DYSTROPHIC DENDRITES INDUCED IN CULTURED PURKINJE-CELLS BY EXPOSURE TO VINBLASTINE

Organotypic cerebellar cultures were exposed to the mitotic spindle in hibitor, vinblastine, and examined by light and electron microscopy, a nd electrophysiologically. Purkinje cells in exposed cultures had stun ted, varicose dendrites when observed in preparations reacted with ant ibody to nonphosphorylated neurofilament protein. Ultrastructurally, m icrotubules were selectively reduced in Purkinje cell dendrites, which contained disarrayed excess smooth endoplasmic reticulum, but no larg e accumulations of densely packed neurofilaments. Spontaneous cortical discharges were initially increased in vinblastine treated cultures a nd then ceased, at which time the cultures became unresponsive to elec trical stimulation. The vinblastine-induced changes were attributed to impaired intracellular transport secondary to disruption of Purkinje cell dendritic microtubules.