Spatial and temporal pattern of Purkinje cell degeneration in shaker mutant rats with hereditary cerebellar ataxia

J Comp Neurol. 1995 May 15;355(4):490-507. doi: 10.1002/cne.903550403.

Abstract

Temporal-spatial patterns of surviving Purkinje cells were studied quantitatively in a rat mutant (shaker) with differential hereditary cerebellar ataxia and Purkinje cell degeneration. Shaker rat mutants are characterized behaviorally as mild if they are ataxic or as strong if they have ataxia and tremor. Purkinje cells degenerate in both mild and strong shaker mutants, but the temporal and spatial patterns of cell death are strikingly different. In mild shaker mutants, Purkinje cell death is temporally restricted, with 31-46% of the Purkinje cells in lobules I-IX dying by 3 months of age. Very few Purkinje cells degenerate after this age. Purkinje cell death is spatially random. In lobules I-IX, every second, third, or fourth Purkinje cell degenerates. Purkinje cells in lobule X do not degenerate. In strong shaker mutants, Purkinje cell degeneration is temporally protracted and spatially restricted. By 3 months of age, most Purkinje cells in lobules I-VIa, -b, and -d have degenerated. Numerous Purkinje cells in the paravermis of lobules VIIb-VIII have also degenerated. Surviving Purkinje cells in the vermis and lateral hemisphere of lobules VIIb-VIII are aligned in parasagittally oriented stripes or transversely oriented bands. Purkinje cells continue to degenerate in localized areas of the posterior lobe such that, by 18 months of age, surviving Purkinje cells are limited primarily to lobules VIc, VIIa, IXd, and X. Quantitative analysis indicates that none of the Purkinje cells in these lobules degenerate.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / physiology
  • Axons / ultrastructure
  • Behavior, Animal / physiology
  • Benzoxazines
  • Calbindins
  • Cerebellar Ataxia / genetics
  • Cerebellar Ataxia / metabolism
  • Cerebellar Ataxia / pathology*
  • Dendrites / physiology
  • Dendrites / ultrastructure
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Mutation
  • Nerve Degeneration / physiology*
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism
  • Oxazines
  • Purkinje Cells / metabolism
  • Purkinje Cells / physiology*
  • Rats
  • Rats, Mutant Strains
  • Rats, Sprague-Dawley
  • S100 Calcium Binding Protein G / immunology
  • S100 Calcium Binding Protein G / metabolism
  • Time Factors

Substances

  • Benzoxazines
  • Calbindins
  • Nerve Tissue Proteins
  • Oxazines
  • S100 Calcium Binding Protein G
  • cresyl violet