PET study of the pre- and post-synaptic dopaminergic markers for the neurodegenerative process in Huntington's disease

Brain. 1997 Mar:120 ( Pt 3):503-14. doi: 10.1093/brain/120.3.503.

Abstract

PET and: markers for the pre- and postsynaptic neurons were used to study the dopamine system in vivo in Huntington's disease. The radioligands used were [11C]SCH 23390 for D1-receptors, [11C]raclopride for D2-receptors and [11C]beta-CIT for dopamine transporters. Five patients with Huntington's disease and five matched controls were recruited. Brain anatomy was examined by MRI. The findings in patients were as follows. Postsynaptic D1- and D2-receptor densities were similarly reduced in the striatum. A reduction in D1-receptor density was shown in the temporal cortex; it draws attention to the cortical degeneration in relation to the cognitive deficits observed in Huntington's disease. The reduction of D1- and D2-receptor binding potentials in the striatum correlated significantly with increasing duration of illness. The correlation between the duration of illness and decline of D1- and D2-receptors make these receptors valuable as quantitative markers for the Huntington's disease degenerative process. Besides postsynaptic changes, a significant 50% decrease of [11C]beta-CIT binding to the dopamine transporter was found in the striatum. A reduced striatal blood flow in Huntington's disease cannot be excluded and could account for a small part of the decrease in [11C]beta-CIT binding. We suggest that the finding reflects a loss of presynaptic terminals or a reduced expression of dopamine transporter in the nigrostriatal dopaminergic system in Huntington's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Benzazepines / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carbon Radioisotopes / metabolism
  • Cocaine / analogs & derivatives
  • Cocaine / metabolism
  • Dopamine Antagonists / metabolism
  • Female
  • Humans
  • Huntington Disease / diagnostic imaging*
  • Huntington Disease / metabolism*
  • Iodine Radioisotopes / metabolism
  • Ligands
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurons / metabolism
  • Raclopride
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Presynaptic / metabolism*
  • Salicylamides / metabolism
  • Tomography, Emission-Computed

Substances

  • Benzazepines
  • Carbon Radioisotopes
  • Dopamine Antagonists
  • Iodine Radioisotopes
  • Ligands
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Presynaptic
  • Salicylamides
  • Raclopride
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Cocaine