Neuroaxonal dystrophy in neuronal storage disorders: Evidence for major GABAergic neuron involvement

Steven U. Walkley, Henry J. Baker, Mario C. Rattazzi, Mark E. Haskins, Jang Yen Wu

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The formation of focal granular enlargements within axons (axonal spheroids or "torpedoes"; neuroaxonal dystrophy) is a well known phenomenon occurring in a variety of neurological diseases. The relative susceptibility of different types of neurons to this kind of axonal pathology, however, is largely unknown. An immunocytochemical study directed at localizing glutamic acid decarboxylase (GAD), the synthetic enzyme for the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in various CNS regions in feline models of lysosomal storage disorders has revealed vast numbers of axonal spheroids containing this enzyme. In some storage diseases (GM1 and GM2 gangliosidosis), GAD-immunoreactive spheroids were a common occurrence in many brain regions, whereas in other disorders these structures were more limited in distribution (α-mannosidosis), or were absent (mucopolysaccharidosis type I). Axonal spheroids unreactive for GAD were encountered in large numbers in subcortical white matter in GM2 gangliosidosis, but were infrequently observed in the other diseases. The incidence and distribution of GAD-immunoreactive spheroids in the various diseases under study were found to correlate closely with the type and degree of neurological deficits exhibited by affected animals. This study indicates that the neuroaxonal dystrophy occurring in some types of storage disorders commonly involves axons of GABAergic neurons and suggests that a resulting defect in neurotransmission in inhibitory circuits may be an important factor underlying brain dysfunction in this family of diseases.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalJournal of the Neurological Sciences
Volume104
Issue number1
DOIs
StatePublished - 1991

Fingerprint

Neuroaxonal Dystrophies
GABAergic Neurons
Glutamate Decarboxylase
GM2 Gangliosidosis
Axons
Mannosidase Deficiency Diseases
GM1 Gangliosidosis
Mucopolysaccharidosis I
Aminobutyrates
Felidae
Brain
Enzymes
Synaptic Transmission
gamma-Aminobutyric Acid
Neurotransmitter Agents
Pathology
Neurons
Incidence

Keywords

  • Axonal pathology
  • Axonal spheroid
  • GABAergic neuron
  • Gangliosidosis
  • Mucopolysaccharidosis
  • Neuroaxonal dystrophy
  • Neuronal storage disease
  • α-Mannosidosis

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Neuroscience(all)
  • Developmental Neuroscience
  • Neurology

Cite this

Neuroaxonal dystrophy in neuronal storage disorders : Evidence for major GABAergic neuron involvement. / Walkley, Steven U.; Baker, Henry J.; Rattazzi, Mario C.; Haskins, Mark E.; Wu, Jang Yen.

In: Journal of the Neurological Sciences, Vol. 104, No. 1, 1991, p. 1-8.

Research output: Contribution to journalArticle

Walkley, Steven U. ; Baker, Henry J. ; Rattazzi, Mario C. ; Haskins, Mark E. ; Wu, Jang Yen. / Neuroaxonal dystrophy in neuronal storage disorders : Evidence for major GABAergic neuron involvement. In: Journal of the Neurological Sciences. 1991 ; Vol. 104, No. 1. pp. 1-8.
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