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Following repeated subcutaneous administrations of 6-OHDA into neonatal rats (a dose; 100 mu/g bw), the effect on the brain development was examined. The striatal dopamine fluorescence never disappeared completely even immediately after multiple administrations of 6-OHDA, however a slight reduction of the fluorescence lasted for a long time. Semithin sections stained with toluidine blue showed numerous dark necrotic neurons appearing at a 15-times higher ratio than that in controls. Such necrotic neurons always accompanied a few granular deposits around the wavy surface. In a certain area of the striatum (0.898 mm2), there were no clear changes in the cell population in neurons and glia, in the ratio of glia to neurons, and in the ratio of each cell type of glia to the total glia, but some neuronal cell loss was speculated to occur slowly. The ultrastructural alteration observed at 28, 35 and 42 postnatal days in 6-OHDA treated rats was characterized by an appearance of myelin-like membranous lamellar bodies in the boutons synapsing with neural soma. In some cases intact small synaptic vesicles were seen around the lamellar body which probably rose from cell membranes in the synaptic area. Most of the necrotic neurons corresponded to the post-synaptic side for the boutons including lamellar bodies. Necrotic neurons displayed a dense cytoplasmic matrix, an increase of polysomes and cisternal swelling in rough ER and in the Golgi apparatus. Membranous lamellar bodies were occasionally observed in the periphery of satellite glial cells, probably oligodendrocytes. In conclusion, a long lasting reduction of striatal dopamine caused by 6-OHDA might disturb the function around the synaptic area and the metabolic regulation in the post-synaptic striatal neuron, thus resulted in the appearance of rather chronic morphological alterations in those areas.

Effect of neonatal administrations of 6-OHDA on the brain development. I. Alteration in the striatum.