Abstract

The major goal of this project was to examine the roles of glial cells in inflammation-related neurodegeneration. We have employed both in vitro and in vivo rodent models of Parkinson's disease by focusing our studies on the mesencephalic dopaminergic neurons. Our laboratory was among the first to report that lipopolysaccharide (LPS)-induced neurotoxicity depended on the presence of glial cells. These cells secrete a variety of proinflammatory factors, including cytokines, free radicals and arachidonate metabolites that are the main contributors to the pathogenesis of inflammation-related neurodegenerative diseases. Recent studies from our laboratory indicate that microglia mediate a variety of environmental (such as rotenone, paraquat) or endogenous (such as amyloid protein, prion) neurotoxin-induced neurotoxicty, which were originally thought to produce neuronal damge by exerting directs effect on neurons. These findings have important implications in the research field of neurodegenerative diseases since our data suggest that microglia, instead of neurons, are the main target of these neurotoxins. Our current efforts focus on determining the relative importance of these proinflammatory factors in glia-mediated neuronal damage.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES090082-07
Application #
6838598
Study Section
(LPC)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Chu, Chun-Hsien; Wang, Shijun; Li, Chia-Ling et al. (2016) Neurons and astroglia govern microglial endotoxin tolerance through macrophage colony-stimulating factor receptor-mediated ERK1/2 signals. Brain Behav Immun 55:260-272
Chu, Chun-Hsien; Chen, Shih-Heng; Wang, Qingshan et al. (2015) PGE2 Inhibits IL-10 Production via EP2-Mediated ?-Arrestin Signaling in Neuroinflammatory Condition. Mol Neurobiol 52:587-600
Zhou, Hui; Zhang, Feng; Chen, Shih-heng et al. (2012) Rotenone activates phagocyte NADPH oxidase by binding to its membrane subunit gp91phox. Free Radic Biol Med 52:303-13
Liu, Shu-Lin; Li, Yi-Heng; Shi, Guey-Yueh et al. (2009) Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice. Cardiovasc Res 82:161-9
Wu, Xuefei; Chen, Po See; Dallas, Shannon et al. (2008) Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene transcription and protect dopaminergic neurons. Int J Neuropsychopharmacol 11:1123-34
Liu, Yuxin; Qin, Liya; Wilson, Belinda et al. (2008) Endotoxin induces a delayed loss of TH-IR neurons in substantia nigra and motor behavioral deficits. Neurotoxicology 29:864-70
Hartz, Anika M S; Bauer, Bjorn; Block, Michelle L et al. (2008) Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier. FASEB J 22:2723-33
Zhang, Dan; Hu, Xiaoming; Wei, Sung-Jen et al. (2008) Squamosamide derivative FLZ protects dopaminergic neurons against inflammation-mediated neurodegeneration through the inhibition of NADPH oxidase activity. J Neuroinflammation 5:21
Yang, Sufen; Zhang, Dan; Yang, Zhengqin et al. (2008) Curcumin protects dopaminergic neuron against LPS induced neurotoxicity in primary rat neuron/glia culture. Neurochem Res 33:2044-53
Gao, Xi; Hu, Xiaoming; Qian, Li et al. (2008) Formyl-methionyl-leucyl-phenylalanine-induced dopaminergic neurotoxicity via microglial activation: a mediator between peripheral infection and neurodegeneration? Environ Health Perspect 116:593-8

Showing the most recent 10 out of 43 publications