Vesicular neurotransmitter transporters in Huntington's disease: Initial observations and comparison with traditional synaptic markers

Citation
M. Suzuki et al., Vesicular neurotransmitter transporters in Huntington's disease: Initial observations and comparison with traditional synaptic markers, SYNAPSE, 41(4), 2001, pp. 329-336
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
SYNAPSE
ISSN journal
0887-4476 → ACNP
Volume
41
Issue
4
Year of publication
2001
Pages
329 - 336
Database
ISI
SICI code
0887-4476(20010915)41:4<329:VNTIHD>2.0.ZU;2-H
Abstract
Markers of identified neuronal populations have previously suggested select ive degeneration of projection neurons in Huntington's disease (HD) striatu m. Interpretations are, however, limited by effects of compensatory regulat ion and atrophy. Studies of the vesicular monoamine transporter type-2 (V-V MAT2) and of the vesicular acetylcholine transporter (VAChT) in experimenta l animals indicate that they are robust markers of presynaptic integrity an d are not subject to regulation. We measured dopamine and acetylcholine ves icular transporters to characterize the selectivity of degeneration in HD s triatum. Brains were obtained at autopsy from four HD patients and five con trols. Autoradiography was used to quantify radioligand binding to VMAT2, V AChT, the dopamine plasmalemmal transporter (DAT), benzodiazepine (BZ) bind ing sites, and D2-type dopamine receptors. The activity of choline acetyltr ansferase (ChAT) was determined as an additional marker of cholinergic neur ons. Autoradiograms were analyzed by video-assisted densitometry and assess ment of atrophy was made from regional structural areas in the coronal proj ection. Striatal VMAT2, DAT, and VAChT concentrations were unchanged or inc reased, while D2 and BZ binding and ChAT activity were decreased in HD. Aft er atrophy correction, all striatal binding sites were decreased. However, the decrease in ChAT activity was 3-fold greater than that of VAChT binding . In addition to degeneration of striatal projection neurons, there are los ses of extrinsic nigrostriatal projections and of striatal cholinergic inte rneurons in HD on the basis of vesicular transporter measures. There is als o markedly reduced expression of ChAT by surviving cholinergic striatal int erneurons. (C) 2001 Wiley-Liss, Inc.