Abnormal Purkinje cell morphogenesis in human renal agenesis. A Golgi study.

The prenatal histogenesis of the human cerebellum in renal agenesis has been studied in four fetuses (32-, 33-, 33-, and 36-week-old) using the rapid Golgi method. A fundamental anomaly involving the developing Purkinje cell has been found. The normal histogenesis of this neuron is aborted about the 32nd-33rd week of gestation. Subsequently, the neuron undergoes a progressive transformation acquiring an abnormal dendritic morphology in only four weeks. The perikaryal basal dendrites are retained rather than disappear, and they continue to grow spreading horizontally through the ganglionic plate and into the internal granular layer. Progressively the basal dendrites become hypertrophic and long and give off accessory apical branches that penetrate into the molecular layer. Concomitantly, the development of the apical dendrites is impeded, and their size and number are progressively reduced. The structure of the transformed Purkinje cell as well as the distribution of its dendrites contrast sharply with those of normal neurons. This transformation reflects a remarkable degree of plasticity of developing neurons and implies structural reorganizations of the local circuitry which could result in functional anomalies. Similar Purkinje cell dendritic anomalies have been described in renal dysplasia and the infantile type of polycystic kidney. The cause of this cerebellar anomaly, or its relationship to congenital renal disorders, remains unexplained. Failure of climbing fiber/Purkinje cell normal interactions is proposed as a possible explanation for the abnormal Purkinje cell histogenesis.