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

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.

journal_name

Glia

journal_title

Glia

authors

Ryu JK,Shin WH,Kim J,Joe EH,Lee YB,Cho KG,Oh YJ,Kim SU,Jin BK

doi

10.1002/glia.10047

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

15-23

issue

1

eissn

0894-1491

issn

1098-1136

pii

10.1002/glia.10047

journal_volume

38

pub_type

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