Cortical dendritic spine loss in rat pups whose mothers were prenatally injected with phenylacetate ('maternal PKU' model).

Pregnant rats injected with phenylacetate produced pups who had structurally abnormal cortical pyramidal cell dendrites. Neurons whose perikarya were in layer 5 had apical dendritic arbors with reduced numbers of dendritic spines which were longer and thinner than controls. Pyramidal cells of other cortical layers, as well as hippocampal pyramidal cells, were qualitatively and quantitatively normal. These results may be pertinent to children born to mothers with hyperphenylalaninemia (untreated PKU), many of whom have microcephaly, seizures and mental retardation. Application of findings in this rat model of maternal PKU to affected human children is uncertain until human histologic data become available.