Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system.

Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. Research Abstract Details 

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Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. Abstract Text:

Randy L Hunter,Natasa Dragicevic,Kristen Seifert,Dong Young Choi,Mei Liu,Hyoung-Chun Kim,Wayne A Cass,Patrick G Sullivan,Guoying Bing,

Evidence suggests that chronic inflammation, mitochondrial dysfunction, and oxidative stress play significant and perhaps synergistic roles in Parkinson's disease (PD), where the primary pathology is significant loss of the dopaminergic neurons in the substantia nigra. The use of anti-inflammatory drugs for PD treatment has been proposed, and inhibition of cyclo-oxygenase-2 (COX-2) or activation of peroxisome proliferator-activated receptor gamma (PPAR-gamma) yields neuroprotection in MPTP-induced PD. Lipopolysaccharide (LPS) induces inflammation-driven dopaminergic neurodegeneration. We tested the hypothesis that celecoxib (Celebrex, COX-2 inhibitor) or pioglitazone (Actos, PPAR-gamma agonist) will reduce the LPS-induced inflammatory response, spare mitochondrial bioenergetics, and improve nigral dopaminergic neuronal survival. Rats were treated with vehicle, celecoxib, or pioglitazone and were intrastriatally injected with LPS. Inflammation, mitochondrial dysfunction, oxidative stress, decreased dopamine, and nigral dopaminergic neuronal loss were observed post-LPS. Celecoxib and pioglitazone provided neuroprotective properties by decreasing inflammation and restoring mitochondrial function. Pioglitazone also attenuated oxidative stress and partially restored striatal dopamine as well as demonstrated dopaminergic neuroprotection and reduced nigral microglial activation. In summary, intrastriatal LPS served as a model for inflammation-induced dopaminergic neurodegeneration, anti-inflammatory drugs provided protective properties, and pioglitazone or celecoxib may have therapeutic potential for the treatment of neuro-inflammation and PD.

Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. Publishing Authors By Initials

RL Hunter,N Dragicevic,K Seifert,DY Choi,M Liu,HC Kim,WA Cass,PG Sullivan,G Bing,

For similar thiazoles: thiazolidinediones research abstracts see: thiazoles: thiazolidinediones research

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Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of neurochemistry

VOLUME: 100

Page Numbers: 1375-86

Journal Abbreviation: J. Neurochem.

ISSN: 0022-3042

DAY: 23

MONTH: 01

YEAR: 2007

Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. Information

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LANGUAGE: eng

NlmUniqueID: 2985190

Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. Keywords Mesh Terms:

KEYWORDS: Thiazolidinediones

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. Information

Substance Name: Receptor, Insulin

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system.

AFFILIATION: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536-0298, USA.

Country: England

AGENCY: United States NINDS

GRANT: NS048191

ACRONYM: NS

MEDLINETA: J Neurochem

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