ABSTRACT

AKIHIKO OGATA*, SEIJI KIKUCHI and KUNIO TASHIRO Departments of Neurology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan

Abstract-In adult Fischer rats sacrificed 12 weeks after infection with Japanese encephalitis virus (JEV) at the age of 13 days, neuronal loss with gliosis was confined mainly to the zona compacta of the bilateral substantia nigra, without lesions in the cerebral cortex and cerebellum. Furthermore, the most severe lesions were in the central part of zona compacta; the lateral cell groups were less affected. In addition, immunohistochemical study with anti-tyrosine hydroxylase (TH) showed that the number of TH-positive neurons was decreased significantly in the substantia nigra compared with that in controls, while comparable TH-positive neurons were found in the basal ganglia in the JEVtreated rats and age-matched controls. Thus, the distribution of the pathologic lesions in infected rats resembled those found in Parkinson's disease. The 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 by reverse transcription-polymerase chain reaction. JEV-infected rats showed marked bradykinesia. Significant behavioral improvement was observed upon administration of L-DOPA. The findings suggest that JEV infection of rats under the conditions described may serve as a model of virus induced Parkinson's disease. We could evaluate the possibilities of some new drugs using this rat model.