Tag Archives: microglia

Loss of NPC1 Enhances Phagocytic Uptake and Impairs Lipid Trafficking in Microglia

Loss of NPC1 triggered enhanced phagocytic uptake and impaired myelin turnover in microglia that precede neuronal death.
[Nature Communications]
Colombo, A., Dinkel, L., Müller, S. A., Sebastian Monasor, L., Schifferer, M., Cantuti-Castelvetri, L., König, J., Vidatic, L., Bremova-Ertl, T., Lieberman, A. P., Hecimovic, S., Simons, M., Lichtenthaler, S. F., Strupp, M., Schneider, S. A., & Tahirovic, S. (2021). Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia. Nature Communications, 12(1), 1158. https://doi.org/10.1038/s41467-021-21428-5 Cite
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Metabolic Labeling with an Alkyne Probe Reveals Similarities and Differences in the Prenylomes of Several Brain-Derived Cell Lines and Primary Cells

Applying the method to three brain-related cell lines including neurons, microglia, and astrocytes showed substantial overlap in the prenylated proteins identified.
[Scientific Reports]
Suazo, K. F., Jeong, A., Ahmadi, M., Brown, C., Qu, W., Li, L., & Distefano, M. D. (2021). Metabolic labeling with an alkyne probe reveals similarities and differences in the prenylomes of several brain-derived cell lines and primary cells. Scientific Reports, 11(1), 4367. https://doi.org/10.1038/s41598-021-83666-3 Cite
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Distinct Amyloid-β and Tau-Associated Microglia Profiles in Alzheimer’s Disease

Scientists performed snRNAseq on 482,472 nuclei from non-demented control brains and Alzheimer’s disease (AD) brains containing only amyloid-β plaques or both amyloid-β plaques and tau pathology. Within the microglia population, distinct expression profiles were identified of which two were AD pathology-associated.
[Acta Neuropathologica]
Gerrits, E., Brouwer, N., Kooistra, S. M., Woodbury, M. E., Vermeiren, Y., Lambourne, M., Mulder, J., Kummer, M., Möller, T., Biber, K., Dunnen, W. F. A. den, De Deyn, P. P., Eggen, B. J. L., & Boddeke, E. W. G. M. (2021). Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease. Acta Neuropathologica. https://doi.org/10.1007/s00401-021-02263-w Cite
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Single-Cell RNA Sequencing Reveals Functional Heterogeneity of Glioma-Associated Brain Macrophages

Scientists showed single-cell RNA sequencing of CD11b+ myeloid cells in naĂŻve and GL261 glioma-bearing mice that reveal distinct profiles of microglia, infiltrating monocytes/macrophages and CNS border-associated macrophages.
[Nature Communications]
Ochocka, N., Segit, P., Walentynowicz, K. A., Wojnicki, K., Cyranowski, S., Swatler, J., Mieczkowski, J., & Kaminska, B. (2021). Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages. Nature Communications, 12(1), 1151. https://doi.org/10.1038/s41467-021-21407-w Cite
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Oxidized Phosphatidylcholines Found in Multiple Sclerosis Lesions Mediate Neurodegeneration and Are Neutralized by Microglia

The authors report that oxidized phosphatidylcholines (OxPCs) found in multiple sclerosis lesions are potent drivers of neurodegeneration. Cultured neurons and oligodendrocytes were killed by OxPCs, and this was ameliorated by microglia.
[Nature Neuroscience]
Dong, Y., D’Mello, C., Pinsky, W., Lozinski, B. M., Kaushik, D. K., Ghorbani, S., Moezzi, D., Brown, D., Melo, F. C., Zandee, S., Vo, T., Prat, A., Whitehead, S. N., & Yong, V. W. (2021). Oxidized phosphatidylcholines found in multiple sclerosis lesions mediate neurodegeneration and are neutralized by microglia. Nature Neuroscience, 1–15. https://doi.org/10.1038/s41593-021-00801-z Cite
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White Matter Aging Drives Microglial Diversity

Using single-cell RNA sequencing from white and gray matter separately, investigators identified white matter-associated microglia, which share parts of the disease-associated microglia gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism.
[Neuron]
Safaiyan, S., Besson-Girard, S., Kaya, T., Cantuti-Castelvetri, L., Liu, L., Ji, H., Schifferer, M., Gouna, G., Usifo, F., Kannaiyan, N., Fitzner, D., Xiang, X., Rossner, M. J., Brendel, M., Gokce, O., & Simons, M. (2021). White matter aging drives microglial diversity. Neuron, 0(0). https://doi.org/10.1016/j.neuron.2021.01.027 Cite
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Neuroinflammation Induces Synaptic Scaling through IL-1β-Mediated Activation of the Transcriptional Repressor REST/NRSF

The authors analyzed RE1-silencing transcription factor (REST) in neuroblastoma cells and mouse cortical neurons treated with activated T cell or microglia supernatant and distinct pro-inflammatory cytokines.
[Cell Death & Disease]
Neuroinflammation induces synaptic scaling through IL-1β-mediated activation of the transcriptional repressor REST/NRSF | Cell Death & Disease. (n.d.). Retrieved February 16, 2021, from https://www.nature.com/articles/s41419-021-03465-6 Cite
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Effects of Innate Immune Receptor Stimulation on Extracellular α-Synuclein Uptake and Degradation by Brain Resident Cells

Investigators examined whether stimulation of Toll-like receptor (TLR) could modulate the cellular uptake and degradation of α-synuclein (α-syn) fibrils despite a lack of direct interaction. They observed that stimulation of TLR2 in vitro accelerated α-syn fibril uptake in neurons and glia while delaying the degradation of α-syn in neurons and astrocytes.
[Experimental and Molecular Medicine]
Kim, C., Kwon, S., Iba, M., Spencer, B., Rockenstein, E., Mante, M., Adame, A., Shin, S. J., Fields, J. A., Rissman, R. A., Lee, S.-J., & Masliah, E. (2021). Effects of innate immune receptor stimulation on extracellular α-synuclein uptake and degradation by brain resident cells. Experimental & Molecular Medicine, 1–10. https://doi.org/10.1038/s12276-021-00562-6 Cite
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TAMEP Are Brain Tumor Parenchymal Cells Controlling Neoplastic Angiogenesis and Progression

The authors investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile that transiently appeared during glioblastoma growth.
[Cell Systems]
Kälin, R. E., Cai, L., Li, Y., Zhao, D., Zhang, H., Cheng, J., Zhang, W., Wu, Y., Eisenhut, K., Janssen, P., Schmitt, L., Enard, W., Michels, F., Flüh, C., Hou, M., Kirchleitner, S. V., Siller, S., Schiemann, M., Andrä, I., … Glass, R. (2021). TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression. Cell Systems, 0(0). https://doi.org/10.1016/j.cels.2021.01.002 Cite
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Engineering Adeno-Associated Viral Vectors to Evade Innate Immune and Inflammatory Responses

The engineered vectors elicited markedly reduced innate immune and T cell responses and enhanced gene expression in clinically relevant mouse and pig models across different tissues
[Science Translational Medicine]
Chan, Y. K., Wang, S. K., Chu, C. J., Copland, D. A., Letizia, A. J., Verdera, H. C., Chiang, J. J., Sethi, M., Wang, M. K., Neidermyer, W. J., Chan, Y., Lim, E. T., Graveline, A. R., Sanchez, M., Boyd, R. F., Vihtelic, T. S., Inciong, R. G. C. O., Slain, J. M., Alphonse, P. J., … Church, G. M. (2021). Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses. Science Translational Medicine, 13(580). https://doi.org/10.1126/scitranslmed.abd3438 Cite
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Two Macrophages, Osteoclasts and Microglia: From Development to Pleiotropy

Investigators discuss that the Pyk2-mediated actin polymerization pathway in osteoclasts and microglia in bone and brain, respectively, is the horizontal pleiotropic mediator of shared risk factors for osteoporosis and Alzheimer’s disease.
[Bone Research]
Lee, J.-W., Lee, I.-H., Iimura, T., & Kong, S. W. (2021). Two macrophages, osteoclasts and microglia: from development to pleiotropy. Bone Research, 9(1), 1–10. https://doi.org/10.1038/s41413-020-00134-w Cite
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