Selective Sparing of a Class of Striatal Neurons in Huntington's Disease

Abstract

A distinct subpopulation of striatal aspiny neurons, containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase, is preserved in the caudate nucleus in Huntington's disease. Biochemical assays confirmed a significant increase in the activity of this enzyme in both the caudate nucleus and putamen in postmortem brain tissue from patients with this disease. The resistance of these neurons suggests that the gene defect in Huntington's disease may be modifiable by the local biochemical environment. This finding may provide insight into the nature of the genetically programmed cell death that is a characteristic of the disease.

High Abundance of GluR1 mRNA and Reduced Q/R Editing of GluR2 mRNA in Individual NADPH-Diaphorase Neurons

“…Extensive study supports that NADPHd(ϩ) neurons are spared from hypoxic-ischemic insults and several neurodegenerative diseases including Huntington's disease (Ferrante et al, 1985) and Parkinson's disease (Hunot et al, 1996). The selective sparing of NADPH-d(ϩ) neurons has been attributed to resistance against N-methyl-d-aspartate (NMDA) or quinolinate toxicity (Koh et al, 1986;Koh and Choi, 1988).…”

Mutant huntingtin can paradoxically protect neurons from death

“…The medium-sized spiny neurons are the first to degenerate in the striatum, whereas largeand medium-sized aspiny striatal interneurons are less affected. 3,4 Although several binding domains (see below for further details) have been identified in Huntingtin, the normal function of the protein is poorly understood. The protein has been suggested to play a role in microtubule-mediated transport and vesicle function.…”

Imaging in cell-based therapy for neurodegenerative diseases

“…There is a preferential degeneration ofaminobutyricacid synthesizing (GABA-ergic) medium-sized spiny neurons and a relative sparing of the other subpopulations of striatal cells, at least in the early course of the disease [60]. Consequently, concentrations of substance P and Met-enkephalin that co-localize with different subsets of GABA neurons in the striatum, as well as the post-synaptic D 1 and D 2 dopaminergic receptors are decreased [61][62][63].…”

“…As a consequence, the most vulnerable GABAergic neurons appear located mostly within the dorsal parts of both caudate and putamen nuclei. Another intriguing neuropathological characteristic of HD is the relative sparing of the medium-sized interneurons positive for NADPH-diaphorase and somatostatin [60]. The preservation of this subset of striatal interneurons is associated with an increase in somatostatin and neuropeptide Y concentrations [66].…”