Pyramidal neurons with ectopic dendrites in storage diseases exhibit increased GM2 ganglioside immunoreactivity

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Abstract

Cortical pyramidal neurons in several types of neuronal storage diseases have been shown by Golgi staining to sprout axon hillock-associated dendritic processes. Based on the relative incidence of this ectopic dendritogenesis, and on quantitative analyses of gangliosides in these same tissues, it has been proposed that abnormal accumulation of a specific metabolic product, GM2 ganglioside, is the pivotal event leading to re-initiation of dendritic sprouting [Siegel D.A. and Walkley S.U. (1994) J. Neurochem.62, 1852-1862]. In the present study, a monoclonal antibody was used to determine the cellular location of this ganglioside within the cerebral cortex of animal models of storage diseases with and without ectopic dendrite growth. Diseases exhibiting ectopic dendritogenesis included inherited and swainsonine-induced (juvenile-onset) α-mannosidosis, mucopolysaccharidosis type I, Niemann-Pick disease type C, and GM1 and GM2 gangliosidosis. Conditions lacking ectopic dendrite growth included adult-onset swainsonine-induced α-mannosidosis, fucosidosis, neuronal ceroid lipofuscinosis (Batten disease) and normal, mature brain. Immunocytochemical staining for GM2 ganglioside indicated that diseases exhibiting new dendritic sprouting, with the exception of GM1 gangliosidosis exhibited abundant GM2-like immunoreactivity within the cortical pyramidal cell population, whereas diseases without dendritic sprouting had GM2-like immunoreactivity limited to glia and/or to non-pyramidal neurons. Cortical tissues from normal animals at comparable ages and processed by similar procedures exhibited occasional glial cell staining but little or no neuronal labelling. Mechanisms by which normal cortical pyramidal neurons regulate dendritic initiation are poorly understood. However, it is known that this event is developmentally restricted, occurring only during early brain development. An exception, however, is in certain types of neuronal storage diseases in which mature pyramidal neurons have been shown to sprout new, ectopic dendrites. Results of the present study show that GM2 ganglioside is elevated within these neurons undergoing ectopic dendritogenesis and that pyramidal cells in storage diseases lacking this phenomenon also lack increases in this ganglioside. These findings, in conjunction with other recent reports, provide compelling eviddence that GM2 ganglioside plays a pivotal role in regulating dendritic initiation on cortical pyramidal neurons.

Original languageEnglish (US)
Pages (from-to)1027-1035
Number of pages9
JournalNeuroscience
Volume68
Issue number4
DOIs
StatePublished - 1995

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G(M2) Ganglioside
Pyramidal Cells
Dendrites
Gangliosides
Mannosidase Deficiency Diseases
Swainsonine
GM1 Gangliosidosis
Neuronal Ceroid-Lipofuscinoses
Staining and Labeling
Neuroglia
Fucosidosis
GM2 Gangliosidosis
Type C Niemann-Pick Disease
Mucopolysaccharidosis I
Neurons
Animal Disease Models
Brain
Growth
Cerebral Cortex
Monoclonal Antibodies

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pyramidal neurons with ectopic dendrites in storage diseases exhibit increased GM2 ganglioside immunoreactivity. / Walkley, Steven U.

In: Neuroscience, Vol. 68, No. 4, 1995, p. 1027-1035.

Research output: Contribution to journalArticle

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abstract = "Cortical pyramidal neurons in several types of neuronal storage diseases have been shown by Golgi staining to sprout axon hillock-associated dendritic processes. Based on the relative incidence of this ectopic dendritogenesis, and on quantitative analyses of gangliosides in these same tissues, it has been proposed that abnormal accumulation of a specific metabolic product, GM2 ganglioside, is the pivotal event leading to re-initiation of dendritic sprouting [Siegel D.A. and Walkley S.U. (1994) J. Neurochem.62, 1852-1862]. In the present study, a monoclonal antibody was used to determine the cellular location of this ganglioside within the cerebral cortex of animal models of storage diseases with and without ectopic dendrite growth. Diseases exhibiting ectopic dendritogenesis included inherited and swainsonine-induced (juvenile-onset) α-mannosidosis, mucopolysaccharidosis type I, Niemann-Pick disease type C, and GM1 and GM2 gangliosidosis. Conditions lacking ectopic dendrite growth included adult-onset swainsonine-induced α-mannosidosis, fucosidosis, neuronal ceroid lipofuscinosis (Batten disease) and normal, mature brain. Immunocytochemical staining for GM2 ganglioside indicated that diseases exhibiting new dendritic sprouting, with the exception of GM1 gangliosidosis exhibited abundant GM2-like immunoreactivity within the cortical pyramidal cell population, whereas diseases without dendritic sprouting had GM2-like immunoreactivity limited to glia and/or to non-pyramidal neurons. Cortical tissues from normal animals at comparable ages and processed by similar procedures exhibited occasional glial cell staining but little or no neuronal labelling. Mechanisms by which normal cortical pyramidal neurons regulate dendritic initiation are poorly understood. However, it is known that this event is developmentally restricted, occurring only during early brain development. An exception, however, is in certain types of neuronal storage diseases in which mature pyramidal neurons have been shown to sprout new, ectopic dendrites. Results of the present study show that GM2 ganglioside is elevated within these neurons undergoing ectopic dendritogenesis and that pyramidal cells in storage diseases lacking this phenomenon also lack increases in this ganglioside. These findings, in conjunction with other recent reports, provide compelling eviddence that GM2 ganglioside plays a pivotal role in regulating dendritic initiation on cortical pyramidal neurons.",
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