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Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: role of microglia.

Authors
Ryu, JK; Shin, WH; Kim, J; Joe, EH; Lee, YB; Cho, KG; Oh, YJ; Kim, SU; Jin, BK
Citation
Glia, 38(1):15-23, 2002
Journal Title
Glia
ISSN
0894-14911098-1136
Abstract
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 N(G)-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.
MeSH terms
Animals*Antigens, CDAntigens, CD147*Antigens, Neoplasm*Antigens, Surface*Avian Proteins*Blood ProteinsCell Death/drug effects/*physiologyDopamine/*metabolismEnzyme Inhibitors/pharmacologyFemaleGangliosides/*metabolism/toxicityGliosis/chemically induced/metabolism/physiopathologyImmunohistochemistryMembrane Glycoproteins/metabolismMicroglia/drug effects/*metabolismNG-Nitroarginine Methyl Ester/pharmacologyNeurons/drug effects/*metabolismNitric Oxide/biosynthesisNitric Oxide Synthase/drug effects/metabolismParkinson Disease/*metabolism/pathology/physiopathologyRatsRats, Sprague-DawleySubstantia Nigra/drug effects/*metabolism/physiopathology
DOI
10.1002/glia.10047
PMID
11921200
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
조, 은혜이, 용범조, 경기김, 승업진, 병관
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