Autoradiographic distribution of [3H]nicotine binding in human cortex: Relative abundance in subicular complex
Department of Neuropathology, Newcastle General Hospital. Westgate Road, Newcastle upon Tyne NE4 6BE, UK Journal of Chemical Neuroanatomy
(Impact Factor: 1.5).
09/1992; 5(5):399-405. DOI: 10.1016/0891-0618(92)90056-V
Distinct patterns of [3H]nicotine (3 nm) binding were apparent in various regions of adult human neo- and archicortex. Receptor binding was greatest in the subicular complex—particularly presubiculum—and entorhinal cortex, where it was prominent in the characteristic parvo- and magnocellular islands of these regions and in middle layers of entorhinal cortex. In somatosensory cortex (Brodmann areas 3, 1 and 2) and occipital (area 17) cortex binding was highest in the upper and lower layers, and relatively sparse in the sensory input, layer IV. In primary motor (area 4) and temporal (area 21) cortex, binding in the outer half of the cortical ribbon was denser than that in the inner half and a distinct band was apparent in temporal and cingulate (area 32) in the lower portion of layer III. In prefrontal association cortex the pattern of binding was less distinct although slightly higher in the lower architectonic layers. There was generally little binding in the hippocampus (areas CA1–4) and dentate gyrus with the exception of the stratum lacunosum moleculare in CA2–3 and, to a lesser extent, supra- and subgranule zones of the dentate. These patterns of reactivity, which are distinct from that of the major cortical cholinergic innervation, suggest that the nicotinic receptor, detected using nanomolar concentrations of [3H]nicotine, may primarily be associated with intracortical circuitry in the neocortex. The relatively high density in entorhinal and subicular regions may be related to the extensive phylogenetic development of these regions which has occurred in conjunction with the development of multimodal association circuitry in the human cortex.
Available from: Dean Spurden
- "Autoradiographic analysis of [ 3 H]nicotinic binding in the human hippocampus and adjacent cortex indicates the highest densities in the subicular complex, stratum lacunosum moleculare, dentate gyrus, and entorhinal cortex (Perry et al 1992; Court et al, previously unpublished data [Figure 1]). This pattern of binding suggests an association with the perforant pathway, although results of a lesion study in rats would tend to refute this (Aubert et al 1994). "
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ABSTRACT: Loss of cortical nicotinic acetylcholine receptors with high affinity for agonists (20-50%) in patients with Alzheimer's disease is a common finding. Recent immunochemical analyses indicate that this deficit is predominantly associated with the loss of alpha4 subunits (30-50%), although modest reductions of alpha3 may occur in some individuals (25-29%). No reduction of beta2 subunit protein expression or levels of alpha3 and alpha4 messenger RNA has been reported. Decline in cortical [(125)I]alpha-bungarotoxin binding and alpha7 protein expression does not appear to be as extensive or widespread as the loss of alpha4 (0-40%), with no reduction in messenger RNA expression. In the thalamus, there was a trend for reduced [(3)H]nicotine binding in the majority of nuclei (0-20%) in Alzheimer's disease; however, there was a significant decline in [(125)I]alpha-bungarotoxin binding in the reticular nucleus. In the striatum [(3)H]nicotine binding was reduced in Alzheimer's disease, and although neuroleptic medication accentuated this change, it occurred in those free of neuroleptics. Changes in nicotinic acetylcholine receptors in Alzheimer's disease are distinct from those in normal aging and are likely to contribute to clinical features and possibly neuropathology.
Biological Psychiatry 03/2001; 49(3):175-84. DOI:10.1016/S0006-3223(00)01116-1 · 10.26 Impact Factor
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ABSTRACT: The vulnerability of the human hippocampal complex to disease, trauma, and aging indicates the necessity to target this area therapeutically. The distribution and density of transmitter receptors provide a rational basis for this approach, and in this study the topography of 11 different pharmacological sites is compared with the cholinergic innervation, which is particularly vulnerable in dementia. The regional distribution of cholinergic innervation to the normal adult human hippocampus and adjacent cortex, marked by acetylcholinesterase (AChE) fiber and terminal reactivity, is notable for its concentration in CA2/3 of Ammon's horn and the dentate fascia. Neither nicotinic (high-affinity nicotine binding) nor muscarinic ("M1" or "M2") cholinergic receptor binding paralleled this distribution. In Ammon's horn, 5-HT2 and kainate receptor binding more closely resembled the pattern of AChE, being concentrated in CA2-4 compared with CA1. By contrast, muscarinic M1 and M2, 5-HT1A, benzodiazepine (including zolpidem-insensitive binding), NMDA (MK801), and AMPA/QUIS receptors were higher in CA1 and/or subiculum. Kainate binding, like AChE, was high in CA4. 5-HT2 and nicotinic binding partially mimicked the pattern of AChE around the granule layer. In the subicular complex and parahippocampal gyrus, where cholinergic activity is relatively lower, muscarinic, 5-HT1A, and benzodiazepine binding were relatively high and the nicotinic receptor was remarkable for its highest density compared to other areas examined. In stratum lacunosum-moleculare of CA1, which was relatively low in AChE activity, there was a dense band of nicotinic, M2, and benzodiazepine receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)
Hippocampus 07/1993; 3(3):307-15. DOI:10.1002/hipo.450030306 · 4.16 Impact Factor
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ABSTRACT: Neuronal nicotinic acetylcholine receptors (nAchRs) are multimeric proteins constituted of two different subunits, alpha and beta, with different subtypes arrangement and different pharmacological and functional properties. nAchRs mediate neurotransmission in many central and peripheral synapses and appear to be affected in human degenerative disorders. We have studied the distribution of nAchR in human brain, particularly in the hippocampus and thalamus, by binding of 3H-nicotine and 3H-cytisine and by in situ hybridization with human alpha 3 and beta 2 nAchR subunits of mRNA. An alpha 3 probe shows a strong hybridization signal in the thalamus, while a beta 2 probe has a good signal at the level of the enthorinal cortex, hippocampus and in caudate and putamen. The alpha 3 and beta 2 mRNA localization is different from that described in other species. 3H-nicotine and 3H-cytisine binding were very similar in terms of anatomical distribution and comparable to the binding described in other animal species. The binding of the two ligands was distributed over the areas labeled by the alpha 3 and beta 2 probes and did not completely overlap with either of the subunits.
Neurochemistry International 08/1994; 25(1):69-71. DOI:10.1016/0197-0186(94)90055-8 · 3.09 Impact Factor
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