A rat model of Parkinson's disease induced by Japanese encephalitis virus.
In Fischer rats infected with Japanese encephalitis virus (JEV) at 13 days after birth and sacrificed 12 weeks later, the major pathological changes resembled those found in Parkinson's disease. Specifically there was neuronal loss with gliosis which was confined mainly to the zona compacta of the substantia nigra, with a notable absence of lesions in the cerebral cortex and cerebellum. Changes were bilateral being most severe in the central part of the zona compacta. Immunohistochemical studies with anti-tyrosine hydroxylase (TH) demonstrated that the number of TH-positive neurons was significantly decreased in the substantia nigra compared to controls, while comparable numbers of TH-positive neurons were found in the basal ganglia in both JEV-treated rats and age-matched controls. JEV-infected rats showed marked bradykinesia, with significant behavioral improvement being observed following administration of L-DOPA. Immunohistochemical studies failed to detect JEV antigens in any region of the rat brain and the JEV genome was undetectable in the substantia nigra and the cerebral cortex using the reverse transcription-polymerase chain reaction (RT-PCR). The findings suggest that JEV infection of rats under the conditions described may serve as a model of virus induced Parkinson's Disease.
Ogata
A
A
Department of Neurology, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan.
Tashiro
K
K
Nukuzuma
S
S
Nagashima
K
K
Hall
W W
WW
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001479:Basal Ganglia / Q000473:pathology; D015415:Biomarkers; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D004672:Encephalitis, Japanese / Q000150:complications* / Q000821:virology; D005911:Gliosis / Q000209:etiology; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000473:pathology; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D000956:Antigens, Viral; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D012367:RNA, Viral; D014446:Tyrosine 3-Monooxygenase