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First published online February 23, 2005
doi: 10.1242/10.1242/jcs.01658

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Re-establishing the regenerative potential of central nervous system axons in postnatal mice

Kin-Sang Cho¹, Liu Yang¹, Bin Lu^1,*, Hong Feng Ma¹, Xizhong Huang¹, Milos Pekny^2, and Dong Feng Chen^1,

¹ Schepens Eye Research Institute, Program in Neuroscience and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA
² The Arvid Carlsson Institute for Neuroscience, Institute of Clinical Neuroscience, Sahlgrenska Academy, Göteborg University, Medicinaregatan 9A, SE-413 90 Göteborg, Sweden

Authors for correspondence (e-mail: dfchen{at}vision.eri.harvard.edu; milos.pekny{at}medkem.gu.se)

Accepted 22 November 2004

At a certain point in development, axons in the mammalian central nervous system lose their ability to regenerate after injury. Using the optic nerve model, we show that this growth failure coincides with two developmental events: the loss of Bcl-2 expression by neurons and the maturation of astrocytes. Before postnatal day 4, when astrocytes are immature, overexpression of Bcl-2 alone supported robust and rapid optic nerve regeneration over long distances, leading to innervation of brain targets by day 4 in mice. As astrocytes matured after postnatal day 4, axonal regeneration was inhibited in mice overexpressing Bcl-2. Concurrent induction of Bcl-2 and attenuation of reactive gliosis reversed the failure of CNS axonal re-elongation in postnatal mice and led to rapid axonal regeneration over long distances and reinnervation of the brain targets by a majority of severed optic nerve fibers up to 2 weeks of age. These results suggest that an early postnatal downregulation of Bcl-2 and post-traumatic reactive gliosis are two important elements of axon regenerative failure in the CNS.

Key words: Astrocyte intermediate filament, GFAP, Vimentin, Bcl-2, Axon regeneration

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