Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration

Toyoko Arimoto; Guoying Bing

doi:10.1016/S0969-9961(02)00017-7

Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration

Toyoko Arimoto, Guoying Bing

Neuroscience

Research output: Contribution to journal › Article › peer-review

174 Scopus citations

Abstract

The present study was designed to examine whether expression of iNOS was involved in LPS-induced neurodegeneration in rat substantia nigra (SN) and to study the role of NO in the loss of the SN dopaminergic neurons. In Western blot analysis, iNOS was induced in the SN after injection of LPS in a time- and dose-dependent manner. Immunofluorescence and immunohistochemical analyses revealed that the iNOS is located in a fully activated microglia with the characteristic amoeboid morphology. Furthermore, LPS-induced loss of dopaminergic neurons was significantly inhibited by the administration of L-N^G-nitroarginine, a selective inhibitor of NOS, and the glucocorticoid dexamethasone. These inhibiting agents for iNOS reduced LPS-induced microglial activation, suggesting that NO has a role in inflammatory-mediated microglial activation. These results demonstrate that LPS induces the expression of iNOS in activated microglia in the SN, and that NO and/or its metabolites may play a crucial role in inflammation-mediated degeneration of dopaminergic neurons.

Original language	English
Pages (from-to)	35-45
Number of pages	11
Journal	Neurobiology of Disease
Volume	12
Issue number	1
DOIs	https://doi.org/10.1016/S0969-9961(02)00017-7
State	Published - Feb 2003

Bibliographical note

Funding Information:
We gratefully acknowledge Sarah Kennedy for her immunohistochemistry technical assistance and Xuan Nguyen for his computer technical assistance, as well as Dr. Robert Lasley for help with the NO analyzer. This work was supported by a grant from NIH (NS 39345 to G.B.).

Funding

We gratefully acknowledge Sarah Kennedy for her immunohistochemistry technical assistance and Xuan Nguyen for his computer technical assistance, as well as Dr. Robert Lasley for help with the NO analyzer. This work was supported by a grant from NIH (NS 39345 to G.B.).

Funders	Funder number
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke	R01NS039345

Keywords

Inducible nitric oxide synthase
Inflammation
Lipopolysaccharide
Microglia
Neurodegeneration
Nitric oxide

ASJC Scopus subject areas

Neurology

Access to Document

10.1016/S0969-9961(02)00017-7

Cite this

@article{890b23070f8848dcb4053b3e7f90a48a,

title = "Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration",

abstract = "The present study was designed to examine whether expression of iNOS was involved in LPS-induced neurodegeneration in rat substantia nigra (SN) and to study the role of NO in the loss of the SN dopaminergic neurons. In Western blot analysis, iNOS was induced in the SN after injection of LPS in a time- and dose-dependent manner. Immunofluorescence and immunohistochemical analyses revealed that the iNOS is located in a fully activated microglia with the characteristic amoeboid morphology. Furthermore, LPS-induced loss of dopaminergic neurons was significantly inhibited by the administration of L-NG-nitroarginine, a selective inhibitor of NOS, and the glucocorticoid dexamethasone. These inhibiting agents for iNOS reduced LPS-induced microglial activation, suggesting that NO has a role in inflammatory-mediated microglial activation. These results demonstrate that LPS induces the expression of iNOS in activated microglia in the SN, and that NO and/or its metabolites may play a crucial role in inflammation-mediated degeneration of dopaminergic neurons.",

keywords = "Inducible nitric oxide synthase, Inflammation, Lipopolysaccharide, Microglia, Neurodegeneration, Nitric oxide",

author = "Toyoko Arimoto and Guoying Bing",

note = "Funding Information: We gratefully acknowledge Sarah Kennedy for her immunohistochemistry technical assistance and Xuan Nguyen for his computer technical assistance, as well as Dr. Robert Lasley for help with the NO analyzer. This work was supported by a grant from NIH (NS 39345 to G.B.).",

year = "2003",

month = feb,

doi = "10.1016/S0969-9961(02)00017-7",

language = "English",

volume = "12",

pages = "35--45",

number = "1",

}

TY - JOUR

T1 - Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration

AU - Arimoto, Toyoko

AU - Bing, Guoying

N1 - Funding Information: We gratefully acknowledge Sarah Kennedy for her immunohistochemistry technical assistance and Xuan Nguyen for his computer technical assistance, as well as Dr. Robert Lasley for help with the NO analyzer. This work was supported by a grant from NIH (NS 39345 to G.B.).

PY - 2003/2

Y1 - 2003/2

N2 - The present study was designed to examine whether expression of iNOS was involved in LPS-induced neurodegeneration in rat substantia nigra (SN) and to study the role of NO in the loss of the SN dopaminergic neurons. In Western blot analysis, iNOS was induced in the SN after injection of LPS in a time- and dose-dependent manner. Immunofluorescence and immunohistochemical analyses revealed that the iNOS is located in a fully activated microglia with the characteristic amoeboid morphology. Furthermore, LPS-induced loss of dopaminergic neurons was significantly inhibited by the administration of L-NG-nitroarginine, a selective inhibitor of NOS, and the glucocorticoid dexamethasone. These inhibiting agents for iNOS reduced LPS-induced microglial activation, suggesting that NO has a role in inflammatory-mediated microglial activation. These results demonstrate that LPS induces the expression of iNOS in activated microglia in the SN, and that NO and/or its metabolites may play a crucial role in inflammation-mediated degeneration of dopaminergic neurons.

AB - The present study was designed to examine whether expression of iNOS was involved in LPS-induced neurodegeneration in rat substantia nigra (SN) and to study the role of NO in the loss of the SN dopaminergic neurons. In Western blot analysis, iNOS was induced in the SN after injection of LPS in a time- and dose-dependent manner. Immunofluorescence and immunohistochemical analyses revealed that the iNOS is located in a fully activated microglia with the characteristic amoeboid morphology. Furthermore, LPS-induced loss of dopaminergic neurons was significantly inhibited by the administration of L-NG-nitroarginine, a selective inhibitor of NOS, and the glucocorticoid dexamethasone. These inhibiting agents for iNOS reduced LPS-induced microglial activation, suggesting that NO has a role in inflammatory-mediated microglial activation. These results demonstrate that LPS induces the expression of iNOS in activated microglia in the SN, and that NO and/or its metabolites may play a crucial role in inflammation-mediated degeneration of dopaminergic neurons.

KW - Inducible nitric oxide synthase

KW - Inflammation

KW - Lipopolysaccharide

KW - Microglia

KW - Neurodegeneration

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=0037330339&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037330339&partnerID=8YFLogxK

U2 - 10.1016/S0969-9961(02)00017-7

DO - 10.1016/S0969-9961(02)00017-7

M3 - Article

C2 - 12609487

AN - SCOPUS:0037330339

SN - 0969-9961

VL - 12

SP - 35

EP - 45

JO - Neurobiology of Disease

JF - Neurobiology of Disease

IS - 1

ER -

Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this