Permanent alterations of the dendritic tree of cerebellar Purkinje neurons in the rat following postnatal exposure to cis-dichlorodiammineplatinum.

The aim of this study was to characterize further the effect of cis-dichlorodiammineplatinum (cisDDP) on cerebellar Purkinje neurons of the immature rat. Ten-day-old rats were treated with cisDDP subcutaneously and killed after 1, 7, 20 or 65 days. The cerebellar vermis was impregnated by the Golgi-Cox method to evaluate the extent of morphological maturation of the Purkinje cell dendritic tree. One day after treatment, the dendritic network of Purkinje cells of treated animals was poorly developed and the cell somata still showed numerous perisomatic processes. This indicates that cisDDP interferes with the organization of microtubules and microfilaments by the cell. Later, several abnormal shapes of the Purkinje cell dendritic tree were observed. These included: (1) elongated primary dendrites; (2) asymmetrical dendrites; (3) sprouting of secondary and spiny branches in two planes of the molecular layer; and (4) damming of spiny branchlets at the pial surface. Moreover, all the dendritic networks of Purkinje cells in treated animals were of a lower Strahler order than in controls. All these data suggest that the late anomalies of the dendritic trees are secondary to the general cisDDP-induced damage of the cerebellar cortex, rather than being a primary effect of the drug on the dendritic tree growth.