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

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. 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) alpha-mannosidosis, mucopolysaccharidosis type I, Niemann-Pick disease type C, and GM1 and GM2 gangliosidosis. Conditions lacking ectopic dendrite growth included adult-onset swainsonine-induced alpha-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 regulate dendritic initiation are poorly understood. However, it is known that this event is developmentally restricted, occurring only during early brain development.(ABSTRACT TRUNCATED AT 250 WORDS)