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

Philip A. March, Mary Anna Thrall, Diane E. Brown, Thomas W. Mitchell, Anne C. Lowenthal, Steven U. Walkley

Research output: Contribution to journalArticle

78 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)164-172
Number of pages9
JournalActa Neuropathologica
Volume94
Issue number2
DOIs
StatePublished - Aug 1997

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Neuroaxonal Dystrophies
Type C Niemann-Pick Disease
Felidae
Axons
Glutamate Decarboxylase
Purkinje Cells
Cerebellum
Brain
Substantia Gelatinosa
Lysosomal Storage Diseases
Calbindins
Parvalbumins
Pyramidal Cells
Neocortex
Carisoprodol
Dendrites
Disease Progression
Spine
Cell Death
Animal Models

Keywords

  • Axonal spheroids
  • Dendritogenesis
  • Ganglioside
  • Glutamic acid decarboxylase
  • Parvalbumin

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

GABAergic neuroaxonal dystrophy and other cytopathological alterations in feline Niemann-Pick disease type C. / March, Philip A.; Thrall, Mary Anna; Brown, Diane E.; Mitchell, Thomas W.; Lowenthal, Anne C.; Walkley, Steven U.

In: Acta Neuropathologica, Vol. 94, No. 2, 08.1997, p. 164-172.

Research output: Contribution to journalArticle

March, Philip A. ; Thrall, Mary Anna ; Brown, Diane E. ; Mitchell, Thomas W. ; Lowenthal, Anne C. ; Walkley, Steven U. / GABAergic neuroaxonal dystrophy and other cytopathological alterations in feline Niemann-Pick disease type C. In: Acta Neuropathologica. 1997 ; Vol. 94, No. 2. pp. 164-172.
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