title: GADD45A protects against cell death in dorsal root ganglion neurons following peripheral nerve injury.
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.
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Lin
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Yang
authors.forename: Chiu-En
authors.initials: CE
authors.lastname: Huang
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Wu
authors.forename: Yi-Shen
authors.initials: YS
authors.lastname: Chen
authors.forename: Shyr-Ming
authors.initials: SM
authors.lastname: Sheen-Chen
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Huang
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy / Q000379:methods; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology; D008024:Ligands; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D020932:Nerve Growth Factor / Q000172:deficiency; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D008024:Ligands; D020932:Nerve Growth Factor; D009687:Nuclear Proteins; C499073:Gadd45a protein, rat; D000097642:GADD45 Proteins