Reduced Purkinje cell dendritic arborization and loss of dendritic spines in essential tremor

Abstract

Based on accumulating post-mortem evidence of abnormalities in Purkinje cell biology in essential tremor, we hypothesized that regressive changes in dendritic morphology would be apparent in the Purkinje cell population in essential tremor cases versus age-matched controls. Cerebellar cortical tissue from 27 cases with essential tremor and 27 age-matched control subjects was processed by the Golgi-Kopsch method. Purkinje cell dendritic anatomy was quantified using a Neurolucida microscopic system interfaced with a motorized stage. In all measures, essential tremor cases demonstrated significant reductions in dendritic complexity compared with controls. Median values in essential tremor cases versus controls were: 5712.1 versus 10 403.2 μm (total dendrite length, P = 0.01), 465.9 versus 592.5 μm (branch length, P = 0.01), 22.5 versus 29.0 (maximum branch order, P = 0.001), and 165.3 versus 311.7 (number of terminations, P = 0.008). Furthermore, the dendritic spine density was reduced in essential tremor cases (medians = 0.82 versus 1.02 μm-1, P = 0.03). Our demonstration of regressive changes in Purkinje cell dendritic architecture and spines in essential tremor relative to control brains provides additional evidence of a pervasive abnormality of Purkinje cell biology in this disease, which affects multiple neuronal cellular compartments including their axon, cell body, dendrites and spines.