Proliferative and degenerative changes in striatal spiny neurons in Huntington's disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry

Abstract

Dysmorphic alterations of dendritic arbors and spines in spiny striatal neurons were identified in section-Golgi impregnations of moderate and severe grades of Huntington's disease (HD). These alterations could be characterized as either proliferative or degenerative changes. Proliferative changes included prominent recurving of distal dendritic segments, short-segment branching along dendrites, and increased numbers and size of dendritic spines. Degenerative alterations consisted of truncated dendritic arborizations, occasional focal dendritic swellings, and marked spine loss. Proliferative changes were found primarily in moderate grades of HD, while degenerative changes were predominantly found in severe grades. Cytopathologic changes increased with neuropathologic severity. Similar morphologic alterations were observed in calbindin D28k (Calb) stained neurons in HD striatum. The immunoreactive intensity of Calb staining was increased in the distal dendrites of positive neurons in HD striatum. The present findings provide morphologic and quantitative evidence that confirms an early and marked involvement of spiny striatal neurons in HD and suggest that neuronal growth, rather than degeneration, may be the harbinger of cell death in this disorder.