Isatin, an endogenous MAO inhibitor, and a rat model of Parkinson's disease induced by the Japanese encephalitis virus.
A single dose of isatin (indole-2,3-dione)(i.p.), an endogenous MAO inhibitor, significantly increased norepinephrine and 5-hydroxytryptamine concentrations in the rat brain and also significantly increased acetylcholine and dopamine (DA) levels in the rat striatum. Urinary isatin concentrations in patients with Parkinson's disease tend to increase according to the severity of disease. We have developed a rat model of Parkinson's disease induced by the Japanese encephalitis virus (JEV). The distribution of the pathological lesions of JEV-rats resemble those found in Parkinson's disease. Significant behavioral improvement was observed in JEV-rats after isatin, L-DOPA and selegiline administration using a pole test. Both isatin and selegiline prevented the decrease in striatum DA levels of JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not selegiline. These findings suggest that JEV-infected rats may serve as a model of Parkinson's disease and that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.
Minami
M
M
The Research Institute of Personalized Health Science, Health Science University of Hokkaido, Ishikari-Tobetsu, Japan. minami-m@touei.or.jp
Hamaue
N
N
Hirafuji
M
M
Saito
H
H
Hiroshige
T
T
Ogata
A
A
Tashiro
K
K
Parvez
S H
SH
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000472:pathogenicity*; D007510:Isatin / Q000627:therapeutic use*; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000821:virology; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D007510:Isatin; D014446:Tyrosine 3-Monooxygenase