Gadd45a protects against cell death in dorsal root ganglion neurons following peripheral nerve injury

Chung Ren Lin, Chien Hui Yang, Chiu En Huang, Chih Hsien Wu, Yi Shen Chen, Shyr Ming Sheen-Chen, Hui Wen Huang, Kuan Hung Chen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

A significant loss of neurons in the dorsal root ganglia (DRG) has been reported in animal models of peripheral nerve injury. Neonatal sensory neurons are more susceptible than adult neurons to axotomy- or nerve growth factor (NGF) withdrawal-induced cell death. To develop therapies for preventing irreversible sensory cell loss, it is essential to understand the molecular mechanisms responsible for DRG cell death and survival. Here we describe how the expression of the growth arrest- and DNA damage-inducible gene 45α (GADD45A) is correlated with neuronal survival after axotomy in vivo and after NGF withdrawal in vitro. GADD45A expression is low at birth and does not change significantly after spinal nerve ligation (SNL). In contrast, GADD45A is robustly up-regulated in the adult rat DRG 24 hr after SNL, and this up-regulation persists as long as the injured fibers are prevented from regenerating. In vitro delivery of GADD45A protects neonatal rat DRG neurons from NGF withdrawal-induced cytochrome c release and cell death. In addition, in vivo knockdown of GADD45A expression in adult injured DRG by small hairpin RNA increased cell death. Our results indicate that GADD45A protects neuronal cells from SNL-induced cell death.

Original languageEnglish
Pages (from-to)689-699
Number of pages11
JournalJournal of Neuroscience Research
Volume89
Issue number5
DOIs
Publication statusPublished - May 1 2011
Externally publishedYes

Keywords

  • Apoptosis
  • Axotomy
  • Small hairpin RNA
  • Viral vector

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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