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Loss of Purkinje cell‐associated benzodiazepine receptors spares a high affinity subpopulation: A study with pcd mutant mice
Author(s) -
Vaccarino F. M.,
Ghetti B.,
Wade S. E.,
Rea M. A.,
Aprison M. H.
Publication year - 1983
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490090308
Subject(s) - cerebellum , receptor , flunitrazepam , granule cell , gabaa receptor , population , mutant , biology , microbiology and biotechnology , purkinje cell , biochemistry , medicine , chemistry , endocrinology , central nervous system , dentate gyrus , environmental health , gene
In order to identify the relative number of benzodiazepine (BZ) receptors in Purkinje and granule cells, the Purkinje cell degeneration (pcd) mutant mouse was used at, different ages. In these mice, Purkinje cells have degenerated almost completely by 45‐50 days of age. Granule cell loss occurs only later, and is most severe between 180 and 300 days. [ 3 H]Flunitrazepam (FNZ) and [ 3 H]ethyl‐carboline‐3‐carboxylate (β‐CC) were used as ligands. In the 45‐50‐day‐old pcd mice, it was found that there is approximately a 50% decrease in the number of receptors as labeled by [ 3 H]/β‐CC or [ 3 H]FNZ, when the binding is expressed as fmol/cerebellum. The binding decreased by approximately 80%in 300‐day‐old pcd mice (frnol/cerebellum). [ 3 H]FNZ was not displaced by 1 μM R05‐4864, ruling out binding to glial cells. Nonlinear regression analysis of FNZ saturation data provided evidence for two populations of receptors (high and low affinity sites). Only the low‐affinity sites were reduced in number at 45 days. [ 3 H]β‐CC saturation data showed, however, only one population of receptors. The total number of receptors (B max ) was significantly lower for β‐CC than for FNZ in the control mice. It appears that 50% of the total BZ receptors is associated with Purkinje cells. In addition, our data on 300‐day‐old pcd mutants strongly suggest the existence of granule cell‐associated BZ receptors.