Alterations in neuron morphology in feline mannosidosis

Abstract

Studies using the Golgi method were performed on neocortical and cerebellar tissues from a 9-month-old cat with a history of progressive neurological deterioration and a subsequently demonstrated deficiency of the lysosomal enzyme α-d-mannosidase in both neural and non-neural tissues. Many cortical pyramidal neurons demonstrated morphological alterations involving formation of abnormal oplargements (meganeurites) at the axon hillock-initial segment area, abnormal sprouting of neurites (secondary neurites) in this same region, and various types of dendritic changes, such as formation of focal enlargements, thinning, and spine loss. Many nonpyramidal neurons also were abnormal but displayed only dendritic changes similar to those seen in pyramidal neurons. Cerebellar Purkinje cells displayed dendritic systems marked by focal swellings and often demonstrated one or more enlargements within axons (axonal spheroids) at some distance from otherwise normal-appearing cell bodies. Feline mannosidosis appears to be another of the lysosomal storage diseases in which highly specialized morphological changes accompany storage of unmetabolized substrate and contribute to the pathogenesis of the disease process.