TY - JOUR
T1 - Neuroaxonal dystrophy in neuronal storage disorders
T2 - Evidence for major GABAergic neuron involvement
AU - Walkley, Steven U.
AU - Baker, Henry J.
AU - Rattazzi, Mario C.
AU - Haskins, Mark E.
AU - Wu, Jang Yen
PY - 1991/7
Y1 - 1991/7
N2 - 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.
AB - 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.
KW - Axonal pathology
KW - Axonal spheroid
KW - GABAergic neuron
KW - Gangliosidosis
KW - Mucopolysaccharidosis
KW - Neuroaxonal dystrophy
KW - Neuronal storage disease
KW - α-Mannosidosis
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U2 - 10.1016/0022-510X(91)90208-O
DO - 10.1016/0022-510X(91)90208-O
M3 - Article
C2 - 1919594
AN - SCOPUS:0025769357
SN - 0022-510X
VL - 104
SP - 1
EP - 8
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1
ER -