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Activin A is essential for neurogenesis following neurodegeneration


It has long been proposed that excitotoxicity contributes to nerve cell death in neurodegenerative diseases. Activin A, AQ3 a member of the transforming growth factor-b superfamily, is expressed by neurons following excitotoxicity. We show for the first time that this activin A expression is essential for neurogenesis to proceed following neurodegeneration. We found that intraventricular infusion of activin A increased the number of newborn neurons in the dentate gyrus, CA3, and CA1 layers of the normal adult hippocampus and also, following lipopolysaccharide administration, had a potent inhibitory effect on gliosis in vivo and on microglial proliferation in vivo and in vitro. Consistent with the role of activin A in regulating central AQ4 nervous system inflammation and neurogenesis, intraventricular infusion of follistatin, an activin A antagonist, profoundly impaired neurogenesis and increased the number of microglia and reactive astrocytes following onset of kainic acid-induced eurodegeneration. These results show that inhibiting activin A is permissive for a potent underlying inflammatory response to neurodegeneration. We demonstrate that the anti-inflammatory actions of activin A account entirely for its neurogenic effects following neurodegeneration because co-administration of nonsteroidal anti-inflammatory drugs reversed follistatin?s inhibitory effects on neurogenesis in vivo. Our work indicates that activin A expression, perhaps working in conjunction with other transforming growth factor-b superfamily molecules, is essential for neurogenesis in the adult central nervous system following excitotoxic neurodegeneration and suggests neurons can regulate regeneration by suppressing the inflammatory response, a finding with implications for understanding and treating acute and chronic neurodegenerative

Type Journal
ISBN 1549-4918 (Electronic)
Authors Adipranoto-Cowley, A.; Park, J.S.; Croucher, D.; Daniel, J.; Henshall, S.M.; Galbraith, S.; Mervin, K.; Vissel, B.
Publisher Name STEM CELLS
Published Date 2009-06-01
Published Volume 27
Published Issue 6
Published Pages 1330-1346
Status Published in-print
DOI 10.1002/stem.80
URL link to publisher's version
OpenAccess link to author's accepted manuscript version