المؤلفون: Rovin, Brad H, Parikh, Samir V, Chan, Su Jing, Jandreski, Luke, Ferber, Kyle, Barbey, Catherine, Reynolds, Taylor L

المصدر: Lupus Nephritis

الإتاحة: https://doi.org/10.1136/lupus-2023-lupus21century.72Test

المؤلفون: Somebang, Kerri, Rudolph, Joshua, Imhof, Isabella, Li, Luyi, Niemi, Erene C, Shigenaga, Judy, Tran, Huy, Gill, T Michael, Lo, Iris, Zabel, Brian A, Schmajuk, Gabriela, Wipke, Brian T, Gyoneva, Stefka, Jandreski, Luke, Craft, Michael, Benedetto, Gina, Plowey, Edward D, Charo, Israel, Campbell, James, Ye, Chun Jimmie, Panter, S Scott, Nakamura, Mary C, Eckalbar, Walter, Hsieh, Christine L

المصدر: Cell Reports. 36(12)

مصطلحات موضوعية: Brain Disorders, Traumatic Brain Injury (TBI), Genetics, Neurosciences, Physical Injury - Accidents and Adverse Effects, Traumatic Head and Spine Injury, 2.1 Biological and endogenous factors, Aetiology, Animals, Antigens, Ly, Brain, Brain Injuries, Traumatic, Chemokine CXCL10, Disease Models, Animal, Down-Regulation, Humans, Interferon Regulatory Factor-7, Interferon Type I, Macrophages, Male, Maze Learning, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia, Monocytes, Receptors, CCR2, CCR2, dendritic cells, innate immunity, macrophages, microglia, monocytes, neuroinflammation, single-cell RNA sequencing, traumatic brain injury, type I IFN, Biochemistry and Cell Biology, Medical Physiology

الوصف: In traumatic brain injury (TBI), a diversity of brain resident and peripherally derived myeloid cells have the potential to worsen damage and/or to assist in healing. We define the heterogeneity of microglia and macrophage phenotypes during TBI in wild-type (WT) mice and Ccr2-/- mice, which lack macrophage influx following TBI and are resistant to brain damage. We use unbiased single-cell RNA sequencing methods to uncover 25 microglia, monocyte/macrophage, and dendritic cell subsets in acute TBI and normal brains. We find alterations in transcriptional profiles of microglia subsets in Ccr2-/- TBI mice compared to WT TBI mice indicating that infiltrating monocytes/macrophages influence microglia activation to promote a type I IFN response. Preclinical pharmacological blockade of hCCR2 after injury reduces expression of IFN-responsive gene, Irf7, and improves outcomes. These data extend our understanding of myeloid cell diversity and crosstalk in brain trauma and identify therapeutic targets in myeloid subsets.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2w10n291Test

المؤلفون: Nagy, Dávid, Ennis, Katelin A., Wei, Ru, Su, Susan C., Hinckley, Christopher A., Gu, Rong-Fang, Gao, Benbo, Massol, Ramiro H., Ehrenfels, Chris, Jandreski, Luke, Thomas, Ankur M., Nelson, Ashley, Gyoneva, Stefka, Hajós, Mihály, Burkly, Linda C.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2021 Feb 01. 118(6), 1-11.

الوصول الحر: https://www.jstor.org/stable/27006267Test

المؤلفون: Cole, Tracy A., Zhao, Hien, Collier, Timothy J., Sandoval, Ivette, Sortwell, Caryl E., Steece-Collier, Kathy, Daley, Brian F., Booms, Alix, Lipton, Jack, Welch, Mackenzie, Berman, Melissa, Jandreski, Luke, Graham, Danielle, Weihofen, Andreas, Celano, Stephanie, Schulz, Emily, Cole-Strauss, Allyson, Luna, Esteban, Quach, Duc, Mohan, Apoorva, Frank Bennett, C., Swayze, Eric E., Kordasiewicz, Holly B., Luk, Kelvin C., Paumier, Katrina L.

المصدر: Translational Neuroscience

الوصف: Parkinson’s disease (PD) is a prevalent neurodegenerative disease with no approved disease-modifying therapies. Multiplications, mutations, and single nucleotide polymorphisms in the SNCA gene, encoding α-synuclein (aSyn) protein, either cause or increase risk for PD. Intracellular accumulations of aSyn are pathological hallmarks of PD. Taken together, reduction of aSyn production may provide a disease-modifying therapy for PD. We show that antisense oligonucleotides (ASOs) reduce production of aSyn in rodent preformed fibril (PFF) models of PD. Reduced aSyn production leads to prevention and removal of established aSyn pathology and prevents dopaminergic cell dysfunction. In addition, we address the translational potential of the approach through characterization of human SNCA-targeting ASOs that efficiently suppress the human SNCA transcript in vivo. We demonstrate broad activity and distribution of the human SNCA ASOs throughout the nonhuman primate brain and a corresponding decrease in aSyn cerebral spinal fluid (CSF) levels. Taken together, these data suggest that, by inhibiting production of aSyn, it may be possible to reverse established pathology; thus, these data support the development of SNCA ASOs as a potential disease-modifying therapy for PD and related synucleinopathies.

العلاقة: https://scholar.barrowneuro.org/neurobiology/2040Test; https://doi.org/10.1172/jci.insight.135633Test

الإتاحة: https://doi.org/10.1172/jci.insight.135633Test
https://scholar.barrowneuro.org/neurobiology/2040Test

المؤلفون: Crotti, Andrea, Sait, Hameetha Rajamohamend, McAvoy, Kathleen M., Estrada, Karol, Ergun, Ayla, Szak, Suzanne, Marsh, Galina, Jandreski, Luke, Peterson, Michael, Reynolds, Taylor L., Dalkilic-Liddle, Isin, Cameron, Andrew, Cahir-McFarland, Ellen, Ransohoff, Richard M.

المصدر: Scientific Reports ; volume 9, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: Despite Bridging INtegrator 1 ( BIN1 ) being the second most statistically-significant locus associated to Late Onset Alzheimer’s Disease, its role in disease pathogenesis remains to be clarified. As reports suggest a link between BIN1, Tau and extracellular vesicles, we investigated whether BIN1 could affect Tau spreading via exosomes secretion. We observed that BIN1-associated Tau-containing extracellular vesicles purified from cerebrospinal fluid of AD-affected individuals are seeding-competent. We showed that BIN1 over-expression promotes the release of Tau via extracellular vesicles in vitro as well as exacerbation of Tau pathology in vivo in PS19 mice. Genetic deletion of Bin1 from microglia resulted in reduction of Tau secretion via extracellular vesicles in vitro , and in decrease of Tau spreading in vivo in male, but not female, mice, in the context of PS19 background. Interestingly, ablation of Bin1 in microglia of male mice resulted in significant reduction in the expression of heat-shock proteins, previously implicated in Tau proteostasis. These observations suggest that BIN1 could contribute to the progression of AD-related Tau pathology by altering Tau clearance and promoting release of Tau-enriched extracellular vesicles by microglia.

الإتاحة: https://doi.org/10.1038/s41598-019-45676-0Test
https://www.nature.com/articles/s41598-019-45676-0.pdfTest
https://www.nature.com/articles/s41598-019-45676-0Test

المؤلفون: Maganti, Rajanikanth J., Hronowski, Xiaoping L., Dunstan, Robert W., Wipke, Brian T., Zhang, Xueli, Jandreski, Luke, Hamann, Stefan, Juhasz, Peter

المصدر: Journal of Histochemistry & Cytochemistry ; volume 67, issue 3, page 203-219 ; ISSN 0022-1554 1551-5044

الوصف: Myelin is composed primarily of lipids and diseases affecting myelin are associated with alterations in its lipid composition. However, correlation of the spatial (in situ) distribution of lipids with the disease-associated compositional and morphological changes is not well defined. Herein we applied high resolution matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS), immunohistochemistry (IHC), and liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS) to evaluate brain lipid alterations in the dysmyelinating shiverer (Shi) mouse and cuprizone (Cz) mouse model of reversible demyelination. MALDI-IMS revealed a decrease in the spatial distribution of sulfatide (SHexCer) species, SHexCer (d42:2), and a phosphatidylcholine (PC) species, PC (36:1), in white matter regions like corpus callosum (CC) both in the Shi mouse and Cz mouse model. Changes in these lipid species were restored albeit not entirely upon spontaneous remyelination after demyelination in the Cz mouse model. Lipid distribution changes correlated with the local morphological changes as confirmed by IHC. LC-ESI-MS analyses of CC extracts confirmed the MALDI-IMS derived reductions in SHexCer and PC species. These findings highlight the role of SHexCer and PC in preserving the normal myelin architecture and our experimental approaches provide a morphological basis to define lipid abnormalities relevant to myelin diseases.

الإتاحة: https://doi.org/10.1369/0022155418815860Test

المؤلفون: Pellerin, Kathryn, Rubino, Stephen J, Burns, Jeremy C, Smith, Benjamin A, McCarl, Christie-Ann, Zhu, Jing, Jandreski, Luke, Cullen, Patrick, Carlile, Thomas M, Li, Angela, Rebollar, Jorge Vera, Sybulski, Jennifer, Reynolds, Taylor L, Zhang, Baohong, Basile, Rebecca, Tang, Hao, Harp, Chelsea Parker, Pellerin, Alex, Silbereis, John, Franchimont, Nathalie, Cahir-McFarland, Ellen, Ransohoff, Richard M, Cameron, Thomas O, Mingueneau, Michael

المساهمون: Biogen

المصدر: Brain ; volume 144, issue 8, page 2361-2374 ; ISSN 0006-8950 1460-2156

الوصف: Autoantibodies are a hallmark of numerous neurological disorders, including multiple sclerosis, autoimmune encephalitides and neuromyelitis optica. Whilst well understood in peripheral myeloid cells, the pathophysiological significance of autoantibody-induced Fc receptor signalling in microglia remains unknown, in part due to the lack of a robust in vivo model. Moreover, the application of therapeutic antibodies for neurodegenerative disease also highlights the importance of understanding Fc receptor signalling in microglia. Here, we describe a novel in vivo experimental paradigm that allows for selective engagement of Fc receptors within the CNS by peripherally injecting anti-myelin oligodendrocyte glycoprotein (MOG) monoclonal antibodies into normal wild-type mice. MOG antigen-bound immunoglobulins were detected throughout the CNS and triggered a rapid and tightly regulated proliferative response in both brain and spinal cord microglia. This microglial response was abrogated when anti-MOG antibodies were deprived of Fc receptor effector function or injected into Fcγ receptor knockout mice and was associated with the downregulation of Fc receptors in microglia, but not peripheral myeloid cells, establishing that this response was dependent on central Fc receptor engagement. Downstream of the Fc receptors, BTK was a required signalling node for this response, as microglia proliferation was amplified in BtkE41K knock-in mice expressing a constitutively active form of the enzyme and blunted in mice treated with a CNS-penetrant small molecule inhibitor of BTK. Finally, this response was associated with transient and stringently regulated changes in gene expression predominantly related to cellular proliferation, which markedly differed from transcriptional programs typically associated with Fc receptor engagement in peripheral myeloid cells. Together, these results establish a physiologically-meaningful functional response to Fc receptor and BTK signalling in microglia, while providing a novel in vivo tool ...

الإتاحة: https://doi.org/10.1093/brain/awab231Test
http://academic.oup.com/brain/article-pdf/144/8/2361/40305825/awab231.pdfTest

المؤلفون: Rajanikanth J. Maganti, Xiaoping L. Hronowski, Dunstan, Robert W., Wipke, Brian T., Xueli Zhang, Jandreski, Luke, Hamann, Stefan, Juhasz, Peter

مصطلحات موضوعية: FOS: Biological sciences, FOS: Clinical medicine, Cell Biology, 69999 Biological Sciences not elsewhere classified, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified

الوصف: Supplemental material, DS_10.1369_0022155418815860 for Defining Changes in the Spatial Distribution and Composition of Brain Lipids in the Shiverer and Cuprizone Mouse Models of Myelin Disease by Rajanikanth J. Maganti, Xiaoping L. Hronowski, Robert W. Dunstan, Brian T. Wipke, Xueli Zhang, Luke Jandreski, Stefan Hamann and Peter Juhasz in Journal of Histochemistry & Cytochemistry

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfdbe59843cbff7792b4c65d7d45fdcaTest

المؤلفون: Ding, Jian, Zhang, Wei, Haskett, Scott, Pellerin, Alex, Xu, Shanqin, Petersen, Britta, Jandreski, Luke, Hamann, Stefan, Reynolds, Taylor L., Zheng, Timothy S., Mingueneau, Michael

المصدر: Clinical Immunology ; volume 169, page 69-79 ; ISSN 1521-6616

مصطلحات موضوعية: Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/j.clim.2016.06.007Test
https://api.elsevier.com/content/article/PII:S152166161630105X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S152166161630105X?httpAccept=text/plainTest

المؤلفون: Maganti, Rajanikanth J., Hronowski, Xiaoping L., Dunstan, Robert W., Wipke, Brian T., Zhang, Xueli, Jandreski, Luke, Hamann, Stefan, Juhasz, Peter

المصدر: Journal of Histochemistry & Cytochemistry; Mar2019, Vol. 67 Issue 3, p203-219, 17p

مصطلحات موضوعية: SPATIAL distribution (Quantum optics), IMMUNOHISTOCHEMISTRY, ELECTROSPRAY ionization mass spectrometry, ANIMAL models in research, LECITHIN

مستخلص: Myelin is composed primarily of lipids and diseases affecting myelin are associated with alterations in its lipid composition. However, correlation of the spatial (in situ) distribution of lipids with the disease-associated compositional and morphological changes is not well defined. Herein we applied high resolution matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS), immunohistochemistry (IHC), and liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS) to evaluate brain lipid alterations in the dysmyelinating shiverer (Shi) mouse and cuprizone (Cz) mouse model of reversible demyelination. MALDI-IMS revealed a decrease in the spatial distribution of sulfatide (SHexCer) species, SHexCer (d42:2), and a phosphatidylcholine (PC) species, PC (36:1), in white matter regions like corpus callosum (CC) both in the Shi mouse and Cz mouse model. Changes in these lipid species were restored albeit not entirely upon spontaneous remyelination after demyelination in the Cz mouse model. Lipid distribution changes correlated with the local morphological changes as confirmed by IHC. LC-ESI-MS analyses of CC extracts confirmed the MALDI-IMS derived reductions in SHexCer and PC species. These findings highlight the role of SHexCer and PC in preserving the normal myelin architecture and our experimental approaches provide a morphological basis to define lipid abnormalities relevant to myelin diseases. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Histochemistry & Cytochemistry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)