Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro

Dongming Cai, Kangwen Deng, Wilfredo Mellado, Junghee Lee, Rajiv R. Ratan, Marie T. Filbin

Research output: Contribution to journalArticlepeer-review

287 Scopus citations

Abstract

Elevation of cAMP can overcome myelin inhibitors to encourage regeneration of the CNS. We show that a consequence of elevated cAMP is the synthesis of polyamines, resulting from an up-regulation of Arginase I, a key enzyme in their synthesis. Inhibiting polyamine synthesis blocks the cAMP effect on regeneration. Either over-expression of Arginase I or exogenous polyamines can overcome inhibition by MAG and by myelin in general. While MAG/myelin support the growth of young DRG neurons, they become inhibitory as DRGs mature. Endogenous Arginase I levels are high in young DRGs but drop spontaneously at an age that coincides with the switch from promotion to inhibition by MAG/myelin. Over-expressing Arginase I in maturing DRGs blocks that switch. Arginase I and polyamines are more specific targets than cAMP for intervention to encourage regeneration after CNS injury.

Original languageEnglish (US)
Pages (from-to)711-719
Number of pages9
JournalNeuron
Volume35
Issue number4
DOIs
StatePublished - Aug 15 2002
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. Roger Persell for critically reading this manuscript and Dr. Lloyd Williams for his assistance with the image analysis. This work was supported by grants from the National Multiple Sclerosis Society, NIH (NINDS NS 37060 to M.T.F. and NS40591 to R.R.R.), a grant to support a Specialized Neuroscience Research Program (SNRP) from NIH (NINDS and NCRR; NS41073) at Hunter College, and a core facility grant from Research Center for Minority Institutions.

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