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.

Effects of dopamine depletion on the morphology of medium spiny neurons in the shell and core of the rat nucleus accumbens

“…Segment length is represented on the abscissa and spine density on the ordinate. McNeil1 et al, 1990), in hippocampal neurons of aged humans (Buell and Coleman, 1981;Flood et al, 1985Flood et al, , 1987, and in striatal cells in moderate grade Huntington's disease (Graveland et al, 1985;Ferrante et al, 1991). In each of these instances, however, the effects are transient and dendritic proliferation is followed by degeneration.…”

Neuroprotection for Huntington’s Disease: Ready, Set, Slow

“…16 The presence of the abnormal huntingtin protein in cells sets off a complex and poorly understood series of deleterious and progressive biochemical events leading in neurons to stress, physiological dysfunction, compensatory responses, neurodegeneration, and eventually cell death. Neurodegeneration appears to be quite a prolonged process, as evidenced by signs of chronic neuroplasticity 17,18 and of the slow involution of neurons with gradual loss of synapses, dendritic spines, dendritic branches, axonal segments, and supportive cytoplasmic resources such as mitochondria and organelles involved in the biosynthesis, modification, transport, and degradation of cellular molecules. The process of neurodegeneration ends in cell death, and dead and dying neurons in situ can cause local inflammatory responses and possibly worsen conditions in their immediate vicinity.…”

Imaging in cell-based therapy for neurodegenerative diseases

“…Decreased numbers of neurons immunoreactive for calbindin D28k, a Ca2+-binding protein present in a subset of striatal medium-sized spiny neurons has also been reported. Interestingly, Golgi staining studies showed that before death many striatal GABAergic neurons show morphological abnormalities in moderate grades of HD [64]. Changes in immunoreactivity for calbindin or Golgi staining indicate the presence of proliferative dendritic changes early in the disease.…”