girard, Simon, Katzdobler, Sabrina, Palleis, Carla, Schädler, Julia, Paetzold, Johannes C., Liebscher, Sabine, Hauser, Anja E., Gokce, Ozgun, Lickert, Heiko, Steinke, Hanno, Benakis, Corinne, Braun, Christian, Martinez-Jimenez, Celia P., Buerger, Katharina, Albert, Nathalie L., Höglinger, Günter, Levin, Johannes, Haass, Christian, Kopczak, Anna, Dichgans, Martin, Havla, Joachim, Kümpfel, Tania, Kerschensteiner, Martin, Schifferer, Martina, Simons, Mikael, Liesz, Arthur, Krahmer, Natalie, Bayraktar, Omer A., Franzmeier, Nicolai, Plesnila, Nikolaus, Erener, Suheda, Puelles, Victor G., Delbridge, Claire, Bhatia, Harsharan Singh, Hellal, Farida, Elsner, Markus, Bechmann, Ingo, Ondruschka, Benjamin, Brendel, Matthias, Theis, Fabian J., and Erturk, Ali

Published
2023
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11. A Developmental Analysis of Juxtavascular Microglia Dynamics and Interactions with the Vasculature

Author

Mondo, Erica, Becker, Shannon C, Kautzman, Amanda G, Schifferer, Martina, Baer, Christina E, Chen, Jiapei, Huang, Eric J, Simons, Mikael, and Schafer, Dorothy P

Subjects
Neurosciences, Underpinning research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Neurological, Animals, CX3C Chemokine Receptor 1, Capillaries, Cerebral Cortex, Female, Humans, Male, Mice, Inbred C57BL, Microglia, Somatosensory Cortex, astrocytes, development, microglia, neural-immune, vasculature, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Microglia, a resident CNS macrophage, are dynamic cells, constantly extending and retracting their processes as they contact and functionally regulate neurons and other glial cells. There is far less known about microglia-vascular interactions, particularly under healthy steady-state conditions. Here, we use the male and female mouse cerebral cortex to show that a higher percentage of microglia associate with the vasculature during the first week of postnatal development compared with older ages and that the timing of these associations is dependent on the fractalkine receptor (CX3CR1). Similar developmental microglia-vascular associations were detected in the human brain. Using live imaging in mice, we found that juxtavascular microglia migrated when microglia are actively colonizing the cortex and became stationary by adulthood to occupy the same vascular space for nearly 2 months. Further, juxtavascular microglia at all ages associate with vascular areas void of astrocyte endfeet, and the developmental shift in microglial migratory behavior along vessels corresponded to when astrocyte endfeet more fully ensheath vessels. Together, our data provide a comprehensive assessment of microglia-vascular interactions. They support a mechanism by which microglia use the vasculature to migrate within the developing brain parenchyma. This migration becomes restricted on the arrival of astrocyte endfeet such that juxtavascular microglia become highly stationary and stable in the mature cortex.SIGNIFICANCE STATEMENT We report the first extensive analysis of juxtavascular microglia in the healthy, developing, and adult brain. Live imaging revealed that juxtavascular microglia within the cortex are highly motile and migrate along vessels as they are colonizing cortical regions. Using confocal, expansion, super-resolution, and electron microscopy, we determined that microglia associate with the vasculature at all ages in areas lacking full astrocyte endfoot coverage and motility of juxtavascular microglia ceases as astrocyte endfeet more fully ensheath the vasculature. Our data lay the fundamental groundwork to investigate microglia-astrocyte cross talk and juxtavascular microglial function in the healthy and diseased brain. They further provide a potential mechanism by which vascular interactions facilitate microglial colonization of the brain to later regulate neural circuit development.

Published
2020

16. Myeloid cell–specific loss of NPC1 in mice recapitulates microgliosis and neurodegeneration in patients with Niemann-Pick type C disease.

Author

Dinkel, Lina, Hummel, Selina, Zenatti, Valerio, Malara, Mariagiovanna, Tillmann, Yannik, Colombo, Alessio, Monasor, Laura Sebastian, Suh, Jung H., Logan, Todd, Roth, Stefan, Paeger, Lars, Hoffelner, Patricia, Bludau, Oliver, Schmidt, Andree, Müller, Stephan A., Schifferer, Martina, Nuscher, Brigitte, Njavro, Jasenka Rudan, Prestel, Matthias, and Bartos, Laura M.

Subjects
MYELOID cells, TRANSLOCATOR proteins, POSITRON emission tomography, LYSOSOMAL storage diseases, MEMBRANE proteins
Abstract

Niemann-Pick type C (NPC) disease is an inherited lysosomal storage disorder mainly driven by mutations in the NPC1 gene, causing lipid accumulation within late endosomes/lysosomes and resulting in progressive neurodegeneration. Although microglial activation precedes neuronal loss, it remains elusive whether loss of the membrane protein NPC1 in microglia actively contributes to NPC pathology. In a mouse model with depletion of NPC1 in myeloid cells, we report severe alterations in microglial lipidomic profiles, including the enrichment of bis(monoacylglycero)phosphate, increased cholesterol, and a decrease in cholesteryl esters. Lipid dyshomeostasis was associated with microglial hyperactivity, marked by an increase in translocator protein 18 kDa (TSPO). These hyperactive microglia initiated a pathological cascade resembling NPC-like phenotypes, including a shortened life span, motor impairments, astrogliosis, neuroaxonal pathology, and increased neurofilament light chain (NF-L), a neuronal injury biomarker. As observed in the mouse model, patients with NPC showed increased NF-L in the blood and microglial hyperactivity, as visualized by TSPO-PET imaging. Reduced TSPO expression in blood-derived macrophages of patients with NPC was measured after N-acetyl-l-leucine treatment, which has been recently shown to have beneficial effects in patients with NPC, suggesting that TSPO is a potential marker to monitor therapeutic interventions for NPC. Conclusively, these results demonstrate that myeloid dysfunction, driven by the loss of NPC1, contributes to NPC disease and should be further investigated for therapeutic targeting and disease monitoring. Editor's summary: Niemann-Pick type C (NPC) disease, a fatal neurological disorder caused by mutations in NPC1, is associated with neuroinflammation and microglial activation. To investigate how microglia are affected by loss of NPC1 and contribute to disease, Dinkel et al. used a mouse model with Npc1 deleted from myeloid cells. These conditional KO mice recapitulated many of the pathological hallmarks seen in patients, such as lipid dyshomeostasis, neurodegeneration, and microgliosis. PET imaging in patients with NPC confirmed the increased microglial activity, and treatment of patients with NALL, an FDA-approved drug for NPC, normalized the phagocytic activity of patient-derived macrophages, suggesting a potential strategy for treatment monitoring. —Daniela Neuhofer [ABSTRACT FROM AUTHOR]

Published
2024
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19. White matter aging drives microglial diversity

Author

Safaiyan, Shima, Besson-Girard, Simon, Kaya, Tuğberk, Cantuti-Castelvetri, Ludovico, Liu, Lu, Ji, Hao, Schifferer, Martina, Gouna, Garyfallia, Usifo, Fumere, Kannaiyan, Nirmal, Fitzner, Dirk, Xiang, Xianyuan, Rossner, Moritz J., Brendel, Matthias, Gokce, Ozgun, and Simons, Mikael

Published
2021
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25. Using a Förster-resonance energy transfer (FRET)-based detection system (FedEcs) to monitor nanoparticle cargo delivery to the brain

Author

Khalin, Igor, primary, Adarsh, Nagappanpillai, additional, Schifferer, Martina, additional, Wehn, Antonia, additional, Boide-Trujillo, Valeria J., additional, Mamrak, Uta, additional, Shrouder, Joshua, additional, Misgeld, Thomas, additional, Filser, Severin, additional, Klymchenko, Andrey, additional, and Plesnila, Nikolaus, additional

Published
2024
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28. Array tomography: trails to discovery

Author

Micheva, Kristina D., Burden, Jemima J., and Schifferer, Martina

Abstract

Tissue slicing is at the core of many approaches to studying biological structures. Among the modern volume electron microscopy (vEM) methods, array tomography (AT) is based on serial ultramicrotomy, section collection onto solid support, imaging via light and/or scanning electron microscopy, and re-assembly of the serial images into a volume for analysis. While AT largely uses standard EM equipment, it provides several advantages, including long-term preservation of the sample and compatibility with multi-scale and multi-modal imaging. Furthermore, the collection of serial ultrathin sections improves axial resolution and provides access for molecular labeling, which is beneficial for light microscopy and immunolabeling, and facilitates correlation with EM. Despite these benefits, AT techniques are underrepresented in imaging facilities and labs, due to their perceived difficulty and lack of training opportunities. Here we point towards novel developments in serial sectioning and image analysis that facilitate the AT pipeline, and solutions to overcome constraints. Because no single vEM technique can serve all needs regarding field of view and resolution, we sketch a decision tree to aid researchers in navigating the plethora of options available. Lastly, we elaborate on the unexplored potential of AT approaches to add valuable insight in diverse biological fields.

Published
2024
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29. ATUM-Tomo: A multi-scale approach to cellular ultrastructure by combined volume scanning electron microscopy and electron tomography

Author

Kislinger, Georg, primary, Fabig, Gunar, additional, Wehn, Antonia, additional, Rodriguez, Lucia, additional, Jiang, Hanyi, additional, Niemann, Cornelia, additional, Klymchenko, Andrey S., additional, Plesnila, Nikolaus, additional, Misgeld, Thomas, additional, Müller-Reichert, Thomas, additional, Khalin, Igor, additional, and Schifferer, Martina, additional

Published
2023
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32. Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease

Author

Ziegler, Karin A., primary, Ahles, Andrea, additional, Dueck, Anne, additional, Esfandyari, Dena, additional, Pichler, Pauline, additional, Weber, Karolin, additional, Kotschi, Stefan, additional, Bartelt, Alexander, additional, Sinicina, Inga, additional, Graw, Matthias, additional, Leonhardt, Heinrich, additional, Weckbach, Ludwig T., additional, Massberg, Steffen, additional, Schifferer, Martina, additional, Simons, Mikael, additional, Hoeher, Luciano, additional, Luo, Jie, additional, Ertürk, Ali, additional, Schiattarella, Gabriele G., additional, Sassi, Yassine, additional, Misgeld, Thomas, additional, and Engelhardt, Stefan, additional

Published
2023
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34. Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex

Author

Mezydlo, Aleksandra, primary, Treiber, Nils, additional, Ullrich Gavilanes, Emily Melisa, additional, Eichenseer, Katharina, additional, Ancău, Mihai, additional, Wens, Adinda, additional, Ares Carral, Carla, additional, Schifferer, Martina, additional, Snaidero, Nicolas, additional, Misgeld, Thomas, additional, and Kerschensteiner, Martin, additional

Published
2023
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35. Myelination generates aberrant ultrastructure that is resolved by microglia

Author

Djannatian, Minou, Radha, Swathi, Weikert, Ulrich, Safaiyan, Shima, Wrede, Christoph, Deichsel, Cassandra, Kislinger, Georg, Rhomberg, Agata, Ruhwedel, Torben, Campbell, Douglas S., van Ham, Tjakko, Schmid, Bettina, Hegermann, Jan, Möbius, Wiebke, Schifferer, Martina, Simons, Mikael, Djannatian, Minou, Radha, Swathi, Weikert, Ulrich, Safaiyan, Shima, Wrede, Christoph, Deichsel, Cassandra, Kislinger, Georg, Rhomberg, Agata, Ruhwedel, Torben, Campbell, Douglas S., van Ham, Tjakko, Schmid, Bettina, Hegermann, Jan, Möbius, Wiebke, Schifferer, Martina, and Simons, Mikael

Abstract

To enable rapid propagation of action potentials, axons are ensheathed by myelin, a multilayered insulating membrane formed by oligodendrocytes. Most of the myelin is generated early in development, resulting in the generation of long-lasting stable membrane structures. Here, we explored structural and dynamic changes in central nervous system myelin during development. To achieve this, we performed an ultrastructural analysis of mouse optic nerves by serial block face scanning electron microscopy (SBF-SEM) and confocal time-lapse imaging in the zebrafish spinal cord. We found that myelin undergoes extensive ultrastructural changes during early postnatal development. Myelin degeneration profiles were engulfed and phagocytosed by microglia using exposed phosphatidylserine as one “eat me” signal. In contrast, retractions of entire myelin sheaths occurred independently of microglia and involved uptake of myelin by the oligodendrocyte itself. Our findings show that the generation of myelin early in development is an inaccurate process associated with aberrant ultrastructural features that require substantial refinement.

Published
2023

37. Myelination generates aberrant ultrastructure that is resolved by microglia

Author

Djannatian, Minou, primary, Radha, Swathi, additional, Weikert, Ulrich, additional, Safaiyan, Shima, additional, Wrede, Christoph, additional, Deichsel, Cassandra, additional, Kislinger, Georg, additional, Rhomberg, Agata, additional, Ruhwedel, Torben, additional, Campbell, Douglas S., additional, van Ham, Tjakko, additional, Schmid, Bettina, additional, Hegermann, Jan, additional, Möbius, Wiebke, additional, Schifferer, Martina, additional, and Simons, Mikael, additional

Published
2023
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39. Neurons on tape: Automated Tape Collecting Ultramicrotomy-mediated volume EM for targeting neuropathology

Author

Kislinger, Georg, Niemann, Cornelia, Rodriguez Martinez, Lucia, Jiang, Hanyi, Fard, Maryam K., Snaidero, Nicolas, Schumacher, Adrian-Minh, Kerschensteiner, Martin, Misgeld, Thomas, and Schifferer, Martina

Subjects
Neurons, Targeting, ATUM, Alzheimer ‘s disease, X-Ray Microtomography, Volume Electron Microscopy, CLEM, methods [Microtomy], Correlation, Mice, Array tomography, Plaques, ddc:570, SEM, Microscopy, Electron, Scanning, Animals, Humans, methods [Imaging, Three-Dimensional], Neuroscience
Abstract

In this chapter, we review Automated Tape Collecting Ultramicrotomy (ATUM), which, among other array tomography methods, substantially simplified large-scale volume electron microscopy (vEM) projects. vEM reveals biological structures at nanometer resolution in three dimensions and resolves ambiguities of two-dimensional representations. However, as the structures of interest—like disease hallmarks emerging from neuropathology—are often rare but the field of view is small, this can easily turn a vEM project into a needle in a haystack problem. One solution for this is correlated light and electron microscopy (CLEM), providing tissue context, dynamic and molecular features before switching to targeted vEM to hone in on the object's ultrastructure. This requires precise coordinate transfer between the two imaging modalities (e.g., by micro computed tomography), especially for block face vEM which relies on physical destruction of sections. With array tomography methods, serial ultrathin sections are collected into a tissue library, thus allowing storage of precious samples like human biopsies and enabling repetitive imaging at different resolution levels for an SEM-based search strategy. For this, ATUM has been developed to reliably collect serial ultrathin sections via a conveyor belt onto a plastic tape that is later mounted onto silicon wafers for serial scanning EM (SEM). The ATUM-SEM procedure is highly modular and can be divided into sample preparation, serial ultramicrotomy onto tape, mounting, serial image acquisition—after which the acquired image stacks can be used for analysis. Here, we describe the steps of this workflow and how ATUM-SEM enables targeting and high resolution imaging of specific structures. ATUM-SEM is widely applicable. To illustrate this, we exemplify the approach by reconstructions of focal pathology in an Alzheimer mouse model and CLEM of a specific cortical synapse.

Published
2023
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41. Spatial Transcriptomics-correlated Electron Microscopy

Author

Androvic, Peter, primary, Schifferer, Martina, additional, Anderson, Katrin Perez, additional, Cantuti-Castelvetri, Ludovico, additional, Ji, Hao, additional, Liu, Lu, additional, Besson-Girard, Simon, additional, Knoferle, Johanna, additional, Simons, Mikael, additional, and Gokce, Ozgun, additional

Published
2022
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43. A new form of axonal pathology in a spinal model of neuromyelitis optica

Author

Herwerth, Marina, primary, Kenet, Selin, additional, Schifferer, Martina, additional, Winkler, Anne, additional, Weber, Melanie, additional, Snaidero, Nicolas, additional, Wang, Mengzhe, additional, Lohrberg, Melanie, additional, Bennett, Jeffrey L., additional, Stadelmann, Christine, additional, Hemmer, Bernhard, additional, and Misgeld, Thomas, additional

Published
2022
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45. Binding of phosphatidylserine‐positive microparticles by PBMCs classifies disease severity in COVID‐19 patients

Author

Rausch, Lisa, primary, Lutz, Konstantin, additional, Schifferer, Martina, additional, Winheim, Elena, additional, Gruber, Rudi, additional, Oesterhaus, Elina F., additional, Rinke, Linus, additional, Hellmuth, Johannes C., additional, Scherer, Clemens, additional, Muenchhoff, Maximilian, additional, Mandel, Christopher, additional, Bergwelt‐Baildon, Michael, additional, Simons, Mikael, additional, Straub, Tobias, additional, Krug, Anne B., additional, Kranich, Jan, additional, and Brocker, Thomas, additional

Published
2021
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48. Niwaki Instead of Random Forests: Targeted Serial Sectioning Scanning Electron Microscopy With Reimaging Capabilities for Exploring Central Nervous System Cell Biology and Pathology

Author

Schifferer, Martina, Snaidero, Nicolas, Djannatian, Minou, Kerschensteiner, Martin, and Misgeld, Thomas

Subjects
Cellular and Molecular Neuroscience, Neuroanatomy, volume EM, ATUM, SEM, Neuroscience (miscellaneous), Review, ddc:610, Anatomy, CLEM, array tomography, targeting
Abstract

Ultrastructural analysis of discrete neurobiological structures by volume scanning electron microscopy (SEM) often constitutes a "needle-in-the-haystack" problem and therefore relies on sophisticated search strategies. The appropriate SEM approach for a given relocation task not only depends on the desired final image quality but also on the complexity and required accuracy of the screening process. Block-face SEM techniques like Focused Ion Beam or serial block-face SEM are "one-shot" imaging runs by nature and, thus, require precise relocation prior to acquisition. In contrast, "multi-shot" approaches conserve the sectioned tissue through the collection of serial sections onto solid support and allow reimaging. These tissue libraries generated by Array Tomography or Automated Tape Collecting Ultramicrotomy can be screened at low resolution to target high resolution SEM. This is particularly useful if a structure of interest is rare or has been predetermined by correlated light microscopy, which can assign molecular, dynamic and functional information to an ultrastructure. As such approaches require bridging mm to nm scales, they rely on tissue trimming at different stages of sample processing. Relocation is facilitated by endogenous or exogenous landmarks that are visible by several imaging modalities, combined with appropriate registration strategies that allow overlaying images of various sources. Here, we discuss the opportunities of using multi-shot serial sectioning SEM approaches, as well as suitable trimming and registration techniques, to slim down the high-resolution imaging volume to the actual structure of interest and hence facilitate ambitious targeted volume SEM projects.

Published
2021
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49. Myelin biogenesis is associated with pathological ultrastructure that is resolved by microglia during development

Author

Djannatian, Minou, primary, Weikert, Ulrich, additional, Safaiyan, Shima, additional, Wrede, Christoph, additional, Deichsel, Cassandra, additional, Kislinger, Georg, additional, Ruhwedel, Torben, additional, Campbell, Douglas S., additional, van Ham, Tjakko, additional, Schmid, Bettina, additional, Hegermann, Jan, additional, Möbius, Wiebke, additional, Schifferer, Martina, additional, and Simons, Mikael, additional

Published
2021
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50. CD8+T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging

Author

Kaya, Tuğberk, Mattugini, Nicola, Liu, Lu, Ji, Hao, Cantuti-Castelvetri, Ludovico, Wu, Jianping, Schifferer, Martina, Groh, Janos, Martini, Rudolf, Besson-Girard, Simon, Kaji, Seiji, Liesz, Arthur, Gokce, Ozgun, and Simons, Mikael

Abstract

A hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. In the present study, we found age-related alterations of oligodendrocyte cell state with a reduction in total oligodendrocyte density in aging murine white matter. Using single-cell RNA-sequencing, we identified interferon (IFN)-responsive oligodendrocytes, which localize in proximity to CD8+T cells in aging white matter. Absence of functional lymphocytes decreased the number of IFN-responsive oligodendrocytes and rescued oligodendrocyte loss, whereas T-cell checkpoint inhibition worsened the aging response. In addition, we identified a subpopulation of lymphocyte-dependent, IFN-responsive microglia in the vicinity of the CD8+T cells in aging white matter. In summary, we provide evidence that CD8+T-cell-induced, IFN-responsive oligodendrocytes and microglia are important modifiers of white matter aging.

Published
2022
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