Advertisement

Acta Neuropathologica

, Volume 94, Issue 2, pp 164–172 | Cite as

GABAergic neuroaxonal dystrophy and other cytopathological alterations in feline Niemann-Pick disease type C

  • P. A. March
  • Mary Anna Thrall
  • Diane E. Brown
  • Thomas W. Mitchell
  • Anne C. Lowenthal
  • S. U. Walkley
Regular paper

Abstract

Feline Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal storage disease which shares many of the clinical, biochemical and pathological features of the corresponding human disorder. Cytopathological alterations in distinct neuronal cell populations were investigated in this animal model to gain a better understanding of the pathogenesis of brain dysfunction. Golgi and immunocytochemical methods were employed to characterize the cell architectural changes occurring in neuronal somata, dendrites and axons at different stages of disease progression. Cortical pyramidal neurons in laminae II, III, and V exhibited various degrees of meganeurite and/or swollen axon hillock formation with or without ectopic dendritogenesis. Enlarged axon hillock regions with neuritic processes and spines were recognized early in the progression of feline NPC but were less prevalent in mid to late stages of the disease. Glutamic acid decarboxylase (GAD) immunocytochemistry demonstrated immunoreactive spheroids in numerous GABAergic axons in neocortex, subcortical areas, and cerebellum. Parvalbumin-immunoreactive axonal spheroid distribution in brain closely mirrored results from the GAD studies, whereas calbindin D-28k-immunoreactive spheroids were conspicuously absent in most cortical and subcortical areas examined. Purkinje cell axonal spheroid formation progressed in a distal to proximal direction, with eventual involvement of recurrent axon collaterals. Purkinje cell death and a concomitant decrease in the numbers of spheroids in the cerebellum were observed late in the disease course. Clinical neurological signs in feline NPC occur in parallel with neuronal structural alterations and suggest that GABAergic neuroaxonal dystrophy is a contributor to brain dysfunction in this disease.

Key words Dendritogenesis Axonal spheroids Ganglioside Glutamic acid decarboxylase Parvalbumin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • P. A. March
    • 1
  • Mary Anna Thrall
    • 2
  • Diane E. Brown
    • 2
  • Thomas W. Mitchell
    • 2
  • Anne C. Lowenthal
    • 1
  • S. U. Walkley
    • 1
  1. 1.Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, NY 10461 USA Tel.: 1-718-430-4025; Fax: 1-718-430-8821US
  2. 2.Department of Pathology, Colorado State University, Fort Collins, CO 80523, USAUS

Personalised recommendations