Effect of prenatal manganese intoxication on [(3)H]glucose uptake in the brain of rats lesioned as neonates with 6-hydroxydopamine.

In the present study we examined the effects of prenatal manganese (Mn) intoxication on [(3)H]glucose uptake in the brain of rats lesioned as neonates with 6-hydroxydopamine (6-OHDA). MnCl(2) . 4H(2)O (10,000 ppm) was added to the drinking water of pregnant Wistar rats for the duration of pregnancy. On the day of parturition, Mn was discontinued as an additive to the drinking water. The control group consisted of rats that consumed water without Mn. Three days after birth, rats in both groups (control and Mn) were pretreated with desipramine hydrochloride (20 mg/kg) and pargyline hydrochloride (50 mg/kg) and injected bilaterally icv with one of three doses of 6-OHDA hydrobromide (15 mug, 30 mug or 67 mug base form in saline on each side) or with saline (control). 6-[(3)H]-D-glucose (500 muCi/kg, ip) was administered to male offspring in adulthood; after 15 min, brain specimens were taken (frontal cortex, hippocampus, striatum, thalamus with hypothalamus, pons and cerebellum) for determination of radioactivity in a liquid scintillation counter. Low dose 6-OHDA (15 mug icv) increased [(3)H]glucose uptake in all brain regions (p < 0.05) in both control and Mn-intoxicated animals. In rats lesioned with a moderate dose of 6-OHDA (30 mug icv), [(3)H]glucose uptake was unaltered in both control and Mn-exposed rats. High dose 6-OHDA (67 mug icv) reduced [(3)H]glucose uptake in all brain regions of Mn-exposed rats (except for cerebellum) compared with the saline group (all, p < 0.05). There was no change in regional brain uptake of [(3)H]glucose in control rats. In conclusion, this study shows that mild neuronal insult (15 mug icv 6-OHDA) increased glucose uptake in the brain while severe damage (concomitant 60 mug icv 6-OHDA and Mn treatment) significantly diminished this process.