Back to Search
Start Over
Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer's brains.
- Source :
-
Neuroscience [Neuroscience] 1994 Dec; Vol. 63 (3), pp. 637-52. - Publication Year :
- 1994
-
Abstract
- The distribution and density of cannabinoid receptor binding and messenger RNA expression in aged human brain were examined in several forebrain and basal ganglia structures. In vitro binding of [3H]CP-55,940, a synthetic cannabinoid, was examined by autoradiography in fresh frozen brain sections from normal aged humans (n = 3), patients who died with Alzheimer's disease (n = 5) and patients who died with other forms of cortical pathology (n = 5). In the structures examined--hippocampal formation, neocortex, basal ganglia and parts of the brainstem--receptor binding showed a characteristic pattern of high densities in the dentate gyrus molecular layer, globus pallidus and substantia nigra pars reticulata, moderate densities in the hippocampus, neocortex, amygdala and striatum, and low densities in the white matter and brainstem. In situ hybridization histochemistry of human cannabinoid receptor, a ribonucleotide probe for the human cannabinoid receptor messenger RNA, showed a pattern of extremely dense transcript levels in subpopulations of cells in the hippocampus and cortex, moderate levels in hippocampal pyramidal neurons and neurons of the striatum, amygdala and hypothalamus, and no signal over dentate gyrus granule cells and most of the cells of the thalamus and upper brainstem, including the substantia nigra. In Alzheimer's brains, compared to normal brains, [3H]CP-55,940 binding was reduced by 37-45% in all of the subfields of the hippocampal formation and by 49% in the caudate. Lesser reductions (20-24%) occurred in the substantia nigra and globus pallidus, internal segment. Other neocortical and basal ganglia structures were not different from control levels. Levels of messenger RNA expression did not differ between Alzheimer's and control brains, but there were regionally discrete statistically significant losses of the intensely expressing cells in the hippocampus. The reductions in binding did not correlate with or localize to areas showing histopathology, estimated either on the basis of overall tissue quality or silver staining of neuritic plaques and neurofibrillary tangles. Reduced [3H]55,940 binding was associated with increasing age and with other forms of cortical pathology, suggesting that receptor losses are related to the generalized aging and/or disease process and are not selectively associated with the pathology characteristic of Alzheimer's disease, nor with overall decrements in levels of cannabinoid receptor gene expression.
- Subjects :
- Aged
Aged, 80 and over
Autoradiography
Brain Chemistry drug effects
Cannabinoids pharmacology
Cyclohexanols pharmacology
Female
Hippocampus metabolism
Humans
Image Processing, Computer-Assisted
In Situ Hybridization
Male
Memory physiology
Middle Aged
Nerve Degeneration physiology
RNA Probes
Receptors, Cannabinoid
Receptors, Drug biosynthesis
Receptors, Drug drug effects
Silver Staining
Aging metabolism
Alzheimer Disease metabolism
Brain Chemistry physiology
Cannabinoids metabolism
RNA, Messenger biosynthesis
Receptors, Drug metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0306-4522
- Volume :
- 63
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 7898667
- Full Text :
- https://doi.org/10.1016/0306-4522(94)90511-8