Glial cell line-derived neurotrophic factor protects midbrain dopaminergic neurons against lipopolysaccharide neurotoxicity

Xing, Bin; Xin, Tao; Zhao, Lingling; Hunter, Randy L.; Chen, Yan; Bing, Guoying

doi:10.1016/j.jneuroim.2010.04.010

« Previous Next »Journal of Neuroimmunology
Volume 225, Issue 1 , Pages 43-51, 25 August 2010

Glial cell line-derived neurotrophic factor protects midbrain dopaminergic neurons against lipopolysaccharide neurotoxicity

Bin Xing
- Department of Anatomy & Neurobiology, Rose 800 Street, University of Kentucky, Lexington, KY 40536, USA
- These authors contributed equally to this work.
- Tel.: +1 214 645 6243.
Tao Xin
- Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University, Jinan 250012, PR China
- These authors contributed equally to this work.
Lingling Zhao
- Xiangya Third Hospital, Central South University, Changsha, Hunan 410013, PR China
Randy L. Hunter
- Department of Anatomy & Neurobiology, Rose 800 Street, University of Kentucky, Lexington, KY 40536, USA
Yan Chen
- Department of Anatomy & Neurobiology, Rose 800 Street, University of Kentucky, Lexington, KY 40536, USA
Guoying Bing
- Department of Anatomy & Neurobiology, Rose 800 Street, University of Kentucky, Lexington, KY 40536, USA
- Corresponding author. Tel.: +1 859 323 9708; fax: +1 859 257 3625.

Received 8 December 2009; received in revised form 18 April 2010; accepted 19 April 2010. published online 17 May 2010.

Abstract

Aberrant microglia activation causes dopaminergic neuronal loss and nitric oxide produced by microglia plays a critical role in dopaminergic neuronal degeneration. However, no study has determined if GDNF protects dopaminergic neurons via inhibiting nitric oxide generation in Parkinson's disease animal model. We report that GDNF not only reduces lipopolysaccharide-induced degeneration of dopaminergic neurons, suppresses microglia activation and nitric oxide generation, but also reverses the inhibition of phosphoinositide 3-kinase (PI3K) in dopaminergic neurons and microglia. It suggests that the neuroprotective effect of GDNF on dopaminergic neurons may be related to its suppression of microglia activation-mediated nitric oxide via releasing the inhibition of PI3K in both neurons and microglia.

Keywords: Parkinson's disease, GDNF, Dopaminergic neurons, Microglia, Nitric oxide, PI3K