Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo
Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo
Abstract Aggregation and accumulation of amyloid-β (Aβ) is a defining feature of Alzheimer’s disease (AD) pathology. To study microglial responses to Aβ, we applied exogenous Aβ peptide, in either oligomeric or fibrillar conformation, to primary mouse microglial cultures and evaluated system level transcriptional changes and then compared these to transcriptomic changes in the brains of CRND8 APP mice. We find that primary microglial cultures have rapid and massive transcriptional change to in response to Aβ. Transcriptomic responses to oligomeric or fibrillar Aβ in primary microglia, though partially overlapping, are distinct and are not recapitulated in vivo where Aβ progressively accumulates. Furthermore, though classic immune mediators show massive transcriptional changes in the primary microglial cultures, these changes are not observed in the mouse model. Together, these data extend previous studies which demonstrate that microglia responses ex vivo are poor proxies for in vivo responses. Finally, these data demonstrate the potential utility of using microglia as biosensors of different aggregate conformation, as the transcriptional responses to oligomeric and fibrillar Aβ can be distinguished.
Wang Xue、Robinson Max、Chakrabarty Paramita、Golde Todd E.、Ladd Thomas、Moore Brenda、Ceballos Carolina、McFarland Karen N.、Funk Cory C、Baloni Priyanka、Allen Mariet、Golde Griffin、Rosario Awilda、Rappaport Noa、Ertekin-Taner Nil¨1fer
Mayo Clinic, Department of Health Sciences ResearchInstitute for Systems BiologyUniversity of Florida, Center for Translational Research in Neurodegenerative Disease||University of Florida, McKnight Brain Institute||University of Florida, Department of NeuroscienceUniversity of Florida, Center for Translational Research in Neurodegenerative Disease||University of Florida, McKnight Brain Institute||University of Florida, Department of NeuroscienceUniversity of Florida, Center for Translational Research in Neurodegenerative Disease||University of Florida, McKnight Brain Institute||University of Florida, Department of NeuroscienceUniversity of Florida, Center for Translational Research in Neurodegenerative Disease||University of Florida, McKnight Brain Institute||University of Florida, Department of NeuroscienceUniversity of Florida, Center for Translational Research in Neurodegenerative Disease||University of Florida, McKnight Brain Institute||University of Florida, Department of NeuroscienceUniversity of Florida, Department of Neurology||University of Florida, Center for Translational Research in Neurodegenerative Disease||University of Florida, McKnight Brain InstituteInstitute for Systems BiologyInstitute for Systems BiologyMayo Clinic, Department of NeuroscienceUniversity of Florida, Center for Translational Research in Neurodegenerative DiseaseUniversity of Florida, Center for Translational Research in Neurodegenerative Disease||University of Florida, McKnight Brain Institute||University of Florida, Department of NeuroscienceInstitute for Systems BiologyMayo Clinic, Department of Neuroscience||Mayo Clinic, Department of Neurology
基础医学神经病学、精神病学生物科学研究方法、生物科学研究技术
Wang Xue,Robinson Max,Chakrabarty Paramita,Golde Todd E.,Ladd Thomas,Moore Brenda,Ceballos Carolina,McFarland Karen N.,Funk Cory C,Baloni Priyanka,Allen Mariet,Golde Griffin,Rosario Awilda,Rappaport Noa,Ertekin-Taner Nil¨1fer.Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivo[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/2021.03.02.433544.点此复制
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