Minocycline blocks 6-hydroxydopamine-induced neurotoxicity and free radical production in rat cerebellar granule neurons.
Neurotoxicity induced by 6-hydroxydopamine (6-OHDA) is believed to be due, in part, to the production of reactive oxygen species (ROS). Anti-oxidants by inhibiting free radical generation, protect neurons against 6-OHDA-induced neurotoxicity. In this study, we investigated whether or not minocycline, a neuroprotective compound, could directly protect neurons against 6-OHDA-induced neurotoxicity and inhibit 6-OHDA-induced free radical production in cultured rat cerebellar granule neurons (CGN). We now report that exposure of CGN to 6-OHDA (100 microM) resulted in a significant increase in free radical production with death of 86% of CGN. Pretreatment with minocycline (10 microM) for 2 h prevented 6-OHDA-induced free radical generation and neurotoxicity. Furthermore, minocycline also attenuated H(2)O(2)-induced neurotoxicity. Our results suggest that minocycline blocks 6-OHDA-induced neuronal death possibly by inhibiting 6-OHDA-induced free radical generation in CGN. Both the antioxidative and neuroprotective effects of minocycline may be beneficial in the therapy of Parkinson's disease and other neurodegenerative diseases.
Lin
Suizhen
S
Department of Neurology, Indiana University School of Medicine, 975 West Walnut Street, Rm 457, Indianapolis, IN 46202, USA.
Wei
Xing
X
Xu
Yong
Y
Yan
Chong
C
Dodel
Richard
R
Zhang
Yuqin
Y
Liu
Junyi
J
Klaunig
James E
JE
Farlow
Martin
M
Du
Yansheng
Y
D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D003594:Cytoplasmic Granules; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008911:Minocycline / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D018663:Adrenergic Agents; D000900:Anti-Bacterial Agents; D005609:Free Radicals; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D008911:Minocycline