Lipopolysaccharide-induced functional and structural injury of the mitochondria in the nigrostriatal pathway.
Accumulating evidence suggests that chronic inflammation plays a role in the progressive dopaminergic neurodegeneration that occurs in Parkinson's disease. It has been hypothesized that inflammation mediates neuronal damage via exacerbation of a vicious cycle of oxidative stress and mitochondrial dysfunction. The bacterial endotoxin, lipopolysaccharide (LPS), induces microglial activation and inflammation driven dopaminergic neurodegeneration. In order to test the hypothesis that LPS-induced inflammatory response might damage mitochondrial structure and function leading to nigral dopaminergic neuron loss, we injected LPS or saline into the striatum of rats. Here, we found that intrastriatal LPS induced deficit in mitochondrial respiration, damage to mitochondrial cristae, mitochondrial oxidation and nitration. Finally, we found significant loss of dopaminergic neurons in the substantia nigra one week after LPS injection. This study indicates that LPS-induced dopaminergic neurodegeneration might be exerted by mitochondrial injury.
Department of Anatomy and Neurobiology, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA.
Randy
R
Hunter
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Uttam
U
Ojha
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Sunil
S
Bhurtel
Department of Anatomy and Neurobiology, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA.
Guoying
G
Bing
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address: dychoi@yu.ac.kr.
Dong-Young
DY
Choi
D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D028361:Mitochondrial Diseases / Q000209:etiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020955:Striatonigral Degeneration / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D008070:Lipopolysaccharides; D024101:Mitochondrial Proteins; D014446:Tyrosine 3-Monooxygenase
Lipopolysaccharide; Mitochondria; Neuroinflammation; Oxidative stress; Parkinson’s disease