Involvement of nitric oxide in neurodegeneration: a study on the experimental models of Parkinson's disease.
The present study was undertaken to explore involvement of nitric oxide (NO) in the experimental models of Parkinson's disease. Neurodegeneration was induced by unilateral injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS) in the right striatum. Lesions were functionally evaluated by amphetamine-induced asymmetrical behaviour and by decrease in the tyrosine hydroxylase (TH) immunostaining. An induction in the expression of iNOS and augmentation in nitrite content was observed in both the models. The extent of increase in iNOS expression was, however, different but the elevation in the nitrite content was comparable in both the models. The increase in iNOS expression inversely correlated with the tyrosine hydroxylase (TH) immunolabeling. Animals pretreated with a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), exhibited complete protection against amphetamine induced rotations in both the models. Thus, augmented NO availability subsequent to iNOS induction seems to play an important role in the initial phase of neurodegeneration.
Singh
Sarika
S
Division of Pharmacology, Central Drug Research Institute, Lucknow, India.
Das
T
T
Ravindran
A
A
Chaturvedi
R K
RK
Shukla
Y
Y
Agarwal
A K
AK
Dikshit
M
M
D000818:Animals; D001921:Brain / Q000473:pathology; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D008070:Lipopolysaccharides; D009573:Nitrites; D009569:Nitric Oxide; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D019331:NG-Nitroarginine Methyl Ester