Effects of neonatal 6-hydroxydopamine treatment on cortical development in mice and rats as monitored by developmental changes of gangliosides.

In a comparative study newborn rats and mice received subcutaneous (s.c.) injections of 6-hydroxydopamine (6-OHDA: 100 mg/kg) on postnatal days (p.d.) 1-3. In rats the treatment permanently reduced synaptosomal 3H-noradrenaline (3H-NA) uptake in the cortex to about 50-60% of control values. Conversely, cortical 3H-NA uptake was only temporarily reduced in treated mice during the first week and central noradrenergic neurons completely recovered during the second and third week. The different response of mice and rats to 6-OHDA is suggested to be due to earlier maturation of the noradrenergic system in mice, making it less vulnerable to neonatal injections of the neurotoxin. To determine whether the development of the cortex would be altered after degeneration of its noradrenergic innervation, developmental changes of cortical ganglioside content and composition of 6-OHDA-treated animals were compared to that of littermate controls. In 18-day-old rats, where reduction of 3H-NA uptake had persisted, ganglioside content was reduced by 16.5%, indicating growth impairment of neuronal membrane structures. Cortical gangliosides of younger rats and all the stages studied in mice were not affected by 6-OHDA treatment.