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Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system.
J Neurochem. 2007 Mar; 100(5):1375-86.JN

Abstract

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.

Authors+Show Affiliations

Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536-0298, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17254027

Citation

Hunter, Randy L., et al. "Inflammation Induces Mitochondrial Dysfunction and Dopaminergic Neurodegeneration in the Nigrostriatal System." Journal of Neurochemistry, vol. 100, no. 5, 2007, pp. 1375-86.
Hunter RL, Dragicevic N, Seifert K, et al. Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem. 2007;100(5):1375-86.
Hunter, R. L., Dragicevic, N., Seifert, K., Choi, D. Y., Liu, M., Kim, H. C., Cass, W. A., Sullivan, P. G., & Bing, G. (2007). Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. Journal of Neurochemistry, 100(5), 1375-86.
Hunter RL, et al. Inflammation Induces Mitochondrial Dysfunction and Dopaminergic Neurodegeneration in the Nigrostriatal System. J Neurochem. 2007;100(5):1375-86. PubMed PMID: 17254027.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. AU - Hunter,Randy L, AU - Dragicevic,Natasa, AU - Seifert,Kristen, AU - Choi,Dong Young, AU - Liu,Mei, AU - Kim,Hyoung-Chun, AU - Cass,Wayne A, AU - Sullivan,Patrick G, AU - Bing,Guoying, Y1 - 2007/01/23/ PY - 2007/1/27/pubmed PY - 2007/4/3/medline PY - 2007/1/27/entrez SP - 1375 EP - 86 JF - Journal of neurochemistry JO - J Neurochem VL - 100 IS - 5 N2 - 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. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/17254027/Inflammation_induces_mitochondrial_dysfunction_and_dopaminergic_neurodegeneration_in_the_nigrostriatal_system_ L2 - https://doi.org/10.1111/j.1471-4159.2006.04327.x DB - PRIME DP - Unbound Medicine ER -