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

Jae K. Ryu, Won H. Shin, Jean Kim, Eun H. Joe, Yong B. Lee, Kyung G. Cho, Young J. Oh, Seung U. Kim, Byung K. Jin

Research output: Contribution to journalArticle

48 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalGlia
Volume38
Issue number1
DOIs
Publication statusPublished - 2002 Apr 1

Fingerprint

Dopaminergic Neurons
Microglia
Substantia Nigra
Nitric Oxide Synthase Type II
Cell Death
trisialoganglioside GT1
Nerve Degeneration
Injections
NG-Nitroarginine Methyl Ester
Sprague Dawley Rats
Parkinson Disease
Nitric Oxide
Central Nervous System
Western Blotting
Immunohistochemistry
Staining and Labeling
Neurons
Membranes
Antibodies

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Ryu, J. K., Shin, W. H., Kim, J., Joe, E. H., Lee, Y. B., Cho, K. G., ... Jin, B. K. (2002). Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: Role of microglia. Glia, 38(1), 15-23. https://doi.org/10.1002/glia.10047
Ryu, Jae K. ; Shin, Won H. ; Kim, Jean ; Joe, Eun H. ; Lee, Yong B. ; Cho, Kyung G. ; Oh, Young J. ; Kim, Seung U. ; Jin, Byung K. / Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons : Role of microglia. In: Glia. 2002 ; Vol. 38, No. 1. pp. 15-23.
@article{04a7e90efea84b2fbf787294aa00dded,
title = "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 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.",
author = "Ryu, {Jae K.} and Shin, {Won H.} and Jean Kim and Joe, {Eun H.} and Lee, {Yong B.} and Cho, {Kyung G.} and Oh, {Young J.} and Kim, {Seung U.} and Jin, {Byung K.}",
year = "2002",
month = "4",
day = "1",
doi = "10.1002/glia.10047",
language = "English",
volume = "38",
pages = "15--23",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

Ryu, JK, Shin, WH, Kim, J, Joe, EH, Lee, YB, Cho, KG, Oh, YJ, Kim, SU & Jin, BK 2002, 'Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: Role of microglia', Glia, vol. 38, no. 1, pp. 15-23. https://doi.org/10.1002/glia.10047

Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons : Role of microglia. / Ryu, Jae K.; Shin, Won H.; Kim, Jean; Joe, Eun H.; Lee, Yong B.; Cho, Kyung G.; Oh, Young J.; Kim, Seung U.; Jin, Byung K.

In: Glia, Vol. 38, No. 1, 01.04.2002, p. 15-23.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons

T2 - Role of microglia

AU - Ryu, Jae K.

AU - Shin, Won H.

AU - Kim, Jean

AU - Joe, Eun H.

AU - Lee, Yong B.

AU - Cho, Kyung G.

AU - Oh, Young J.

AU - Kim, Seung U.

AU - Jin, Byung K.

PY - 2002/4/1

Y1 - 2002/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0036544646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036544646&partnerID=8YFLogxK

U2 - 10.1002/glia.10047

DO - 10.1002/glia.10047

M3 - Article

C2 - 11921200

AN - SCOPUS:0036544646

VL - 38

SP - 15

EP - 23

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 1

ER -