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Selective vulnerability in Huntington's disease: Preferential loss of cannabinoid receptors in lateral globus pallidus
Author(s) -
Richfield Eric K.,
Herkenham Miles
Publication year - 1994
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410360406
Subject(s) - putamen , globus pallidus , striatum , neuroscience , cannabinoid , biology , ventral pallidum , cannabinoid receptor , neuropathology , receptor , neurodegeneration , huntington's disease , basal ganglia , pathology , disease , medicine , central nervous system , dopamine , agonist , biochemistry
Selective neuronal vulnerability is a key feature of the neuropathology of Huntington's disease. We used [ 3 H]CP‐55,940, a synthetic cannabinoid, to label cannabinoid receptors in tissue sections from individuals dying with Huntington's disease and from normal control subjects. The density of cannabinoid receptors in striatum and pallidum was measured using quantitative autoradiography. There was a greater loss of cannabinoid receptors on striatal nerve terminals in the lateral pallidum compared to the medial pallidum, in Huntington's disease of all neuropathological grades. The disparity in binding density between the lateral and medial pallidum increased with higher grades of disease. There was also a greater loss of receptors in the lateral pallidum than in the putamen. The disproportionate loss of receptors in the lateral pallidum compared to the putamen increased in magnitude with severity of neuropathological grade. These data support the relative preferential loss or dysfunction of striatal neurons projecting to the lateral pallidum compared to neurons projecting to the medical pallidum. Terminals in the lateral pallidum containing cannabinoid receptors may be affected earlier or more severely than terminals in the medial pallidum, and both pallidal segments may be affected before or more severely than cell bodies or dendrites in the striatum. Terminal loss of markers may represent a response to perikaryal injury or dysfunction, or less likely, may indicate the primary site of neuronal damage in Huntington's disease.