Journal
NATURE
Volume 541, Issue 7638, Pages 481-487Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature21029
Keywords
-
Categories
Funding
- National Institutes of Health [R01 AG048814, RO1 DA15043, P50 NS38377]
- Christopher and Dana Reeve Foundation
- Novartis Institute for Biomedical Research
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- JPB Foundation
- Cure Alzheimer's Fund
- Glenn Foundation
- Esther B O'Keeffe Charitable Foundation
- Maryland Stem Cell Research Fund [2013-MSCRFII-0105-00, 2012-MSCRFII-0268-00, 2014-MSCRFF-0665]
- Australian National Health and Medical Research Council [GNT1052961]
- Glenn Foundation Glenn Award
- Merck Research Laboratories postdoctoral fellowship
- NEI [K99EY024690]
- Damon Runyon Cancer Research Foundation [DRG-2125-12]
- German Research Foundation (DFG) [SCHI 1330/1-1]
- Foundation's Parkinson's Disease Program [M-2014]
- Stanford Alzheimer's disease research Centre [AG047366]
- Stanford Health Care Brain Bank
- Multiple Sclerosis Society of Great Britain and Northern Ireland [207495]
Ask authors/readers for more resources
Reactive astrocytes are strongly induced by central nervous system (CNS) injury and disease, but their role is poorly understood. Here we show that a subtype of reactive astrocytes, which we termed A1, is induced by classically activated neuroinflammatory microglia. We show that activated microglia induce A1 astrocytes by secreting Il-1 alpha, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A1 astrocytes. A1 astrocytes lose the ability to promote neuronal survival, outgrowth, synaptogenesis and phagocytosis, and induce the death of neurons and oligodendrocytes. Death of axotomized CNS neurons in vivo is prevented when the formation of A1 astrocytes is blocked. Finally, we show that A1 astrocytes are abundant in various human neurodegenerative diseases including Alzheimer's, Huntington's and Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis. Taken together these findings help to explain why CNS neurons die after axotomy, strongly suggest that A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders, and provide opportunities for the development of new treatments for these diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available