Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism

Dongming Cai, Shen Yingjing, Maria Elena De Bellard, Song Tang, Marie T. Filbin

Research output: Contribution to journalArticlepeer-review

466 Scopus citations

Abstract

MAG is a potent inhibitor of axonal regeneration. Here, inhibition by MAG, and myelin in general, is blocked if neurons are exposed to neurotrophins before encountering the inhibitor; priming cerebellar neurons with BDNF or GDNF, but not NGF, or priming DRG neurons with any of these neurotrophins blocks inhibition by MAG/myelin. Dibutyryl cAMP also overcomes inhibition by MAG/myelin, and cAMP is elevated by neurotrophins. A PKA inhibitor present during priming abrogates the block of inhibition. Finally, if neurons are exposed to MAG/myelin and neurotrophins simultaneously, but with the G(i) protein inhibitor, inhibition is blocked. We suggest that priming neurons with particular neurotrophins elevates cAMP and activates PKA, which blocks subsequent inhibition of regeneration and that priming is required because MAG/myelin activates a G(i) protein, which blocks increases in cAMP. This is important for encouraging axons to regrow in vivo.

Original languageEnglish
Pages (from-to)89-101
Number of pages13
JournalNeuron
Volume22
Issue number1
DOIs
StatePublished - Jan 1999
Externally publishedYes

Fingerprint

Dive into the research topics of 'Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism'. Together they form a unique fingerprint.

Cite this