Senescent microstructural changes in rat cerebellum.

Senescent changes in Sprague-Dawley rat cerebellar microstructure have been quantified, 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 micron2/cell in 6-month-old rats to 17,088 +/- 1,107 micron2/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 micron thick sagittal sections) declines from 16.6 +/- 0.8 cells/mm in young rats to 12.5 +/- 0.2 cells/mm in old rats. As Purkinje cells are lost, so too are ethanolic phosphotungstic 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 micron2 thin sections) decreases significantly from an average of 150,485 +/- 3,641 synapses/mm2 in 6-month rats to an average of 125,000 +/- 4,849 synapses/mm2 in 26-month rats. These changes are consistent with previous electrophysiologic and biochemical data showing age pathology of the cerebellum.