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

doi:10.1016/0022-510X(91)90208-O

Journal of the Neurological Sciences

Volume 104, Issue 1, July 1991, Pages 1-8

https://doi.org/10.1016/0022-510X(91)90208-O Get rights and content

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.

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

Abstract

Brain Res.

Brain Res.

Brain Res.

Neuroscience

Int. Rev. Neurobiol.

Brain Res.

Dev. Brain Res.

Brain Res.

The clinical course of mannosidosis

Ann. Clin. Res.

Neuronal GM1 gangliosidosis in a Siamese cat with β-galactosidase deficiency

Science

Disorders of glycoprotein degradation: mannosidosis, fucosidosis, sialidosis, and aspartyl-glycosamininuria

Premier cas juvénile de neurolipidose complexe et de dystrophie neuroaxonale associée du système nerveux central

Arch. Suisses Neurol. Neurochir. Psychiat.

GM2 ganglioside lysosomal storage disease in cats with β-hexosaminidase deficiency

Science

The clinical and pathologic heterogeneity of feline alpha-mannosidosis

J. Vet. Intern. Med.

Lysosphingolipids inhibit protein kinase C: implication for the sphingolipidoses

Science

Alpha-L-iduronidase deficiency in a cat: A model of mucopolysaccharidosis I

Pediatr. Res.

The pathology of the feline model of mucopoly-saccharidosis I

Am. J. Pathol.

Infantile neuroaxonal dystrophy: A disease characterized by altered terminal axons and synaptic endings

Neurology

GABA neurons in the cerebral cortex

Neuroaxonal dystrophy: Its natural history and related disorders

Progr. Neuropathol.

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