Senescent microstructural changes in rat cerebellum

Abstract

Senescent changes in Sprague-Dawley rat cerebellar microstructure have beenquantified, focusing on the dominant element of cerebellar information processing, the Purkinje cell. In Golgi-Kopsch sections, many 26-month-old Purkinje cells appear defoliated, with small distal dendrites and spiny branchlets being most affected. The mean Purkinje cell area (soma plus dendrites) in computer-oriented sagittal sections is significantly decreased from 20,675±1,355 μm 2/cell in 6-month-old rats to17,088±1,107 μm 2/cell in 26- month rats. These morphologic changes may be the hallmark of dying cells: in hematoxylin and eosin (H+E)-stained sections from the same rats we also observe a significant senescent decrease in Purkinje neuron density in every vermis lobule examined (lobules II-VII). Overall, the mean number of Purkinje cells/mm of Purkinje cell layer (measured in 10 μm thick sagittal sections) declines from 1 acid-stained (EPTA) synapses in the upper molecular layer of the cerebellar vermis (lobules VIII-X), and there is a highly significant within-subjects correlation between Purkinje cell density and synaptic density. Overall, synaptic density (in sagittal, 842 μm 2 thin sections) decreases significantly from an average of 150,485 ± 3,641 synapses/mm 2 in 6-month rats to an average of 125,000 ± 4,849 synapses/mm 2 in 26-month rats. These changes are consistent with previous electrophysiologic and biochemical data showing age pathology of the cerebellum.