The effects of postnatal lead exposure on Purkinje cell dendritic development in the rat.

Rat pups, suckled by mothers maintained after parturition on a diet containing 4% lead acetate, were killed at 30 days and their cerebella examined. The blood lead was greatly increased in these animals (258.20 +/- 6.72 micrograms/100 ml) as compared with controls (4.75 +/- 0.75 micrograms/100 ml) and their mean body weight was reduced by 28%. Cerebellar weight, however, remained unchanged. Histologically the vermis showed vacuolation of the white matter and an increase in the size of Purkinje cell bodies. The total number of Purkinje and granule cells and their densities were unchanged except in animals with encephalopathy when these parameters were reduced. Network analysis of the dendritic trees of Purkinje cells indicated a 34.8% reduction in total dendritic length, due to reduction in total segment number and in the length of distal segments. Dendritic density and the frequency of trichotomous branching were unchanged by the experimental treatment. The density of dendritic spines over the periphery of the network was normal. The topology of the dendritic trees of Purkinje cells was abnormal in that branching patterns deviated from the normal pattern generated by random terminal growth. These results suggest that lead causes changes in Purkinje cell metabolism which reduce the rate of dendritic growth and cause abnormal branching. It remains to be determined whether these are direct effects or secondary to the vascular changes known to occur in the cerebellum during lead intoxication.