TY - JOUR
T1 - Neurotransmitter receptor alterations in Huntington's disease
T2 - Autoradiographic and homogenate studies with special reference to benzodiazepine receptor complexes
AU - Whitehouse, Peter J.
AU - Trifiletti, Rosario R.
AU - Jones, Bruce E.
AU - Folstein, Susan
AU - Price, Donald L.
AU - Snyder, Solomon H.
AU - Kuhar, Michael J.
PY - 1985/8
Y1 - 1985/8
N2 - In vitro receptor autoradiography was used to construct semiquantitative maps of subtypes of muscarinic cholinergic (labeled with [3H]N‐methylscopolamine), benzodiazepine ([3H]flunitrazepam), γ‐aminobutyric acid ([3H]muscimol), dopamine, and serotonin ([3H]spiperone) receptors in frontal cortex, parietal cortex, caudate, putamen, and globus pallidus in tissue sections from 5 patients with clinically well‐evaluated Huntington's disease and 5 controls matched with respect to age, sex, and postmortem delay. Homogenates were prepared from the remaining cortical and striatal tissue and used to characterize pharmacologically these same receptors, as well as histamine, adenosine, and nitren‐dipine receptors. Neuronal loss and gliosis were assessed in the contralateral formalin‐fixed caudate and putamen. All binding sites measured (except serotonin) were reduced relative to control values in striatum primarily because of changes in the number of receptors rather than in affinity. Autoradiographic studies generally revealed that these changes were greater in the caudate than the putamen, paralleling the more severe neuropathological changes present in the caudate. In addition, autoradiographic studies demonstrated an increase in γ‐aminobutyric acid‐related receptors in the globus pallidus. In the cortex, receptor alterations were limited to an increase in the number of benzodiazepine receptors in the frontal cortex which was most prominent in superficial cortical layers.
AB - In vitro receptor autoradiography was used to construct semiquantitative maps of subtypes of muscarinic cholinergic (labeled with [3H]N‐methylscopolamine), benzodiazepine ([3H]flunitrazepam), γ‐aminobutyric acid ([3H]muscimol), dopamine, and serotonin ([3H]spiperone) receptors in frontal cortex, parietal cortex, caudate, putamen, and globus pallidus in tissue sections from 5 patients with clinically well‐evaluated Huntington's disease and 5 controls matched with respect to age, sex, and postmortem delay. Homogenates were prepared from the remaining cortical and striatal tissue and used to characterize pharmacologically these same receptors, as well as histamine, adenosine, and nitren‐dipine receptors. Neuronal loss and gliosis were assessed in the contralateral formalin‐fixed caudate and putamen. All binding sites measured (except serotonin) were reduced relative to control values in striatum primarily because of changes in the number of receptors rather than in affinity. Autoradiographic studies generally revealed that these changes were greater in the caudate than the putamen, paralleling the more severe neuropathological changes present in the caudate. In addition, autoradiographic studies demonstrated an increase in γ‐aminobutyric acid‐related receptors in the globus pallidus. In the cortex, receptor alterations were limited to an increase in the number of benzodiazepine receptors in the frontal cortex which was most prominent in superficial cortical layers.
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U2 - 10.1002/ana.410180207
DO - 10.1002/ana.410180207
M3 - Article
C2 - 2994554
AN - SCOPUS:0021843719
SN - 0364-5134
VL - 18
SP - 202
EP - 210
JO - Annals of neurology
JF - Annals of neurology
IS - 2
ER -