THE EFFECTS OF POSTNATAL LEAD EXPOSURE ON Purkinje cell DENDRITIC DEVELOPMENT IN THE RAT

Abstract

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.

Low lead levels stunt neuronal growth in a reversible manner.

“…The effect of lead on neuronal morphology that we and others (40)(41)(42)(43)(44)(45) observe may be due to impaired assembly or stability of the cytoskeleton (46). Our interpretation is consistent with the ability of lead to interfere with calciumdependent events (47) including calcium-sensitive protein kinases (48)(49)(50), which have been implicated in neuronal growth in a variety of neurons (51)(52)(53)(54), including frog retinal axons (38,55).…”

Association between essential tremor and blood lead concentration.

“…There is also evidence that lead toxicity causes cerebellar pathology. Rat pups fed a diet containing 4% lead acetate demonstrated changes in the topology of Purkinje cell dendritic trees due to a change in Purkinje cell metabolism (McConnell and Berry 1979). Perinatal exposure to inorganic lead results in degenerative changes in Purkinje cells in the rabbit cerebellum (Walsh and Tilson 1984).…”

Comparative observations on inorganic and organic lead neurotoxicity.

“…Unfortunately, clear-cut neuropathologic findings associated with low-level lead exposure in humans are illdescribed, and animal models have revealed confusing results. The neuropathologic changes, if true, have been detailed through morphometric analysis and have revealed alterations in dendritic arborization and density of synaptic complexes in the cerebral cortex (12,13), a decrease in hippocampal pyramidal neuron spine density (14), reduction in dentate granule neuron dendritic field (15), decreased mossy fiber terminal proliferation in hippocampus (16,17), and abnormal dendritic branching of cerebellar Purkinje cells (18). In this latter study, the authors precluded the role of undernutrition in contribufing to the dendritic abnormality and also demonstrated occurrence of these changes at blood levels insufficient to produce overt clinical toxicity.…”