Transmitter biochemistry and histochemistry of the hypoplastic cerebellum in mice after neonatal administration of cytosine arabinoside.

Administration of cytosine arabinoside, a DNA polymerase inhibitor, to mice (50 mg/kg body weight) on postnatal days 2, 3 and 4 resulted in severe hypoplasia of the cerebellar cortex accompanied by a large decrease in the cerebellar DNA and RNA contents. On postnatal days 10, 20, 30 and 70, concentrations of the putative neurotransmitters, noradrenaline and serotonin, were significantly increased in the affected cerebellum. In contrast, gamma-aminobutyric acid concentration was little changed, although a decrease in the content of gamma-aminobutyric acid per cerebellum was observed from postnatal day 20. No changes were found in the concentrations of these transmitter candidates nor in dopamine in the cerebral cortex or the brain stem. Histofluorescence observations revealed abnormally dense noradrenergic fibers in a poorly organized cerebellar cortex. The distribution of these fibers was characterized by a honeycomb pattern in the Purkinje cell and granular layers, and a dense plexus in the lower part of the thin molecular layer. However, the significance of neither the density of the noradrenergic fibers nor their abnormal distribution was apparent from the results of this study.