Jae K. Ryu and Won H. Shin contributed equally to this work.
Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: Role of microglia
Version of Record online: 15 FEB 2002
Copyright © 2002 Wiley-Liss, Inc.
Volume 38, Issue 1, pages 15–23, 1 April 2002
How to Cite
Ryu, J. K., Shin, W. H., Kim, J., Joe, E. H., Lee, Y. B., Cho, K. G., Oh, Y. J., Kim, S. U. and Jin, B. K. (2002), Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: Role of microglia. Glia, 38: 15–23. doi: 10.1002/glia.10047
- Issue online: 15 FEB 2002
- Version of Record online: 15 FEB 2002
- Manuscript Accepted: 28 NOV 2001
- Manuscript Received: 10 JUL 2001
- KOSEF. Grant Number: 1999-2-210-002-5
- Frontier 21 Project
- neuronal cell death;
- inducible nitric oxide synthase;
- Parkinson's disease
We recently showed that trisialoganglioside (GT1b) induces cell death of dopaminergic neurons in rat mesencephalic cultures (Chung et al., Neuroreport 12:611–614, 2001). The present study examines the in vivo neurotoxic effects of GT1b on dopaminergic neurons in the substantia nigra (SN) of Sprague-Dawley rats. Seven days after GT1b injection into the SN, immunocytochemical staining of SN tissue revealed death of nigral neurons, including dopaminergic neurons. Additional immunostaining using OX-42 and OX-6 antibodies showed that GT1b-activated microglia were present in the SN where degeneration of nigral neurons was found. Western blot analysis and double-labeled immunohistochemistry showed that inducible nitric oxide synthase (iNOS) was expressed in the SN, where its levels were maximal at 8 h post-GT1b injection, and that iNOS was localized exclusively within microglia. GT1b-induced loss of dopaminergic neurons in the SN was partially inhibited by NG-nitro-L-arginine methyl ester hydrochloride, an NOS inhibitor. Our results indicate that in vivo neurotoxicity of GT1b against nigral dopaminergic neurons is at least in part mediated by nitric oxide released from activated microglia. Because GT1b exists abundantly in central nervous system neuronal membranes, our data support the hypothesis that immune-mediated events triggered by endogenous compounds such as GT1b could contribute to the initiation and/or the progression of dopaminergic neuronal cell death that occurs in Parkinson's disease. GLIA 38:15–23, 2002. © 2002 Wiley-Liss, Inc.