Neuroinflammatory reactive astrocytes in acute injury and neurodegenerative disease
Guttenplan KA1, Liddelow SA1, Münch AE1, Weigel MK1, Clarke LE1, Bennett FC1, Bennett ML11 Wilton DK2, Frouin A2, Panicker N3, Kumar M3, Dawson VL3, Dawson TM3, Stevens B2, Barres BA1 1Department of Neurobiology, Stanford University 2Department of Neurology, Boston Children's Hospital 3Department of Neuroscience, Johns Hopkins University
Reactive astrocytes are strongly induced by central nervous system injury and disease, but their role is poorly understood. We previously found that a subtype of reactive astrocytes is induced by Il-1a, TNFa, and C1q secreted from neuroinflammatory microglia. Further, we showed that these neuroinflammatory reactive astrocytes secrete a factor(s) that kills neurons and oligodendrocytes and saw upregulation of these reactive astrocytes in tissue from patients with neurodegenerative diseases. We are now using our serum-free system for astrocyte culture to determine the identity of the astrocyte-secreted toxin(s) and using genetic mouse lines that inhibit reactive astrocyte formation to determine if reactive astrocytes contribute to neurodegenerative disease.
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