A comparison was made of cerebellar dendritic development in the normal rat and in a new model of phenylketonuria, the phenylacetate-treated suckling rat. Golgi stain analysis of the Purkinje cells shows striking regional variations in the dendritic growth. These variations were observed in both the control and phenylacetate-treated animals and were especially striking before 15 days of life. Quantitative analysis of the dendritic tree revealed, in the phenylacetate-treated rat, a significant reduction in the total number of dendritic branches. However, the individual terminal dendritic length was largely unaltered. These effects of phenylacetate differ from those of deafferentation, and starvation. Results of this investigation clearly define the harmful effects of phenylacetate on developing neurons and are compatible with the clinical observation that brain damage in phenylketonuria occurs mainly during the first few years of life, the critical period of neuronal development.
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