The NADPH oxidase is involved in lipopolysaccharide-mediated motor neuron injury.
Recent evidence indicates that neuroinflammation is a key event in amyotrophic lateral sclerosis (ALS). However, the precise impact of inflammation on motor neurons remains elusive. By using organotypic spinal cord slice cultures, we demonstrate that exposure to lipopolysaccharide (LPS) led to the demise of motor neurons in a dose- and time- dependent manner, whereas interneurons were impaired relatively mildly. The ultrastructure of motor neurons showed extensive vacuolation and swollen mitochondria. Motor neurons lacked the expression of calretinin, and BAPTA-AM, an intracellular calcium chelator, ameliorated motor neuron injury, indicating that the low capacity of calcium buffering may partially account for the vulnerability of motor neurons. NADPH oxidase was activated upon LPS challenge, and apocynin, the selective inhibitor of this enzyme, prevented inflammation-mediated toxicity to motor neurons, suggesting that NADPH oxidase may play a critical role in motor neuron death caused by LPS-induced inflammation.
Li
Bin
B
Department of Neurology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 05000, People's Republic of China.
Guo
Yan-Su
YS
Sun
Meng-Meng
MM
Dong
Hui
H
Wu
Shu-Yu
SY
Wu
Dong-Xia
DX
Li
Chun-Yan
CY
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009046:Motor Neurons / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology*; D013997:Time Factors
D000098:Acetophenones; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; C056165:acetovanillone; D019255:NADPH Oxidases