Ability of GDNF to diminish free radical production leads to protection against kainate-induced excitotoxicity in hippocampus

Henrich Cheng, Fu Show Fu, Jiun Wen Guo

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The primary aim of this study is to explore the protective mechanisms of glial-derived neurotrophic factor (GDNF) during excitotoxicity by kainate in the hippocampus. After a 15-min microinjection with kainate, excitotoxicity was induced in the rat hippocampus. The protective effect of GDNF in the hippocampus was evaluated by administering GDNF 14 min after injection of kainate. The resulting hydroxyl free radicals were quantified by microdialysis of the hippocampus. The results show that GDNF can effectively suppress the production of kainate-induced hydroxyl free radical production. In addition, histological observation indicated the ability of GDNF to decrease the damage level of pyramidal neurons in the CA3 and CA4 areas of the hippocampus. Superoxide dismutase (SOD) activity in the hippocampus was elevated significantly at 30 min and 7 days after kainate induction, while glutathione peroxidase (cGPx) activity did not increase significantly until the seventh day. With GDNF treatment, SOD and cGPx activity in the hippocampus was elevated significantly 7 days after kainate induction. We suggest that mechanisms including a decrease in free radical generation and scavenging of free radicals might be involved in GDNF protection against kainate-induced excitotoxicity.

Original languageEnglish
Pages (from-to)77-86
Number of pages10
JournalHippocampus
Volume14
Issue number1
DOIs
StatePublished - 2004

Keywords

  • Antioxidants
  • Growth factor
  • Neuroprotection
  • Neurotoxicity
  • Trophic factor

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