Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage.

Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage. Research Abstract Details 

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Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage. Abstract Text:

Donald M Kuhn,Dina M Francescutti-Verbeem,David M Thomas,

Methamphetamine (METH) intoxication leads to persistent damage of dopamine (DA) nerve endings of the striatum. Recently, we and others have suggested that the neurotoxicity associated with METH is mediated by extensive microglial activation. DA itself has been shown to play an obligatory role in METH neurotoxicity, possibly through the formation of quinone species. We show presently that DA-quinones (DAQ) cause a time-dependent activation of cultured microglial cells. Microarray analysis of the effects of DAQ on microglial gene expression revealed that 101 genes were significantly changed in expression, with 73 genes increasing and 28 genes decreasing in expression. Among those genes differentially regulated by DAQ were those often associated with neurotoxic conditions including inflammation, cytokines, chemokines, and prostaglandins. In addition, microglial genes associated with a neuronally protective phenotype were among those that were downregulated by DAQ. These results implicate DAQ as one species that could cause early activation of microglial cells in METH intoxication, manifested as an alteration in the expression of a broad biomarker panel of genes. These results also link oxidative stress, chemical alterations in DA to its quinone, and microglial activation as part of a cascade of glial-neuronal crosstalk that can amplify METH-induced neurotoxicity.

Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage. Publishing Authors By Initials

DM Kuhn,DM Francescutti-Verbeem,DM Thomas,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

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Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Annals of the New York Academy of Sciences

VOLUME: 1074

Page Numbers: 31-41

Journal Abbreviation: Ann. N. Y. Acad. Sci.

ISSN: 0077-8923

DAY: 3

MONTH: Aug

YEAR: 2006

Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage. Information

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LANGUAGE: eng

NlmUniqueID: 7506858

Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: pathology

Chemical & Substance for Abstract: Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage. Information

Substance Name: Dopamine

Registry Number: 51-61-6

Grant and Affiliation Information for Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage.

AFFILIATION: John D. Dingell VA Medical Center, Research & Development Service (11R), 4646 John R, Detroit, MI 48201, USA. donald.kuhn@wayne.edu

Country: United States

AGENCY: United States NIDA

GRANT: DA17327

ACRONYM: DA

MEDLINETA: Ann N Y Acad Sci

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